Post on 29-May-2022
Antimicrobial Treatment
Guidelines for Common
Infections
October 2017
Published by: The NB Provincial Health Authorities Anti-infective Stewardship Committeeunder the direction of the Drugs and Therapeutics Committee
Introduction:
These clinical guidelines have been developed or endorsed by the NB Provincial Health Authorities Anti-infective Stewardship Committee and its Working Group, a sub-committee of the New Brunswick Drugs and Therapeutics Committee. Local antibiotic resistance patterns and input from local infectious disease specialists, medical microbiologists, pharmacists and other physician specialists were considered in their development. These guidelines provide general recommendations for appropriate antibiotic use in specific infectious diseases and are not a substitute for clinical judgment.
Website Links For Horizon Physicians and Staff:
http://skyline/patientcare/antimicrobial
For Vitalité Physicians and Staff:
http://boulevard/FR/patientcare/antimicrobial
To contact us: antimicrobial.stewardship@rha-rrs.ca
When prescribing antimicrobials:
Carefully consider if an antimicrobial is truly warranted in the given clinical situation Consult local antibiograms when selecting empiric therapyInclude a documented indication, appropriate dose, route and the planned duration of
therapy in all antimicrobial drug ordersObtain microbiological cultures before the administration of antibiotics (when possible)Reassess therapy after 24-72 hours to determine if antibiotic therapy is still warranted
or effective for the given organism or clinical situation. Reassess based on relevantclinical data, microbiologic and/or radiographic information
Assess for de-escalation as appropriate based on available microbiology culture andsusceptibility results
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Antimicrobial Treatment Guidelines For Common Infections
(Click arrow buttons to navigate)
Section 1: Anatomical Page Foot Diabetic Foot Infections 4
Gastrointestinal Clostridium difficile Infection 5 Intra-Abdominal Infections 6
Respiratory Acute Bacterial Rhinosinusitis 8 Acute Exacerbation of Chronic Obstructive Pulmonary Disease 9 Community Acquired Pneumonia 10
Skin and Soft Tissue Cellulitis/Erysipelas 11
Genitourinary When to Send a Urine for Culture and Urinalysis 12 Positive Urine Culture Assessment Algorithm Urinary Tract Infection Treatment Guideline
Drug Use Guidelines Aminoglycoside Dosing and Monitoring Guidelines 15 Antimicrobial Dosing Tool Management of Penicillin and β-Lactam Allergy 43 Antimicrobial Allergy Evaluation Tool 52 IV-to-PO Conversion Criteria 58 Surgical Prophylaxis Guidelines Vancomycin Dosing and Monitoring Guidelines Nevirapine for Perinatal HIV Transmission Prophylaxis
Other Splenectomy Vaccination Kit 81
References 88
3
13 14
31
59 74 80
EMPIRIC ANTIMICROBIAL THERAPY FOR DIABETIC FOOT INFECTION (Endorsed by NB Health Authorities Anti-Infective Stewardship Committee February 2016)
Infection Severity Preferred Empiric Regimens1 Alternative Regimens1 Comments Mild • Cellulitis less than 2 cm
and without involvement ofdeeper tissues
• Non-limb threatening• No signs of systemic toxicity
Wound less than 4 weeks duration • cephalexin 500 mg PO four times daily*Wound greater than 4 weeks duration • sulfamethoxazole/trimethoprim 800/160 mg PO twice daily* +
metroNIDAZOLE 500 mg PO twice daily
Wound less than 4 weeks duration • clindamycin 300 – 450 mg PO four times daily (only if
severe β-lactam allergy)Wound greater than 4 weeks duration • amoxicillin/clavulanate 875/125mg PO twice daily* OR• doxycycline 100 mg PO twice daily + metroNIDAZOLE
500 mg PO twice daily
• Outpatient management recommended
• Tailor regimen based on C&Sresults & patient response
Moderate • Cellulitis greater than 2
cm or involvement of deeper tissues
• Non-limb threatening• No signs of systemic toxicity
Wound less than 4 weeks duration • ceFAZolin 2 g IV q8h* OR• cefTRIAXone 2 g IV once daily (to facilitate outpatient management when
ambulatory administration of ceFAZolin not possible)Wound greater than 4 weeks duration • ceFAZolin 2 g IV q8h* + metroNIDAZOLE 500 mg PO twice daily OR• cefTRIAXone 2 g IV once daily + metroNIDAZOLE 500 mg PO twice daily
(to facilitate outpatient management when ambulatory administration of ceFAZolin not possible)
Wound less than 4 weeks duration • levofloxacin 750mg IV/PO once daily* (only if severe
β-lactam allergy)Wound greater than 4 weeks duration • levofloxacin 750mg IV/PO once daily* +
metroNIDAZOLE 500 mg PO twice daily (only if severe β-lactam allergy)
• Initial management with outpatient parenteral therapy with rapid step-down to oral therapy after 48 to 72 hours based on patient response recommended
• Tailor regimen based on C&Sresults & patient response
Severe • Systemic signs of sepsis• Limb or foot threatening• Extensive soft tissue
involvement• Pulseless foot
• piperacillin-tazobactam 3.375 g IV q6h* • imipenem/cilastatin 500 mg IV q6h* OR• levofloxacin 750 mg IV once daily* + metroNIDAZOLE
500 mg PO/IV twice daily (only if severe β-lactam allergy)
• Inpatient management recommended
• Urgent vascular assessment if pulseless foot
• Tailor regimen based on C&Sresults & patient response
Clinical Pearls: 1 If high risk for MRSA, should include sulfamethoxazole/
trimethoprim 800/160 mg PO twice daily * or doxycycline 100 mg PO twice daily for mild infections and vancomycin weight- based dosing to a target trough of 15 – 20 mg/L for moderate- severe infections
• Debridement, good glycemic control and proper wound care are important for the management of diabetic foot infections
• Cultures: prefer tissue specimens post-debridement and cleansing of wound; surface or wound drainage swabs not recommended
• In a clinically infected wound a positive probe-to-bone (PTB)test is highly suggestive of osteomyelitis
• Imaging: recommend plain radiography (radionuclide imaging unnecessary)
Duration of Therapy • Soft tissue only – 2 weeks• Bone involvement with complete surgical resection of all infected bone – 2 weeks• Bone involvement with incomplete surgical debridement of infected bone – 4-6 weeks IV• Bone involvement with no surgical debridement or residual dead bone postoperatively – 6 weeks IV, followed by 6 weeks PO
References: 1. Bowering K, Embil JM. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in
Canada: Foot Care. Can J Diabetes 37(2013) S145-S1492. Lipsky BA, Berendt AR, Cornia PB et al. 2012 Infectious Disease Society of America Clinical Practice Guidelines for the Diagnosis and Treatment
of Diabetic Foot Infections. CID 2012:54(12):132-1733. Lipsky BA, Armstrong DG, Citron DM et al. Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective,
randomized, controlled, double-blinded, multicentre trial. Lancet 2005; 366:1695 – 17034. Blond-Hill E, Fryters S. Bugs & Drugs An Antimicrobial/Infectious Diseases Reference. 2012. Alberta Health Services
* Dose adjustment required in renal impairment
9782-10650-04-2016
4
Diarrhea: 3 or more unformed or watery stools in 24 hrs or less
Results pending but high clinical suspicion
Send stool for Clostridium difficile testing
Colonoscopic/histopathologic findings of pseudomembranous colitis
Positive results
1. Discontinue therapy with the inciting antimicrobial agent if possible
2. Stop all anti-peristaltic & pro-motility agents unless clearly indicated1
3. Begin Infection Control Precautions
- Accommodate patient in a private room (if possible)- Gowns and gloves (masks unnecessary)- Perform hand hygiene (preferably soap and water)
4. Classify & treat according to severity of CDI
Mild or ModerateCriteria
WBC 15x109/L or less ORSerum creatinine level less than 1.5 x baseline level
SevereCriteria:
WBC greater than 15x109/L ORSerum creatinine level 1.5 x baseline level or greater ORClinical judgement (e.g. ICU Admission)
Severe, ComplicatedCriteria:
Hypotension or shock ORIleus ORMegacolon
Initial Episode
metroNIDAZOLE 500 mg POthree times daily x 10 - 14 days
Any Episode
vancomycin 125 mg POfour times daily x 10 - 14 days
Any Episodevancomycin 125 mg2 PO/NG four times daily
+/- metroNIDAZOLE 500 mg IV three times daily
(Add vancomycin 500 mg in 100mL NS retention enema four times daily if ileus)Duration: Generally 10 - 14 days but may
extend depending on clinical scenario.
First Recurrence:
Treat same as for initial episode and according to CDI severitySecond Recurrence:
Vancomycin taper regimen: 125 mg PO four times daily x 14 days, then 125 mg PO twice daily x 7 days, then 125 mg PO once daily x 7 days, then 125 mg PO every 2 days x 2 weeks then discontinueThird Recurrence:
Consider ID consult
Recurrent Clostridium difficile Infection
Clinical Pearls- Pregnancy/breast feeding: use vancomycin PO (avoid metroNIDAZOLE)- Symptoms of CDI usually begin 2 - 3 days after colonization- Test for cure is not recommended- Vancomycin administered intravenously is ineffective for CDI- Fidaxomicin is a non-formulary item that should only be considered under extenuating clinical circumstances, ID consultation required1Examples: loperamide, diphenoxylate, opioids, metoclopramide, domperidone, etc2For complicated severe episodes some authorities recommend vancomycin doses up to 500 mg; appropriate dose has not beenestablished in clinical trials
Antimicrobial Management of Clostridium difficile Infection (CDI)
(NB Provincial Health Authorities Anti-Infective Stewardship Committee, May 2014)
Adapted from: Vancouver Coastal Health Antimicrobial Stewardship Treatment Guidelines for Common Infections March 2011 1st Edition5
Antimicrobial Therapy for Intra-Abdominal Infections (NB Provincial Health Authorities Anti-Infective Stewardship Committee, November 2015) Origin/Severity of Intra-
Abdominal Infection Probable
Pathogens Preferred Empiric
Regimens Alternative Empiric
Regimens Comments Community Acquired Infection, Mild to Moderate severity:
• i.e. gastroduodenalperforation, cholangitisa,cholecystitisa, appendicitis,diverticulitisb, primary(spontaneous) bacterialperitonitis
• With no evidence of systemictoxicity (APACHE II score lessthan 15)
Core: Enterobacteriaceae (i.e. E.coli, Klebsiella spp, Proteus spp, Enterobacter spp.) Anaerobes (i.e. B. fragilis, Clostridium spp. etc…), Streptococcus spp, ± Enterococcus spp (see below if isolated)
ceFAZolin 2 g IV q8hg,* + metroNIDAZOLE 500 mg IV/PO q12ha,b
Intravenous-to-Oral Conversionc: amoxicillin/clavulanate 875/125 mg po q12hh,*
CefOXitin 2 g IV q6hh,* OR
gentamicin 5 – 7 mg/kg IV q24h* + metroNIDAZOLE 500 mg IV/PO q12h
ORciprofloxacin 400 mg IV OR 500 mg PO q12h* + metroNIDAZOLE 500 mg IV/PO q12h
Duration of Therapy, dependent on clinical picture:
o 5 – 7 days usually sufficient ifoptimal source control obtained
o If intra-abdominal abscess:antimicrobial therapy may beprolonged, with duration dependanton resolution (up to 4 to 6 weeks)
o Day of intervention (drainage,surgery, etc.) considered as day 1of therapy
Stop antimicrobial within 24 hours if: o acute stomach, duodenum &/or
proximal jejunum perforation if no acid-reducing therapy or malignancy and source control achieved OR
o penetrating bowel trauma repairedwithin 12 hours OR
o intraoperative contamination of asurgical field from enteric contents OR
o acute appendicitis withoutperforation, abscess or local peritonitis OR
o patients undergoingcholecystectomy for acute cholecystitis unless evidence of infection outside wall of the gallbladder (ex. perforation)
Community Acquired Infection, Severe:
• As above with APACHE IIscore greater than or equal to15, signs of systemic toxicity,greater than 70 years old,immunocompromised,secondary peritonitis, cancer,poor nutritional status orincomplete or delayed sourcecontrol
Core cefTRIAXone 2 g IV q24hg + metroNIDAZOLE 500 mg IV/PO q12h
Intravenous-to-Oral Conversionc: As for mild to moderate above
piperacillin/tazobactam 3.375 g IV q6hd,e,h,*
OR
ampicillin 2 g IV q6hh,* + gentamicin 5 – 7 mg/kg IV q24h* + metroNIDAZOLE 500 mg IV q12h
OR
ciprofloxacin 400 mg IV q12h* + metroNIDAZOLE 500 mg IV q12h
Healthcare Associated • Hospitalized greater than 48
hours at time of onset, recentprolonged hospitalization,post-operative infection, longterm care, rehab, dialysis,nursing home, recentantibiotics
Core Plus: Pseudomonas, Multidrug Resistant
(MDR) Gram-negative bacteria,
MRSA (see below if isolated)
piperacillin/tazobactam 3.375 g IV q6hd,e,h,*
imipenem-cilastin 500 mg IV q6he,g,*
(preferred if suspected MDR Gram-negative)
OR
ciprofloxacin 400 mg IV q12h* + metroNIDAZOLE 500 mg IV q12h + vancomycin 15 mg /kg IV q12hf,*
(continued on next page)
6
Origin/Severity of Intra-Abdominal Infection
Probable Pathogens
Preferred Directed Regimens
Alternative Directed Regimens Comments
If MRSA Suspected (colonized or history of MRSA infection)
Add vancomycin 15 mg/kg IV q12h* (for target trough of 15 – 20 mg/L)
If Candida isolated Add fluconazole 800 mg IV/PO then 400 mg IV/PO q24h* micafungin 100 mg IV q24h
• micafungin preferred if Candida krusei orCandida glabrata isolated
If Enterococci isolated Add ampicillin 2 g IV q6hh,*(not required if on piperacillin/tazobactam or imipenem-cilastin)
Immediate (IgE-mediated) penicillin allergy or penicillin resistant: vancomycin 15 mg/kg IV q12hf,*
• Enterococcal coverage only necessary if: isolated as predominant organism in
culture OR healthcare associated infection OR patient is immunocompromised OR Blood culture positive
• If Enterococcus faecium isolated andcriteria for treatment met, use vancomycinas empiric therapy and reassess based onsusceptibility results
Clinical Pearls: • Antimicrobial therapy does not preclude source control (ex. percutaneous drainage or surgery)• Patients with recent prolonged hospitalization (5 or more days) or recent antimicrobials (2 or more days) within the previous 3 months pose risk for resistance and
treatment failure, treat as healthcare associated• Empiric Enterococci coverage is not recommended for mild-moderate severity community-acquired intra-abdominal infections. It should be reserved for patients in
whom this pathogen is more frequently found (healthcare-associated infections, particularly those with postoperative infection, presence of severeimmunosuppression, recurrent infection, patients who receive long-term cephalosporin treatment, and those with valvular heart disease or prosthetic intravascularmaterials)
• CAUTION: Significant E.coli resistance (greater than 20%) to fluoroquinolones and amoxicillin exist in some areas of the province; check local antibiogram andconfirm C&S results when available
• Pathogen directed therapy should be used when culture and susceptibility results are availableWorkup:• Recommend blood, intraoperative and/or abscess fluid cultures in patients with post-operative or healthcare-associated infections; those with treatment failure and/or
requiring re-operation; or recently on antimicrobial therapy• Blood cultures recommended if patient has sepsis syndrome• Reassess initial empiric therapy based on clinical state & results of microbiological analysisa Anaerobic coverage not indicated for cholecystitis & cholangitis unless biliary-enteric anastomosis is present or aggravating factors (advanced age, immunosuppression
or metabolic instability) b Most cases of diverticulitis can be managed with oral antibiotic therapy c Intravenous-to-Oral conversion: consider if infection well controlled, afebrile x 24 hrs., hemodynamically stable, tolerating oral intake and no clinical, radiographic or
surgical sign of intra-abdominal collection from non-optimal drainage d For Pseudomonas aeruginosa infection, piperacillin/tazobactam dosage may be increased to 4.5 gm IV q6h e Anaerobic coverage adequate, addition of metroNIDAZOLE or clindamycin to piperacillin/tazobactam or imipenem-cilastin not necessary f Adjust vancomycin dose to target a trough level of 10 to 20 mg/L g Appropriate therapy option for patients with an immediate Type-1 (IgE-mediated) hypersensitivity reaction to penicillin (i.e. anaphylaxis, angioedema, laryngeal edema, urticaria) h Avoid in patients with immediate Type-1 (IgE-mediated) hypsensitivity reaction to penicillin, significant risk of cross-reactivity exists. *Dose adjustment required in renal impairment
7
Antimicrobial Therapy for Acute Bacterial Rhinosinusitis (ABRS) (NB Provincial Health Authorities Anti-Infective Stewardship Committee, November 2015) Treatment Criteria Clinical diagnosis and differentiation of acute bacterial from viral rhinosinusitis is based on the characteristic patterns of clinical presentations taking
into account duration of symptoms, severity of illness, temporal progression and “double-sickening” in the clinical course The following clinical presentations (any of the 3) are recommended for identifying patients with acute bacterial vs. viral rhinosinusitis:
1. Onset with persistent symptoms or signs compatible with acute rhinosinusitis, lasting for greater than or equal to 10 days without any evidence of clinical improvement2. Onset with severe symptoms or signs of high fever (greater than or equal to 39 °C) and purulent nasal discharge or facial pain lasting for at least 3 to 4 consecutive days at the
beginning of illness3. Onset with worsening symptoms or signs characterized by the new onset of fever, headache or increased in nasal discharge following a typical viral upper respiratory infection
that lasted 5 – 6 days and were initially improving (“double sickening”) Initiation of empiric antimicrobial therapy is recommended as soon as the clinical diagnosis of ABRS is established based on the above criteria; if
diagnosis is uncertain due to mild symptoms then consider observing without antibiotic therapy for 3 days
Presentation Preferred Empiric Regimen
Alternative Empiric Regimen Duration Comments
Mild – Moderate Symptoms less than 10 days duration
Symptomatic therapy only Consider intranasal saline irrigation
5 – 7 days
+/- intranasal corticosteroids
Mild – Moderate Symptoms greater than 10 days OR worsening after 5 to 6 days OR Severe Symptoms for 3 to 4 consecutive days
doxycycline 100 mg po q12h amoxicillin 1000 mg po q8h* OR amoxicillin/clavulanate 875/125 mg po q12h* OR sulfamethoxazole/trimethoprim 800/160 mg po q12h*
• Consider adjunctive intranasal saline irrigation• Consider adjunctive intranasal corticosteroids in
patients with a history of allergic rhinitis• If a patient has been on antibiotic therapy in the
past month the antimicrobial therapy chosenshould be based on a different mechanism ofaction regardless of the clinical success
Failure of Initial Therapy (symptoms worsening after 48 – 72 hrs. or failure to improve after 3 – 5 days of initial empiric antimicrobial therapy)
amoxicillin/clavulanate 875/125 mg po q12h* + amoxicillin 1000 mg po q12h* (high-dose amoxicillin with clavulanate)
levofloxacin 500 mg po q24h*
OR
cefuroxime 500 mg po q12h*
• Consider adjunctive intranasal saline irrigation• Consider adjunctive intranasal corticosteroids in
patients with a history of allergic rhinitis• Patients who fail to respond should be assessed
for possible causes including infection withresistant organism, inadequate dosing andnoninfectious cause
• Select an agent with broader spectrum of activityand from a different antimicrobial class
Clinical Pearls • Compatible Signs and Symptoms: purulent nasal discharge; nasal congestion or obstruction; facial swelling, congestion or fullness; facial pain or pressure; fever; hyposmia or anosmia;
or dental pain • Majority of cases of acute sinusitis are viral and resolve within 5 to 7 days without the need for antibiotics; only 0.5 – 2% of viral upper respiratory infections are complicated by bacterial
infection• Colour of nasal discharge or sputum is related to the presence of neutrophils, not bacteria, and should not be used to diagnose bacterial rhinosinusitis• Macrolides are not recommended for empiric therapy due to growing resistance rates for Streptococcus pneumoniae and Haemophilus influenzae within the Province• Respiratory fluoroquinolones (e.g. levofloxacin, moxifloxacin) should be reserved for failure of first-line options due to the potential for increasing resistance, risk of Clostridium difficile
infection and their importance in the management of other infections• Respiratory fluoroquinolones (e.g. levofloxacin, moxifloxacin) have not been found to be superior to β-lactams in the management of ABRS• Antibiotics have not been shown to be beneficial in chronic rhinosinusitis without acute clinical deterioration• Consider ID consultation for refractory nosocomial rhinosinusitis • Decongestants (topical or oral) and/or antihistamines are not recommended as adjunctive therapy
*Dose adjustment required in renal impairment8
Antimicrobial Therapy for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (NB Provincial Health Authorities Anti-Infective Stewardship Committee, November 2015) Treatment Criteria The use of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is controversial Antimicrobial therapy is only recommended when AECOPD are accompanied by all 3 cardinal symptoms or at least 2 of the 3 cardinal symptoms, if increased sputum purulence is one
of the 2 symptoms:1. Increased dyspnea2. Increased sputum volume3. Increased sputum purulence
Patients receiving invasive or non-invasive ventilation for AECOPD should be initiated on intravenous antimicrobial therapy Antibiotic selection should be based on patient symptoms and risk factors If infiltrate on chest x-ray or pneumonia suspected then treat as per pneumonia treatment guidelines
Risk Stratification Probable Organism
Preferred Empiric Regimen
Alternative Empiric Regimens Duration Comments
Acute Bronchitis • patients presenting with only 1 of
the 3 cardinal symptoms
Viral in most cases Antimicrobial therapy not recommended Symptomatic therapy only
Simple (Low-Risk Patients) • Less than 4 exacerbations per year
Streptococcus pneumoniae Haemophilus
influenzae Moraxella catarrhalis
doxycycline 100 mg po q12h amoxicillin/clavulanate 875/125 mg po q12h* OR sulfamethoxazole/trimethoprim 800/160 mg po q12h* OR cefuroxime 500 mg po q12h* OR clarithromycin 500 mg po q12h
5 days
• If a patient has received an antibioticin the last 3 months the therapychosen should be a regimen basedon a different mechanism of actionregardless of the clinical success
• Tailor antibiotic therapy for sputumculture results if available
Complicated (High Risk Patients) At least one of: • Forced expiratory volume in 1
second (FEV1) less than 50%predicted
• Greater than or equal to 4exacerbations per year
• Ischemic heart disease• Use of home oxygen• Chronic steroid use
As in simple plus: Klebsiella spp and other Gram-negatives, Increased probability of beta-lactam resistance
Oral Therapy: amoxicillin/clavulanate 875/125 mg po q12h*
Intravenous Therapy: cefTRIAXone 1-2 g IV q24h
Oral Therapy: cefuroxime 500 mg po q12h* OR clarithromycin 500 mg po q12h* OR levofloxacin 750 mg po q24h*
Intravenous Therapy: levofloxacin 750 mg IV q24h*
5 – 10 days
5 days (for levofloxacin)
• If a patient has received an antibioticin the last 3 months the therapychosen should be a regimen basedon a different mechanism of actionregardless of the clinical success
• Tailor antibiotic therapy for sputumculture results if available
Bronchiectasis/ End-stage Lung Disease
As in simple and complicated plus: Pseudomonas
aeruginosa, Staphylococcus
aureus, MRSA Other non-
fermenting Gram negative bacilli
Oral Therapy: amoxicillin/clavulanate 875/125 mg po q12h* ± ciprofloxacin 500 -750 mg po q12h* (if Pseudomonas aeruginosa is suspected) Intravenous Therapy: cefTRIAXone 1-2 g IV q24h OR piperacillin/tazobactam 4.5 g IV q6h* (if Pseudomonas aeruginosa is suspected)
Oral Therapy: levofloxacin 750 mg po q24h*
Intravenous Therapy: levofloxacin 750 mg IV q24h*
7 – 14 days
• Tailor antibiotic therapy forsputum culture results (past orcurrent)
Clinical Pearls • Macrolides are not recommended as first line empiric therapy due to growing resistance rates for Streptococcus pneumoniae and Haemophilus influenzae• Fluoroquinolones should be reserved for only severe cases, failure of first line options or β-lactam allergy in complicated cases due to the potential for increasing resistance, risk of Clostridium difficile infection
and their importance in the management of other infections• Empiric therapy for atypical organisms (Mycoplasma pneumoniae & Chlamydophilia pneumoniae) not recommended• Consider obtaining cultures if not improving after 72 hours of antimicrobial therapy• Consider systemic corticosteroids for moderate to severe exacerbations of COPD (prednisone 40 mg po once daily for 5 days)• Influenza vaccination and pneumococcal vaccination recommended
*Dose adjustment required in renal impairment9
Antimicrobial Therapy for Adult Community Acquired Pneumonia¶
(NB Provinical Health Authorities Anti-Infective Stewardship Committee, November 2014)
Treatment Considerations: Having taken antibiotics within the past 3 months significantly increases the risk of resistant S. pneumoniae. Choose an antibiotic from a different class¶Exclusion: patient with predisposing conditions such as cancer or immunosuppression, acute exacerbation of chronic obstructive pulmonary disease (COPD), bronchitis, macro-aspiration, or
MRSA.
