Drugs for Bugs What’s new in 2012?

Drugs for Bugs What’s new in 2012?

Valerie Creswell MD FACP

July 10, 2012

• Or the wonderful bugs you can meet when illness knocks you off your feet!

How do antibiotics work?

• Inhibition or disruption of cell wall growth– Beta-lactams, vancomycin, bacitracin

• Inhibition of protein synthesis– 50S ribosomal unit

• macrolide, clindamycin, chloramphenicol

– 30S ribosomal unit• aminoglycosides and tetracycline

• Interference with DNA or RNA synthesis– Quinolones, Trimethoprim/sulfa

Empiric Antibiotics

• 77 yo WF presents with fevers, chills, myalgias and a productive cough

• PE T 101 P100 R16BP110/60

• You order a CBC with man dif, BMP, BC x2, CXR and UA. The cost is:

• A. $500• B. $1000• C. $2000+

RADIOLOGY COSTS 2011

Chest X-ray, Port. $480

Chest X-ray, PA/lat $523

KUB $480


• Renal sonogram $970

• Gallbladder sono $1258

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CT Scan With and WithoutBrain $3590Chest $4696Abd/pelvis $7065

Radiology Costs 2011

• MRI with/without contrast

• Brain $4326

• Chest $4377 (without)

Inpatient LAB COSTS 2011

• Urine culture $97

• Sputum c & s $310

• Blood c & s $409 for one set

• Clostridium difficile toxin $159

Inpatient LAB COSTS 2011

• Serum creatinine $161• Basic metabolic profile $320• Comprehensive metabolic profile $376• CBC man diff– $236 auto diff-- $174• CBC $144• Urinalysis w/ microscopic $105

• Drug levels --vancomycin $320

--gentamicin $288

Vanco levels-My pet peeves

• Don’t order “Vanco with am lab” unless a random level will be helpful

• Don’t order when Vanco will be discontinued within 3 days if cultures are negative

• Do order a TROUGH before the fourth dose if:– Staph aureus in the blood or CSF (level 15-20)– Changes in renal function– High doses required ( young patients with good

kidneys)

Empiric Antibiotics for our 77 yo man

• Antibiotic choice– A. None– B. Ceftriaxone 1 gm IV q24hr and

azithromycin 500 mg load, then 250 mg daily for total of 5 days (i.e. Use the community acquired pneumonia order set form 243 at Wesley)

– C. Meropenem 500 mg IV q 6hrs– D. Vancomycin 1 gm IV q 12hrs

CAP Grade Card

• Blood cultures before antibiotics (ICU)

• Appropriate antibiotics and within 4 (6)hours of admission-ICU admissions-IV levofloxacin

• Pneumococcal vaccination (year round)(needed every 5 years) and Influenza vaccination (during flu season)(needed yearly)

VCH Pneumonia Order Set

Via Christi Antibiogram/Empiric Guide

VCH Empiric Antibiotic Guide

Pregnant Women, Newborns, and Influenza Vaccination

• Pregnant women are at increased risk of complications of influenza– women who are or will be pregnant during

influenza season should receive influenza vaccine (TIV only)

• Infants younger than 6 months of age are at very high risk of complications and hospitalization from influenza– no vaccine is available for infants younger than

6 months

MMWR 2010;59(RR-8)

PPSV is recommended for:

• People who are 65 years of age and older• People 2 years of age and older who have a

chronic illness such as:• Cardiovascular or lung disease• Sickle cell disease• Diabetes• Alcoholism• Chronic liver disease• Cerebrospinal fluid (CSF) leak• A cochlear implant


2 years of age and older with a weakened immune system

Due to illnesses such as:HIV infectionAIDSChronic renal failureNephrotic syndromeOrgan or bone marrow transplantationHodgkin's diseaseLeukemia,lymphoma,multiple myelomaGeneralized malignancy


• Those receiving immunosuppressive therapy (e.g., steroids)

• Those who have had their spleen removed or whose spleen is dysfunctional due to an illness such as sickle cell disease.

• Residents of nursing homes or long-term care facilities

• People 19 through 64 years of age who smoke cigarettes or have asthma.

One of the most importantreasons adults identify for not

receiving a vaccine is the lack ofa provider recommendation for

the vaccine.

