Bacteremia and Bacteremia and EndocarditisEndocarditis

Monday, September 15, 2008Monday, September 15, 2008

Blood CulturesBlood Cultures 2 sets, >15 minutes apart 2 sets, >15 minutes apart

and preferable 2 sitesand preferable 2 sites Clearly document sourceClearly document source Now continuous Now continuous

monitoringmonitoring No entry of bacteria for No entry of bacteria for

monitoringmonitoring lysis-centrifugation system lysis-centrifugation system

(Isolator) used for either (Isolator) used for either routine bacteria, fungi, routine bacteria, fungi, mycobacteria, or mycobacteria, or fastidious organisms such fastidious organisms such as as BartonellaBartonella or or BrucellaBrucella Labor intensiveLabor intensive More contaminationMore contamination

TechniqueTechnique 70% alcohol, followed by 70% alcohol, followed by

tincture of iodine (1 minute) tincture of iodine (1 minute) or povidone iodine (2 or povidone iodine (2 minutes). minutes).

septum of the culture bottle septum of the culture bottle or tube need only be wiped or tube need only be wiped with 70% alcohol with 70% alcohol

transported to the lab transported to the lab promptly promptly

volume of blood cultured and volume of blood cultured and number of sets drawn are number of sets drawn are important important

current recommendations for current recommendations for adults are to draw at least adults are to draw at least two separate blood cultures two separate blood cultures totaling 30 to 40 ml of blood. totaling 30 to 40 ml of blood.

Separate venipunctures-to Separate venipunctures-to help interpret cultures that help interpret cultures that contain skin floracontain skin flora

Classification of Classification of BacteremiaBacteremia

Community-acquiredCommunity-acquired NosocomialNosocomial Healthcare-associated BacteremiaHealthcare-associated Bacteremia

indwelling cathetersindwelling catheters HDHD receiving other outpatient therapyreceiving other outpatient therapy

Wound care Wound care nursing home residents nursing home residents

Friedman: Ann Intern Med, Volume 137(10).November 19, 2002.791-797

Martin: N Engl J Med, Volume 348(16).April 17,

2003.1546-1554

Martin: N Engl J Med, Volume 348(16).April 17,

2003.1546-1554

Staph aureusStaph aureus bacteremia bacteremia

up to 13% of cases of up to 13% of cases of S. aureusS. aureus nosocomial or community-acquired nosocomial or community-acquired bacteremia may become complicated bacteremia may become complicated with infective endocarditis, even in with infective endocarditis, even in the absence of cardiac risk factors the absence of cardiac risk factors (some studies suggest even higher (some studies suggest even higher risk), regardless of other identifiable risk), regardless of other identifiable sourcesource

““contaminant” vs contaminant” vs transienttransient

Single set positive for skin flora, Single set positive for skin flora, especially if polymicrobial, very likely to especially if polymicrobial, very likely to be contaminantbe contaminant

If suspect contaminant, before starting an If suspect contaminant, before starting an antibiotic (if you must), repeat BCxantibiotic (if you must), repeat BCx

Exceptions occurExceptions occur Prosthesis or port infectionProsthesis or port infection

Pathogens LIKELY TO BE skin organismsPathogens LIKELY TO BE skin organisms Transient (true) bacteremia also occursTransient (true) bacteremia also occurs

ToothbrushingToothbrushing ERCPERCP Abscess drainageAbscess drainage

Infectious Endocarditis Infectious Endocarditis (IE)(IE)

Traditional risk factor of RHD decreasing, newer factors Traditional risk factor of RHD decreasing, newer factors increasingincreasing

Emergence of enterococci and Staph, particularly MRSA Emergence of enterococci and Staph, particularly MRSA and VRE, also VISA and VRSAand VRE, also VISA and VRSA