Severity CURB65§ Mortality Treatment
Site Empiric Therapy
∞ (start antibiotics within 4 hours)
Duration of
Therapy Comments
Low 0-1Less than
3%
Home
OR
Hospitalized for reason other than pneumonia
amoxicillin 500 mg – 1000 mg PO three times daily*
OR
doxycycline 100 mg PO twice daily
OR
Macrolide PO (clarithromycin 500 mg PO twice daily* OR azithromycin 500 mg PO on day one then 250 mg once daily x 4 days)
5 - 7 days
amoxicillin-clavulanate 875/125 mg PO bid* should be used instead of amoxicillin to provide coverage against Gram-negative bacilli and S.aureus when required (e.g., post-influenza, alcoholism, COPD, nursing home)
Amoxicillin is the oral beta-lactam thatoffers the best coverage against S.pneumoniae.
Microbiology Tests: None routinely (unless hospitalized, see below)
Moderate 2 9% Hospital
amoxicillin 1000 mg PO three times daily* + [macrolide PO or doxycycline 100
mg PO bid]
OR
ampicillin 2 g IV q6h* + [macrolide IV (azithromycin 500 mg IV once daily x 3
days) or doxycycline100 mg PO bid]
Penicillin Allergy
cefuroxime 1.5 g IV q8h + [macrolide IV or PO OR doxycycline100 mg PO bid]
7 days
Microbiology Tests: Always order: -Blood cultures (2 sets)-Sputum culture-Urine antigen for pneumococcusand legionellosis
‡
(Depending on clinical context, consider investigation for atypical
pathogens and viruses)
High 3 or
greater 15-40%
Hospital (consider
ICU)
cefTRIAXone 2 g IV once daily + [macrolide IV or PO OR doxycycline 100 mg
PO bid]
OR
levofloxacin 750 mg IV once daily* + ampicillin 2 g IV q6h*
For critically ill patients, combinations including doxycycline are not preferred
If legionellosis strongly suspected, consider using levofloxacin
Care with use of levofloxacin: association with C. difficile and nosocomial MRSAcolonization
7 - 10 days
[may extend to 14-21 days according to
clinical judgment (e.g.
S. aureus,)]
§ CURB65 calculator, 1 point for any of the following: -Confusion (new)
-Urea (greater than 7 mmol/L)
-Respiration (greater than or equal to 30/min)
-Blood Pressure (less than 90 mm Hg systolic or less than or equal to 60 mm Hg diastolic)
-Age ( 65 or greater)
Interpretation of CURB65 score in conjunction with clinical judgment. Too loose an interpretation of “severe pneumonia” contributes to overprescribing third generation cephalosporins and respiratory fluoroquinolones
IV-to-PO Step Down:
Parenteral drug Suggested oral stepdown
azithromycin azithromycin or clarithromycin
Cephalosporin (any) amoxicillin + clavulanic acid
levofloxacin + ampicillin levofloxacin alone ± amoxicillin
Please note, oral monotherapy vs combined therapy (atypicals) → clinical judgment.
*Dose adjustment required in renal impairment‡If antigen is positive for Legionella, efforts must be made to obtain sputum and advise laboratory that Legionella culture is required. This is important for epidemiological purposes in case of an outbreak.
∞If microbial cause of infection known, treat accordingly
10
Treatment of Cellulitis/Skin Infection(NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
Cellulitis/Erysipelas Severity
Preferred Empiric Regimens Duration of
Therapy Comments
Mild (no signs of systemic toxicity)
- Assess for risk factors1 or
clinical evidence of MRSA(e.g. purulent boil withspreading cellulitis, previousMRSA infections orcolonization)
cephalexin 500 - 1000 mg PO q6h2
OR
cefadroxil 500 - 1000 mg PO q12h2,3
True immediate allergy4 to a beta-lactam at risk of cross-reactivity with cephalexin or
cefadroxil: cefuroxime 500 mg PO q8-12h
2
Severe delayed reaction5 to a beta-lactam where their future use is not recommended:
clindamycin 300 - 450 mg PO q6h
MRSA Suspected: sulfamethoxazole/trimethoprim 800/160 mg to 1600/320 mg (1 or 2 DS tablets) PO q12h
2,6
OR
doxycycline 100 mg PO q12h6
5 days (may extend duration if not improved)
Work-up: None, unless there is an associated fluctuant pustule that can be drained and sent for culture
Moderate (signs of systemic toxicity)
OR
Progression on oral therapy7
ceFAZolin 2 g IV q8h2
Alternative for outpatient management: probenecid 1 g PO followed 30 - 60 min later by ceFAZolin 2 g IV, repeated q24h
2
OR
cefTRIAXone 2 g IV q24h
Severe delayed reaction5 where future use of β-lactams not recommended:
clindamycin 600-900 mg IV q8h
MRSA suspected, add: vancomycin 25 to 30 mg/kg IV x 1 dose then 15 mg/kg IV q8-12h
2
(adjust based on levels to a trough target of 15 - 20 mg/L)
5 days (may extend duration if not improved)
If on IV therapy assess every 48 hours for appropriateness for IV to PO conversion
8 (see
PO options available under mild severity)
Work-up: As above plus: Consider blood cultures (2 sets)
Severe (sepsis syndrome, Necrotizing Fasciitis [clinical features of NF include systemic toxicity, deep severe pain – more severe than expected for skin findings, violaceous bullae, rapid spread along fascial planes, gas in soft tissues])
ceFAZolin 2 g IV q8h with or without clindamycin 900 mg IV q8h
Risk of mixed bacterial infection: piperacillin-tazobactam 3.375 g IV q6h
2 with or without
clindamycin 900 mg IV q8h
MRSA suspected, add: vancomycin 25 to 30 mg/kg IV x 1 dose then 15 mg/kg IV q8-12h
2
(adjust based on levels to a trough target of 15 - 20 mg/L)
Consult with specialists
Work-up: As above plus: urgent surgical assessment for diagnostic biopsy and/or debridement
Clinical pearls: These guidelines are for basic skin infections only, any complicating features on history may require alternative management (Specific but not exclusive examples include:
immunocompromised patients, diabetic foot infections, cellulitis associated with a surgical site, trauma or animal/human bites)
Consider looking for predisposing feature (e.g. Tinea pedis) as source of cellulitis1 Risk factors for MRSA infection include: known or previous colonization, recent hospitalization, homelessness, injection drug use, member of First Nations community and incarcerated person
2 Dose adjustment required in renal impairment
3 Non-formulary agent not available within hospital
4 True, immediate IgE-mediated allergies include, but are not limited to: anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, and pruritis.
5 Stevens-Johnson syndrome, toxic epidermal necrolysis, immune hepatitis, DRESS, serum sickness, hemolytic anemia or interstitial nephritis
6 Poor coverage for beta-hemolytic streptococci, consider combining with cephalexin or cefadroxil
7 Assessment of clinical response within 48 hours should be based on pain and fever; mild progression of erythema expected during this timeframe
8 IV to PO conversion appropriate when patient: afebrile, hemodynamically stable, clinically improving, and able to tolerate oral intake (see IV to PO conversion policy for more details)
11
When to Send a Urine for Culture and Urinalysis (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
UTI SymptomsCystitis
• Dysuria • ↑ frequency • ↑ urgency • Suprapubic
pain
Catheter-Associated UTI • Fever• Acute hematuria • Delirium• Rigors• Flank Pain • ± Lower tract symptoms
if catheter removed
Pyelonephritis • Fever• Nausea, vomiting • Costovertebral pain • Flank pain • ± lower tract
symptoms
Cloudy and/or foul smelling urine are NOT symptoms of UTI
Start
Does a non-UTI diagnosis likely account for the
symptoms?
Does the patient have
any UTI symptoms?
Consider empiric antibiotics*
Send urine for culture (if patient catheterised send culture
from new catheter)
Review urine culture results to tailor antibiotic
therapy
Do NOT send urine for culture and/or urinalysis
(Unless pregnant or for urologic procedure where mucosal bleeding
expected)
Work-up other cause for symptoms Yes
No
Yes
No Clinical Pearls • “Changes in cognitive function and declines in activities of
daily living REQUIRE careful clinical assessment. DO NOTassume they are secondary to UTI.” VCH/ASPIRES 2014
• Urine culture and susceptibility and urinalysis testing is NOT necessary orbeneficial in healthy, non-pregnant, premenopausal, non-diabetic women withacute cystitis (at least 2 of 3 cardinal symptoms – dysuria, urgency orfrequency) and NO vaginal discharge without functional or anatomicalabnormalities of the urinary tract.
• Always obtain a culture for: pregnant women; patients with sign and symptomsof pyelonephritis; premenopausal adult females with recurrent cystitis; urologicalprocedure; patients with complicated urinary tract infections (i.e. structuralabnormality, obstruction, recent urologic procedure, male sex,immunosuppression, poorly controlled diabetes, spinal cord injury orcatheterization)
*Refer to NB-ASC UTI Treatment Guideline for antibiotic selection
12
Positive Urine Culture
Catheter-Associated UTI
DefinitionPresence of symptoms with greater than 106 CFU/L of ≥ 1 bacterial species in a single catheter urine specimen or in a midstream voided urine after catheter removal for 48 hours, with a positive urinalysis for pyuria
Possible Signs & Symptoms:New onset or worsening fever, rigors, altered mental status, malaise, or lethargy with no other identified cause; flank pain; costovertebral tenderness; acute hematuria; pelvic discomfort and in those with catheter removed dysuria, urgent or frequent urination or suprapubic pain or tenderness.
· If spinal cord Injury, symptoms may also include increased spasticity, autonomic
dysreflexia OR a sense of unease
Symptomatic Bacteriuria
Cystitis (lower UTI)Dysuria, urgency, frequency, or suprapubic pain with no fever or flank pain; change in cognitive function or activities of daily living REQUIRE careful clinical assessment, never assume these are due to UTI
Pyelonephritis (upper UTI)Fever, flank pain, costovertebral tenderness, abdominal/pelvic pain, nausea,
vomiting with or without signs/symptoms of lower tract UTI
Asymptomatic Bacteriuria
See NB-ASC UTI Treatment Guideline1 for Treatment Options
(Adjust Antimicrobial Therapy According to Urine C&S Results)
Treat according to urine C&S only if
symptoms present (adjust according to C&S
results)
If catheter required, obtain urine culture and urinalysis through new catheter prior
to initiation of antimicrobial therapy OR
If catheter is not required, culture voided midstream urine prior to initiation of
antimicrobial therapy
Was the catheter changed immediately before urine culture
was collected?
YES
NO
Treat according to NB-ASC UTI Treatment Guideline1 if
symptoms present(adjust according to C&S results)
Urological Procedure
(mucosal bleeding expected)
Pregnant
Surgical Prophylaxis2
Do NOT Treat
Treat according to
urine C&S
YESYES
NO
NO
YES
1Treatment of Adult Urinary Tract Infections (NB Health Authorities Anti-Infective Stewardship Committee, May 2014)2Surgical Prophylaxis Guidelines (NB Health Authorities Anti-Infective Stewardship Committee, May 2015)*Urine culture may be contaminated by colonized bacteria.
Positive Urine Culture Assessment Algorithm(NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
13
Treatment of Adult Urinary Tract Infections (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
Indication Empiric Therapy (Tailor regimen based on urine/blood C&S results) Duration Comments
Asymptomatic Bacteriuria
Antibiotic therapy only recommended for: -Prophylaxis for urological procedures when mucosal bleedingexpected-Treatment in pregnancy
(Select antimicrobial therapy according to urine C&S)
Urological procedures: see surgical prophylaxis guideline
Pregnancy: 3 – 7 days
• Asymptomatic bacteriuria with pyuria is NOT an indication for antimicrobial therapyPregnancy • Repeat culture and urinalysis 1 week after therapy complete as a test of cure; if positive repeat
treatment according to urine C&S• Monthly repeat urine cultures recommended for screening until completion of pregnancy• Consider prophylactic/suppressive antibiotic therapy for persistent bacteriuria• Intrapartum prophylaxis of early-onset Group B Streptococcal (GBS) disease is recommended if
GBS is isolated in urine or vaginal swabUncomplicated Cystitis (Lower UTI) (Female patients with dysuria, urgency, frequency, or suprapubic pain with no fever or flank pain)
Preferred Regimen: nitrofurantoin monohydrate/macrocrystals 100 mg PO q12h (Not recommended if CrCl less than 40 mL/min; in pregnancy, avoid near term (36-42 weeks) due to risk of haemolytic anemia in the new born)
Alternative Regimens: cefuroxime 500 mg PO q8h OR fosfomycin 3 g PO once4 OR sulfamethoxazole/trimethoprim 800/160 mg PO q12h1,3 (Not recommended in pregnant women)
5 days
7 days One dose 3 days
Pregnancy • Repeat culture and urinalysis 1 week after therapy complete as a test of cure; if positive repeat
treatment according to urine C&S• Monthly repeat urine cultures recommended for screening until completion of pregnancy• Consider prophylactic/suppressive antibiotic therapy for persistent or recurrent cystitis• Intrapartum prophylaxis of early-onset Group B Streptococcal (GBS) disease is recommended if
GBS is isolated in urine or vaginal swab
Acute Uncomplicated Pyelonephritis (Upper UTI) (Signs/Sx: fever, flank pain, costovertebral tenderness, abdominal/pelvic pain, nausea, vomiting with or without signs/sx of lower tract UTI)
OR
Complicated UTI (Complicating Factors: structural abnormality, obstruction, recent urogenital procedure, male sex, immunosuppression, poorly controlled diabetes, spinal cord injury, catheterization or Signs/Sx greater than 7 days)
Systemically Well: Preferred Regimen: cefixime 400 mg PO q24h3 Alternative Regimens: amoxicillin/clavulanate 875/125 mg PO q12h3
Additional options if culture confirmed susceptibility: sulfamethoxazole/trimethoprim 800/160 mg PO q12h1,3 OR ciprofloxacin 500 mg PO q12h1,3
Systemically Unwell/Pregnant: cefTRIAXone 1 g IV q24h2 OR ampicillin 2 g IV q6h + (tobramycin OR gentamicin) 5 mg/kg IV once daily2,3,5 ORpiperacillin/tazobactam 3.375 g IV q6h2,3
See Comments
Acute Uncomplicated Pyelonephritis • Outpatient management an option if female, not pregnant, no nausea/vomiting, no evidence of
dehydration, sepsis or high fever• Treat for 14 days• May treat for 7 days if female, uncomplicated and using ciprofloxacin• For treatment using oral β-lactams, consider an initial single intravenous dose of cefTRIAXone 1
g IV and use a 14 day total duration of antimicrobial therapy
Complicated UTI: • Treat 7 days if prompt response, female and only lower urinary tract infection• Treat 14 days if male, delayed response, structural abnormality, or upper tract symptoms
Catheter-Associated UTI:• Pyuria not diagnostic, only treat if symptomatic• Catheters frequently colonized, obtain culture through new catheter• Change catheter if in place for greater than 2 weeks & still requiredPregnancy • Treat for 10 to 14 days• Prophylactic/suppressive antibiotic therapy recommended for the remainder of the pregnancy• Repeat culture and urinalysis 1 week after therapy complete as a test of cure; if positive repeat
treatment according to urine C&S• Monthly repeat urine cultures recommended for screening until completion of the pregnancy• Intrapartum prophylaxis of early-onset Group B Streptococcal (GBS) disease is recommended if
GBS is isolated in urine or vaginal swabClinical Pearls: • Cloudy and foul smelling urine alone are NOT considered signs of infection and are NOT an indication for a urine culture and sensitivity• Urinalysis interpretation:
o Presence of nitrites and leukocytes (leukocyte esterase positive or WBC) and new UTI symptoms: good positive predictive value of UTIo Absence of nitrites and/or leukocytes (negative leukocyte esterase or WBC): good negative predictive value
• Therapy should be adjusted according to culture and sensitivity results• Blood cultures should be drawn if febrile, septic, signs and symptoms suggestive of pyelonephritis or immunocompromised• Post-treatment culture not recommended except in case of persistent or recurrent symptoms or pregnancy• nitrofurantoin and fosfomycin are not appropriate for men, complicated UTI or systemic infections1CAUTION: Significant E.coli resistance (greater than 20%) to fluoroquinolones, sulfamethoxazole/trimethoprim and amoxicillin exist in some areas of the province; check local antibiogram and confirm urine C&S
results when available 2De-escalate according to urine/blood C&S and switch IV to PO based on conversion criteria 3Dose adjustment required in renal impairment 4Fosfomycin criteria for use: for multi-drug resistant E.coli or Enterococcus faecalis with limited oral options OR where recommended alternatives are not appropriate due to allergies, drug interactions, poor renal function or other considerations 5Please see aminoglycoside dosing guide for more details on appropriate dosing adjustments and monitoring
14
AMINOGLYCOSIDES DOSING AND MONITORING GUIDELINES
NB Provincial Health Authorities Anti-Infective Stewardship Committee
GENERAL COMMENTS
• Aminoglycosides (AG) include gentamicin, tobramycin, amikacin and streptomycin• AG exert bactericidal activity against gram-negative bacteria• Combination of gentamicin with a cell-wall active agent (i.e. beta-lactam) results in a synergistic
effect on certain gram-positive bacteria such as Enterococci and Streptococci in the treatment ofendocarditis
• Amikacin is generally reserved for infections due to organisms with documented resistance togentamicin and tobramycin; refer to amikacin section for dosing and monitoring information
• Streptomycin is used infrequently to treat drug resistant tuberculosis and nontuberculousmycobacterial infections; its dosage and monitoring are not included in these guidelines
• There are three dosing strategies for AG:o Conventional dosing of AG: weight-based dose administered three times a day, or less
frequently in decreased renal functiono Extended-interval dosing of AG (also called “once daily dosing”): a larger weight-based
dose (approximately triple conventional dosing) administered once a day, or lessfrequently in decreased renal function
o Synergistic dosing for gram-positive infections• AG exhibit concentration-dependent killing: higher serum concentrations result in higher rates and
extent of bacterial killing• AG demonstrate a post-antibiotic effect: suppression of bacterial growth is continued even after
serum concentrations have decreased below the minimum inhibitory concentration (MIC)• AG are nephrotoxic, ototoxic and can produce neuromuscular blockade
15
GENTAMICIN AND TOBRAMYCIN IN ADULT PATIENTS
ADULT EXTENDED INTERVAL DOSING • Use extended interval dosing whenever possible• Takes advantage of concentration-dependent killing and post-antibiotic effect properties of AG with the goals
of enhancing efficacy with higher peaks and potentially decreasing toxicity with greater drug-free intervals• Extended interval AG dosing should NOT be used in:
o Patients requiring dialysiso Patients with rapid clearance of AG, including burns exceeding 20% of body surface areao Patients with gram-positive infections where AG is used for synergy (i.e. endocarditis)
• Extended interval AG dosing should be used with CAUTION in:o Patients with creatinine clearance (CrCl) less than 20 mL/mino Patients with chronic ascites or serious liver disease (altered volume of distribution)o Patients with known auditory or vestibular disease or pre-existing impairmento Pregnant women
Initial Dose • 5-7 mg/kg IV
o based on ideal body weight or dosing weight (see appendix B)o use 7 mg/kg for serious infections or infections due to Pseudomonas aeruginosa or multidrug
resistant organismso round dose to nearest 20 mg
• An initial dosing interval is chosen based on renal function as per the following table
Creatinine Clearance Dosing Interval greater than or equal to 60 mL/min q24h 40 to 59 mL/min q36h 20 to 39 mL/min q48h; consider conventional dosing less than 20 mL/min Give first dose then draw serial serum drug
levels to determine when to give next dose. Consider conventional dosing.
Levels • Monitoring of trough levels alone is generally sufficient with extended interval dosing• Trough levels verify that AG is being adequately eliminated and is not accumulating• Peak levels are typically NOT required, as the larger doses used are expected to produce concentrations well
above those required for clinical efficacy• Peak levels are done in the rare cases where individualized pharmacokinetic monitoring is requiredTarget serum concentrations: • Trough levels: less than 1 mg/L• Peak levels [only if indicated]: 15-25 mg/L
o Optimal bactericidal activity for AG is achieved when maximum serum concentrations areapproximately 8 to 10 times the MIC
Levels recommended are in: • Treatment anticipated to be longer than 3-5 days• Patients more than 65 years of age• Patients with renal dysfunction (CrCl less than 60 mL/min ) or significant changes in renal function from
baseline• Patients receiving other nephrotoxic drugs (i.e. vancomycin, NSAIDs, diuretics, ACE-I, ARBs, etc.)• Patients with a large volume of distribution (e.g., ascites, third spacing)• Pregnant women
16
Serum sampling: • Trough levels are taken immediately before a dose (within 30 minutes)• Peak levels are taken 90 minutes after the END of drug infusion, to allow for distribution• The timing and duration of drug administration and sample collection must be carefully documentedTiming of serum levels: • The notion of steady state does not apply with extended-interval dosing; therefore levels may be
taken prior to the 2nd doseInterpreting serum levels and adjusting dose: • Ensure serum samples were collected at the appropriate time• Trough level result of 1 mg/L or more suggests accumulation; extend dosing intervalHartford Hospital Nomogram (see appendix D): • A random level taken between 8 to 12 hours after the START of drug infusion may be used to
determine appropriate dosing interval using the Hartford Hospital nomogram• Only to be used with a 7 mg/kg dose; has not been validated with other doses
Monitoring and patient counselling Subsequent serum levels: • After a change in dose• At least once a week for most patientsMonitor: • Clinical response• Renal function
o Serum creatinine (SCr) at baseline and every 2 to 3 days during therapyo AG can cause renal dysfunction; typically reversible if discontinued in a timely manner; close
monitoring is warranted• Ototoxicity
o Patients should be advised to watch for and report signs & symptoms of cochlear toxicity (e.g.,tinnitus, sense of fullness in ears, loss of hearing) and of vestibular toxicity (e.g., disequilibrium,oscillopsia, cognitive dysfunction, visual sensitivity, nausea/vomiting, vertigo, headache, nystagmus).
o AG should be discontinued immediately if any signs/symptoms of toxicity develop; ototoxicity causedby AG may be irreversible.
o Audiometry and vestibular testing recommended for patients receiving AG for 7 days or more, or atany time if ototoxicity suspected. Consult Audiology.
o If prolonged therapy expected (greater than 7 days) baseline audiometry may be consideredo Assess need for continued AG therapy based on microbial susceptibilities, clinical response, side
effects, duration of therapy, etc.