Saving 100,000 Lives Campaign

• Hospital associated pneumonia

• Central line infections

• Hospital associated UTIs

• Surgical site Infections

HAC vs. HAI

•HAC (Healthcare Associated Condition)= based on physician documentation obtained thru administrative data

•HAI (Healthcare Associated Infection) = based on standardized surveillance definition from the CDC/HNSN reviewed and reported by infection prevention

The Center for Medicare and Medicaid Services (CMS) 2007

• Serious Preventable Events (SPAE)• Effective October 2008, CMS no longer

reimburses for these identified events including– CA-UTI fractures/other– Decubitus Ulcers surgery foreign obj– IV catheter infections– Mediastinitis post CABG– Air embolism– Blood incompatibilites

CAUTI• Surveillance Definition: CDC/NHSN only considers

symptomatic CAUTI; catheter must be in place within 48 hours prior to specimen collection or when catheters removed within previous 48 hours and meet the stated criteria in following slides. Asymptomatic bacteriuria no longer qualifies as a surveillance case definition.

• Asymptomatic bacteriuria does NOT require treatment regardless of colony count or presence of pyuria except pregnant women or patients undergoing an invasive urological procedure. Do NOT order routine urinalysis or culture unless the patient has signs and symptoms of a urinary tract infection. Cloudy or foul smelling urine is not an indication for a urine culture.

CAUTI Criteria #1a• Patient has an indwelling catheter in place

at the time of specimen collection and at least 1 of the following sign and symptoms without another cause:– Fever (>38o C) – Suprapubic tenderness or costovertebral pain

or tenderness and

• A positive urine culture of ≥105 CFU/ml with no more than 2 species

CAUTI Criteria #2a• Patient had a in dwelling urinary catheter in

place removed within 48 hours prior to specimen collection and at least 1 of the following without another cause:– fever (>38oC)– urgency, frequency, dysuria– Suprapubic tenderness or costovertebral pain or

tenderness and

• A positive urine culture of ≥105 CFU/ml with no more than 2 species

Indications for an Indwelling Urinary Catheter

• Urinary tract obstruction

• Prostatic hyperplasia

• Acute or chronic urinary retention

• Hypotonic bladder• Neurogenic bladder

• Critically ill patients • Management of

refractory incontinence

• Pre and post-pelvic surgery

• Accurate ins and outs• Active labor• Clot retention• Chemotherapy

Reasons We Hear

• The patient is on lasix

• I haven’t gotten around to it yet

• I forgot it was still in

• The patient is getting bumex…..

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Key points

• Avoid catheterization if at all possible• Reevaluate the need for a foley daily and remove

ASAP (RN driven protocol)• Do not order “cath prn”• Do not routinely change catheter• Yeast in the urine is best treated by simply

removing the catheter• Don’t irrigate the foley unless the foley is clogged

with blood clots

Central Line Associated Bloodstream infections (CLABSI)

• Bloodstream infections (BSIs) are a major cause of healthcare-associated morbidity and mortality– Up to 35% attributable mortality– BSI leads to excess hospital length of stay of 24

days• Central Line (CL) use a major risk factor for BSI• More than 250,000 central line-associated BSIs

(CLABSIs) in US yearly• Rates of CLABSI appear to vary by type of catheter

Pittet et al. JAMA 1994; 271 1598-1601.Klevens et al. Public Health Reports 2007;122:160-6.

Background: Pathogenesis CLABSI

More Common Mechanisms1. Pathogen migration along

external surface

- more common early (< 7days)

2. Hub contamination with intraluminal colonization

-more common >10 daysLess Common Mechanisms1. Hematogenousseeding from another source2. Contaminated infusates

HICPAC. Guideline for Prevention of Intravascular Device-Related Infections. 1996

Hub Contamination

Contaminated Infusate

Hematogenous spread

Extraluminal Contamination

Healthcare Personnel Hand Contamination

Contamination of insertion site

Background: Epidemiology

Modifiable Risk Factors

Characteristic Risk Factor Hierarchy

Insertion circumstances Emergency > elective

Skill of inserter General > specialized

Insertion site Femoral > subclavian

Skin antisepsis 70% alcohol, 10% povidone-iodine > 2% chlorhexidine

Catheter lumens Multilumen > single lumen

Duration of catheter use Longer duration of use greater risk

Barrier precautions Submaximal > maximal

Background: Prevention Strategies Interventions

• Michigan Keystone Project• Decrease in CLABSI in 103 ICUs in Michigan

(66% reduction)• Basic interventions:

– Hand hygiene– Full barrier precautions during CL insertion– Skin cleansing with chlorhexidine– Avoiding femoral site– Removing unnecessary catheters– Use of insertion checklist– Promotion of safety culture

Pronovost et al. NEJM 2006;355:2725-32.