Viridans Strep now emerging MDR strainsViridans Strep now emerging MDR strains SubtypesSubtypes

native value IEnative value IE RHDRHD MVP (10-100 fold increased risk if regurgitant)MVP (10-100 fold increased risk if regurgitant) Degenerative/inherited valve disorders Degenerative/inherited valve disorders

prosthetic valve IE prosthetic valve IE Early (Staph epi, Staph aureus)Early (Staph epi, Staph aureus) Late (Strep, HACEK)Late (Strep, HACEK)

IE in intravenous drug usersIE in intravenous drug users Healthcare-associated IEHealthcare-associated IE nosocomial IEnosocomial IE

Microbiologic Etiology in 1779 Patients With Definite Endocarditis

From:   Fowler: JAMA, Volume 293(24).June 22/29, 2005.3012–3021

Trends in Age- and Sex-Adjusted Incidence Rates of Infective Endocarditis Caused by Staphylococcus aureus and Viridans Group Streptococci From 1970 to 2000 in Olmsted County, Minnesota From:   Tleyjeh: JAMA, Volume 293(24).June 22/29, 2005.3022–3028

IDU-associated IEIDU-associated IE median age 30 and 40 yrsmedian age 30 and 40 yrs up to 40% of cases of IE in San Francisco up to 40% of cases of IE in San Francisco tricuspid valve > 50% of cases, aortic in 25%, tricuspid valve > 50% of cases, aortic in 25%,

mitral in 20%, mixed right- and left-sided IE mitral in 20%, mixed right- and left-sided IE unusual.unusual.

injections of impure drugs and particulates might injections of impure drugs and particulates might produce microtrauma to the tricuspid leaflets, produce microtrauma to the tricuspid leaflets, facilitating microbial colonizationfacilitating microbial colonization

20–40% of IDU with IE have pre-existing cardiac 20–40% of IDU with IE have pre-existing cardiac lesionslesions

Bacteria often originate from the skinBacteria often originate from the skin streptococci and others also seenstreptococci and others also seen Pseudomonas aeruginosaPseudomonas aeruginosa and fungi may produce and fungi may produce

severe IE. severe IE. mortality of IE higher in patients who have AIDSmortality of IE higher in patients who have AIDS

Nosocomial IENosocomial IE The incidence is increasing. The incidence is increasing. Many patients have other debilitating underlyingMany patients have other debilitating underlying < 50% had obvious cardiac predisposing factors < 50% had obvious cardiac predisposing factors In most circumstances a potential source of In most circumstances a potential source of

bacteremia could be identified, (lines, procedures) bacteremia could be identified, (lines, procedures) staphylococci and enterococci most commonstaphylococci and enterococci most common other organisms-Gram-negative bacteria and fungi. other organisms-Gram-negative bacteria and fungi. Right-sided IERight-sided IE is increasingly recognized in is increasingly recognized in

association with central venous lines, pulmonary association with central venous lines, pulmonary artery catheters and pacemakers. artery catheters and pacemakers.

procedures that produce transient bacteremia procedures that produce transient bacteremia represent risk in hospitalized patients, especially represent risk in hospitalized patients, especially when the circulating organism is when the circulating organism is S. aureusS. aureus. .

mortality of nosocomial IE is greater than 50%.mortality of nosocomial IE is greater than 50%.

Culture-negative IECulture-negative IE

HACEKHACEK HaemophilusHaemophilus spp. spp. Actinobacillus actinomycetemcomitansActinobacillus actinomycetemcomitans Cardiobacterium hominisCardiobacterium hominis Eikenella corrodensEikenella corrodens Kingella kingaeKingella kingae

Nutritionally-deficient Nutritionally-deficient Strep spp.Strep spp. Fastidious GNRFastidious GNR

Culture-negative IECulture-negative IE

Coxiella burnetiiCoxiella burnetii (Q fever) (Q fever) BrucellaBrucella Bartonella quintanaBartonella quintana ChlamydiaChlamydia Tropheryma whippeliiTropheryma whippelii