17
ADULT CONVENTIONAL DOSING • Use conventional dosing when extended-interval dosing is not indicatedInitial Dose Loading dose: • 2 mg/kg IV
o based on ideal body weight or dosing weight (see appendix B)o round dose to nearest 20 mgo loading doses DO NOT need to be adjusted in patients with renal dysfunction; only maintenance
dosing interval requires adjustmentMaintenance dose: • 1.5 to 2 mg/kg IV
o based on ideal body weight or dosing weight (see appendix B)o round dose to nearest 20 mg
Dosing interval: • Interval depends on patient’s renal function
Creatinine Clearance Dosing Interval greater than or equal to 80 mL/min q8h 50 to 79 mL/min q12h 20 to 49 mL/min q24h less than 20 mL/min q48-72h; give first dose and draw
serial serum drug levels to determine when to give next dose; close monitoring is recommended
Levels • Therapeutic drug monitoring of AG dosed conventionally is typically done by measuring both peak and trough
levels at steady state to confirm that therapeutic concentrations have been achieved and that drugaccumulation has not taken place
Target serum concentrations: Infection Desired minimal (trough)
plasma concentration (mg/L)
Desired maximum (peak) plasma concentration (mg/L)
Lower urinary tract infection less than 1 4-6Pelvic inflammatory disease (e.g., endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis) Chorioamnionitis Pyelonephritis Peritonitis Soft tissue infections
less than 2 6-8
Sepsis Neutropenia Burns Pneumonia Infections due to Pseudomonas (non-urinary) Bone and joint infections
less than 2 8-10
Cystic fibrosis less than 2 10-15Levels are recommended in: • Treatment anticipated to be longer than 3-5 days• Patients more than 65 years of age
18
• Patients with renal dysfunction (CrCl less than 60 mL/min) or significant changes in renal function frombaseline
• Patients receiving other nephrotoxic drugs (e.g., vancomycin, NSAIDs, diuretics, ACE-I, ARBs, etc.)• Patients with a large volume of distribution (e.g., ascites, third spacing)• Pregnant womenSerum sampling: • Trough levels are taken immediately before a dose (within 30 minutes)• Peak levels are taken 30 to 60 minutes after the END of the IV infusion• The timing and duration of drug administration and sample collection must be carefully documentedTiming of serum levels: • Levels should be taken at steady state, typically before and after the 3rd dose in patients with normal renal
function• Steady state (SS) occurs in 4 to 5 half-lives and can be estimated by the following equations:
o Ke (gentamicin) = CrCl x 0.00285 + 0.015o Ke (tobramycin) = CrCl x 0.0031 + 0.01o T½ = 0.693/Ke
o SS = 4 to 5 T½Interpreting serum levels and adjusting dose: • Ensure serum samples were collected at the appropriate time and at steady state• Adjust AG dose if serum concentrations are not within the desired range as follows:
high trough extend dosing interval high peak decrease dose low peak increase dose
• AG exhibit linear kinetics; decreasing or increasing the dose by a specific percentage will result in an equaldecrease/increase in percentage of peak levels
• Pharmacokinetic calculations may be used determine the dose most likely to produce the desired levels, basedon the pre and post levels obtained from the patient. Contact Pharmacy.
Monitoring and patient counselling Subsequent serum levels: • After a change in dose, levels should be repeated at new steady state• At least once a week for most patientsMonitor: • Clinical response• Renal function
o Serum creatinine (SCr) at baseline and every 2 to 3 days during therapyo AG can cause renal dysfunction; typically reversible if discontinued in a timely manner; close
monitoring is warranted• Ototoxicity
o Patients should be advised to watch for and report signs & symptoms of cochlear toxicity (e.g.,tinnitus, sense of fullness in ears, loss of hearing) and of vestibular toxicity (e.g., disequilibrium,oscillopsia, cognitive dysfunction, visual sensitivity, nausea/vomiting, vertigo, headache, nystagmus).
o AG should be discontinued immediately if any signs/symptoms of toxicity develop; ototoxicity causedby AG may be irreversible.
o Audiometry and vestibular testing recommended for patients receiving AG for 7 days or more, or atany time if ototoxicity suspected. Consult Audiology.
o If prolonged therapy expected (greater than 7 days) baseline audiometry may be considered• Assess need for continued AG therapy based on microbial susceptibilities, clinical response, side effects,
duration of therapy, etc.
19
ADULT GENTAMICIN SYNERGISTIC DOSING • Used in combination therapy for endocarditis due to Viridans Group Streptococcus, Streptococcus gallolyticus
(formerly Streptococcus bovis) or Enterococcus (refer to most recent IDSA/AHA Endocarditis Clinical PracticeGuidelines for details)
• Only gentamicin is routinely used in this setting• Dose: gentamicin 1 mg/kg q8h or 3 mg/kg q24h, depending on the organism identified
o dosing based on IBW (see appendix B)o no initial loading doseo round dose to nearest 20 mgo in patients with renal impairment, consider using 1 mg/kg dosing strategy and lengthening the
interval based on the table belowCreatinine Clearance Dosing Interval
greater than or equal to 80 mL/min
q8h
50 to 79 mL/min q12h 20 to 49 mL/min q24h less than 20 mL/min q48-72h; give first dose then draw serial serum
drug levels to determine when to give next dose; close monitoring is recommended
• Draw gentamicin trough level before the 3rd dose and at least once a week thereafter if patient is stableo Goal of monitoring is to avoid toxicityo Target trough level : less than 1 mg/Lo If trough more than 1 mg/L, increase interval
• Peaks are NOT routinely recommendedo If done, target peak level: 3 to 5 mg/L
20
GENTAMICIN AND TOBRAMYCIN IN PEDIATRIC PATIENTS
DEFINITIONS • Neonate: 0-4 weeks of age
o Gestational age: number of weeks from first day of the mother’s last menstrual period until the birthof the baby
o Postnatal age: chronological age since birtho Corrected Gestational Age: gestational age plus postnatal age
Ex.: baby born at 28 weeks, presently 21 days old corrected gestational age = 31 weeks (28 weeks + 3 weeks)
• Infant: 1 month to 1 year of age• Child: 1-12 years of age
PEDIATRIC EXTENDED INTERVAL DOSING • Extended interval AG dosing should NOT be used in pediatric patients who
o have renal insufficiency at baseline (CrCl less than 50 mL/min)o require dialysiso have gram-positive infections where AG is used for synergy (use conventional dosing)o have endocarditis (use conventional dosing)o have rapid clearance of drug (e.g., burns exceeding 20% of body surface area)o have altered volume of distribution (e.g., ascites)o have meningitiso are receiving AG for surgical prophylaxis
• Use conventional dosing if any of the above exclusion criteria for extended interval dosing are metNeonates Initial dose in neonates (less than 1 month of age):
Corrected Gestational Age (weeks)
Postnatal Age (days) mg/kg/dose IV Interval
(hours)
29* or less 0-7 5 48
8-28 4 36 29 or more 4 24
30-340-7 4.5 36
8 or more 4 24 35 or more all 4 24
*or significant asphyxia, Patent Ductus Arteriosus (PDA) or treatment with indomethacin or ibuprofen
• round dose to nearest 5 mgLevels Target serum concentrations at 22 hours: • 1.2 mg/L or lessLevels recommended in: • Treatment anticipated to be longer than 48hSerum sampling: • A random level (or interval level) should be drawn 22 hours after the first dose regardless of the dosing
interval• The timing and duration of drug administration and sample collection must be carefully documented
21
Interpreting serum levels and adjusting dose: Level at 22 hours (mg/L) Suggested dosing interval 1.2 or less q24h 1.3 to 2.6 q36h 2.7 to 3.5 q48h 3.6 or more hold dose and repeat level in 24 hours; base dosing interval on
time to achieve a level less than 2 mg/L
Infants and children Initial dose of gentamicin/tobramycin • Infants and children 1 month – up to 9 years:
o 7-9 mg/kg IV q24h• Children 9 years and older:
o 7 mg/kg IV q24hInitial dose of tobramycin for Febrile Neutropenia • Infants and children 1 month – up to 6 years:
o 10 mg/kg IV q24h• Children 6 years and older:
o 8 mg/kg IV q24hDose: • based on actual body weight, unless 20% above IBW, in which case use dosing weight (appendix C)• maximum of 400 mg/24h prior to levels• round dose to nearest 5 mgLevels • Monitoring of trough levels alone are generally sufficient with extended interval dosing of AG
o verifies that AG is being adequately eliminated• Peak levels are typically NOT required, as the larger doses used are expected to produce concentrations well
above those required for clinical efficacyo may be done in the rare cases where individualized pharmacokinetic monitoring is required
Target serum concentrations: • Trough level : less than 1 mg/L• Peak level [only if indicated]: 15-25 mg/LLevels recommended in: • Treatment anticipated to be longer than 48hSerum sampling: • Trough levels are taken immediately before a dose (within 30 minutes)• Peak levels are taken 90 minutes after the END of drug infusion• The timing and duration of drug administration and sample collection must be carefully documentedTiming of serum levels: • The notion of steady state does not apply with extended-interval dosing; therefore trough levels may be taken
prior to the 2nd doseInterpreting serum levels and adjusting dose: • Trough level of 1 mg/L or more suggests accumulation; extend dosing intervalMonitoring • Serum creatinine every 2 to 3 days while on therapy; daily if unstable renal function• Coordinate blood work when possible to minimize the number of times the child has blood drawn
22
PEDIATRIC CONVENTIONAL DOSING Initial dose Neonates (less than 1 month of age):
Weight (kg) Postnatal Age (days) mg/kg/dose IV Interval
(hours) Less than 1.2 0-28 2.5 18-24
1.2 to 2 less than 7 2.5 12 7 or more 2.5 8 to 12
more than 2 less than 7 2.5 12 7 or more 2.5 8
• round dose to nearest 5 mg
Infants and children: • 1 month to less than 5 years of age: 2.5 mg/kg IV q8h• children 5 years of age and older: 2 to 2.5 mg/kg IV q8h• for treatment of cystic fibrosis: 2.5 to 3.3 mg/kg IV q6-8h • for synergy: 1 mg/kg IV q8h • dose based on actual body weight, unless 20% above IBW, in which case use dosing weight (appendix C)• round dose to nearest 5 mg
Levels • Therapeutic drug monitoring of AG dosed conventionally is typically done by measuring both peak and trough
levels at steady state to confirm that therapeutic concentrations have been achieved and that drugaccumulation has not taken place
Target serum concentrations: Infection Desired minimal (trough)
plasma concentration (mg/L)
Desired maximum (peak) plasma concentration (mg/L)
Synergy for gram-positive infections
less than 1 3-5
Lower urinary tract infection and mild-moderate infections
less than 2 4-8
Severe infections (Pneumonia, Sepsis, etc.)
less than 2 8-10
Cystic Fibrosis less than 2 10-15Levels are recommended in: • Treatment anticipated to be longer than 48hSerum sampling: • Trough levels are taken immediately before a dose (within 30 minutes)• Peak levels are taken 30 to 60 minutes after the END of drug infusion.• The timing and duration of drug administration and sample collection must be carefully documentedTiming of serum levels: • Level should be taken at steady state, typically before and after 3rd dose in patients with normal renal functionInterpreting serum levels and adjusting dose: • Ensure serum samples were collected at the appropriate time and at steady state• Adjust AG dose if serum concentrations are not within the desired range as follows:
high trough extend dosing interval high peak decrease dose low peak increase dose
• AG exhibit linear kinetics; decreasing or increasing the dose by a specific percentage will result in an equaldecrease/increase in percentage of peak levels.
23
• Pharmacokinetic calculations may be used determine the dose most likely to produce desired levels, based onthe pre and post levels obtained from the patient. Contact Pharmacy.
Monitoring • Serum creatinine every 2 to 3 days while on therapy; daily if unstable renal function• Coordinate blood work when possible to minimize the number of times the child has blood drawn
24
EXTENDED-INTERVAL TOBRAMYCIN IN CYSTIC FIBROSIS (PEDIATRIC and ADULT)
GENERAL COMMENTS • Patients with Cystic Fibrosis (CF) will have increased AG requirements secondary to increased clearance• Extended interval dosing is as efficacious as conventional dosing of tobramycin in the treatment of CF
pulmonary exacerbations in adults and children• Amikacin may also be used to treat CF; data is limited with gentamicin. There are insufficient data in CF
patients for guiding extended interval dosing of AG apart from tobramycin. If other AG is needed, useconventional dosing.
• For conventional dosing, refer to previous adult and pediatric sections. Target peak levels are 10 to 15 mg/L,while target trough levels are less than 2 mg/L.
DOSE AND LEVELS Dose (pediatric and adults; from 1 months of age) • Treatment naïve:
Creatinine Clearance Initial tobramycin dose greater than or equal to 50 mL/min 10 mg/kg IV q24h 30-49 mL/min 10 mg/kg IV q36h 20-29 mL/min 10 mg/kg IV q48h less than 20 mL/min avoid maximum tobramycin dose of 600 mg/day prior to levels
• Previously treated with tobramycin: dose based on previous therapeutic drug monitoring• Dose based on ideal body weight (see appendix B)Levels: • Monitoring of trough levels alone are generally sufficient with extended interval dosing of AG; trough levels
verify that AG is being adequately eliminated• Peak levels are NOT routinely measured, but may be ordered to allow for individualized pharmacokinetic
monitoring if concern about clinical progresso Because CF patients have more rapid clearance of AG, extrapolated peaks can be substantially higher
than reported values.Target serum concentrations: • Trough levels: less than 1 mg/L• Peak levels [only if indicated]: 20-30 mg/L, peaks NOT to exceed 50 mg/LSerum sampling: • Trough levels are taken immediately before a dose (within 30 minutes)• Peak levels are taken 90 minutes after the END of drug infusion• The timing and duration of drug administration and sample collection must be carefully documentedTiming of serum levels: • notion of steady state does not apply in extended-interval dosing; trough levels may be taken before 2nd doseInterpreting serum levels and adjusting dose: • Ensure serum samples were collected at the appropriate time• If tobramycin is being administered via inhalation in addition to IV, absorption of inhaled tobramycin may
contribute to tobramycin serum concentrations• If trough is less than 1 mg/L, continue current dose• Adjust AG dose if serum concentrations are not within the desired range as follows:
high trough extend dosing interval high peak decrease dose low peak increase dose
Subsequent serum levels: • Trough levels should be monitored every 7 days or sooner if clinically necessary
25
GENTAMICIN AND TOBRAMYCIN IN INTERMITTENT HEMODIALYSIS
GENERAL COMMENTS • Extended interval dosing not indicated for patients on hemodialysis; use conventional dosing• In patients on intermittent hemodialysis, AG is given on dialysis days, typically 3 times a week• AG doses are administered after dialysis• Give the first dose of AG the day it is ordered and subsequent doses on dialysis days• AG are removed by hemodialysis (to a greater extent than vancomycin)
o High-flux dialyzers reduce AG serum concentrations by approximately 50%Example: pre-dialysis gentamicin serum concentration is 5 mg/L; following a 4h hemodialysis session,post-dialysis gentamicin serum concentration is approximately 2.5 mg/L
DOSE Loading dose: • 1.5-2 mg/kg IV
o based on dry weight/dosing weight (see appendix B)o round dose to nearest 20 mg
Initial maintenance dose: • 1 mg/kg IV
o based on dry weight/dosing weight (see appendix B)o round dose to nearest 20 mgo administered at the end of dialysis session
Dosing weight: Patient’s dry weight…. Use as dosing weight is less than ideal body weight dry weight is less than 20% above ideal body weight dry weight is more than 20% above ideal body weight adjusted weight
Adjusted weight = 0.4 x (actual body weight – IBW) + IBW
LEVELS Trough levels: • Draw trough level within 30 minutes before the start of the hemodialysis session• Target pre-hemodialysis level: 1.5 to 3 mg/LPeak levels: • NOT commonly done• Measure peak level 60 minutes after END of drug infusion, if required• Target peak: 6-10 mg/L, depending on the indication (refer to section “Adults-Conventional Dosing of
Gentamicin and Tobramycin”: target serum concentrations)
26
GENTAMICIN AND TOBRAMYCIN IN PREGNANCY
CONSIDERATIONS ON THE USE OF AMINOGLYCOSIDES IN PREGNANCY • Glomerular filtration rate can be increased by up to 50% in pregnant and post-partum patients, resulting in a
shorter half-life compared to nonpregnant women• Volume of distribution is increased in pregnancy, while the post-partum period is associated with increased
mobilization of fluid followed by diuresis as the body eliminates the increased fluid volume of pregnancy• Extended interval dosing
o Data limited on extended interval dosing of AG in pregnancy; use with cautiono More data on extended-interval dosing of AG is available in post-partumo For pregnant and post-partum patients, the actual body weight should be used. For obese pregnant
and post-partum patients, use maximum 500 mg dose prior to levels.o Initial dose and interval
5 mg/kg IV q24h (if CrCl greater than or equal to 60 mL/min) dose based on actual body weight maximum 500 mg/24h prior to levels dosing interval adjusted based on renal function
o Monitoring Trough levels, taken within 30 minutes before 2nd dose
• target less than 1 mg/L• Conventional dosing
o Initial dose and interval 2 mg/kg IV x 1 loading dose, then 1.5-2 mg/kg IV q8h (if CrCl greater than or equal to 80 mL/min) dose based on actual body weight dosing interval adjusted based on renal function
o Monitoring target levels – refer to “Adults-Conventional Dosing of Gentamicin/Tobramycin” section
27
AMIKACIN
GENERAL COMMENTS, DOSING AND MONITORING • Amikacin is a less commonly used AG with similar spectrum of activity and toxicity profile as gentamicin and
tobramycin• Dosing and serum concentrations are different compared to gentamicin and tobramycin• Determination of serum concentration is sent to a laboratory outside the province; expect delays in obtaining
results• Extended interval dosing
o Initial dose 15 mg/kg IV; dose based on IBW or dosing weight (see appendix B); rounded to nearest 25
mgo Initial interval
Creatinine Clearance Dosing Interval greater than or equal to 60 mL/min q24h 40 to 59 mL/min q36h 20 to 39 mL/min q48h; consider conventional dosing less than 20 mL/min Give first dose then draw serial serum drug levels
to determine when to give next dose. Consider conventional dosing.
• Conventional dosingo Initial dose
7.5 mg/kg IV x 1 loading dose may be considered, then 5 to 7.5 mg/kg IV; dose based on IBW or dosing weight; rounded to nearest 25 mg
o Initial intervalCreatinine Clearance Dosing Interval
greater than or equal to 80 mL/min q8h 50 to 79 mL/min q12h 20 to 49 mL/min q24h less than 20 mL/min q48-72h; give first dose then draw serial serum
drug levels to determine when to give next dose; close monitoring is recommended
• For extended interval dosing of amikacin,o Target trough level: less than 4 mg/Lo Target peak level [only if indicated]: 35-50 mg/Lo Hartford Hospital nomogram may be used to determine appropriate dosing interval based on a
random level taken 8-12h after the first dose, provided a 15 mg/kg dose was used Divide serum amikacin level obtained in half, then plot on graph (see Appendix D)
• For conventional dosing of amikacin, target serum concentrations:Desired minimal (trough) concentration (mg/L)
Desired maximum (peak) concentration (mg/L)
Moderate infections less than 4 20-25Severe infections less than 2 25-30
28
APPENDIX A: Calculation of Creatinine Clearance (CrCl)
Women Men CrCl = (140-age) x weight (in kg)†
SCr (in mcmol/L) CrCl = (140-age) x weight (in kg)† x 1.2
SCr (in mcmol/L) IBW = 45.5 Kg + (0.92 x cm above 150 cm) or 45.5 kg + (2.3 x inches above 60 inches)
IBW = 50 kg + (0.92 x cm above 150 cm) or 50 kg + (2.3 x inches above 60 inches)
†use actual body weight unless it is 20% above ideal body weight (IBW), in such case use adjusted weight: Adjusted weight = 0.4 x (actual body weight – IBW) + IBW
APPENDIX B: Adult Ideal Body Weight, Dosing Weight and Dry Weight
Patient’s weight…. Use is less than ideal body weight actual body weight is less than 20% above ideal body weight ideal body weight is more than 20% above ideal body weight dosing weight =
0.4 x (actual body weight – IBW) + IBW
Ideal body weight (IBW)
Women Men IBW = 45.5 kg + (0.92 x cm above 150 cm) or
45.5 kg + (2.3 x inches above 60 inches) IBW = 50 kg + (0.92 x cm above 150 cm) or
50 kg + (2.3 x inches above 60 inches)
Dry body weight in hemodialysis: defined as the lowest tolerated post-dialysis weight at which there are minimal signs or symptoms of hypovolemia or hypervolemia
APPENDIX C: Pediatric Ideal Body Weight and Dosing Weight
Child’s weight…. Use is less than 20% above ideal body weight actual body weight is more than 20% above ideal body weight dosing weight =
0.4 x (actual body weight – IBW) + IBW
Ideal body weight (1 to 18 years of age):
• Children less than 5 feet tall: height (cm)2 x 1.65 1000
• Boys 5 feet and taller: 39 kg + (2.3 x inches above 60 inches)• Girls 5 feet and taller: 42.2 kg + (2.3 x inches above 60 inches)
29
APPENDIX D: Hartford Hospital nomogram
• This nomogram is only to be used for a 7 mg/kg dose of gentamicin or tobramycin• This nomogram assumes a Vd of 0.3 L/kg• If interval falls in areas marked as q24h, q36h, q48h, dosing interval should be every 24,
36, or 48 hours respectively.• If the interval level is on one of the sloping lines, choose the longer interval.• If the interval level is above the q48h dosing interval area, stop extended interval dosing
and switch to conventional dosing.• If the interval level is below the nomogram (i.e., less than 2 mg/L), AG dosing/therapy
should be reassessed if patient not improved.• For amikacin the Hartford Hospital nomogram may be used to determine appropriate
amikacin dosing interval based on a random level taken 8-12h after the first dose,provided a 15 mg/kg dose was used
o Divide serum amikacin level obtained in half, then plot on graph
30
Introduction
The dosing recommendations presented here are for adults with moderate-to-severe infections and are based on published literature, the Clinical & Laboratory Standards Institute’s reference dosing for susceptibility interpretation and clinical experience. The recommended doses should only be used as a reference tool. Patient dosing should be individualized and based on pharmacokinetic and clinical evaluation where possible.
Recommendations for renal dose adjustment are made according to estimated creatinine clearance (CrCl) calculated using the Cockroft-Gault equation, which is used in practice. Estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease 4 (MDRD4) equation, commonly reported with most serum creatinine levels, is NOT interchangeable with CrCl calculated using the Cockroft-Gault equation. The two equations may result in different antimicrobial dosing recommendations in up to 20 to 36% of cases with potential clinical significance.20 Recommendations for renal dose adjustment in the table below are for modifications of the maintenance doses; no adjustments are required for loading doses where applicable.
For patients on intermittent hemodialysis (IHD), antimicrobial dosages and administration times may need to be adjusted. If an antimicrobial is significantly removed by hemodialysis (HD) and recommended to be given post-HD then administration of the dose prior to or during HD should be avoided because drug loss could result in subtherapeutic levels post-HD. The dosing schedule should be adjusted on dialysis days so that the scheduled dose is administered immediately after dialysis. Other strategies may include supplementary doses administered post-HD to replace the amount of antimicrobial removed during HD or intermittent post-HD administration (ex. ceFAZolin 2 g IV post-HD 3 times weekly). Please consult your local pharmacy department for guidance in patients receiving peritoneal dialysis, continuous veno-venous hemofiltration, continuous veno-venous hemodiafiltration or continuous renal replacement therapy. Dosing adjustment may also be necessary in patients with severe liver impairment.
In critically ill patients (ex: sepsis), antimicrobial pharmacokinetics can be significantly altered and unstable potentially resulting in sub-optimal dosing. Critically ill patients may also suffer from acute renal failure (ARF) that can be rapidly reversible; therefore, since the serum creatinine level is not stable, the Cockroft-Gault equation should NOT be used to estimate renal function in ARF. A pharmacy consultation could be considered to optimize antimicrobial doses in this patient population.