CLABSI: Specimen Collection• For patients with suspected CLABSI :

– Collect blood cultures prior to initiating antimicrobial therapy.

– Two peripheral venous blood cultures (separate sticks) are preferred over paired blood samples drawn from the catheter and a peripheral vein.

– Collecting both sets of blood cultures from multiple lumens of the catheter may be necessary in patients with immunosuppression, leukopenia and thrombocytopenia and for patients with poor peripheral vascular access.

• Do not routinely culture catheter tips on removal unless there are clinical signs and symptoms for infection.

NHSN CLABSI Surveillance Definitions

Surveillance Definition: Central line in place at the time of or within 48 hours before onset of event.

• Criteria 1: Patient has a recognized pathogen cultured from one or more blood cultures (at least one bottle), and organism cultured is not related to another site of infection. Recognized pathogen excludes organisms considered common skin contaminants

Guidance on Interpretation of Culture Results

1. Results: The same organism grow from at least 1 percutaneous blood culture and a quantity of >15 colonies from the catheter tip. Interpretation: This probably is a catheter-associated infection.

2. Results: Paired blood cultures, either from two peripheral separate sticks or one drawn from a catheter hub and the other from a peripheral vein, growing the same organism in a patient with clinical signs and symptoms and no other recognized source. Interpretation: This is a catheter-associated infection.

Central Venous Catheter Blood Stream -Infections (CVC-BSI)

• Definition

• Pt with a CVC up to 48 hours after removal with a positive blood culture not related to another source

• Use “insertion bundle”

• Remove ASAP

Surgical Site Infections (SSI) and MRSA

• SSIs prolong hospitalizations and increase morbidity and mortality

• Staphylococcus aureus is the most common cause of SSI and healthcare-associated pneumonia and a leading cause of nosocomial bacteremia in the US

Infection Control

• Hand Hygiene– Foam in Foam out every time you enter a pts

room

• PPE-Personal Protective Equiptment– Use when performing a task when body fluid

exposure could occur• i.e. removing lines or tubes

Infection Control-Precautions

• Contact– Resistant organisms-MRSA, Clostridium

difficile(wash your hands with soap and water)

• Droplet– Suspected Neisseria meningitidis or Hemophilus

influenza meningitis-for 24 hours from the first dose of appropriate antibiotics

– Influenza, pertussis etc.

• Airborne– Suspected Tuberculosis-keep the door closed!

Antimicrobial Therapy Selection

• Broad - Spectrum Therapy– empiric -- infecting organism(s) unknown

• Narrow - Spectrum Therapy– culture and sensitivity data known

Selection of Antibiotic Therapy

• Active agents have comparable efficacy

• Compliance is necessary for cure

• The least toxic and least expensive effective drug should be used

• Resistance can be the result of antibiotic pressure

Mayo Clinic Proc 1998;73:1114-1122

Selected Bacteria and Targeted Antimicrobial Therapy

• Penicillins

• Vancomycin

• Gentamicin synergy

• Daptomycin

• Linezolid

Enterococci

MRSA Empiric Therapy

Outpatient• MRSA only

– Clindamycin– TMP/SMX– Minocycline or doxycyline– Linezolid

• MRSA + β-hemolytic Strep– Clindamycin– TMP/SMX + β-lactam– Mino/Doxy + β-lactam

Inpatient• Vancomycin• Linezolid• Daptomycin• Clindamycin

IDSA MRSA Guidelines CID 2011; 52: 1-3849


• Metronidazole

• Clindamycin

• B-lactam plus B-lactamase inhibitor (Piperacillin/

Tazobactam, Ampicillin/sulbactam, Amoxicillin/clavulanate)

• Cefotetan

• Carbapenems

Anaerobes


• Piperacillin

• Cefepime

• Ceftazidime

• Carbapenems– (not ertapenem)

• Ciprofloxacin

• Aminoglycosides (in combination, don’t use alone)

Pseudomonas aeruginosa


• Carbapenems

• Cephamycins (cefotetan)

• Aminoglycosides ?

• Quinolones ?

• Many beta-lactams may appear sensitive in vitro, but this is at a low inoculum. At higher bacterial concentrations as in human infections amount of beta-lactamase produced can overwhelm most beta-lactams

Extended Spectrum Beta-lactamase Producing Organisms

ESBL’s

• 52 yo white female admitted to the MICU with fevers, hypotension and now intubated. Blood cultures x 2 are drawn.

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Empiric Antibiotics

• The next morning, the lab informs you that the patient has 1 blood culture with gram positive cocci. You…

• A. Add Vancomycin 1 gram IV q12 hours with peak and trough with the third dose.