PathogenesisPathogenesis Basic lesion is endothelial Basic lesion is endothelial

damagedamage IE pathogens possess IE pathogens possess

surface ligands that surface ligands that mediate attachment to mediate attachment to extracellular matrix extracellular matrix proteins of the host proteins of the host (MSCRAMMs)(MSCRAMMs)

direct invasion of direct invasion of endothelial cells may also endothelial cells may also occur occur

Transient bacteremias Transient bacteremias occur during chewing, occur during chewing, toothbrushing and other toothbrushing and other normal activities, and normal activities, and from more invasive from more invasive proceduresprocedures

PathogenesisPathogenesis

Microscopic appearance of a vegetation from a patient suffering mitral valve infective endocarditis due to Streptococcus sanguis. The purple area represents clusters of streptococci packed within a fibrin-platelet meshwork. Professional phagocytes are essentially absent from the lesion.

IE ProphylaxisIE Prophylaxis Goals:Goals:

identification of patients at risk; identification of patients at risk; determination of the procedures or circumstances that may result in determination of the procedures or circumstances that may result in

bacteremias; bacteremias; choice of an appropriate antimicrobial regimen; and choice of an appropriate antimicrobial regimen; and balancing of the known risks against the possible benefits of intervention.balancing of the known risks against the possible benefits of intervention.

No controlled studiesNo controlled studies Regimens used in humans are based upon their proven efficacy in Regimens used in humans are based upon their proven efficacy in

animal models of IE animal models of IE successful prophylaxis does not require bactericidal antibiotics successful prophylaxis does not require bactericidal antibiotics Antiseptic mouth rinses applied immediately prior to dental Antiseptic mouth rinses applied immediately prior to dental

procedures may reduce the incidence or magnitude of bacteremia procedures may reduce the incidence or magnitude of bacteremia Cover most probable pathogens circulating in the blood during a Cover most probable pathogens circulating in the blood during a

given proceduregiven procedure oropharyngeal manipulation-streptococcioropharyngeal manipulation-streptococci gastrointestinal or urogenital manipulations, it should be aimed at gastrointestinal or urogenital manipulations, it should be aimed at

enterococci (plus results of a preprocedure urine culture)enterococci (plus results of a preprocedure urine culture) skin or other infected lesions-staphylococci skin or other infected lesions-staphylococci

If already on antibiotics, choose another class.If already on antibiotics, choose another class.

Recommendations by the American Heart Association

Authors Dajani A, Taubert K, Wilson W, Bolger A, Bayer A, Ferrieri P, Gewitz M, et al. 

Source JAMA. 277:1794-1801. June 11, 1997. 

Institutions American Heart Association; American Dental Association; Infectious Diseases Society of America;

American Academy of Pediatrics; American Society of Gastrointestinal Endoscopy. 

SBE prophylaxisSBE prophylaxis

Negligible risk 

These cardiac conditions are felt not to require prophylaxis. 

  Isolated ostium secundum ASD and surgically

repaired ASD, VSD and PDA (beyond 6 months and without sequelae). 

Mitral valve prolapse without mitral regurgitation and without thickened leaflets. 

Innocent or physiologic murmurs (echo required in the adult population to rule out valvular lesion). 

Cardiac pacemakers and defibrillators.  History of isolated bypass surgery, history of

Kawasaki disease without valvular dysfunction and history of rheumatic fever without valvular

dysfunction. 

High risk 

These conditions are:   

All prosthetic heart valves (including bioprostheses and homografts). 

Any history of previous bacterial endocarditis.  Complex cyanotic congenital heart disease and

surgically constructed systemic pulmonary shunts. 

Moderate risk 

Most cardiac conditions requiring prophylaxis will fall into this category. 

  Congenital cardiac malformations, not falling into the high or negligible risk categories (such as PDA, VSD,

ostium primum ASD, bicuspid aortic valve and coarctation). 

Acquired valvular heart disease (such as rheumatic heart disease, valvular stenosis and regurgitation). 

MVP with regurgitation and/or myxomatous leaflets.  Hypertrophic cardiomyopathy.