ADULT ANTIMICROBIAL DOSING TOOL (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
31
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
32
Penicillins
amoxicillin (PO)1,2,3,4,5,6 500 mg – 1 g q8h 500 mg q12h 500 mg q24h 500 mg q24h;
administer dose after dialysis on dialysis days
amoxicillin/clavulanate (PO)1,2,7
- Dose listed as amoxicillincomponent
- Do not use 875 mg tablets ifCrCl less than 30 mL/min
- Less diarrhea with 875 mg given q12h vs.500 mg q8h
500 mg q8h
500 mg q12h 500 mg q24h 500 mg q24h;
administer dose after dialysis on dialysis days 875 mg q12h
ampicillin (IV)1,3,5 Dose 2 g q4h for endocarditis and other deep space infections‡
1 – 2 g q4-6h 1 – 2 g q6-8h 1 – 2 g q8-12h 1 – 2 g q12-24h 1 – 2 g q12-24h;
administer dose after dialysis on dialysis days
cloxacillin (PO)1,5 500 – 1000 mg q6h
cloxacillin (IV)1,2,5 Dose 2 g q4h for endocarditis and deep space infections‡
1 – 2 g q4-6h
penicillin G (IV)1,5 Dose 4 million units q4h for endocarditis and deep space infections‡
2 – 4 million units q4-6h 75% of usual dose q4-6h 20 – 50% of usual
dose q4-6h
20 – 50% of usual dose q4-6h; administer dose after dialysis on
dialysis days
penicillin V (PO)2,5,8,9 300 – 600 mg q6h 300 – 600 mg q8h 300 – 600 mg q12h
piperacillin/tazobactam (IV)1,2,3,5
Dose listed as piperacillin plus tazobactam components
3.375 g q6h (CrCl greater than
40 mL/min) 2.25 g q6h (CrCl 20 – 40 mL/min)
2.25 g q8h (CrCl less than 20
mL/min)
2.25 g q12h; administer supplementary dose of 0.75 g after dialysis session
Hospital acquired pneumonia, febrile neutropenia and Pseudomonas spp infections
4.5 g q6h (CrCl greater than
40 mL/min) 3.375 g q6h (CrCl 20 – 40 mL/min)
2.25 g q6h (CrCl less than 20
mL/min)
2.25 g q8h; administer supplementary dose of 0.75 g after dialysis session
piperacillin (IV)1,3,5 3 – 4 g q6h
(CrCl greater than 40 mL/min)
3 – 4 g q8h (CrCl 20-40mL/min)
3 – 4 g q12h (CrCl less than 20 mL/min)
2 g q8h; administer supplementary dose
of 1 g after dialysis session
Cephalosporins
ceFAZolin (IV)1,5,19 (1st generation) 2 g q8h 2 g q12h 1 – 2 g q24h
1 – 2 g q24h; administer dose after dialysis on dialysis days
OR 2 g after dialysis three times
weekly if receiving dialysis three times weekly
cephalexin (PO)1,3,5 (1st generation) 500 mg – 1 g q6h 500 mg q8h 500 mg q12h 500 mg q12-24h
500 mg q12-24h; administer dose after dialysis on
dialysis days
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
33
cefadroxil£ (PO)1,3,5 (1st generation)
Dose 1 g twice daily for complicated UTI 500 mg – 1 g q12h 500 mg – 1 g q24h 500 mg q36h
500 mg – 1 g three times weekly after dialysis if receiving dialysis
three times weekly
cefaclor£ (PO)1,3,5
(2nd generation) 250 - 500 mg q8h 250 mg q8h 250 mg q8h ; administer
supplementary dose of 250 mg after dialysis session
cefuroxime axetil (PO)1,2,3,5, 22, 23 (2nd generation) 500 mg q8-12h 500 mg q12h 500 mg q24h
500 mg q24h; administer dose after dialysis on
dialysis days
cefuroxime (IV)1,2,5 (2nd generation)
1.5 g q8h (CrCl greater than 20 mL/min)
1.5 g q12h (CrCl 10-19
mL/min) 1.5 g q24h
1.5 g q24h; administer dose after dialysis on
dialysis days
cefOXitin (IV)1,5,10 (2nd generation)
Dose 2 g q6h for moderate to severe infections such as intra-abdominal infections
1 – 2 g q6-8h 1 – 2 g q8h 1 – 2 g q12h 1 – 2 g q24h 1 – 2 g q24h;
administer dose after dialysis on dialysis days
cefprozil (PO)1,3,5 (2nd generation) 500 mg q12h 250 mg q12h
250 mg q12h; administer supplementary dose of 250 mg after dialysis session
cefixime (PO)2,3 (3rd generation) 400 mg q24h 200 mg q24h 200 mg q24h
cefTRIAXone (IV)1 (3rd generation)
Dose 2 g q12h for CNS infections or Enterococcus faecalis endocarditis in combination with ampicillin
1 – 2 g q24h
cefotaxime (IV)1,2,3 (3rd generation)
Moderate to severe infection 1 – 2 g q6-8h 1 – 2 g q12h 1 – 2 g q24h 1 – 2 g q24h;
administer dose after dialysis on dialysis days
CNS infection 2 g q4h 2 g q6h 2 g q8h 2 g q12h 2 g q12-24h;
administer dose after dialysis on dialysis days
cefTAZidime (IV)1,3,5 (3rd generation)
2 g 8h 2 g q12h 2 g q24h 1 g q24h
1 g q24h; administer dose after dialysis on
dialysis days OR
2 g after dialysis three times weekly if receiving dialysis three
times weekly
cefepime£ (IV)1,2 (4th generation)
Uncomplicated mild to moderate infections 1 – 2 g q8-12h 1 – 2 g q12 – 24h
(ClCr 30-59 mL/min 1 – 2 g q24h 1 g q24h
1g q24h; administer dose after dialysis on
dialysis days OR
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
34
cefepime£ (IV)1,2 (4th generation)
Severe infections including febrile neutropenia, hospital acquired pneumonia, deep space infections‡ or coverage for Pseudomonas aeruginosa
2 g q8h 2 g q12h (ClCr 30-59 mL/min
2 g q24h 1 g q24h
2 g after dialysis three times weekly if receiving dialysis three
times weekly
Carbapenems
ertapenem£ (IV/IM)13,5 1 g q24h 500 mg q24h
500 mg q24h; administer supplementary dose of 150 mg after dialysis session if daily dose given less than 6 hr
before start of HD
imipenem/cilastatinR (IV)1,11 Meropenem preferred for CNS infections and when CrCl less than 30 mL/min
500 – 1000 mg q6h (CrCl greater than
70 mL/min)
500 mg q6-8h (CrCl 31 – 70
mL/min)
500 mg q8-12h (CrCl 21 – 30
mL/min)
250 – 500 mg q12h (CrCl less than 20
mL/min)
250 – 500 mg q12h; administer dose after dialysis on
dialysis days
meropenemR (IV)1,2,3,5
q6h dosing regimen: Caution: do NOT use this regimen for CNS infections
500 mg q6h 500 mg q8h
(CrCl 26 – 50 mL/min)
500 mg q12h (CrCl 10 – 25
mL/min) 500 mg q24h
500 mg q24h; administer dose after dialysis on
dialysis days
q8h dosing regimen: Dose 2 g q8h for CNS infections
1000 – 2000 mg q8h 1000– 2000 mg q12h 500 mg – 1000 mg q24h
500 mg – 1000 mg q24h; administer dose after dialysis on
dialysis days Aminoglycosides – Adjust dose for serum drug levels where applicable. For prolonged therapies consider pharmacy consult for appropriate dosing and monitoring
gentamicin/tobramycin (IV) Extended Interval Dosing2,4,14
- 7 mg/kg for seriousinfections
- Dosing based on IBW,unless actual body weightgreater than 20% aboveIBW, then use dosing weight
5 – 7 mg/kg q24h (CrCl greater than or equal to 60 mL/min)
5 – 7 mg/kg q36h (CrCl 40 – 59
mL/min)
5 – 7 mg/kg q48h (CrCl 20 – 39
mL/min) OR
Consider conventional
dosing
5 – 7 mg/kg IV to start then use serial serum drug levels to
adjust (CrCl less than 20 mL/min)
OR Consider
conventional dosing
1.5 – 2 mg/kg loading dose followed by 1 mg/kg
maintenance dose at the end of each dialysis session;
dose adjustments based on pre-dialysis levels
(dosing based on patient’s dry weight if not obese; if dry weight is greater than 20% above IBW
then use dosing weight) gentamicin/tobramycin (IV) Conventional Dosing 2,4,14
- Dosing based on IBW,unless actual body weightgreater than 20% aboveIBW, then use dosing weight
- Consider a loading dose of2 mg/kg to start
1.5 – 2 mg/kg q8h (CrCl greater than or equal to 80 mL/min)
1.5 – 2 mg/kg q12h (CrCl 50 – 79
mL/min)
1.5 – 2 mg/kg q24h (CrCl 20 – 49
mL/min)
1.5 – 2 mg/kg q48-72hrs OR
Single dose, then use serial drug levels to adjust; close monitoring recommended
(CrCl less than 20 mL/min)
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
35
gentamicin/tobramycin (IV) Synergy Dosing2,3,14
- For Gram positive infectionsonly; tobramycin not forsynergy againstEnterococcus spp infections
- Dosing based on IBW,unless actual body weightgreater than 20% aboveIBW, then use dosingweight
1 mg/kg q8h (CrCl greater than or
equal to 80 mL/min)
1 mg/kg q12h (CrCl 50 – 79 mL/min)
1 mg/kg q24h (CrCl 20 – 49
mL/min)
1 mg/kg q48-72hrs OR
Single dose, then use serial drug levels to adjust; close monitoring recommended
(CrCl less than 20 mL/min)
1 mg/kg at the end of each dialysis session;
dose adjustments based on pre-dialysis levels
(dosing based on patient’s dry weight if not obese; if dry weight is greater than 20% above IBW
then use dosing weight)
amikacin (IV) Extended Interval Dosing1,2,4
Dosing based on IBW, unless actual body weight greater than 20% above IBW, then use dosing weight
15 mg/kg q24h (CrCl greater than or
equal to 60 mL/min)
15 mg/kg q36h (CrCl 40 – 59 mL/min)
15 mg/kg q48h (CrCl 20 – 39
mL/min) OR
Consider conventional
dosing
15 mg/kg to start then use serial
serum drug levels to adjust (CrCl less than 20 mL/min)
OR Consider
conventional dosing
5 – 7.5 mg/kg at the end of each dialysis session;
dose adjustments based on pre-dialysis levels
(dosing based on patient’s dry weight if not obese; if dry weight is greater than 20% above IBW
then use dosing weight) amikacin (IV) Conventional Dosing1,2,4
- Dosing based on IBW,unless actual body weightgreater than 20% aboveIBW, then use dosing weight
- Consider a loading dose of7.5 mg/kg to start
5 – 7.5 mg/kg q8h (CrCl greater than or equal to 80 mL/min)
5 – 7.5 mg/kg q12h (CrCl 50 – 79
mL/min)
5 – 7.5 mg/kg q24h (CrCl 20 – 49
mL/min)
5 – 7.5 mg/kg q48-72hrs OR
use serial serum drug levels to adjust; close monitoring recommended
(CrCl less than 20 mL/min)
Macrolides erythromycin (IV)1,2 500 – 1000 mg q6h 50 – 75% dose q6h
erythromycin (PO)1,2,3
Formulary product: •erythromycin 250 mgcapsules containing EC pellets
250 – 500 mg q6h 50 – 75% dose q6h
azithromycin (IV)1 500 mg q24h x 3-5 days
Use with caution – No dose adjustment provided azithromycin (PO)1
500 mg q24h x 3 days OR
500 mg on day one, then 250 mg daily for days 2 to 5
clarithromycin (PO)1,3,4 500 mg q12h 500 mg q24h 500 mg q24h;
administer dose after dialysis on dialysis days
clarithromycin XL£ (PO)1,3 1000 mg q24h 500 mg q24h 500 mg q24h;
administer dose after dialysis on dialysis days
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
36
Quinolones
ciprofloxacin (IV)1,2,8
400 mg q12h
400 mg q24h 400 mg q24h;
administer dose after dialysis on dialysis days Severe infections; infections
due to Pseudomonas aeruginosa
400 mg q8h 400 mg q12h
ciprofloxacin (PO) (regular release oral solid )1,2,9
500 mg q12h
500 mg q24h 250 – 500 mg q24h;
administer dose after dialysis on dialysis days
Infection of the bone or skin, infections due to Pseudomonas spp or severe infections
750 mg q12h 500 mg q12h
levofloxacin (PO/IV)1
500 mg q24h
500 mg once then 250 mg q24h (CrCl 20 – 49
mL/min)
500 mg once then 250 mg q48h (CrCl less than 20 mL/min or IHD)
High dose for bacteremia, complicated UTI, pyelonephritis, complicated skin infection, nosocomial pneumonia, intra-abdominal infections, infections due to Pseudomonas spp
750 mg q24h 750 mg q48h (CrCl 20 – 49
mL/min) 750 mg once then 500 mg q48h (CrCl less than 20 mL/min or IHD)
moxifloxacin(PO/IV)1 400 mg q24h
norfloxacin£ (PO)1,3 400 mg q12h 400 mg q24h
Tetracyclinesdoxycycline (PO)1 100 mg q12h
minocycline£ (PO)1,3,5 200 mg then 100 mg q12h Usual dose (Doxycycline preferred)
tetracycline (PO)1,3,5
250 – 500 mg q6h (CrCl greater than
80 mL/min)
250 – 500 mg q8-12h
(CrCl 50 to 80 mL/min)
250 – 500 mg q12 – 24h (doxycycline preferred)
250 – 500 mg q24h (doxycycline preferred)
Use not recommended
tigecyclineR (IV)1 100 mg initially, then 50 mg q12h
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
37
Other
clindamycin (IV)1 600 – 900 mg q8h
clindamycin (PO)1,12 300 – 450 mg q6-8h
DAPTOmycinR (IV)1,3
Skin and soft tissue infections: 4 mg/kg q24h
Severe infections: 8-10 mg/kg q24h
Monitor baseline and weekly creatine kinase levels
6 – 8 mg/kg q24h Usual dose q48h if CrCl less than 30 mL/min
Usual dose q48h Administer dose after dialysis on
dialysis days
fosfomycin (PO) Uncomplicated UTI 3 g ONCE
linezolidR (PO/IV)1,2,3 600 mg q12h 600 mg q12h
Administer dose after dialysis on dialysis days
metroNIDAZOLE (PO/IV)1,2 Dose 500 mg q8h for Clostridium difficile infection or CNS infection
500 mg q12h
500 mg q12h Consider a supplemental dose after dialysis if administration cannot be separated from the
dialysis session
nitrofurantoin monohydrate/macrocrystal sustained release capsules (MACROBID) (PO)1
100 mg q12h
Contraindicated if CrCl less than 40 mL/min (will NOT be effective in these patients)
nitrofurantoin regular release oral solidR,1
50 – 100 mg q6h
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
38
sulfamethoxazole + trimethoprim (IV) •Each mL of injectable containssulfamethoxazole 80 mg andtrimethoprim 16 mg1,2,8
- Dose listed as trimethoprim(TMP) component
- Use of sulfamethoxazole +trimethoprim in moderate tosevere renal dysfunction hasnot been not adequatelystudied, close monitoring ofpatient response,electrolytes and serumcreatinine recommended
8 – 20 mg TMP/kg/day divided q6-12h
Pneumocystis jiroveci Treatment: 15 – 20 mg/kg/day divided q6-8h
50% of usual dose (CrCl 15 – 29
mL/min)
Pneumocystis jiroveci
Treatment (CrCl 15 – 30 mL/min): 15 – 20 mg/kg/day divided q6-8h for 48 hr then 7 – 10 mg/kg/day divided
q12h
Generally not recommended, but if
required: 4 – 6 mg/kg/day divided
q12-24h (CrCl less than 15
mL/min)
Pneumocystis jiroveci Treatment (CrCl less than15
mL/min): 7 – 10 mg/kg/day divided q12-24h
2.5 – 10 mg/kg q24h; administer dose after dialysis on dialysis
days OR
4-6 mg/kg 3 times weekly afterdialysis if receiving dialysis three
times weekly
Pneumocystis jiroveci Treatment:
7 – 10 mg/kg after dialysis three times weekly if receiving dialysis
three times weekly
sulfamethoxazole + trimethoprim (PO) • Each regular strength tablet
contains sulfamethoxazole 400mg and trimethoprim 80 mg
• Each double-strength (DS) tabletcontains sulfamethoxazole 800mg and trimethoprim 160 mg
• Each mL of oral suspensioncontains sulfamethoxazole 40 mgand trimethoprim 8 mg1,2,8
sulfamethoxazole/trimethoprim 800/160 to 1600/320 mg q12h
Pneumocystis jiroveci Treatment: 15 – 20 mg/kg/day divided q6-8h
trimethoprim (PO)2 100 mg q12h 50 mg q12h
(CrCl 15 – 29 mL/min)
Generally not recommended if CrCl less than 15
mL/min, but if required: 50 mg
q24h
50 mg q24h Administer dose after dialysis on
dialysis days
vancomycin (IV)2,8,13
- Consider a loading dose of25-30 mg/kg if severeinfection, adjustingmaintenance doses basedon renal function
- Dosing based on actualbody weight
- Maximum of 2 g per dose formaintenance doses
- Adjust dose for serum druglevels where applicable. Forprolonged therapiesconsider pharmacy consultfor appropriate dosing andmonitoring
Target Trough 10 – 15 mg/L
15 mg/kg q12h (CrCl greater than
80 mL/min)
15 mg/kg q24h (CrCl 40 – 80
mL/min)
Target Trough 10 – 15 mg/L
15 mg/kg q36h
(CrCl 20 – 39 mL/min)
Target Trough 10 – 15 mg/L
15 mg/kg q48h (CrCl 10 –19
mL/min) Consider loading dose of 25 – 30 mg/kg; then use
serial serum drug levels to adjust
Less than 70 kg: 1000 mg loading dose then 500 mg maintenance dose infused after dialysis on dialysis days;
70-100 kg:1250 mg loading dose then 750 mg maintenance dose infused after dialysis on dialysis days;
Greater than 100 kg: 1500 mg loading dose then 1000 mg maintenance dose
infused after dialysis on dialysis days
(Adjust maintenance doses based on pre-dialysis
vancomycin trough levels)
Target Trough 15 – 20 mg/L
15 mg/kg q8h (CrCl greater than
80 mL/min)
15 mg/kg q12h (CrCl 40 – 80
mL/min)
Target Trough 15 – 20 mg/L
15 mg/kg q24h (CrCl 20 – 39
mL/min)
Target Trough 15 – 20 mg/L
15 mg/kg q48h (CrCl 10 – 19
mL/min)
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
39
vancomycin (PO)1 C. difficile infection ONLYSee NB-ASC Clostridiumdifficile Infection treatmentguidelines for more details
125 – 500 mg q6h
Antivirals
acyclovir (IV)1,2,3,9
Dose based on ideal or dosing body weight Herpes zoster (shingles)/ Herpes simplex/ Varicella-zoster (chickenpox) in an immunocompromised host or patient with severe disease or encephalitis: 10 - 15 mg/kg q8h
5 – 10 mg/kg q8h 5 – 10 mg/kg q12h
(CrCl 25 – 49 mL/min)
5 – 10 mg/kg q24h (CrCl 10 – 24
mL/min) 2.5 – 5 mg/kg q24h
2.5 – 5 mg/kg q24h Administer after dialysis on
dialysis days
acyclovir (PO)1 Herpes zoster, and Varicella zoster: 800 mg five times a day
400 – 800 mg q8h to five times a day 400 – 800 mg q8h 200 – 800 mg q12h 200 - 800 mg q12h
Administer dose after dialysis on dialysis days
famciclovir£ (PO)1,2,3,8
Herpes zoster (shingles) 500 mg q8h
(CrCl greater than or equal to 60 mL/min)
500 mg q12h (CrCl 40 – 59
mL/min)
500 mg q24h (CrCl 20 – 39
mL/min)
250 mg q24h (CrCl less than 20
mL/min)
250 mg after each dialysis session
Primary genital herpes 250 mg q8h
(CrCl greater than 40 mL/min)
250 mg q12h (CrCl 20 – 40 mL/min)
250 mg q24h (CrCl less than 20
mL/min)
250 mg after each dialysis session
Recurrent Genital herpes
1000 mg q12h x 1 day
(CrCl greater than 40 mL/min)
500 mg q12h x 1 day
(CrCl 40 – 59 mL/min)
500 mg as a single dose
(CrCl 20 – 39 mL/min)
250 mg as a single dose (CrCl <20
mL/min)
250 mg as a single dose after a dialysis session
ganciclovir (IV)1,8
Induction
5 mg/kg q12h or 2.5 mg/kg q12h if
(CrCl 50 – 69 mL/min)
2.5 mg/kg q24h 1.25 mg/kg q24h 1.25 mg/kg 3 times weekly (following dialysis, if receiving dialysis three times weekly)
Maintenance
5 mg/kg q24h or 2.5 mg/kg q24 h if
(CrCl 50 – 69 mL/min)
1.25 mg/kg q24h 0.625 mg/kg q24h 0.625 mg/kg three times weekly (following dialysis, if receiving dialysis three times weekly)
oseltamivir (PO)1,2,15
Treatment (for 5 days)
75 mg q12h (CrCl greater than
60 mL/min)
30 mg q12h (CrCl 30 – 60
mL/min) 30 mg q24h Use with caution:
75 mg ONCE 75 mg after each dialysis
session over a period of 5 days
Prophylaxis (for 10 to 14 days)
75 mg q24h (CrCl greater than
60 mL/min)
30 mg q24h (CrCl 30 – 60
mL/min) 30 mg q2days Use with caution:
30 mg ONCE
An initial 30 mg dose may be given prior to HD if exposed during the 48 hours between
dialysis sessions. Then administer 30 mg after alternate dialysis sessions over a period
of 10-14 days
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
40
valACYclovir (PO)1,2,16
Herpes zoster (shingles) 1 g q8h 1 g q12h 1 g q24h 500 mg q24h 1 g three times weekly after dialysis, if receiving dialysis
three times weekly
Herpes labialis 2g q12h x 2 doses 1 g q12h x 2 doses 500 mg q12h x 2 doses
500 mg as a single dose
500 mg as a single dose Administer dose after a dialysis
session
Primary genital herpes 1g q12h 1g q24h 500 mg q24h 500 mg PO q24h
Administer dose after dialysis on dialysis days
Recurrent genital herpes 500 mg q12h x 3 days or 1g q24h x 5 days 500 mg q24h
500 mg PO q24h Administer dose after dialysis on
dialysis days
Herpes simplex/ Varicella zoster treatment in oncology patients
1 g q8h 1 g q12h 1 g q24h 500 mg q24h 1 g three times weekly after dialysis, if receiving dialysis
three times weekly
Herpes simplex/ Varicella zoster prophylaxis in oncology patients
500 mg q8-12h 500 mg q12h 500 mg q24h 500 mg PO q24h
Administer dose after dialysis on dialysis days
valGANciclovir (PO)1,2,8
Induction
900 mg q12h (CrCl greater than or equal to 60 mL/min)
450 mg q12h (CrCl 40 – 59
mL/min)
450 mg q24h (CrCl 25 – 39
mL/min)
450 mg q48h (CrCl 10 – 24
ml/min) Consider ID or Transplant consult
Maintenance
900 mg q24h (CrCl greater than or equal to 60 mL/min)
450 mg q24h (CrCl 40 – 59
mL/min)
450 mg q2days (CrCl 25-39 mL/min)
450 mg 2x/week (CrCl 10 – 24
ml/min) Consider ID or Transplant consult
zanamivir£ (inhaled)1,15 Treatment 10 mg inhaled orally q12h
Prophylaxis 10 mg inhaled orally q24h
Antifungals amphotericin B (IV)1,2,4,8 (FUNGIZONE) 0.5-1 mg/kg q24h
amphotericin B, lipid complex£ (IV)1,4,8
(ABELCET) 5 mg/kg q24h
amphotericin B, liposomal (IV)1,8 (AMBISOME) 3 – 6 mg/kg q24h
anidulafungin£ (IV)1 200 mg once then 100 mg q24h
caspofungin£ (IV)1 70 mg once, then 50 mg q24h
ADULT ANTIMICROBIAL DOSING TOOL
Drug General Comments Usual Adult Dose (CrCl greater than
or equal to 50 mL/min)
CrCl 30 - 49 mL/min
CrCl 10 - 29 mL/min
CrCl less than 10 mL/min
Intermittent Hemodialysis (IHD)
41
micafungin (IV)1,17
100 mg q24h
Esophageal candidiasis OR invasive aspergillosis 150 mg q24h
Prophylaxis of Candida infection in hematopoietic stem cell transplantation
50 mg q24h
fluconazole (PO/IV)1 Candidemia: 800 mg loading dose on day 1 then 400 mg daily
200 – 800 mg q24h 50% of the dose if CrCl 50 mL/min or less
Administer usual dose after dialysis on dialysis days; on
non-dialysis days, reduce dose by 50 %
itraconazole (PO)1
*Capsules and oral solution are NOTbioequivalent; favor the oral solution
Aspergillosis: Consider loading dose of 200 mg q8h x 3 days; then 200 mg q12h
100 – 200 mg q24h
posaconazole (IV)1,8,9
Loading dose, 300 mg IV infusion q12h on day 1, followed
by 300 mg IV infusion q24h
starting on day 2
Accumulation & resultant toxicity of the diluent can occur if CrCl less than 50 mL/min.
posaconazole (PO)1,8,9
Delayed release tablet and oral suspension are NOT bioequivalent; favor the delayed release tablet.