• B. Add Vancomycin 1gram IV q 12 hours with a trough with the third dose

• C. Add Vancomycin 1 gram IV q 12 hours.• D. Repeat blood cultures x 2

Empiric Antibiotics

BC grows S. aureus:

• A. Repeat blood cultures• B. Continue IV antibiotics

X 2 weeks if removable source

• C. Continue IV antibiotics x4 weeks if no removable source

BC grows S. epi:

• A. Repeat blood cultures

• B. Continue IV antibiotics x 2 weeks

• C. Discontinue vanco

Why is MRSA such an issue?

• MRSA is the most commonly identified antibiotic resistance pathogen

• MRSA in the community is increasing

• Resistance is increasing

• Limited Treatment Options– Different options based on type of infection


Staphylococcus Aureus Resistance

• 1942—PCN available• 1943—Penicillin resistance• 1960—Penicillinase resistant (methicillin)

PCN introduced• 1961—Methicillin resistance• 1990s—Community acquired MRSA• 2002—Vancomycin resistance• 2005—Daptomycin resistance

Appelbaum. CID 2007; 45:S165-70.Deresinski. CID 2005; 40:562-73.Sievert. CID 2008; 46:668-74.Hayden. J Clinc Micro. 2005; 43: 5285-7.

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Skin & Soft Tissue Infections

Pathogen Cutaneous Abscess(n=77)

SSTI with complicating factors (n= 73)

S. aureus 65% 45%

MRSA 34% 30%

Streptococci 38% 42%

S. aureus or Streptococci

97% 96%

• Streptococci is still a significant pathogen in cellulitis

• S. aureus is the primary pathogen in cutaneous abscess

Jenkins. CID 2010; 51: 895-903. 58

Cutaneous Abscess

• I&D is the primary treatment (A-II)• Antibiotics are recommended if (A-III):

– Severe or extensive disease– Rapid progression in association with cellulitis– Signs & symptoms of systemic illness– Immunosuppresion– Extremes in age (very young or very old)– Abscess in a difficult to drain area – Septic phlebitis– Lack of response to I&D


MRSA Bacteremia Definitions

• Uncomplicated Bacteremia (ALL of the below)– Positive blood cultures (BC) without

endocarditis or implanted prosthesis – Repeat BC are negative– Defervescence 72 hours after appropriate

therapy– No evidence of metastatic infection


Uncomplicated vs Complicated

Uncomplicated

• Empiric Treatment– Vancomycin– Daptomycin 6 mg/kg

• Length of Therapy– At least 2 weeks

Complicated

• Empiric Treatment– Vancomycin– Daptomycin 6 mg/kg

• May use 8-10 mg/kg (B-III)

• Length of Therapy– 4-6 weeks

61IDSA MRSA Guidelines CID 2011; 52: 1-38

S. aureus Endocarditis

• The most common cause of infective endocarditis (IE) in the developed world

• Mortality of 30-37% for MRSA IE

• Vancomycin is less effective for MSSA bacteremia and endocarditis


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Endocarditis

• Empiric Therapy– Vancomycin– Daptomycin 6 mg/kg

• Treat 6 weeks• Native Valve Endocarditis

– Gentamicin is NOT recommended (A-II)– Rifampin is NOT recommended (A-I)

• Prosthetic Valve– Vancomycin + Rifampin x 6 weeks– + Gentamicin 1 mg/kg/dose Q8 hours x 2 weeks

63IDSA MRSA Guidelines CID 2011; 52: 1-38

CNS Infections

• Bacterial meningitis –Streptococcus pneumoniae, Neisseria meningitidis, rarely Hemophilus influenza

• Viral meningitis

Enterovirus (PCR)

Herpes Simplex (PCR)

Other

MRSA Therapeutic Pearls

• Vancomycin– Drug of choice for MRSA infections– Troughs <10 μg/mL promote resistance– Poor penetration into bone, CSF & lungs– Cidal is a slower killer than β-lactams– MIC 1 μg/mL may be “sensitive” but there

may still be failures

IDSA MRSA Guidelines CID 2011; 52: 1-38IDSA Guidelines on Vancomycin AJHP 2009; 66:82-98.

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Pearls

Daptomycin• For bacteremia• Bactericidal• Concentration dependent• Vancomycin cross

resistance– Optimize the dosing

• Rhabdomyolysis – Baseline CK then weekly– Hold statins, fibrates etc.