Procedures Prophylaxis recommendations

Dental and oral procedures

Dental procedures with bleeding:      •extractions •cleaning •periodontal procedures •dental implant placement •endodontic surgery (root canal) •initial placement of orthodontic bands •intraligamentary local anesthesia

Prophylaxis recommended In addition, consider antiseptic rinse immediately prior to procedure 

Dental procedures unlikely to cause bleeding:  •Restorative dentistry (including cavity filling) •Nonintraligamentary local anesthesia •Intracanal endodontic treatment post-placement •Suture removal •Placement and adjustment of orthodontic and prosthodontic devices 

Not recommended  If unanticipated bleeding, consider antibiotic prophylaxis within 2 hours 

Respiratory tract

•Surgical operations involving respiratory mucosa, including tonsillectomy/adenoidectomy  •Bronchoscopy with rigid bronchoscope

Recommended

•Flexible bronchoscopy, with or without biopsy High risk patients: Optional Others: not recommended

•Endotracheal intubation  •Tympanostomy tube insertion

Not recommended

Gastrointestinal tract

•Esophageal sclerotherapy and dilatation  •ERCP in the presence of obstruction and biliary tract surgery  •Surgery involving the intestinal mucosa 

High risk: recommended Moderate risk: optional

•Endoscopy, with or without biopsy  •Transesophageal echocardiography 

High risk: optional Others: not recommended

Genito-urinary tract

•Prostate surgery  •Urethral dilatation  •Cystoscopy 

In the presence of infection: •Urethral catheterization  •Uterine D&C; therapeutic abortion; sterilization; insertion or removal of IUD 

Recommended In case of infection, culture guided therapy (until sterilization, when possible) 

•Vaginal hysterectomy  •Vaginal delivery

High risk: optional Others: not recommended

•Caesarean section 

In uninfected tissue: •Urethral catheterization  •Uterine D&C; therapeutic abortion; sterilization; insertion or removal of IUD 

Not

Procedure and situation Prophylactic regimen recommended

Dental, oral, respiratory tract and esophageal procedures

Standard regimen Amoxicillin 2.0 g orally one hour before procedure

Unable to take orallyAmpicillin 2.0 g IM or IV, within 30 minutes before procedure

Penicillin allergic

Clindamycin 600 mg or  Azithromycin 500 mg or  Clarithromycin 500 mg or   for patients who have not had an immediate local or systemic reaction to a pencillin (urticaria, angioedema or anaphylaxis) and who can tolerate first generation cephalosporins: Cephalexin or Cefadroxil 2.0 g  orally, 1 h before procedure 

Pencillin allergic and unable to take orally

Clindamycin 600 mg IV or  Cefazolin 1.0 g IM or IV (for patients who can tolerate, see above)  within 30 minutes before procedure 

Genitourinary and gastrointestinal (not esophageal) procedures

High risk patients

Ampicillin 2.0 g IV or IM plus gentamycin 1.5 mg/kg (up to 120 mg) within 30 min of starting procedure  followed by ampicillin 1.0 g IV/IM or amoxicillin 1 g orally 6 hours later 

High risk patients allergic to ampicillin

Vancomycin 1.0 g IV over 1-2 h plus gentamycin 1.5 mg/kg IV/IM (up to 120 mg) to be completed within 30 min of starting procedure

Moderate risk patientsAmoxicillin 2.0 g orally 1 h before procedure or ampicillin 2.0 g IM/IV within 30 min of starting procedure

Moderate risk patients allergic to ampicillin

Vancomycin 1.0 g IV over 1-2 hr, to be completed within 30 min of starting procedure

The lower dose of amoxicillin and the lack of a second dose 6 hours post-procedure for oral regimens is a substantial change from the previous recommendations. The lack of an erythromycin regimen for oral procedures is another substantial change. 

What’s different?What’s different?