Delayed-Release Tablet Loading dose of 300 mg q12h on day 1 followed by 300 mg q24h starting on day 2
Oral Suspension Prophylaxis: 200 mg three times daily
Treatment of invasive fungal infections: 400 mg q12h or 200 mg four times daily for patients unable to tolerate a meal or nutritional supplement
voriconazole (IV)1
Therapeutic drug monitoring may be considered
6 mg/kg q12h x 2 doses then 4 mg/kg
q12h thereafter
Accumulation & resultant toxicity of the diluent can occur if CrCl less than 50 mL/min. Use oral voriconazole at normal doses
voriconazole (PO)1,18 Therapeutic drug monitoring may be considered
For patients weighing greater than or equal to 40 kg: 400 mg q12h x 2 doses then 200 mg q12h ; OR for patients less than 40 kg: 200 mg q12h x 2 doses then 100 mg q12h
IDSA recommendations for invasive aspergillosis: may consider oral therapy in place of IV with dosing of 4 mg/kg rounded up to convenient tablet dosage form every 12 hours. IV administration preferred in serious infections as comparative efficacy with
the oral route has not been established.
Legend: R: restricted antimicrobial £: antimicrobial not listed on NB Hospital Formulary ‡: deep space infections include meningitis, septic arthritis,complicated abscesses, etc IBW: ideal body weight Dry body weight in hemodialysis: defined as the lowest tolerated post-dialysis weight at which there are minimal signs or symptoms of hypovolemia or hypervolemia.21 Obesity: defined as an actual body weight greater than 20% above patient’s calculated ideal body weight.
Cockcroft-Gault equation for estimated creatinine clearance (mL/min): CrCL (females) = (140 – age) x weight (kg)*
serum creatinine (mcmol/L)
CrCl (males) = CrCl (females) x 1.2
*For weight, use ideal body weight unless actual body weight is greater than 20% of ideal body weight, inwhich case use dosing body weight.
Ideal body weight (IBW): IBW (females) = 45.5 kg + 0.92 x (height in cm – 150 cm) OR 45.5 kg + 2.3 × (height in inches – 60 inches) IBW (males) = 50 kg + 0.92 x (height in cm – 150 cm) OR 50 kg + 2.3 × (height in inches – 60 inches) Dosing weight (kg) = IBW + 0.4 × (actual body weight – IBW)
ADULT ANTIMICROBIAL DOSING TOOL (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
42
Management of Penicillin and Beta-Lactam Allergy (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017)
Key Points • Beta-lactams are generally safe; allergic and adverse drug reactions are over diagnosed and over reported• Nonpruritic, nonurticarial rashes occur in up to 10% of patients receiving penicillins. These rashes are usually not allergic and are
not a contraindication to the use of a different beta-lactam• The frequently cited risk of 8 to 10% cross-reactivity between penicillins and cephalosporins is an overestimate based on studies
from the 1970’s that are now considered flawed• Expect new intolerances (i.e. any allergy or adverse reaction reported in a drug allergy field) to be reported after 0.5 to 4% of all
antimicrobial courses depending on the gender and specific antimicrobial. Expect a higher incidence of new intolerances inpatients with three or more prior medication intolerances1
• For type-1 immediate hypersensitivity reactions (IgE-mediated), cross-reactivity among penicillins (table 1) is expected due tosimilar core structure and/or major/minor antigenic determinants, use not recommended without desensitization
• For type-1 immediate hypersensitivity reactions, cross-reactivity between penicillins (table 1) and cephalosporins is due tosimilarities in the side chains; risk of cross-reactivity will only be significant between penicillins and cephalosporins with similarside chains
• Only type-1 immediate hypersensitivity to a penicillin manifesting as anaphylaxis, bronchospasm, angioedema, hypotension,urticaria or pruritic rash warrant the avoidance of cephalosporins with similar side chains and other penicillins
• Patients with type-1 immediate hypersensitivity to a penicillin may be safely given cephalosporins with side chains unrelated tothe offending agent (See figure 1 & 2 below)o For example, ceFAZolin does not share a side chain with any beta-lactam and is not expected to cross react with other
agents• Cross-reactivity between cephalosporins is low due to the heterogeneity between side chains; therefore, a patient with a
cephalosporin allergy may be prescribed another cephalosporin with a dissimilar side chain• Cross-reactivity between penicillins and carbapenems is low. Carbapenems would be a reasonable option when antibiotics are
required in patients with type-1 immediate hypersensitivity reaction to penicillins• Patients with reported Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic
symptoms, immune hepatitis, hemolytic anemia, serum sickness or interstitial nephritis secondary to beta-lactam use should avoidbeta-lactams and not receive beta-lactam skin testing, re-challenging or desensitization
• Penicillin skin tests can be used to predict penicillin sensitivity and have a 97-99% negative predictive value• Any patient with possibility of type-1 immediate hypersensitivity to a beta-lactam should be referred for allergy confirmation
Management of the Beta-Lactam Allergy (Figure 1 & Figure 2) 1,2,3,4 1. Avoid the unnecessary use of antimicrobials, particularly in the setting of viral infections.2. Complete a thorough investigation of the patient’s allergies, including, but not limited to: the specific drug the patient
received, a detailed description of the reaction, temporal relationship of the onset of the reaction with respect towhen the drug was given, concomitant drugs received when the reaction occurred, the time elapsed since thereaction occurred and tolerability of any structurally related compounds. If the patient:
a. reports intolerance (e.g. nausea, vomiting, diarrhea, headache) – likely not allergic, attempt beta-lactamtherapy
b. has a documented severe non-IgE mediated hypersensitivity reaction to a beta-lactam (e.g. interstitialnephritis, immune hepatitis, hemolytic anemia, serum sickness, severe cutaneous reactions such asStevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia andsystemic symptoms (DRESS), etc…) – avoid all beta-lactam antibiotics including their use for allergytesting, desensitization and re-challenge.
Treatment options include non-beta-lactam antibioticsc. has a documented severe type-1 immediate (IgE-mediated) hypersensitivity reaction to a penicillin (e.g.
anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, pruritis) – avoid other penicillinsand cephalosporins with similar side chain, unless patient undergoes desensitization.
Treatment options include cephalosporins with dissimilar side chains or carbapenems or non-beta-lactam antibiotics – Note: ceFAZolin does not share a side chain with any beta-lactam agent.
d. has a documented severe type-1 immediate (Ige-mediated) hypersensitivity reaction to a cephalosporin(e.g. anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, pruritis) – avoidcephalosporins with similar side chains and penicillins with similar side chains (see figure 2) unlessdesensitization is performed.
Treatment options include penicillins with dissimilar side chains, cephalosporins with dissimilarside chains, carbapenems or non-beta-lactam antibiotics.
43
Figure 1: Management Diagram
Reported Penicillin Allergy
Assess the nature of the allergy
Onset within 1-72 hours of administration
of: Anaphylaxis, hypotension,
bronchoconstriction, allergic rhinitis,
early onset urticaria, stridor,
angioedema
Intolerance such as: Diarrhea, Nausea, Vomiting, Headache
Onset after more than 72 hours of
administration of: non-pruritic
morbiliform rash, maculopapular rash
Onset after more than 72 hours of
administration of: Stevens-Johnson syndrome, toxic
epidermal necrolysis, immune hepatitis, DRESS, serum
sickness, hemolytic anemia or interstitial
nephritis
Avoid testing, desensitizing and re-challenging with all
beta-lactam antibiotics
Ok to attempt beta-lactam
therapy
Further assess the allergy
How long ago? What specific agent?
Re-challenged? Penicillin skin testing available?
Positive Penicillin Skin Test
Avoid all penicillins as well as beta-lactams
with a similar side chain (see figure 2) or
consider desensitization or select a non-beta-lactam antibiotic
Convincing history of an IgE-mediated
reaction: Avoid all penicillins as well as beta-lactams
with a similar side chain (see figure 2) or
consider desensitization or select a non-beta-lactam antibiotic.
Yes No
Negative Penicillin Skin test
Consider oral challenge in a
monitored setting; if negative, penicillin
class antibiotics may be used
Ok to attempt therapy with a different beta-
lactam
44
Beta-lactam cross-allergy
pe
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pip
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lin
ticarc
illi
n
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alo
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faclo
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PENICILLINS
penicillin X X X X X X X
amoxicillin X X X X X X X X X
ampicillin X X X X X X X X X
cloxacillin X X X X X
piperacillin X X X X X
ticarcillin X X X X X
1ST GENERATION
CEPHALOSPORION
cefadroxil X X X X X
ceFAZolin
cephalexin X X X X X
cephalothin X X X
2ND GENERATION
CEPHALOSPORIN
cefaclor X X X X X
cefprozil X X X X X
cefuroxime X
cefOXitin X X X
3RD GENERATION
CEPHALOSPORIN
cefixime
cefotaxime X X X
cefTAZidime X
cefTRIAXone X X
4TH GEN CEPH cefepime X X
CARBAPENEMSmeropenem X X
imipenem X X
ertapenem X X
Monobactam aztreonam X
Each ‘X’ in the matrix indicates side-chain and/or major/minor antigenic similarity between two antibiotics. For type-1 immediate hypersensitivity there is a risk of cross-allergenicity between pairs due to similar side-chains and/or major/minor antigenic determinants, use NOT recommended without desensitization.
For example: a patient allergic to amoxicillin would likely manifest a reaction to ampicillin, cloxacillin, piperacillin, ticarcillin, cefadroxil, cephalexin, cefaclor and cefprozil but NOT to ceFAZolin, cefuroxime or cefTRIAXone, etc.
Figure 2: Matrix of Beta-Lactam Cross Allergy (based on similar core and/or side chains) 5,6,7,8,9:
*Please note that the Matrix of Beta-Lactam Cross Allergy should only be used to evaluate the risk ofcross-reactivity in patients with type 1 immediate (IgE-mediated) hypersensitivity reactions to a beta-lactam (e.g. anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, pruritis). Pleaserefer to figure 1 for all other types of reactions.
45
Therapeutic Review
Beta-lactam antibiotics are the most commonly prescribed class of antimicrobials and include penicillins, cephalosporins, carbapenems and monobactams (table 1).9 Due to similarities in their beta-lactam ring structure it has been widely accepted that penicillins, cephalosporins and carbapenems have significant cross-reactivity with other classes of beta-lactams.5,9,10,11 Historically it has been reported that approximately 10% of patients allergic to penicillins are also allergic to cephalosporins and up to 50% cross-reactivity has been reported between penicillins and carbapenems.4,5,9,10,11 Therefore, it has been commonly recommended that patients with a severe allergic reaction to one class of beta-lactam antibiotic should not receive any beta-lactam antibiotic.9 This historic over-estimation of cross-sensitivity between classes of beta-lactams is inaccurate and based on flawed methodologies.12
Studies have shown that physicians are more likely to prescribe antimicrobials from other classes when patients have a documented penicillin or cephalosporin allergy.13,14 Non beta-lactam alternatives may be: less effective, more toxic, broader spectrum, more expensive and more likely to lead to infection or colonization with resistant organisms.4,13,15,16,17 The inaccurate documentation of a penicillin allergy can lead to undesirable patient outcomes. For example, one study showed that patients with a documented penicillin allergy at admission spend more time in hospital and are more likely to be exposed to antibiotics associated with C.difficile and vancomycin resistant Enterococcus.18 In addition they had increased prevalence rates for infections secondary to C.difficile, vancomycin-resistant Enterococcus and methicillin-resistant Staphylococcus aureus.18 Another study showed that patients with an “allergy” label (to any antimicrobial) in their medical record were more likely to have longer hospital stays, to be admitted to an intensive care unit, to receive more than one antibiotic during their hospitalisation, and to die during hospitalisation.36
Practice however is changing because allergies have been better defined and the role of the chemical structure on the likelihood of cross-reactivity is now better understood. Recent data shows that the rate of allergic cross-reactivity between penicillins and other beta-lactams is much lower than previous estimates.4,5,9,11
Determining the nature of the patient’s reaction is an important step in differentiating between an allergic reaction and an adverse drug reaction such as nausea, vomiting, diarrhea and headache.5,9 Immunologic reactions to medications are generally classified according to the Coombs and Gell classification of hypersensitivity reactions (see table 2).5,9 The onset and presentation of the reaction can be used to help classify the reaction and determine whether or not a beta-lactam antibiotic may be used (table 2).5,9 Type-1, immediate hypersensitivity reactions, are immunoglobulin (Ig) E-mediated reactions and are the only true allergic reactions where the potential risk of cross-reactivity between beta-lactams should be considered.5,9 Type-1 immediate hypersensitivity reactions usually occur within 1 hour of exposure and typically manifest as anaphylaxis, bronchospasm, angioedema, stridor, wheezing, hypotension, urticaria or a pruritic rash.5 The incidence of these reactions is very low.19 Nonurticarial and nonpruritic rashes are almost certainly not IgE-mediated.5
Penicillins
Penicillin is the most frequently reported drug allergy and is reported in 5-10% of the population.20,21,22 Studies have shown that between 80 and 95% or more of those patients reporting a penicillin allergy
46
do not in fact have true hypersensitivity reactions and the vast majority of these patients can tolerate beta-lactams.1,10,21,22,23,24,25
The use of penicillins can be associated with a nonimmediate, nonpruritic, nonurticarial rash in up to 10% of patients that is unlikely to be IgE-mediated and most often idiopathic or T-cell mediated.5,26 While inconvenient, these reactions have not been associated with anaphylaxis and pose no risk of cross reactivity with other beta-lactams.26 An example is the nonpruritic maculopapular rash commonly seen after the administration of ampicillin or amoxicillin to children suffering from infectious mononucleosis secondary to the Epstein-Barr virus.27
Only a type-1 immediate (IgE-mediated) hypersensitivity reaction to a penicillin manifesting as: anaphylaxis, bronchospasm, angioedema, hypotension, urticaria or pruritic rash warrants the avoidance of other penicillins and cephalosporins with similar side chains.4,5,9,11 Cross-reactivity between penicillins (figure 2) may be due to shared common antigenic determinants based on similarities in their core ring structure that is common to all penicillins and/or the side chains that distinguish different penicillins from one another; therefore, cross-reactivity cannot be based on side chain similarities alone.
Currently, there is one Health Canada-approved standardized penicillin skin test. PRE-PEN contains the major antigenic determinant of penicillin and is used to rule out a type-1 immediate (IgE-mediated) penicillin allergy. Available literature suggests that the skin test using both major and minor antigenic determinants are roughly 50-60% predictive of penicillin hypersensitivity with a 97-99% negative predictive value.4 When penicillin skin testing is not available, the approach to penicillin allergic patients is based on their reaction history and the need for treatment with a penicillin.28 While patients with a convincing reaction history are more likely to be allergic, those with vague histories cannot be discounted as they may also be penicillin allergic.28 The time passed since the reaction is useful because 50-80% of penicillin allergic patients lose their sensitivity after 5 and 10 years respectively.2,29,30
Skin testing, desensitization or re-challenge with a beta-lactam should not be performed in those patients with a history of Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, serum sickness, immune hepatitis, hemolytic anemia or interstitial nephritis.5
Cephalosporins
Cephalosporin-induced skin reactions, described as urticarial, rash, exanthema and pruritus, occur in approximately 1 to 3% of patients.31
Early analysis of cephalosporin use in penicillin allergic patients was complicated by the uncritical evaluation of “allergic reaction”.5,9,11 Any adverse reaction to cephalosporins was often classified as “allergic”.5,9,11 This, accompanied with possible penicillin contamination in early cephalosporin production, resulted in overestimations of cross-sensitivity.5,9 In addition, penicillin allergic patients are more likely to have an allergy to any drug when compared to other patients.4,5,9,10,11 Investigations have shown that individuals with a penicillin allergy are three times more likely to develop new allergies to unrelated compounds, leading to further overestimations of cross-reactivity.5,9,10
Cross-reactivity between penicillins and cephalosporins is due to similarities in side chains at the C-3 or C-7 position as shown in table 3 and not similarities in beta-lactam ring structure as previously speculated.4,5,9,11 The American Academy of Pediatrics states that the likelihood of a penicillin allergic
47
patient reacting to a cephalosporin with a different side chain is similar to that of a non-penicillin allergic patient.5 A prospective study with skin test or challenge dose confirmed penicillin allergy demonstrated a 0% cross-reactivity to ceFAZolin, cefuroxime and cefTRIAXone. None of these agents share a side chain with penicillin.32 Meanwhile the risk of cross-reactivity may be up to 40% between penicillins and cephalosporins with the similar R-group side chains.3,33 A retrospective population based analysis of 3.9 million patients revealed that there was no significant difference between the rates of anaphylaxis to a cephalosporin in patients with and without documented penicillin “allergy”. This study also highlighted that the practice of avoiding 1st and 2nd generation cephalosporins and using 3rd or 4th generation cephalosporins instead was associated with higher rates of C. difficile infection. The authors go on to say: “Warnings against the administration of cephalosporins to patients with unconfirmed penicillin allergy should be removed from electronic medical record systems.The public would be better served by warnings that the use of cephalosporins, particularly third- or higher generation parenteral cephalosporins, is associated with an increased risk of C difficile infection within 90 days.”38
Cross-reactivity between cephalosporins is low because of the significant heterogeneity of the side chains at the C-3 and C-7 positions.9,34 Therefore, if a patient has a cephalosporin allergy, one can safely prescribe another cephalosporin that has dissimilar side chains at both C-3 and C-7 positions.34 A prospective study evaluating the possibility of using alternative cephalosporins in patients with confirmed cephalosporin allergy demonstrated that cephalosporin allergies are not a class effect, and that patients with confirmed cephalosporin allergy can safely receive cephalosporins with dissimilar side chains.37
CeFAZolin is not expected to cross react with any penicillin or cephalosporin as it does not share a side chain with any beta-lactam.4,34
Carbapenems
Early studies evaluating the risk of cross-reactivity between penicillin and carbapenems found rates upwards of 47%. However, these studies had poor definitions of allergy and variable methods for determining allergy status.9 A more recent systematic review was completed to collect and combine all published data on pediatric and adult patients reported to have a clinical history of type-1 immediate hypersensitivity (IgE-mediated) to a penicillin and/or cephalosporin who were then given a carbapenem.35 Within the study allergic reactions were classified as proven, suspected or possible IgE-mediated and non-IgE-mediated.35 Overall, for patients with a history of proven, suspected or possible IgE-mediated reaction to a penicillin; 4.3% (36/838) had a suspected hypersensitivity reaction to a carbapenems but only 20 were compatible with an IgE-mediated reaction and only one was considered to be proven.35 The authors concluded that carbapenems would be a reasonable option when antibiotics are required in patients with IgE-mediated reactions to penicillins.35 They advise that clinicians proceed with caution by administering the first dose of carbapenem in a setting where anaphylaxis can be managed and to consider giving via a graduated challenge.35 If at any stage the patient reacts then the options are to use a carbapenem desensitization protocol or switch to a non-beta-lactam antibiotic.35
48
Desensitization
Desensitization, or temporary induction of drug tolerance, is used for patients with a documented or convincing history of type-1 immediate (IgE-mediated) beta-lactam allergy and/or positive skin test and a serious infection where non-cross-reacting alternatives are not appropriate.2,28 The goal of desensitization is to modify a patient’s immune response to allow safe treatment with the allergenic drug.28
Desensitization will not prevent non-IgE mediated reactions and should never be attempted in patients with reactions involving major organs or severe cutaneous reactions (e.g. interstitial nephritis, SJS, TEN, DRESS, etc.).2
Desensitization is performed by administering incremental doses of the allergenic drug.3 Usually the procedure is complete within hours and starts in the microgram range.28 Dosages are usually doubled every 15 to 30 minutes until therapeutic doses are achieved.28 When the desensitization process is complete, treatment with the select beta-lactam should be started immediately and must not be interrupted during the treatment course.2,28 Desensitization is usually lost within two days of cessation and must be repeated if the beta-lactam is required in the future.2,28
Graduated Challenge
Graduated challenges are used when there is a low likelihood of drug allergy and differ from desensitization in that they do not alter the patient’s underlying immune response to the drug in question.28 Their purpose is to allow cautious administration in patients unlikely to be allergic when there is no intention to alter the patient’s immune response.28 If the graduated challenge is tolerated the patient is then considered not to be allergic and not at increased risk for future reactions.28 Graduated challenges should never be performed in patients with reactions involving major organs or non-IgE mediated severe cutaneous reactions (e.g. interstitial nephritis, SJS, TEN, DRESS, etc…).28
The starting dose of a graduated challenge is often higher than that used for desensitization and usually only involves 2 to 3 steps and completed within hours.28 For a graduated challenge for an intravenous antibiotic, 1% of the full dose is administered, then 10 % of the full dose, then the full dose, separated by 30 minutes to 1 hour each and under careful observation.2,3 If at any point a reaction occurs the graduated challenge is stopped.
The decision to use a graduated challenge is based on the risk of cross-reactivity and the description and remoteness of the allergic reaction in question. Treatment options requiring desensitization or graduated challenge should be avoided in severe infections (ex. febrile neutropenia, sepsis, meningitis, etc.) where delays in appropriate drug therapy are associated with poor patient outcome, in these scenarios a non-beta lactam treatment option should be considered for empiric therapy.
Allergy assessment
Allergy evaluation and “de-labelling” is emerging as a new antimicrobial stewardship intervention. Recent IDSA guidelines recommend that antimicrobial stewardship programs promote allergy assessments and penicillin skin testing when appropriate, as these may enhance the use of first-line agents.39 A multicenter prospective trial demonstrated that antimicrobial stewardship pharmacists performing beta-lactam allergy skin testing and graduated challenge at the point of care was
49
associated with greater use of preferred beta-lactam therapy without increasing the risk of adverse drug reactions.40
Table 1: Classification of Beta-Lactams
Penicillins Cephalosporins
Carbapenems Monobactam First Generation
Second Generation
Third Generation
Fourth Generation
penicillin ampicillin amoxicillin cloxacillin piperacillin ticarcillin
cefadroxil cefaclor cefOXitin cefprozil cefuroxime
cefTAZidime cefixime cefTRIAXone cefotaxime
cefepime ertapenem aztreonam ceFAZolin imipenem cephalexin meropenem
Table 2: Coombs and Gell Classification of Hypersensitivity Reactions4,5,31,38,41,42,43,44 Type Mediator Onset Clinical Reaction Comments
I - Immediate and Acute hypersensitivity
IgE antibodies Less than 1hr (Rarely up to 72 hours)
Anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, pruritis
Anaphylaxis: Penicillins 0.015 – 0.2%
Cephalosporins 0.0001 – 0.1%
Avoid the offending agent and side chain related agents (See Figure 2)
II – Delayed cytotoxic antibody-mediated hypersensitivity
IgG and IgM antibodies
Greater than 72 hours
Hemolytic anemia, thrombocytopenia, neutropenia
Drug specific, avoid the offending agent
III – Antibody complex-mediated hypersensitivity
IgG and IgM complexes
Greater than 72 hours
Serum sickness, glomerulonephritis, small vessel vasculitis, drug fever
Antibody-antigen complexes precipitate in tissues and potentially affect any end organ
IV – Delayed type hypersensitivity
T-Cells Greater than 72 hours
Contact dermatitis, pustulosis
Incidence is low. Ex: Eosinophilia, bullous exanthems, severe exfoliative dermatoses (ex. SJS/TEN), interstitial nephritis, immune hepatitis and some morbilliform or maculopapular rashes
Idiopathic Reactions Unknown Usually greater than 72 hours
Maculopapular or morbilliform rashes
1 – 4% of patients receiving beta-lactams Not a contraindication to future use of beta-lactam antibiotics
*Anaphylaxis: defined as serious hypersensitivity reaction that is rapid in onset and may cause death, typically involving theskin, mucosal tissue or both and either respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced peakexpiratory flow, hypoxemia) or reduced blood pressure or the associated symptoms and signs of end-organ dysfunction.