• Renally dose adjusted

Linezolid

• For pneumonia• Bactiostatic NOT cidal• Duration limiting toxicities

– Hematologic toxicity– Optic neuritis– Peripheral neuropathy

• Weak MAOI-B inhibitor• Good lung and tissue

penetration• IV & PO options available

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Pearls

Clindamycin• Cidal or static depending

on location of infection• Resistance • 600 mg IV/PO Q8 hours

– Pts will not tolerate– Use higher doses IV – 300-450 mg PO Q6

• Excellent tissue penetration

• May be an option for MRSA pneumonia

Doxycyline/Minocycline

• Static• Resistance• Cannot give to children

<8 years (teeth discoloration)

• Option for SSTI, bone & joint infections

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• Vancomycin is still the drug of choice for MRSA infections– Monitor patients closely for improvement– Low threshold for changing therapy if MRSA

has an MIC of 1 or 2μg/mL– Troughs should NEVER be <10 μg/mL

• TMP/SMX should not be used alone for non-purulent cellulitis

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Case

• A 75 yo wm with a history of severe COPD and frequent acute bronchitis presents with diarrhea. The next step

• A. Inquire about antibiotic use• B. Send stool for Clostridium difficile toxin• C. Send stool for Clostridium difficile toxin times 3• D. Consider empiric metronidazole

Treatment of C. dif

• If on antibiotics and if possible, stop the antibiotics-25% of patients will respond without further therapy.

• Treatment oral therapy with metronidazole 500m g q 8 hrs

• Meantime for diarrhea to stop;~2-4 days• Treat for 10 days• Treat ~ 7 days before declaring drug failure if patient is

stable• Avoid peristaltic agents• Do not perform a test of cure-i.e. repeat stool for C. dif

toxin» Dale Gerding Loyola Univ. SHEA 2005

Recurrences• In pts with 1 recurrence-45% chance of additional

recurrences• Treatment

– 1. Vanco regimens– 2. Biotherapeutics– 3. passive treatment with immunoglobulins– 4. toxin binding agents– 5. fecal reconstitution

Acid Suppression

• Studies indicate 900 low risk patients need to be treated to prevent one ulcer

• One-third of low risk patients receive acid suppression during hospitalization

• 50% of low risk patients are discharged with prescriptions for acid suppression

1. DeVault KR, Castell DO. Am J Gastroentrol 2005;100:190-200. 2. Heidelbaugh JJ, Inadomi JM. Am J Gastroenterol 2006;107:1-6. 3. Mostafa G, Sing RF, Matthews BD, Pratt BL, Norton HF, Heniford BT. Am Surg 2002;68:146-150. 4. Nardino RJ, Vender RJ, Herbert PN. Am J Gastroenterol 2000;95:3118-3122. 5. Naunton M, Peterson GM, Bleasel MD. J Clin Pharm Ther 2000;25:333-340. 6. Pham CoQD, Regal RE, Bostwick TR, Knauf KS. Ann Pharmacother 2006;40:1261-1266. 7. Pham CoQD, Sadowski-Hayes LM, Regal RE. P&T 2006;31:159-167. 8. Yang Y, Lewis JD, Epstein S, Metz DC. JAMA 2006;296:2947-2953.

Complications of Acid Suppression

• Infection: C. difficile, MSSA, MRSA, VRE, community acquired pneumonia

• Drug-drug interactions

• Drug-nutrient interactions

• Increased costs

1. DeVault KR, Castell DO. Am J Gastroentrol 2005;100:190-200. 2. Heidelbaugh JJ, Inadomi JM. Am J Gastroenterol 2006;107:1-6. 3. Mostafa G, Sing RF, Matthews BD, Pratt BL, Norton HF, Heniford BT. Am Surg 2002;68:146-150. 4. Nardino RJ, Vender RJ, Herbert PN. Am J Gastroenterol 2000;95:3118-3122. 5. Naunton M, Peterson GM, Bleasel MD. J Clin Pharm Ther 2000;25:333-340. 6. Pham CoQD, Regal RE, Bostwick TR, Knauf KS. Ann Pharmacother 2006;40:1261-1266. 7. Pham CoQD, Sadowski-Hayes LM, Regal RE. P&T 2006;31:159-167. 8. Yang Y, Lewis JD, Epstein S, Metz DC. JAMA 2006;296:2947-2953.

• Vancomycin is the perfect antibiotic because resistance has never developed and it never will.– Anonymous ID physician 1985

• I used to be Snow White but I drifted.

Mae West

Drugs for Bugs What’s new in 2012?

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