DiagnosisDiagnosis Duke criteriaDuke criteria Classic exam/lab findingsClassic exam/lab findings

Osler nodesOsler nodes SplenomegalySplenomegaly Janeway lesionsJaneway lesions Microscopic hematuriaMicroscopic hematuria Elevated ESR and CRPElevated ESR and CRP Septic pulmonary emboli (right)Septic pulmonary emboli (right)

Classic findings may be absentClassic findings may be absent Repeating TEE 7 to 10 days after an initial Repeating TEE 7 to 10 days after an initial

"negative" result may be advisable"negative" result may be advisable Posttreatment echocardiography is recommended Posttreatment echocardiography is recommended

Peripheral Stigmata of IEPeripheral Stigmata of IE Osler node=small, raised, Osler node=small, raised,

tender cutaneous lesion, tender cutaneous lesion, usually on the pads of usually on the pads of fingers or toes (vasculitic)fingers or toes (vasculitic)

Janeway lesion=flat, Janeway lesion=flat, painless small hemorrhages painless small hemorrhages with a slightly nodular with a slightly nodular appearance that occur on appearance that occur on the palms and soles (septic the palms and soles (septic emboli)emboli)

Splinter hemorrhagesSplinter hemorrhages PetechiaePetechiae Roth spots=hemorrhage in Roth spots=hemorrhage in

the retina with a white the retina with a white center center

Janeway lesionsJaneway lesions

Roth spotRoth spot

Definite infective endocarditis

    Pathological criteria

        Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen

        Pathological lesions; vegetation or intracardiac abscess confirmed by histological examination showing active endocarditis

    Clinical criteria

        2 major criteria; or

        1 major criterion and 3 minor criteria; or

        5 minor criteria

    Possible IE

        1 major criterion and 1 minor criterion; or

        3 minor criteria

    Rejected

        Firm alternative diagnosis explaining evidence of IE; or

        Resolution of IE syndrome with antibiotic therapy for <4 days; or

        No pathological evidence of IE at surgery or autopsy, with antibiotic therapy for <4 days; or

        Does not meet criteria for possible IE as above

Major criteria

     Blood culture positive for IE

        Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus; or

        Microorganisms consistent with IE from persistently positive blood cultures defined as follows: At least 2 positive cultures of blood samples drawn >12 h apart; or all of 3 or a majority of  4 separate cultures of blood (with first and last sample drawn at least 1 h apart)

        Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer >1:800

    Evidence of endocardial involvement

        Echocardiogram positive for IE: defined as follows: oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or abscess; or new partial dehiscence of prosthetic valve; new valvular regurgitation (worsening or changing or preexisting murmur not sufficient)

Minor criteria

    Predisposition, predisposing heart condition, or IDU

    Fever, temperature >38°C

    Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway’s lesions

    Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor

    Microbiological evidence: positive blood culture but does not meet a major criterion as noted above* or serological evidence of active infection with organism consistent with IE

    Echocardiographic minor criteria eliminated

SurgerySurgery

IndicationIndication Severe CHF (reduced mortality with surgery)Severe CHF (reduced mortality with surgery) Persistent bacteremiaPersistent bacteremia Certain pathogens (fungal, GNR)Certain pathogens (fungal, GNR) Embolic events Embolic events

Large vegetation on mitral valve highest riskLarge vegetation on mitral valve highest risk Valve abscess/dehiscenceValve abscess/dehiscence

TimingTiming 7-fold higher risk of recurrent IE if valve 7-fold higher risk of recurrent IE if valve

replaced during active infectionreplaced during active infection

TreatmentTreatment

If using synergistic agents give them If using synergistic agents give them togethertogether

Day 1 is first day documented negative Day 1 is first day documented negative blood culturesblood cultures

postoperative treatment regimen should postoperative treatment regimen should be one that is recommended for be one that is recommended for prosthetic valve treatment rather than prosthetic valve treatment rather than one that is recommended for native valve one that is recommended for native valve treatment treatment

Start over if cultures positiveStart over if cultures positive

Viridans StrepViridans Strep community-acquired native valve community-acquired native valve

endocarditis in patients who are endocarditis in patients who are not intravenous drug users not intravenous drug users (IDUs). (IDUs).