50
Table 3: Beta-Lactam Groups with Similar Side-Chains Similar C-7 Side Chain
(Cross Reactions between agents within one group is possible)
Similar C-3 Side Chain (Cross reactions between agents within one group is possible)
Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Group 7 penicillin cefOXitin
amoxicillin ampicillin cefaclor cephalexin cefadroxil cefprozil
cefepime cefotaxime cefTRIAXone
cefadroxil cephalexin
cefotaxime cephalothin
cefuroxime cefOXitin
cefixime cefTAZidime aztreonam
Note: • CeFAZolin does not share a side chain with any beta-lactam and is not expected to cross react with other agents• Amoxicillin, ampicillin, penicillin, cloxacillin, piperacillin and ticarcillin share common major allergic determinants
based on similarities in their core structure and/or side chains; therefore, cross-reactivity cannot be based on sidechain similarities alone
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Antimicrobial Allergy Evaluation Tool (NB Provincial Health Authorities Anti-Infective Stewardship Committee, May 2016)
Reaction (as indicated in the patient’s chart or described by the patient )
Personal history Asthma Autoimmune disease Atopic dermatitis Latex allergy Prior anaphylaxis Multiple drug intolerance syndrome Multiple drug allergy syndrome Food allergy: ________________Other:_________________________________________________________________________________
Patient questionnaire 1. When did the reaction take place? _________________________________________________________
2. How old was the patient at the time of the reaction? ___________________________________________
3. Does the patient recall the reaction? If not, who informed them of the reaction? ___________________________________________________________________________________________________________
4. Does the patient remember which medication? _______________________________________________
5. What was the medication prescribed for? ____________________________________________________
6. What was the route of administration? ______________________________________________________
7. How long after starting the medication did the reaction begin? ________________________________________________________________________________________________________________________
8. Describe the reaction: ________________________________________________________________________________________________________________________________________________________
9. Did the patient seek medical care due to the reaction? _________________________________________
10. Was the medication discontinued? If so, what happened after it was discontinued? ________________________________________________________________________________________________________
11. Did the patient have any other ongoing medical problem at the time of the reaction? _______________________________________________________________________________________________________
12. What other medications was the patient taking? Why and when were they prescribed? _____________________________________________________________________________________________________
13. Has the patient taken any similar medications before or after the reaction? If so, what was the result? _________________________________________________________________________________________
14. Has the patient ever experienced this reaction without intake of the suspected medication? _________________________________________________________________________________________________
Assessment Probable non-severe delayed hypersensitivity
reaction (non-IgE mediated) Probable non-allergic adverse reaction or
intolerance
Probable type 1 immediate hypersensitivity reaction(IgE mediated)
Probable severe delayed hypersensitivity reaction(non-IgE mediated)
Completed by:___________________________________________ Date/time:_______________________ 52
Table 1: Patient questionnaire1,2,4,5,6,7,12,13,14
Question Comments When did the reaction take place? Patients with type 1 immediate (IgE-mediated) hypersensitivity reactions
to penicillin may lose their sensitivity over time (50% after 5 years, and 80% after 10 years)
How old was the patient at the time of the reaction?
Certain confounding factors may be more common depending on the patient’s age. (Example: viral exanthems in pediatric patients)
Does the patient recall the reaction? If not, who informed them of the reaction?
Vague histories do not rule out serious reactions. However, it is less likely to be a serious hypersensitivity reaction if the patient or family cannot recall the specifics of the reaction.
Does the patient remember which medication? Knowing the specific antimicrobial which caused the reaction can help in determining safe alternatives.
What was the medication prescribed for? Sometimes patients confuse symptoms of the condition with adverse reactions of the medication. (e.g.: Strep. pyogenes scarlet fever rash being confused as a drug-reaction)
What was the route of administration? Hypersensitivity reactions can be more common when medications are administered intravenously compared to orally.
How long after starting the medication did the reaction begin?
Timeframe is essential to distinguish between an IgE-mediated immediate hypersensitivity reaction or non-IgE mediated delayed reaction.
Describe the reaction. Obtain specific information from the patient. (Ex: if a rash; determine location, morphology, etc.)
Did the patient seek medical care due to the reaction?
Can be of value to stratify how severe the reaction was.
Was the medication discontinued? If so, what happened after it was discontinued?
Discontinuing the medication will have varying results. (e.g.: depending on the type of skin reaction, symptoms may or may not improve after discontinuation)
Did the patient have any other ongoing medical problem at the time of the reaction?
Certain viral infections [e.g. Epstein-Barr virus (EBV), Herpes simplex virus (HSV), Human immunodeficiency virus (HIV), Cytomegalovirus (CMV)] are associated with non-IgE mediated cutaneous drug reactions that are often misdiagnosed as “allergic reactions”.
What other medications was the patient taking? Why and when were they prescribed?
Concomitant medications could cause or contribute to the reaction.
Has the patient taken any similar medications before or after the reaction? If so, what was the result?
Tolerance of structurally similar medications is not always indicative of tolerance of the suspected medication; however, it can assist in determining safe alternatives.
Has the patient ever experienced this reaction without intake of the suspected medication?
If the same reaction has occurred without exposure to the suspected medication, it may be caused by other factors.
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Therapeutic review
Allergy evaluation is an essential component of patient care. Beta-lactams, as a class, are generally safe; allergic and adverse reactions are over diagnosed and over reported. For example, up to 10% of the population will report a penicillin allergy; but up to 95% (or more) of these patients do not have a true allergy.4,6,11
Fearing a potential anaphylaxis secondary to beta-lactam use, many clinicians will over diagnose penicillin allergy or simply accept a diagnosis of penicillin allergy from patients without a proper history of the reaction.2 Studies have shown that physicians are more likely to prescribe antimicrobials from other classes when patients have a documented penicillin or cephalosporin allergy.2,9 Non beta-lactam alternatives may be: less effective, more toxic, broader spectrum, more expensive and more likely to lead to infection or colonization with resistant organisms.6,9 Unfortunately, a penicillin allergy label is not benign. Simply being labelled as having an allergy to penicillin increases the likelihood of prolonged hospital stay and increases the risk of infections due to Clostridium difficile, vancomycin-resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus Aureus (MRSA).10
Most patients have no current physical findings that can either prove or disprove their allergy label.2 The initial probability of a true allergy is almost always determined by the allergy history.2 The included patient questionnaire can assist clinicians in obtaining a detailed allergy history.
A detailed investigation of the patient’s allergy history is necessary to differentiate between true type 1 (IgE-mediated) immediate hypersensitivity reactions (true allergic reactions) and non IgE-mediated hypersensitivity reactions or intolerances/adverse reactions. While some of the non IgE-mediated reactions are minor, other types of reactions can be severe (e.g. interstitial nephritis, immune hepatitis, hemolytic anemia, serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, etc.). Table 2 below subdivides the reactions based on the Coombs and Gell classification of hypersensitivity reactions:
Table 2: Coombs and Gell Classification of Hypersensitivity Reactions 6,7
Type Mediator Onset Clinical Reaction Comments I - Immediate and Acute hypersensitivity
IgE antibodies Within 1hr (Rarely up to 72 hours)
Anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, pruritis
Anaphylaxis: Penicillins 0.01-0.05%
Cephalosporins 0.0001-0.1%
II – Delayed cytotoxic antibody-mediated hypersensitivity
IgG and IgM antibodies
Greater than 72 hours
Hemolytic anemia, thrombocytopenia, neutropenia
Drug specific
III – Antibody complex-mediated hypersensitivity
IgG and IgM complexes
Greater than 72 hours
Serum sickness, glomerulonephritis, small vessel vasculitis, drug fever
Antibody-antigen complexes precipitate in tissues and potentially affect any end organ
IV – Delayed type hypersensitivity
T-Cells Greater than 72 hours
Contact dermatitis, pustulosis
Incidence is low. Ex: Eosinophilia, bullous exanthems, severe exfoliative dermatoses (ex. SJS/TEN), interstitial nephritis, immune hepatitis and some morbilliform or maculopapular rashes
Idiopathic Reactions Unknown Usually greater than 72 hours
Maculopapular or morbilliform rashes
1 – 4% of patients receiving beta-lactams
The time to onset of the reaction can be a helpful tool in determining if the reaction was in fact a true type 1 immediate (IgE-mediated) hypersensitivity reaction. Type 1 reactions usually occur within an hour of exposure, with the possibility of occurring up to 72 hours post-exposure, and can include anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor and pruritis.5,6,7
54
Cutaneous reactions
Many patients may report a “rash” as an allergic reaction; however more information should be sought to assist in defining the true nature of the reaction. Cutaneous reactions can range from non-severe delayed maculopapular rashes to life-threatening toxic epidermal necrolysis; therefore it is essential to further question the patient.
Certain infections can either cause cutaneous reactions or predispose patients to reacting to antimicrobials. Patients suffering from certain bacterial infections (e.g. Streptococcus pyogenes, Mycoplasma pneumoniae) can develop cutaneous symptoms, irrespective of which antibiotic is used.18,22 Certain viral infections [e.g. Epstein-Barr virus (EBV), Herpes simplex virus (HSV), Human immunodeficiency virus (HIV), Cytomegalovirus (CMV)] can also directly cause cutaneous symptoms.14,18,22 Patients suffering from these viral infections may also be at a higher risk to react to certain antimicrobials.2,4,12,13 A notable example is the delayed morbilliform rash that often develops when patients suffering from EBV are treated with an aminopenicillin, such as amoxicillin.4,18
Please see table 3 below for a brief description of certain cutaneous reactions.
Table 3 – Cutaneous reactions 1,2,15,16,18,19,20,21 Type of skin reaction Chronology Description
Angioedema Onset: Usually immediate (0-6 hours)
Duration: Resolution within 24-72 hours
Region(s) affected: Lips, eyelids, earlobes, tongue, mouth, larynx, genitalia
Morphology: Skin-coloured circumscribed edema involving the subcutaneous tissues. (can be asymmetrical/unilateral)
More details: Non-pruritic; often very frightening for patients; can be painful
DRESS syndrome (Drug Rash with
Eosinophilia and Systemic Symptoms)
Onset: 1-8 weeks after exposure
Duration: Weeks- months (even after discontinuing the suspected medication)
Region(s) affected: Classic distribution: Face, upper trunk, extremities (but can progress anywhere on the surface of the skin and can sometimes have mucosal involvement)
Morphology: Most commonly begins as an erythematous, pruritic, morbilliform rash
More details: Pruritis and fever usually precede cutaneous eruptions. Can cause facial edema, which can be mistaken for angioedema.
Systemic systems involved: - Lymphatic: lymphadenopathy is very common- Hematologic: leukocytosis, eosinophilia, lymphocytosis- Hepatic: hepatosplenomegaly, hepatitis, elevated livertransaminases, elevated alkaline phosphatase- Renal: hematuria, proteinuria, elevated BUN and creatinine- Other: pulmonary, cardiac, neurologic
Erythema multiforme Onset: Within 3-5 days (May include prodromal symptoms of an upper respiratory infection)
Duration: Approximately 2 weeks
Region(s) affected: Often appear on the extremities (hands, palms, extensor of the forearms, soles of the feet, etc.) and can spread inwards towards the trunk. May involve mucous membranes of the mouth and genitalia.
Morphology: Well-demarcated, circular, erythematous papules; often “target” or “iris”-like.
More details: - Can be difficult to discern from Stevens-Johnson Syndrome- Often associated with HSV or mycoplasma infections- Fever, if present, is usually mild
55
Type of skin reaction Chronology Description Maculopapular rash /
Morbilliform rash / Exanthems
Onset: Delayed (often more than 72 hours), within the first 2-4 weeks following the initial dose
Duration: Usually fades within 2 weeks
Region(s) affected: Commonly begin on head, neck or upper torso, and progress downward to the extremities.
Morphology: Often bilateral and symmetrical. Usually flat, barely raised, erythematous patches (one to several mm in diameter). Can also include papules.
More details: - With or without pruritis- Can develop into confluent areas- Can be the result of several mechanisms (ex: viral infection,idiopathic, etc.)- Mild eosinophilia is possible, but not common- Fever rarely associated; but is mild if present
Photosensitivity / Phototoxicity
Onset: 5-20 hours after drug + UV light exposure
Duration: N/A
Region(s) affected: Areas most often exposed to the sun (ex: face, back of the hands, back and sides of the neck, extensor surfaces of the forearm, etc.). Classical presentation spares shaded areas, such as under the chin, under the nose, behind the ears.
Morphology: Often resembles exaggerated sunburn, sometimes with blisters. Sharp demarcation at sites where clothing or jewelry were present during light exposure.
More details: Not common with beta-lactam antibiotics
Pruritis Onset: N/A
Duration: N/A
Region(s) affected: Localized or generalized itching; more often generalized when drug induced.
Morphology: Does not require visible cutaneous signs of a reaction.
More details: Mechanism not always clear
Stevens-Johnson syndrome
Onset: Delayed (within 8 weeks of first exposure), but with abrupt onset of symptoms.
Duration: Up to 6 weeks
Region(s) affected: Less than 10% of the body surface is affected. Can affect the skin, eyes, and mucous membranes; such as the lips, mouth, and genital mucous membranes.
Morphology: Often begins with dusky red, flat lesions (sometimes target-like, similar to erythema multiforme), progressing to bullae and necrotic lesions. Leads to blisters and dislodgement of the epidermis.
More details: - Is accompanied by any (or all) of: high fever, malaise, myalgia,arthralgia, headache, ocular involvement, painful stomatitis- A medical emergency; in-hospital mortality = 5-12 %
Toxic epidermal necrolysis Onset: Delayed (within 8 weeks of first exposure), but with abrupt onset of symptoms.
Duration: Up to 6 weeks
Region(s) affected: Greater than 30% of the body surface is affected. Can affect the skin, eyes, and mucous membranes; such as the lips, mouth, and genital mucous membranes. Hairy regions of the skin are often spared.
Morphology: See Stevens-Johnson Syndrome; eventually can resemble extensive second degree burns
More details: - Is accompanied by any (or all) of: high fever, fatigue, vomiting,diarrhea, malaise, myalgia, angina, arthralgia, headache, ocularinvolvement, painful stomatitis- A medical emergency; in-hospital mortality more than 30%
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Type of skin reaction Chronology Description Urticaria Onset: Immediate,
usually within 36 hours
Duration: Rarely persist for more than 24 hours
Region(s) affected: Can occur in any location. Involves the superficial portion of the dermis, and not subcutaneous tissues.
Morphology: Raised, erythematous areas of edema (wheals), sometimes with central pallor. Will often blanch with pressure.
More details: - Often pruritic- May or may not be accompanied by angioedema, can progress toanaphylaxis
For more information, please see the Management of Penicillin and Beta-Lactam Allergy guideline prepared by the NB Provincial Health Authorities Anti-Infective Stewardship Committee.
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Antimicrobial Route of Administration (IV to PO) Therapeutic Conversion
Patients on the targeted IV antimicrobials should be assessed within 72 hours of the start of IV therapy and regularly thereafter for the appropriateness of IV to PO conversion based on the following criteria (see below for list of targeted antimicrobials and their renal dose adjustments).
GENERAL CRITERIA The patient:
� is tolerating food, enteral feeds and/or other oral medications AND � is not showing evidence of malabsorption (e.g.diarrhea/vomiting) AND � does not have continuous nasogastric suctioning, gastrectomy, malabsorption syndrome, GI obstruction or
ileostomy
ANTIMICROBIAL CRITERIA The patient:
� is clinically improving (which may include documented improved clinical signs and symptoms of infection, normalizing white blood cell count, etc…) AND
� is hemodynamically stable AND � has been afebrile for at least 48 hours (i.e. temperature less than 38°C) AND � is not being treated for a condition where parenteral therapy is clinically indicated, including but not
limited to: endocarditis, CNS infection, osteomyelitis, S. aureus bacteremia, undrained or complicated abscess, cystic fibrosis, febrile neutropenia AND
� doesn’t have a pathogenic isolate showing resistance to the suggested antibiotic
Version: 20160317
Table 1: Route of Administration (IV to PO) Conversion Protocol for Targeted Antimicrobials
Drug IV dose PO drug/dose Interval azithromycin 250 or 500 mg q24h azithromycin 250 mg q24h
ceFAZolin1 1000 mg q8h cephalexin1,2 500 mg q6h 2000 mg q8h cefTRIAXone (For community-acquired pneumonia or acute exacerbation of COPD)
1000 mg q24h amoxicillin/clavulanate1,2 875/125 mg q12h 2000 mg q24h
ciprofloxacin1 400 mg q12h or q24h ciprofloxacin1 500 mg Same as IV 400 mg q8h ciprofloxacin1 750 mg q12h
clindamycin 600-900 mg q8h or q12h clindamycin 450 mg q6h metroNIDAZOLE1 500 mg q8h or q12h metroNIDAZOLE1 500 mg Same as IV moxifloxacin 400 mg q24h moxifloxacin 400 mg q24h levofloxacin1 500-750 mg q24h levofloxacin1 (dose same as IV) Same as IV 1Dose adjustment required in renal impairment 2Assess for true penicillin allergy
Table 2: Antimicrobial Dosing in Renal Impairment
Drug Usual adult dose
(CrCl equal to or greater than 50 mL/min)
CrCl 30 - 49 mL/min CrCl 10 - 29 mL/min CrCl less than 10 mL/min
amoxicillin + clavulanate 875/125 mg q12h no adjustment 500/125 mg q12h 500/125 mg q24h cephalexin 500 mg q6h 500 mg q8h 500 mg q12h 500 mg q24h
ceFAZolin 1000 mg q8h no adjustment 1000 mg q12h 1000 mg q24h 2000 mg q8h no adjustment 2000 mg q12h 2000 mg q24h
ciprofloxacin PO 250–500 mg q12h no adjustment extend interval to q24h extend interval to q24h 750 mg q12h 500 mg q12h 500 mg q24h 500 mg q24h
ciprofloxacin IV 400 mg IV q12h no adjustment 400 mg q24h 400 mg q24h 400 mg IV q8h 400 mg q12h 400 mg q24h 400 mg q24h
metroNIDAZOLE 500 mg q8h or q12h no adjustment no adjustment 500 mg q12h
levofloxacin 750 mg q24h CrCl 20-49 mL/min
750 mg q48h CrCl less than 20 mL/min
500 mg q48h
500 mg q24h CrCl 20-49 mL/min 250 mg q24h
CrCl less than 20 mL/min 250 mg q48h
58
Surgical Prophylaxis Guidelines 2016
Section 1: General Principles Page Timing of Prophylaxis 60Duration of Antibiotic 60Choice of Prophylactic Antibiotic 60Antibiotic Dosing 61
Intraoperative Dosing 61 Renal or Hepatic Impairment 61 Gentamicin Dosing 61 Vancomycin Dosing 61 Dosing in Obesity 62
Section 2: Surgical Prophylaxis Recommendations Cardiac 63Gastrointestinal
Appendectomy 63 Colorectal 63 Gastroduodenal 63 Hepatic/Pancreatic/Biliary 64 Hernia Repair 65 Small Intestine 65
Head and Neck 65Neurosurgery 66Obstetrics and Gynecology 66Ophthalmology 67Oral and Maxillofacial 67Orthopedics 67Plastic Surgery 78Spine 70Thoracic 70Trauma 70Urology 71Vascular 72
Section 3: Other Intra-operative Antibiotic Prophylaxis 73Pediatric Prophylactic Antibiotic Dosing 73
References 98
59
These guidelines provide general recommendations for appropriate prophylactic antibiotic use for
common surgical procedures; the list of surgical procedures is not all inclusive.
GENERAL PRINCIPLES OF ANTIMICROBIAL PROPHYLAXIS
The accepted principles of antimicrobial prophylaxis for surgical procedures involve:
Surgical procedures for which antimicrobial prophylaxis has been demonstrated to be beneficial.
General, patient related risk factors for surgical site infection are extremes of age, nutritional
status, obesity, diabetes mellitus, tobacco use, co-existent remote body site infection, altered
immune response, corticosteroid therapy, recent surgical procedure, length of preoperative
hospitalization, and colonization with microorganisms.
TIMING OF PROPHYLACTIC ANTIMICROBIAL DOSE:
Preoperative doses of antimicrobials must be given in the 60 minutes before the first surgical
incision. This is a more-specific time frame than the previously recommended time, which was
“at induction of anesthesia.” Some agents, such as fluoroquinolones and vancomycin, require
administration over one to two hours; therefore, the administration of these agents should
begin within 120 minutes before surgical incision.
Patients receiving therapeutic antimicrobials for an infection before surgery should be given
additional antimicrobial prophylaxis before surgery.
DURATION OF PROPHYLACTIC ANTIBIOTIC:
If antimicrobial prophylaxis is continued postoperatively, the duration should be less than 24
hours, regardless of the presence of intravascular catheters or indwelling drains.
CHOICE OF PROPHYLACTIC ANTIMICROBIAL:
Antimicrobial prophylaxis is generally unnecessary for “clean” surgical procedures.
For the majority of surgical procedures in which antimicrobial prophylaxis is indicated, a single 2
g dose of ceFAZolin given within the 60 minutes before the first surgical incision is appropriate.
Beta-lactam allergy: Obtain a reliable history and document exact nature of the reaction! Non-
beta-lactam options may be more toxic and less effective. For example, clindamycin is losing
coverage of gram-positive bacteria
o For immediate or Type 1 (IgE-mediated) hypersensitivity reactions (e.g. anaphylaxis,
urticaria, angioedema, hypotension, bronchospasm, stridor, pruritus), cross-reactivity
between cephalosporins and penicillins is due to similarity in side-chains and was
overestimated in the past. There is only significant risk of cross-reactivity among penicillins
and between penicillins and cephalosporins with similar side-chains.
o Immediate or Type 1 (IgE-mediated) hypersensitivity reactions to penicillin – warrants the
avoidance of cephalosporins with similar side chains and other penicillins.
60
o Cross reactivity among cephalosporins is low due to heterogeneity among side chains.
Cephalosporin allergic patients may safely receive another cephalosporin that has dissimilar
side chains.
o CeFAZolin does not share a side chain with any beta-lactam and is not expected to cross
react with other beta-lactams. CeFAZolin is the only systemic beta-lactam included in this
guide and may safely be given to patients with immediate or Type 1 (IgE-mediated)
hypersensitivity reactions to penicillins or other cephalosporins. It should only be avoided in
patients allergic to ceFAZolin or who have a severe non-IgE mediated reaction to a beta-
lactam antibiotic (see below).
o Severe non-IgE mediated hypersensitivity reactions (Stevens-Johnson syndrome, toxic
epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, immune
hepatitis, hemolytic anemia, serum sickness, interstitial nephritis, small vessel vasculitis) -
warrants the avoidance of all beta-lactams.
o Idiopathic reactions: Not clearly immune mediated (non-pruritic morbilliform rash) and are
not a contraindication to taking a different beta-lactam such as ceFAZolin
DRUG DOSING
Intraoperative dosing:
For antimicrobials with short half-life intraoperative dosing recommended if: prolonged surgical
procedure (> 2 half-lives of the antimicrobial) OR major blood loss (>1.5L). If massive blood loss
occurs, a second dose should be given promptly. See Table 1 for recommendations.
Renal or Hepatic Impairment:
Antimicrobial prophylaxis for patients with renal or hepatic dysfunction often does not need to
be modified when given as a single dose pre-op before surgical incision
Gentamicin dosing:
Gentamicin 5 mg/kg (based on dosing body weight) ,extended interval dose, provides at least 24
hours of antimicrobial coverage
Dose based on IBW, unless actual body weight greater than 20% above IBW, then use dosing
weight
If patient’s actual weight is more than 20% above ideal body weight (i.e. obesity, pregnancy),
the dosing weight can be calculated as follows:
Dosing body weight = ideal body weight + 0.4 (actual body weight – ideal body weight)
Ideal body weight (males) = 50 kg + (0.92 x cm above 150 cm) OR 50 kg + (2.3 kg x inches above
60 inches)
Ideal body weight (females) = 45.5 kg + (0.92 x cm above 150 cm) OR 45.5 kg + (2.3 kg x inches
above 60 inches)
Vancomycin Dosing:
Vancomycin 15 mg/kg based on patient’s actual body weight and rounded to the nearest 250
mg.
61
Drug dosing in obesity:
Conclusive recommendations for weight-based dosing for antimicrobial prophylaxis in obese
patients cannot be made because data demonstrating clinically relevant decreases in SSI rates
from the use of such dosing strategies instead of standard doses in obese patients are not
available in the published literature.
Considering the low cost and favorable safety profile of ceFAZolin, the minimum dose should be
2 g. Increasing the dose to 3 g for those weighing greater than or equal to 120 kg can easily be
justified. For simplification, these guidelines recommend 2 g ceFAZolin doses for all adult
patients.
Note: This guideline is intended for adults only. A pediatric dosing table is provided in Table 2.
62
Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
CARDIAC
CABG
Prosthetic valve
Open heart surgery
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
Less than 24 hours
Cardiac device insertion(pacemaker implantation)
Ventricular assist devices
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
No Antibiotics
Cardiac catheterization +/- stenting
No Antibiotics N/A N/A
APPENDECTOMY
Appendectomy for uncomplicated appendicitis
metroNIDAZOLE 500 mg Plus ceFAZolin 2 g¶
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
No Antibiotic
If gangrenous orperforated appendicitisor intestine, treatmentcourse must start
COLORECTAL
All patients metroNIDAZOLE 500 mg Plus ceFAZolin 2 g¶
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
No Antibiotics
GASTRODUODENAL
Procedures involving entry into lumen of GI tract (bariatric, pancreaticoduodenectomy)
ceFAZolin 2 g¶ clindamycin 900 mg Plus gentamicin 5 mg/kg
No Antibiotics
Procedures not involving incision in GI tract lumen (ex. Antireflux, highly selective vagotomy) High risk patients only
↓ gastric acidity
↓GI motility
Obstruction
Hemorrhage
gastric ulcer or malignancy
therapy with H2 blocker/PPI
morbid obesity
gastroduodenal perforation
ASA classification of ≥3
ceFAZolin 2 g¶ clindamycin 900 mg Plus gentamicin 5 mg/kg
No Antibiotics
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
63
Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
HEPATIC PANCREATIC BILIARY TRACT (HPB) – Minor Procedures
Low Risk Procedures
Elective laparoscopiccholecystectomy without riskfactors (see below for risk factors)
Liver biopsy
No Antibiotics (Note: many risk factors may not be known until intra-operatively, so may be reasonable to give every patient a single pre-op dose of antibiotic)
N/A N/A
High risk Procedures
Laparoscopiccholecystectomy with riskfactors which include:(performance of emergencyprocedures, diabetes, anticipatedprocedure duration exceeding 120minutes, intraoperative gallbladderrupture, age of greater than 70years, open cholecystectomy, riskof conversion of laparoscopic toopen cholecystectomy, AmericanSociety of Anesthesiologists Physical Status Classification System (ASA) equal or greater than 3, episode of colic within 30 days before the procedure, re-intervention in less than a monthfor non-infectious complications ofprior biliary operation, acute cholecystitis, anticipated bile spillage, jaundice, pregnancy, non-functioning gallbladder, biliaryobstruction, obstructive jaundice orcommon bile duct stones and immunosuppression)
Open cholecystectomy
Insertion of prosthetic device
ERCP
Liver Resection
ceFAZolin 2 g¶ clindamycin 900 mg Plus gentamicin 5 mg/kg
No antibiotics for most patients except
Acute cholecystitis:
2 – 5 days
Emphysematouscholecystitis:
5 – 7 days
Gangrene orperforated gallbladder:
change to broadspectrum antibioticfor treatment
HEPATIC PANCREATIC BILIARY TRACT (HPB) – Major Procedures
Major Procedures metroNIDAZOLE 500 mg Plus ceFAZolin 2 g¶
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
No Antibiotics
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
64
Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
HERNIA REPAIR
All patients
Herniorraphy
Hernioplasty
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
No Antibiotics
SMALL INTESTINE SURGERY
Non-obstructed ceFAZolin 2 g¶ clindamycin 900 mg Plus gentamicin 5 mg/kg
Less than 24 hours
Obstructed ceFAZolin 2 g¶ Plus metroNIDAZOLE 500 mg
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
Less than 24 hours
HEAD AND NECK (MAJOR)
Clean procedures:
no incision of the oral orpharyngeal mucosa
no implantation of prostheticmaterial
thyroidectomy
parotidectomy
submandibular gland excision
all of above with no neckdissections and/or skull baseinvolvement
No Antibiotics N/A N/A
Clean Cancer Surgery: ceFAZolin 2 g¶ clindamycin 900 mg 24 hours
Clean with placement of prosthesis (excluding tympanostomy tubes)
ceFAZolin 2 g¶ clindamycin 900 mg 24 hours
Clean-contaminated procedures:
Require penetration of theoral or pharyngeal mucosa
Complex resection withreconstruction procedures
Revision and salvagesurgeries
Cancer surgery
ceFAZolin 2 g¶
Plus metroNIDAZOLE 500 mg
clindamycin 900 mg Plus gentamicin 5 mg/kg
24 hours
Tonsillectomy
Functional endoscopic sinusprocedure
Septoplasty
Adenoidectomy
Tympanoplasty
No Antibiotics N/A N/A
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
65
Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
NEUROSURGERY
Craniotomy (elective, clean,non-implant)
Elective implantation ofintrathecal pump
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
No Antibiotics
Craniotomy
clean-contaminated
crosses sinuses ornaso/oropharynx
emergency surgery
operation ≥2 hours
CSF leakage
Subsequent operation
Transsphenoidal surgery (Allpatients)
ceFAZolin 2 g¶ Plus metroNIDAZOLE 500 mg
vancomycin 15 mg/kg Plus metroNIDAZOLE 500 mg
No Antibiotics
CSF Shunting ceFAZolin 2 g¶ clindamycin 900 mg OR vancomycin 15 mg/kg
Less than 24 hours
OBSTETRICS AND GYNAECOLOGY
Therapeutic termination of pregnancy
doxycycline 100 mg PO 1 hr pre-op
azithromycin 1 g PO No Antibiotics OR doxycycline 200 mg PO 30 min post-op (if doxycycline used pre-op)
Caesarian sectiono Administer antibiotics
prior to skin incision NOTafter cord clamping
ceFAZolin 2 g¶ clindamycin 900 mg Plus gentamicin 5 mg/kg
No Antibiotics
Radical and totalhysterectomy (abdominal,laparoscopic or vaginal)
Vulvectomy with or withoutlymphadenectomy
Vaginectomy
Urogynecological procedureso Laparoscopic Burcho 2-Team sling
ceFAZolin 2 g¶ clindamycin 900 mg Plus gentamicin 5 mg/kg
No Antibiotics
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
66
Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
OPHTHALMIC
Ophthalmic Procedures:
Cataract extractions
Vitrectomies
Keratoplasties
Intraocular lens implantation
Glaucoma procedures
Strabotomies
Retinal detachment repair
Laser in situ keratomileusis
Laser-assisted subepithelialkeratectomy
4th generation topical fluoroquinolones (gatifloxacin or moxifloxacin) given as 1 drop every 5-15 min for 5 doses within the hour before the start of the procedure
Addition of ceFAZolin 100 mg by subconjunctival injection or intracameral ceFAZolin 1 – 2.5 mg or cefuroxime 1 mg at the end of the procedure is optional
ORAL AND MAXILLOFACIAL
No oral or sinus cavityinvolvement
ceFAZolin 2 g¶ clindamycin 900 mg No Antibiotics
Oral cavity or sinus cavityinvolvement
Comminuted andcompounded fractures
Implants/prosthesis; bonegraft
Orthognathic
ceFAZolin 2 g¶ Plus metroNIDAZOLE 500 mg
clindamycin 900 mg No Antibiotics
Gunshot wound
Animal or human bite injuries
Grossly contaminated anddirty injury
ceFAZolin 2 g¶ Plus gentamicin 5 mg/kg Plus metroNIDAZOLE 500 mg
clindamycin 900 mg Plus gentamicin 5 mg/kg
24 hours
For grosslycontaminated/dirtywounds, consider acourse of treatmentwith broad spectrumantibiotics
ORTHOPEDIC
Major procedures:
Difficult fracturereconstruction
Total hip and kneereplacement
Other procedures requiringprophylaxis
Total joint replacement
Implantation of internalfixation devices
Hip fracture repair
ceFAZolin 2 g¶ clindamycin 900 mg OR vancomycin 15 mg/kg
Less than or equal to 24 hours
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
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Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
ORTHOPEDIC (continued)
Minor procedures:
Arthroscopy
Procedures not involvingimplantation or prostheticmaterial
Clean operations involvingfoot, hand, knee.
No antibiotics N/A N/A
PLASTIC SURGERY
Clean Procedures (Low Risk)
Dermatologic
Facial bone fracture
Tumor excision
Simple rhinoplasty orseptoplasty
Simple lacerations
Flexor tendon injuries
Hand surgery
No Antibiotics N/A No Antibiotics
Clean Procedures (High Risk)
Placement of prostheticmaterial
Skin irradiation
Procedures below waist
ceFAZolin 2 g¶1 clindamycin 900 mg OR vancomycin 15 mg/kg
No Antibiotics
Clean Contaminated Procedures
Contaminatedskin/mucosa/intertriginousareas (oral cavity, upperrespiratory tract, axilla,groin, perineum)
Wedge excision lip/ear
Flaps on nose/head/neck
Grafts
ceFAZolin 2 g¶ clindamycin 900 mg OR vancomycin 15 mg/kg
No Antibiotics
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
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Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
PLASTIC SURGERY (continued)
Breast: High risk patients only14,15
Breast Cancer Surgery
Recent neoadjuvantchemotherapy or radiationtherapy
Prosthetic material or mesh
Re-operation or recent priorbreast surgery
Reconstruction surgeries
Operation duration ≥2 hours
Immunocompromisedpatients (diabetics, steroids,etc)
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
No Antibiotics
Hand: Complex Clean Procedures:
Mutilating and crushinginjuries
from home & industrialsource
Bone, joint, tendon (exceptopen flexor tendon injuries –see below) and nerveinvolvements
Implants/ prosthesis
Flap reconstruction
Injuries require amputations
High risk patients withmedical comorbidities and/orimmunosuppressive drugs
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
24 hours
Hand: Clean-contaminated and Contaminated Procedures: • Mutilating and crushing
injuries from farmenvironment
• Grossly contaminated anddirty injuries
• Animal and human bites• Open fractures• Use of leeches
ceFAZolin 2 g¶2 Plus gentamicin 5 mg/kg Plus metroNIDAZOLE 500 mg
clindamycin 900 mg Plus gentamicin 5 mg/kg
24 hours
For grosslycontaminated/ dirtywounds and injurieslonger than 6 hoursconsider a course oftreatment with broadspectrum antibiotics
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
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Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
SPINE
Fusion
Decompression
Instrumentation
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
Less than 24hours
THORACIC
Non-cardiac procedures:
Lobectomy
Pneumonectomy
Lung resection
Thoracotomy
VATS (video assistedthorascopic surgery)
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
Less than 24 hours
TRAUMA – Orthopedics
Gunshot fracture wound ceFAZolin 2 g¶ vancomycin 15 mg/kg
48 hours
Gunshot fracture wound with
Large soft tissue defects orcavitary lesions
AND/OR
Fracture of the extremities(about the hand, foot andankle)
ceFAZolin 2 g¶ Plus gentamicin 5 mg/kg
vancomycin 15 mg/kg Plus gentamicin 5 mg/kg
48 hours
Gunshot fracture wound with
Large soft tissue defects orcavitary lesions
AND/OR
Fracture of the extremities(about the hand, foot andankle)
PLUS
Gross contamination of thewound and environment
o Occurred in rural/woodedarea
o Grossly dirty skin andclothes
o Bowel communication
ceFAZolin 2 g¶ Plus gentamicin 5 mg/kg Plus metroNIDAZOLE 500 mg
vancomycin 15 mg/kg Plus gentamicin 5 mg/kg Plus metroNIDAZOLE 500 mg
48 hours For grossly contaminated/dirty wounds and injuries longer than 6 hours consider a course of treatment with broad spectrum antibiotics.
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
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Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
TRAUMA – Abdomen
Penetrating abdominal trauma
Hollow viscus injury
metroNIDAZOLE 500 mg Plus ceFAZolin 2 g¶
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
24 hours
Penetrating abdominal trauma
Non hollow viscus injury
metroNIDAZOLE 500 mg Plus ceFAZolin 2 g¶
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
No Antibiotics
URINARY DIVERSION PROCEDURES INVOLVING BOWEL SEGMENTS (assuming all patients have urine culture performed and all positive urine culture patients are treated before
surgery)
Ileal conduit procedures orprocedures involving bowelsegments
metroNIDAZOLE 500 mg Plus ceFAZolin 2 g¶
metroNIDAZOLE 500 mg Plus gentamicin 5 mg/kg
Less than 24 hours
UROLOGY (assuming all patients have urine culture performed and all positive urine culture patients are treated before
surgery)
Lower tract instrumentation:
Transrectal prostate biopsy,cystoscopy etc.
High Risk only o Advanced ageo Poor nutritional statuso Diabetes mellituso Smokingo Obesityo Coexisting infection at a
remote body siteo Colonization with
microorganisms
ciprofloxacin 500 mg PO OR sulfamethoxazole/ trimethoprim 800/160mg PO OR ceFAZolin 2 g¶ IM/IV OR gentamicin 5 mg/kg
Note: PO regimens, give 1 – 2 hours pre-op
gentamicin 5 mg/kg with or without clindamycin 900 mg
Less than 24 hours
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
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Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
UROLOGY (continued) (assuming all patients have urine culture performed and all positive urine culture patients are treated before
surgery)
Clean without entry into urinary tract
ceFAZolin 2 g¶ clindamycin 900 mg OR vancomycin 15 mg/kg
Less than 24 hours
Clean no entry into urinary tract + prosthesis
ceFAZolin 2 g¶ with or without Gentamicin 5 mg/kg
(clindamycin 900 mg OR vancomycin 15 mg/kg) with or without gentamicin 5 mg/kg
Less than 24 hours
Clean with entry into urinary tract
ceFAZolin 2 g¶ with or without gentamicin 5 mg/kg (only if prosthesis involved)
ciprofloxacin 500 mg OR (gentamicin 5 mg/kg with or without clindamycin 900 mg)
Less than 24 hours
Clean Contaminated ceFAZolin 2 g¶ Plus metroNIDAZOLE 500 mg
ciprofloxacin 500 mg OR (gentamicin 5 mg/kg Plus metroNIDAZOLE 500 mg)
Less than 24 hours
VASCULAR SURGERY43,44
lower limb amputation
abdominal and lower limbvascular surgery
procedures involving groinincision or prostheticmaterial
carotid endarterectomy andbrachial arterial repair withprosthetic graft only
ceFAZolin 2 g¶ vancomycin 15 mg/kg OR clindamycin 900 mg
Less than or equal to 24 hours
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
72
Patient Selection Pre-Operative Antibiotic Recommendation
Post-Operative IV Antibiotic Duration Preferred
Alternate (See Principles)
VASCULAR (continued) SU
Low risk carotid endarterectomy, brachial artery repair, endovascular stenting without implantation of prosthetic graft material
No Antibiotics N/A N/A
¶ May consider ceFAZolin 3 g for patients weighing greater than or equal to 120 kg
Table 1. Intra-operative Antibiotic Prophylaxis
For antimicrobials with a short half-life intraoperative dosing recommended for patients with normal
renal function if:
Prolonged surgical procedure (greater than 2 half-lives of the antimicrobial) OR
Major blood loss (greater than 1.5 L)
Prophylactic Antibiotic Half-life (hours)
Recommended re-dosing interval
(from time of administration of
the pre-op dose)
ceFAZolin 1.2–2.2 Q4h
clindamycin 2-4 Q6h
gentamicin 2-3 N/A*
metroNIDAZOLE 6-8 N/A*
vancomycin 4-8 N/A* *Recommended redosing intervals marked as “not applicable” (N/A) are based on typical case length; for unusually longprocedures, redosing may be needed except for gentamicin dosed at 5 mg/kg.
aThis table applies only to pediatric patients weighing 40kg or less. bThe maximum pediatric dose should not exceed the usual adult dose cThis table does not specifically address new born infants
Table 2. Pediatric Prophylactic Antibiotic Dosing a,b,c,
Antibiotic Recommended Dose
ampicillin 50 mg/kg
ceFAZolin 30 mg/kg
cefTRIAXone 50-70 mg/kg
ciprofloxacin 10 mg/kg
clindamycin 10 mg/kg
gentamicin 2.5 mg/kg based on dosing weight
metroNIDAZOLE 15 mg/kg
piperacillin-
tazobactam
Infants 2 – 9 months: 80 mg/kg of the piperacillin component
Children greater than 9 months and less than or equal to 40kg: 100mg/kg of
the piperacillin component
vancomycin 15 mg/kg
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VANCOMYCIN DOSING AND MONITORING GUIDELINES
NB Provincial Health Authorities Anti-Infective Stewardship Committee
GENERAL COMMENTS • Vancomycin is a glycopeptide antibiotic with bactericidal activity• It is active against gram-positive bacteria, including methicillin-resistant staphylococcus (MRSA)• Vancomycin is less effective than beta-lactams against Staphylococcus aureus that is susceptible to
cloxacillin/methicillin• Vancomycin exhibits time-dependent killing: its effect depends primarily upon the time the concentration
exceeds the organism’s Minimum Inhibitory Concentration (MIC)• These guidelines pertain to IV vancomycin only; they do not apply to PO vancomycin, which is not absorbed• Ensure that an adequate mg/kg dose and appropriate interval are ordered initially. Adjust the dose if
necessary immediately; do not wait for a confirmatory trough level.• When managing a severe Staphylococcus aureus infection (e.g., bacteremia), an Infectious Diseases
consultation is strongly encouraged.
VANCOMYCIN IN ADULT PATIENTS
ADULT INITIAL DOSE Loading dose: • 25-30 mg/kg IV
o based on actual body weight, for 1 dose, followed by maintenance dose separated by recommendeddosing interval
o consider capping the loading dose at a maximum of 3.5 go loading doses DO NOT need to be adjusted in patients with renal dysfunction; only maintenance
dosing interval requires adjustment• Consider using a loading dose in patients with:
o severe infections where rapid attainment of target level of 15-20 mg/mL is desiredo significant renal dysfunction in order to decrease the time required to attain steady state
Maintenance dose: • 15-20 mg/kg IV
o based on actual body weight; maximum of 2g/dose for initial maintenance doses (prior tovancomycin levels)
o doses greater than 500 mg – round to the nearest 250 mgo doses less than 500 mg – round to the nearest 50 mg
74
Dosing interval: • Interval depends on patient’s renal function and targeted serum vancomycin concentration
Target trough of 15 to 20 mg/L Target trough of 10 to 15 mg/L Creatinine Clearance Dosing Interval Creatinine Clearance Dosing Interval
greater than 80 mL/min q8h greater than 80 mL/min q12h 40 to 80 mL/min q12h 40 to 80 mL/min q24h 20 to 39 mL/min q24h 20 to 39 mL/min q36h 10 to 19 mL/min q48h 10 to 19 mL/min q48h less than 10 mL/min consider a loading dose,
then adjust maintenance dose based on serial serum drug levels to target trough
less than 10 mL/min consider a loading dose, then adjust maintenance dose based on serial serum drug levels to target trough
• Estimated creatinine clearance (CrCl)Women Men CrCl = (140-age) x weight (in kg)†
SCr (in mcmol/L) CrCl = (140-age) x weight (in kg)† x 1.2
SCr (in mcmol/L) IBW = 45.5 kg + (0.92 x cm above 150 cm) or 45.5 kg + (2.3 x inches above 60 inches)
IBW = 50 kg + (0.92 x cm above 150 cm) or 50 kg + (2.3 x inches above 60 inches)
†Use ideal body weight unless it is 20% above ideal body weight (IBW), in such case use adjusted body weight. Adjusted body weight = 0.4 x (actual body weight – IBW) + IBW If actual weight is less than ideal body weight, use actual weight.
LEVELS • The ratio of Area Under the Curve to Minimum Inhibitory Concentration (AUC/MIC) is thought to be the best
pharmacokinetic parameter associated with a clinical and bacterial response to vancomycin; however,because of its relative impracticality to determine in clinical practice, trough levels are used as a surrogate forefficacy.
• Peak (post) levels are generally NOT recommended because they are not correlated with improved clinicaloutcome; they should only be ordered in rare circumstances to facilitate individualized patientpharmacokinetic analysis.
• Vancomycin’s efficacy depends primarily upon the time above the MICTarget serum concentrations:
Infection Desired minimal (trough) plasma concentration
-All MRSA infections-Invasive and/or deep space infections, including but
not limited to:o Osteomyelitiso Pneumoniao CNS infectiono Endocarditiso Bacteremiao Prosthetic joint infection
15-20 mg/L
Uncomplicated skin and soft tissue infections Urinary tract infections 10-15 mg/L
vancomycin levels should always be maintained above 10 mg/L to avoid development of resistance
Levels are recommended in: o patients who are severely ill and/or require target trough of 15-20 mg/Lo patients with anticipated therapy duration of 7 days or greatero patients with impaired renal function (CrCl 50 mL/min or less) or unstable renal function (change in
75
baseline serum creatinine (SCr) of 40 mcmol/L or greater, or change of 50% or more from baseline) o patients on dialysiso concomitant use of other nephrotoxic drugs (i.e. aminoglycoside, NSAID, diuretics, ACEI, ARB, etc.)o patients with altered volume of distribution or clearance of vancomycin, including
morbidly obese patients (190% or greater of ideal body weight or BMI 40 kg/m2 or greater) cystic fibrosis burns more than 20% BSA pregnancy
• Routine trough (pre) levels are generally not necessary when:o vancomycin is used for empiric therapy as it may be discontinued once final culture results are
availableSerum sampling: • Trough (pre) levels are taken immediately before a dose (within 30 minutes)• The timing of drug administration and sample collection must be carefully documented• Do not hold next vancomycin dose while waiting for results of vancomycin levels unless there is a specific
reason to do so, e.g. significant decline in renal functionTiming of serum levels: • First trough level should be taken at steady state, typically
o prior to 4th dose if q12h intervalo prior to the 5th dose if q8h interval
• Steady state (SS) occurs in 4 to 5 half-lives and can be estimated for vancomycin by the following equations:o Ke = CrCl x 0.00083 + 0.0044o T½ = 0.693/Ke
o SS = 4 to 5 T½• Vancomycin clearance is enhanced in obesity. Consider drawing first level sooner (i.e. before the 3rd dose if
normal renal function) in morbidly obese patientsINTERPRETING TROUGH LEVELS AND ADJUSTING DOSE • Verify the timing of the trough in relations to the dose that preceded it and the dose that followed• Verify if the trough was taken at steady state• Verify for changes in renal function since the trough was drawn• Consider alternate sources of vancomycin that may be contributing to measured serum concentrations (e.g.,
vancomycin instilled intra-operatively, or added to cement during orthopedic surgery)• If the trough is below the target level, ensure the dose is 15-20 mg per actual body weight, and consider
shortening the dosing interval (e.g., if was dosed q12h, change to q8h)• If the trough is above 20-25 mg/L, consider decreasing the dose and/or lengthening the dosing intervalMONITORING Subsequent serum levels: • With dosage change: trough should be repeated at new steady state as described in “Levels” section• Once target trough achieved: trough should be taken approximately every 7 days in hemodynamically stable
patients; more frequently if hemodynamically unstable, renal function changing, if concurrent nephrotoxicdrugs, or underlying renal dysfunction
Monitor: • patient’s clinical response to vancomycin• CBC at least weekly on long-term vancomycin therapy• SCr at least twice a week initially, then at least weekly on long-term therapy; more frequent monitoring should
be considered if renal function changing, if concurrent nephrotoxic drug, underlying renal dysfunction or agegreater than 60.
o If SCr increases significantly (i.e. greater than 15 – 20% from baseline), draw trough level to assess forneed for dosage adjustment as vancomycin accumulation may occur
Adverse effects of vancomycin include: • Nephrotoxicity: 5-43%; more common with higher troughs levels, longer durations, critically ill patients,
76
concomitant nephrotoxic drugs, elderly patients or pre-existing renal dysfunction; rise in SCr usually reversible upon discontinuation of vancomycin
• Red Man Syndrome: 5-10%; ensure appropriate duration of infusion to minimize risk (refer to Parenteral DrugManual)
• Neutropenia: less than 2%, delayed onset (15-40 days), reversible
VANCOMYCIN IN PEDIATRIC PATIENTS
DEFINITIONS • Neonate: 0-4 weeks of age
o Gestational age: number of weeks from first day of the mother’s last menstrual period until the birthof the baby
o Postnatal age: chronological age since birtho Corrected Gestational Age: gestational age plus postnatal age
Ex.: baby born at 28 weeks, presently 21 days old corrected gestational age = 31 weeks (28 weeks + 3 weeks)
• Infant: 1 month to 1 year of age• Child: 1-12 years of age
PEDIATRIC INITIAL DOSE Initial dose in neonates (less than 1 month of age):
Corrected Gestational Age (weeks)
Postnatal Age (days) mg/kg/dose IV Interval
(hours)
29 or less 0-14 10 - 15 18
15 or more 10 - 15 12
30-360-14 10 - 15 12
15 or more 10 - 15 8
37-440-7 10 - 15 12
8 or more 10 - 15 8 45 or more all 10 - 15 6
Initial dose in infants and children (1 month to 12 years of age): • Traditional:
o 40-60 mg/kg/day, divided in q6h-8ho max dose of 2g/day prior to levels
• Alternative (for more severe infections):o 15 mg/kg/dose IV q6ho max dose of 4g/day prior to levels
LEVELS • Trough levels are taken 30 minutes or less prior to the next dose• Peak levels are generally NOT recommendedTarget trough levels in neonates (less than 1 month of age):
o 5-15 mg/Lo up to 20 mg/L for severe infections where vancomycin penetration to the site may be poor or high
MIC is suspected (osteomyelitis, meningitis and endocarditis or infection with MRSA)Target trough levels in infants and children (1 month to 12 years of age):
o 15-20 mg/L for most infectionso 10-15 mg/L for less severe infections
• First trough level should be taken at steady state, typically prior to 4th dose
77
INTERPRETING TROUGH LEVELS AND ADJUSTING DOSE • Verify the timing of the trough in relations to the dose that preceded it and the dose that followed• Verify if the trough was taken at steady state• Verify for changes in renal function since the trough was drawn• If the trough is below the target level, consider shortening the dosing interval• If the trough is high, consider lengthening the dosing intervalSUBSEQUENT TROUGH LEVELS AND MONITORING • See Adults section for guidance
VANCOMYCIN IN INTERMITTENT HEMODIALYSIS
GENERAL COMMENTS • In patients undergoing intermittent hemodialysis, vancomycin IV is given on dialysis days, typically 3 times a
week• Give the first dose of vancomycin the day it is ordered and subsequent doses on dialysis days• Vancomycin doses are administered during the last portion of the hemodialysis session (intradialytic
administration) or after hemodialysisDOSE • Patient with weight less than 70 kg:
vancomycin 1000 mg IV for the first dose, then 500 mg IV for subsequent doses• Patient with weight 70 to 100 kg:
vancomycin 1250 mg IV for the first dose, then 750 mg IV for subsequent doses• Patient with weight above 100 kg:
vancomycin 1500 mg IV for the first dose, then 1g IV for subsequent dosesLEVELS Target pre-dialysis vancomycin levels:
o 15-20 mg/Lo 10-15 mg/L may be acceptable for uncomplicated skin and soft tissue infections and urinary tract
infections; see Adults section for more information• Vancomycin levels are drawn before the beginning of the hemodialysis session• Do not hold post-dialysis vancomycin dose while waiting for results of pre-dialysis vancomycin levels unless
there is a specific reason to do so• If the trough is below the target level, consider a top-up dose and increase the next maintenance dose
accordingly• If the trough is high, consider decreasing the next maintenance dose• Vancomycin trough levels should be obtained before each dialysis until desired trough is attained. After that,
vancomycin trough levels should be obtained once a week before dialysis.