-hemolytic -hemolytic S sanguisS sanguis, , S oralis (mitis)S oralis (mitis), , S S

salivariussalivarius, , S mutansS mutans, and , and Gemella Gemella morbillorummorbillorum (formerly called (formerly called S S morbillorummorbillorum). ).

S anginosusS anginosus group ( group (S S intermediusintermedius, , anginosusanginosus, and , and constellatusconstellatus) aka ) aka S milleriS milleri group group

tends to form abscesses and tends to form abscesses and cause hematogenously cause hematogenously disseminated infection (eg, disseminated infection (eg, myocardial and visceral myocardial and visceral abscesses, septic arthritis, abscesses, septic arthritis, vertebral osteomyelitis).vertebral osteomyelitis).

S intermediusS intermedius usually is sensitive usually is sensitive to penicillin, but some strains to penicillin, but some strains may exhibit variable penicillin may exhibit variable penicillin resistance.resistance.

Abiotrophia defectiva and Abiotrophia defectiva and Granulicatella species (G elegans, Granulicatella species (G elegans, G adiacens, G paraadiacens, and G G adiacens, G paraadiacens, and G balaenopterae; formerly known as balaenopterae; formerly known as nutritionally variant streptococci), nutritionally variant streptococci),

have nutritional deficiencies that have nutritional deficiencies that hinder their growth hinder their growth

GemellaGemella ( (morbillorummorbillorum, , bergeriaebergeriae, , sanguinissanguinis, and , and hemolysanshemolysans))

share some physiological share some physiological characteristics with characteristics with nutritionally variant nutritionally variant streptococcistreptococci

should be treated with more should be treated with more aggressive combination therapyaggressive combination therapy

S bovisS bovis expresses the group D expresses the group D antigen, but it can be antigen, but it can be distinguished from group D distinguished from group D EnterococcusEnterococcus by appropriate by appropriate biochemical tests. biochemical tests.

should undergo colonoscopyshould undergo colonoscopy

TreatmentTreatment Native valve, highly susceptible viridans Native valve, highly susceptible viridans

Strep or Strep bovis (MIC <.12)Strep or Strep bovis (MIC <.12) Aq Pen G x 4 wksAq Pen G x 4 wks Rocephin x 4 wksRocephin x 4 wks Aq Pen G + gent x 2 wks (synergy)Aq Pen G + gent x 2 wks (synergy) Rocephin + gent x 2 wksRocephin + gent x 2 wks Vanc x 4 wksVanc x 4 wks

Viridans Group Streptococci and Viridans Group Streptococci and S bovisS bovis With Penicillin MIC >0.12 to 0.5 µg/mlWith Penicillin MIC >0.12 to 0.5 µg/ml Aq pen or Rocephin x 4 wks + gent 1Aq pen or Rocephin x 4 wks + gent 1stst 2 wks 2 wks

(single daily dose)(single daily dose) vancomycinvancomycin

TreatmentTreatment A defectivaA defectiva, , GranulicatellaGranulicatella species, and species, and GemellaGemella species and a species and a

microorganism with an MIC to penicillin >0.5 µg/mL should be microorganism with an MIC to penicillin >0.5 µg/mL should be treated with a regimen that is recommended for enterococcal treated with a regimen that is recommended for enterococcal endocarditisendocarditis

prosthetic valves should receive 6 weeks of therapy with prosthetic valves should receive 6 weeks of therapy with penicillin or ceftriaxone with or without gentamicin for the first penicillin or ceftriaxone with or without gentamicin for the first 2 weeks2 weeks