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VANCOMYCIN IN PREGNANCY
CONSIDERATIONS ON THE USE OF VANCOMYCIN IN PREGNANCY • Pregnancy is associated with accelerated renal clearance of vancomycin due to increased renal blood flow• Pregnancy is associated with higher volumes of distribution• Pharmacokinetic changes become more pronounced in the later stages of pregnancy and gradually return to
pre-pregnancy values a few days following delivery• Dose and target trough levels same as other adults• Will likely achieve steady state sooner• May require higher dosage and shorter dosing intervals to achieve target levels compared to non-pregnant
individuals• Recommend routine trough levels in pregnant patients• If target levels difficult to achieve, consider drawing two levels (trough and peak) to enable individualized
pharmacokinetic calculations
OUTPATIENT VANCOMYCIN IV THERAPY
NOTES FOR TRANSITIONS TO OUTPATIENT IV VANCOMYCIN THERAPY • Prior to discharge on outpatient IV vancomycin therapy, the healthcare team should:
o Review the treatment plan to confirm that oral alternatives are not available or appropriate forpatient management
o Review the feasibility and safety of the treatment and care plano Review the patient’s concomitant medications to identify any nephrotoxic agents (e.g.
aminoglycoside, NSAID, diuretic, ACEI, ARB, etc.) and evaluate whether any should be held for theduration of treatment
o Communicate the treatment and care plan to the patient and/or care givers and communityhealthcare providers; including necessary blood work, target levels and duration of therapy
o Communicate the importance of proper timing of blood work in relation to administration of thevancomycin dose to allow interpretation of vancomycin serum concentrations
o Educate and inform the patient and their caregivers on the signs and symptoms of potential adversereactions to report or act on
o Arrange all necessary monitoring test and follow-up appointmentso Avoid scheduling blood work on Fridays because interpretation may be delayed
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Provincial Drugs & Therapeutics Committee “April 28, 2014” Communication
Topic: Nevirapine (VIRAMUNE) for Perinatal HIV Transmission Prophylaxis
A decision was made in October 2013 to list nevirapine (VIRAMUNE) 10 mg/mL oral suspension on the New Brunswick Hospital Formulary.
The oral suspension dosage form of nevirapine is only available in Canada via Health Canada’s Special Access Programme.
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with an established role in the prevention of vertical transmission of HIV to neonates born to mothers who received no antenatal anti-retroviral therapy or with a recent or projected HIV viral load greater than 1000 copies/mL.1 Nevirapine isused in combination with other antiretroviral drugs for this indication.
National Institutes of Health (NIH, 2012) guidelines recommend that HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis receive 3 doses of nevirapine in the first week of life (1st
dose at birth, 2nd dose 48 hours after the 1st, 3rd dose 96 hours after the 2nd). Infants weighing 1.5- 2 kg atbirth receive 8 mg/dose by mouth, while those weighing greater than 2 kg receive 12 mg/dose by mouth.2
For women who did not receive any antiretroviral therapy during pregnancy, the British Columbia (BC, 2013) guidelines recommend a single intrapartum dose of nevirapine 200 mg as soon as possible after the onset of labour or at least 2 to 3 hours prior to caesarian section. This recommendation varies from the updated NIH guidelines, which no longer includes maternal single dose nevirapine. The BC guidelines recommend the same infant dose and schedule of nevirapine as recommended by NIH.
Canadian guidelines (2003)3 are currently being updated.
As the likelihood of its use is deemed to be low, but the time-sensitivity for acquisition is high, a small centrally-located supply of nevirapine oral suspension is being held at the Dr. Everett Chalmers Hospital pharmacy department in Fredericton for use on request by any facility in the province.
Requests to ship nevirapine to other facilities can be made by calling the DECH pharmacy department at (506) 452-5284 (inventory) or (506) 452-5280 (dispensary) or (506) 452-5700 (switchboard after hours,ask for Administrative Officer).
Discussion with an Infectious Diseases physician is strongly encouraged.
1 Money D, Tullock K, Boucoiran I, Alimenti A et al. British Columbia Guidelines for the Care of HIV Positive
Pregnant Women and Interventions to Reduce Perinatal Transmission. July 23, 2013; CMA Infobase. 2 Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.
Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1- Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. 3 Burdge DR, Money DM, Forbes JC, Walmsley SL, Smaill FM, Boucher M, et al. on behalf of the Canadian HIV Trials
Network Working Group on Vertical HIV Transmission. Canadian Consensus Guidelines for the management of pregnancy, labour and delivery and for postpartum care in HIV-positive pregnant women and their offspring [online appendix]. CMAJ 2003; 168(13): Online-1 to Online 14. Available: www.cmaj.ca/cgi/data/168/13/1671/DC1/1
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Prevention of Overwhelming Postsplenectomy Infection in Adults
Introduction The spleen is the largest lymphatic organ in the body and its primary functions are to filter damaged red blood cells and micro-organisms from the blood and to aid in the production of antibodies to enhance the immune response.1 Asplenic patients or patients who suffer from functional asplenia have an increased risk of infection and are at risk of contracting a syndrome known as overwhelming postsplenectomy infection (OPSI).2Overwhelming postsplenectomy infection has been defined as ”septicaemia and/or meningitis, usually fulminant but not necessarily fatal, occurring at any time after removal of the spleen”.3 The incidence of OPSI has been difficult to establish due to a wide variation in occurrence rates among different groups of patients, but lifetime risk has been estimated at 5%.2 Risk of OPSI has been found to be dependent on age at which splenectomy occurs, time interval from splenectomy, cause for asplenia and immune status of the patient.4
Although the incidence of OPSI is low, the estimated mortality is high (38 – 69%).2 Therefore, prevention and early identification of OPSI have been identified as key strategies to improve patient outcome.2 Some of the current strategies being used and recommended to decrease a patient’s risk of OPSI include vaccination, communication of hyposplenic state to other healthcare providers and patient education.1,2,5 In addition, some groups recommend either short term or lifelong prophylactic antibiotics to reduce the risk of OPSI.8 However, the use of antibiotics for the prevention of OPSI is often limited by poor compliance and antibiotic resistance; therefore, its use should be assessed on a case-by-case basis.8 Recommendations from the Canadian Pediatric Society include the administration of prophylactic antibiotics until the patient is 60 months of age with consideration to be given for lifelong prophylaxis.14 Experts and some guidelines also recommend that patients have a home supply of antibiotics for urgent use.15,16
The Provincial Anti-infective Stewardship Committee (ASC) has prepared resources to facilitate recommended vaccination orders, vaccine distribution, patient education and communication to the primary care provider. Recommendations regarding the prophylactic or as needed use of antibiotics are beyond the scope of these guidelines, please consult a local infectious disease specialist for recommendations.
Vaccinations Asplenic patients are at risk of OPSI with any micro-organism but particularly encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.2,4 Encapsulated bacteria are more difficult for the body to clear because they resist antibody binding and their clearance is primarily completed by the spleen.4 Therefore, it is important that attention be paid to providing optimal protection against encapsulated bacteria using appropriate immunizations.6 The National Advisory Committee on Immunization (NACI) and the Canadian Immunization Guideline currently recommend the following vaccines for adult asplenic or hyposplenic patients: pneumococcal 13-valent conjugate vaccine (PNEU-C-13), pneumococcal 23-valent polysaccharide vaccine (PNEU-P-23), Haemophilus influenzae type b conjugate (Hib) vaccine, meningococcal ACYW-135 conjugate (Men-C-ACYW) vaccine, all routine immunizations and yearly influenza vaccine.6,7 NACI also recommends multi-component meningococcal serogroup B (4CMenB) vaccination for active immunization of patients with anatomical or functional asplenia who are greater than 2 months of age.11
Streptococcus pneumoniae is responsible for 50 – 90% of all cases of OPSI. 4 Pneumococcal polysaccharide vaccine (PNEUMOVAX 23) provides protection against 23 serotypes of Streptococcus pneumoniae and is the vaccine of choice for adult patients at high risk of invasive pneumococcal disease (IPD). 6 The pneumococcal polysaccharide vaccine has been found to have an efficacy of 50 to 80% against IPD among the elderly and high risk groups.6 However, after immunization with PNEU-P-23 vaccine, antibody levels begin to decline after 5 to 10 years and the duration of immunity is unknown.6 In an effort to improve the duration of immunity the current NACI guidelines recommend for adults with asplenia or hyposplenia one dose of PNEU-C-13 vaccine (PREVNAR 13) followed at least 2 months later by one dose of PNEU-P-23 vaccine.6 If PNEU-P-23 vaccine has been previously received, then wait 1 year before giving PNEU-C-13 vaccine. 10 In the case where only one vaccine can be given then it should be the PNEU-P-23 vaccine. A single booster of PNEU-P-
81
23 vaccine is recommended 5 years after the initial dose.6 Due the increased risk of invasive pneumococcal disease and rapid decline in antibodies following PNEU-P-23 vaccination, patients age 65 years and over, regardless of previous vaccination history, should receive one dose of PNEU-P-23 vaccine as long as 5 years have passed since the previous PNEU-P-23 vaccine dose.12 The Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices released a statement in October 2012 with similar recommendations for all adult patients 19 years of age or greater.10
A single dose of Haemophilus influenzae type b (HiB) conjugate vaccine is recommended in all patients who are functionally or anatomically asplenic and greater than 5 years of age regardless of previous Hib immunization.5,6 Current Hib vaccine should be given at least one year after any previous dose.6 This is despite limited efficacy data and a low overall risk of Haemophilus influenzae sepsis in patients greater than 5 years of age.6
Meningococcal ACYW-135 conjugate vaccine, MENACTRA or MENVEO, is recommended for all groups at high risk of invasive meningococcal infection when long-term protection is required.6,7 MENVEO (Men-C-ACYW-CRM) has the A, C, Y and W-135 serogroup oligosaccharides conjugated to the CRM197 protein. 6,13 Men-C-ACYW-CRM (MENVEO) can be administered concomitantly with routine childhood vaccines but further studies are needed with respect to concomitant administration with other CRM197 conjugate vaccines such as the pneumococcal 13-valent conjugate vaccine (PREVNAR); therefore, Men-C-ACYW-CRM vaccine has been left off the clinical order set to avoid this concomitant administration.6,13 Recommendations are to give 2 doses of meningococcal ACYW-135 conjugate vaccine at least 8 weeks apart for patients with anatomic or functional asplenia between the ages of 1 – 55.6 Based on limited evidence and expert opinion, current NACI guidelines recommend that 2 doses of meningococcal ACYW-135 conjugate vaccine given 8 weeks apart is also appropriate for individuals greater than 55 years of age, despite lacking authorization for use in this age group.6,7 Booster doses are recommended every 3 - 5 years in individuals vaccinated at 6 years of age or younger and every 5 years for individuals vaccinated at greater than 6 years of age.6 Multi-component meningococcal serogroup B (4CMenB) vaccine (BEXSERO) given as a 2 dose series 4 weeks apart is also recommended.11
In addition, all routine immunizations and yearly influenza vaccination should be given as there are no contraindications to the use of any vaccine in patients with functional or anatomical hyposplenia. 6 When an elective splenectomy is planned, the necessary vaccines are recommended to be given two weeks before removal of the spleen. 6 In the case of an emergent splenectomy, vaccines should be given two weeks post-splenectomy or prior to hospital discharge if there is a concern that the patient may not return for vaccination. 6
Asplenic patients are at increased risk of travel related infectious diseases, including malaria and babesiosis.9Expert advice should be sought prior to travel to endemic areas.
Patient Education Education has also been cited as an essential component for successful prevention of OPSI. 2 Patients should be educated regarding their increased risk of developing life threatening sepsis, what to do at the first sign of infection, to inform all healthcare providers of their hyposplenic state and to take appropriate precautions to prevent OPSI.2 Education may be provided through thorough discussion and provision of appropriate reading materials.2
Document Updated by: Tim MacLaggan, BSc(Pharm), ACPR Document reviewed and approved by: New Brunswick Anti-infective Stewardship Committee – September 2017
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**The following clinical order set is provided as a sample only and would have to be modified to an individual zone’s format for local use**
Clinical Order Set Post-Splenectomy Vaccinations – Adult Provincial Anti-infective Stewardship Committee
Patient: INSTRUCTIONS
Allergies:
1. The following orders will be carried out by a nurse only on the authority of a physician/nurse practitioner.2. A bullet preceding an order indicates the order is standard and should always be implemented. 3. A check box preceding an order indicates the order is optional and must be checked off to be implemented. 4. Applicable boxes to the right of an order must be checked off and initialed by the person implementing the order.5. Date and time of administration must be recorded
Contraindications
• Hypersensitivity to any vaccine component• Anaphylactic reaction to previous dose of any of the vaccines listed below
Vaccinations (if not received pre-operatively for elective surgeries or if not received previously)
• Haemophilus influenzae type b conjugate vaccine (ACT-HIB) 0.5 mL intramuscularly in deltoid
• Meningococcal ACYW-135 conjugate vaccine (MENACTRA) 0.5 mL intramuscularly in deltoid(additional dose of meningococcal ACYW-135 conjugate vaccine required in 2 months followedby a booster every 5 years)
• Multicomponent Meningococcal Serogroup B (4CMenB) Vaccine (BEXSERO) 0.5 mLintramuscularly in the deltoid (additional dose of Multicomponent Meningococcal Serogroup B(4CMenB) Vaccine required in 1 month)
Pneumococcal Vaccination: � If pneumococcal 23-valent polysaccharide vaccine (PNEUMOVAX 23) not previously received
or received greater than one year ago then give Pneumococcal 13-valent conjugate vaccine (PREVNAR 13) 0.5 mL intramuscularly in deltoid (Pneumococcal 23-valent polysaccharide vaccine (PNEUMOVAX 23) required 8 weeks later if not previously received. Single lifetime booster of Pneumococcal 23-valent polysaccharide (PNEUMOVAX 23) required 5 years after first dose.)
OR � If Pneumococcal 23-valent polysaccharide vaccine (PNEUMOVAX 23) previously received but less
than one year ago then wait 1 year from that date to give Pneumococcal 13-valent conjugate vaccine (PREVNAR 13). Single lifetime booster of Pneumococcal 23-valent polysaccharide (PNEUMOVAX 23) required 5 years after first dose.
• Seasonal Influenza Vaccine (if not already received)
Notes
-Vaccinations should be given two weeks post-operatively or on hospital discharge if there is aconcern that he or she might not return for vaccination.-All vaccinations may be administered simultaneously. Separate syringes and separate injection sitesshould be used if more than one vaccine is administered on the same day.
Adapted with permission from Antimicrobial Handbook-2010 Capital Health, Nova Scotia Revised and Approved September 2017
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Adult Splenectomy Vaccines Documentation for Primary Care Provider and Public Health Please complete and forward to patient’s primary care provider and local Public Health office on discharge.
Adapted with permission from Antimicrobial Handbook-2010 Capital Health, Nova Scotia Revised and Approved September 2017
Asplenic patients are known to be at risk of infection, and are particularly susceptible to encapsulated organisms. Vaccinations are recommended to reduce the risk of infection in this patient population.
Your patient received the following vaccinations while in hospital after splenectomy. Please update your records, and note the patient’s need for future vaccinations.
Meningococcal ACYW-135 conjugate vaccine (MENACTRA) (2 doses, 2 months apart) Date 1st dose given: Lot#: Dose: Administration Site: Date 2nd dose given: Lot#: Dose: Administration Site: A booster is recommended every 5 years
Multicomponent Meningococcal Serogroup B (4CMenB) Vaccine (BEXSERO) (2 doses, 1 month apart) Date 1st dose given: Lot#: Dose: Administration Site: Date 2nd dose given: Lot#: Dose: Administration Site:
Haemophilus influenzae type b conjugate vaccine (ACT-HIB) Date given: Lot#: Dose: Administration Site:
Pneumococcal 13-valent conjugate vaccine (PREVNAR 13) Date given: Lot#: Dose: Administration Site:
Pneumoccocal polysaccharide vaccine (PNEUMOVAX 23) due 8 weeks after pneumococcal 13-valent conjugate vaccine (PREVNAR 13) Date given: Lot#: Dose: Administration Site: A single booster dose of pneumococcal polysaccharide vaccine is recommended after 5 years.
- Yearly influenza vaccine recommended.
If you have any questions regarding these vaccinations please call the numbers above, or contact the Department of Public Health for further information.
Thank you. This message is CONFIDENTIAL. If you received this fax by mistake, please notify us immediately.
From:
Phone: Fax:
To: Local Public Health Office Fax
#:____________________
Re. Patient Name:
HCN:
D.O.B:
To: _______________________
Fax #: ___________________
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Splenectomy Information for Patients
Role of the spleen: • The spleen has many functions, including removal of damaged
blood cells. It also plays an important role in removal of certaintypes of bacteria.
• The spleen may be removed (splenectomy) if it becomesoveractive, stops working or is ruptured in an accident.
Life without a spleen: • Adults can live a normal life without a spleen. However, you
may be at risk of developing infections caused by certaintypes of bacteria which are normally removed by the spleen.
• The most serious possible infection is called overwhelming post-splenectomy infection(OPSI). This infection is rare, but can progress rapidly and may result in the loss of limbs ordeath.
How to reduce the risk of infection: • Inform all doctors, dentists and other health care professionals that you do not have a
spleen.• A series of vaccinations is recommended for patients who have their spleen removed.
These vaccines are two doses of meningococcal quadrivalent conjugate vaccine,pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine (due 2 monthsafter pneumococcal conjugate vaccine), two doses of multi-component meningococcalserogroup B vaccine and Haemophilus influenzae type b conjugate vaccine.
• You should receive a single booster of pneumococcal polysaccharide vaccine in 5 years.• You should receive a booster dose of meningococcal conjugate vaccine every 5 years.• You should receive a yearly flu shot.• Your primary care provider will receive a letter explaining the vaccinations you received in
hospital, as well as recommendations for future vaccinations.• Seek expert medical advice before travel. Patients without a spleen are at increased risk of
travel-related infectious diseases, including severe malaria. Additional vaccines and/or oneor more medications may be recommended to prevent or treat travel-related infectiousdiseases. Where malaria is endemic, preventative measures including antimalarialmedications, insect repellent and barrier precautions should be used.
Identification: • Wallet card (included with this information) includes information on vaccinations you have
received.• Medic-Alert™ bracelet should be worn. It should indicate that you had your spleen
removed.
When to seek medical attention: • If you receive a tick or animal bites/scratches. You may be at risk of developing a serious
infection.• Fever, shakes and/or chills may be a sign of a serious infection. Proceed immediately to the
nearest emergency department for further evaluation and care. If you have been providedantibiotics to use on an as needed basis for infection, take one dose immediately and thenproceed to the nearest emergency department.
Adapted with permission from Antimicrobial Handbook-2010 Capital Health, Nova Scotia Approved September 2017
85
Wallet card for Asplenic Patients Please complete card and give to patient on hospital discharge.
Adapted with permission from Antimicrobial Handbook-2010 Capital Health, Nova Scotia Approved September 2017
Medical AlertAsplenic Patient
Patient Name: Name: Phone:
Patient is at risk of potentially fatal, overwhelminginfections. Medical attention required for:
Signs of infection- fever > 38ºC, sore throat, chills,unexplained cough. Tick and animal bites/scratches.
Vaccination Record Patient has received the following vaccinations:
Meningococcal ACYW-135 conjugate vaccine (MENACTRA) 2 doses 8 weeks apart Date 1st dose given: Date 2nd dose given:
Meningococcal ACYW-135 conjugate vaccine booster (MENACTRA or MENVEO)
Dates due: every 5 yearsDates given:
Multicomponent Meningococcal Serogroup B (4CMenB) Vaccine (BEXSERO) 2 doses 4 weeks apart
Date 1st dose given: Date 2nd dose given: Pneumococcal 13-valent conjugate vaccine (PREVNAR 13)
Date given: Pneumococcal polysaccharide vaccine (PNEUMOVAX 23)
Date due: 8 weeks after pneumococcal 13-valent conjugate vaccine (PREVNAR 13) Date given:
Pneumococcal polysaccharide booster (PNEUMOVAX 23) Date due: single dose 5 years after initial vaccineDate given:
Haemophilus influenzae type b conjugate vaccine (ACT-HIB) Date given:
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Splenectomy Vaccine Checklist
1) Post-Splenectomy Vaccinations Clinical Order Set
2) Vaccines as per clinical order set plus package inserts
3) Splenectomy Vaccines – Documentation for Primary Care Providerand Public Health Form
4) Splenectomy – Information for Patients Sheet
5) Wallet Card for Asplenic Patients Sheet
Adapted with permission from Antimicrobial Handbook-2010 Capital Health, Nova Scotia Approved September 2017
87
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5. Van Eyk, N, van Schalkwyk J, et al. Antibiotic Prophylaxis in Gynaecologic Procedures. J Obstet Gynaecol Can 2012;34(4):382–391
Principles of Antimicrobial Prophylaxis in Surgery: 1,2,4 Appendectomy: 1,2 Cardiac: 1,2 Colorectal: 1, 2 Gastroduodenal: 1,2 Small Intestine: 1 Head and Neck: 1,2 Hepatic Pancreatic Biliary Tract (Minor and Major Procedures): Minor: 1,2,3 Major: 2,3 Hernia: 1,2 Neurosurgery: 1,2 Obstetrics and Gynecology: 1,2,3,5 Orthopedics: 1,2 Spine: 1,2 Thoracics: 1,2 Trauma (orthopedics): 2 Trauma (abdomen): 2 Urinary Diversion (involving bowel segments): 2 Urology: 1,2 Vascular: 1,2 Opthalmic: 1 Plastic: 1,2,3 Maxillofacial: 2 Appendix A: 2,3
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