S pneumoniaeS pneumoniae, , S pyogenesS pyogenes, and Groups B, C, and G , and Groups B, C, and G StreptococciStreptococci highly penicillin-susceptible highly penicillin-susceptible S pneumoniaeS pneumoniae should receive 4 weeks should receive 4 weeks

of antimicrobial therapy with penicillin, cefazolin, or ceftriaxone of antimicrobial therapy with penicillin, cefazolin, or ceftriaxone High-dose penicillin or a third-generation cephalosporin can be used High-dose penicillin or a third-generation cephalosporin can be used

in patients with penicillin-resistant infection and without meningitis in patients with penicillin-resistant infection and without meningitis If the isolate is resistant (MIC 2 µg/mL) to cefotaxime, then the If the isolate is resistant (MIC 2 µg/mL) to cefotaxime, then the

addition of vancomycin and rifampin should be considered. addition of vancomycin and rifampin should be considered. Consider gentamicin for at least the first 2 weeks of a 4- to 6-week Consider gentamicin for at least the first 2 weeks of a 4- to 6-week

course of antimicrobial therapy for group B, C, and G strep course of antimicrobial therapy for group B, C, and G strep (relatively pen res)(relatively pen res)

Aq pen G for Gp A Aq pen G for Gp A

Coagulase-negative Staph Coagulase-negative Staph (CoNS)(CoNS)

Usually associated Usually associated with PVEwith PVE

Occasionally native Occasionally native valve, usually valve, usually damageddamaged

More indolent than More indolent than Staph aureusStaph aureus

Staph lugdinensis Staph lugdinensis more virulentmore virulent

Staph aureus Staph aureus endocarditisendocarditis

Nosocomial bacteremia Nosocomial bacteremia previously thought to be previously thought to be lower risk for lower risk for endocarditisendocarditis

health care–associated health care–associated infection was the single infection was the single most common form of most common form of S S aureusaureus IE IE

health care–associated health care–associated IE is distinguished by a IE is distinguished by a relative infrequency of relative infrequency of classic clinical stigmata classic clinical stigmata of IEof IE

S aureusS aureus bacteremia bacteremia associated with health associated with health care has increased care has increased among hospitalized among hospitalized patients and among patients and among those receiving those receiving outpatient medical outpatient medical therapytherapy

MRSA in both hospital MRSA in both hospital and community and community increased dramaticallyincreased dramatically

implanted medical implanted medical devices devices prosthetic heart valvesprosthetic heart valves grafts grafts hemodialysis catheters hemodialysis catheters pacemakerspacemakers

EndocarditisEndocarditis Factors associated with Staph aureus SBE:Factors associated with Staph aureus SBE:

Native valveNative valve HemodialysisHemodialysis Invasive proceduresInvasive procedures Other chronic diseaseOther chronic disease Multiple pulmonary emboliMultiple pulmonary emboli Intravascular device sourceIntravascular device source TricuspidTricuspid Healthcare-associatedHealthcare-associated IDU-associatedIDU-associated Persistent bacteremia, emboli requiring surgeryPersistent bacteremia, emboli requiring surgery Complications including stroke, other emboli, deathComplications including stroke, other emboli, death

Factors associated with non-Staph aureus SBEFactors associated with non-Staph aureus SBE Aortic valveAortic valve Prosthetic valveProsthetic valve Congenital heart diseaseCongenital heart disease Dental workDental work Symptoms >1 monthSymptoms >1 month

International Collaboration on Endocarditis-Prospective Cohort Study from June

2000 to December 2003.

                                                                                                  Figure. In-Hospital Mortality Rates Among Patients With Health Care–Associated Staphylococcus aureus Endocarditis. Includes both nosocomial and nonnosocomial health care–associated infections, community-acquired injection drug use–associated S aureus endocarditis, and community-acquired noninjection drug use–associated S aureus endocarditis by geographic region. From:   Fowler: JAMA, Volume 293(24).June 22/29, 2005.3012–3021

                                                                                                                                                Table 4. Clinical Characteristics and Outcomes of 424 Prospectively Identified Patients With Definite Endocarditis Due to Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus* From:   Fowler: JAMA, Volume 293(24).June 22/29, 2005.3012–3021

TreatmentTreatment Staph aureus IDU (right)Staph aureus IDU (right)

parenteral ß-lactam +/- gent x 2 wks parenteral ß-lactam +/- gent x 2 wks (uncomplicated)(uncomplicated)

Oral also effective (Cipro + rifampin x 4 wks)Oral also effective (Cipro + rifampin x 4 wks) Vancomycin requires 4 wksVancomycin requires 4 wks

Staph aureus non-IDUStaph aureus non-IDU Beta lactam x 4-6wks, gent 1Beta lactam x 4-6wks, gent 1stst few days if fulminant few days if fulminant

Faster clearance of bacteremiaFaster clearance of bacteremia Not better mortalityNot better mortality

Vanc only if anaphylactoid history to PENVanc only if anaphylactoid history to PEN Clinda not recommended, high relapse rateClinda not recommended, high relapse rate Consider desensitizing or daptomycin.Consider desensitizing or daptomycin. PVE add gentamicin for 2 wks, plus rifampin full 6 PVE add gentamicin for 2 wks, plus rifampin full 6

wkswks

TreatmentTreatment MRSAMRSA

Vancomycin (same gent caveats, plus possible Vancomycin (same gent caveats, plus possible increased ototox)increased ototox)

LinezolidLinezolid SynercidSynercid DaptomycinDaptomycin PVE add gentamicin for 2 wks, plus rifampin full 6 PVE add gentamicin for 2 wks, plus rifampin full 6

wkswks CoNSCoNS

Assume meth-resistantAssume meth-resistant Vancomycin for 6 wksVancomycin for 6 wks PVE add gentamicin for 2 wks, plus rifampin full 6 PVE add gentamicin for 2 wks, plus rifampin full 6

wkswks

EnterococciEnterococci Group DGroup D test MICs to penicillin and vancomycin and for high-level test MICs to penicillin and vancomycin and for high-level

resistance to gentamicin and streptomycinresistance to gentamicin and streptomycin trough antibiotic concentration in serum must be trough antibiotic concentration in serum must be

maintained above the MIC.maintained above the MIC. relatively resistant to penicillin, ampicillin, and relatively resistant to penicillin, ampicillin, and

vancomycin. vancomycin. requires the synergistic action of penicillin, ampicillin, or requires the synergistic action of penicillin, ampicillin, or

vancomycin in combination with either gentamicin or vancomycin in combination with either gentamicin or streptomycin. streptomycin.

relatively impermeable to aminoglycosides. relatively impermeable to aminoglycosides. cell wall–active agents raise the permeability of the cell wall–active agents raise the permeability of the

enterococcal cell so that a bactericidal effect can be enterococcal cell so that a bactericidal effect can be achieved achieved

If resistant to high concentrations of an aminoglycoside If resistant to high concentrations of an aminoglycoside (500 µg/mL of gentamicin or 1000 µg/mL of streptomycin), (500 µg/mL of gentamicin or 1000 µg/mL of streptomycin), then the combination of an aminoglycoside with the cell then the combination of an aminoglycoside with the cell wall–active agent will not result in bactericidal activity, nor wall–active agent will not result in bactericidal activity, nor will it predictably produce a microbiological cure.will it predictably produce a microbiological cure.

<3 months’ duration of symptoms 4 weeks; >3 months’ <3 months’ duration of symptoms 4 weeks; >3 months’ duration of symptoms 6 weeks duration of symptoms 6 weeks

PVE 6 wksPVE 6 wks

EnterococciEnterococci

Beta lactam resistant-vancomycinBeta lactam resistant-vancomycin VREVRE

vancomycin-resistant vancomycin-resistant E faecalisE faecalis and and E E gallinarumgallinarum//casseliflavuscasseliflavus usually are usually are penicillin susceptible penicillin susceptible

LinezolidLinezolid DaptomycinDaptomycin Synercid (faecium only)Synercid (faecium only)

HACEKHACEK fastidious Gram-negative fastidious Gram-negative

bacilli (grow slowly )bacilli (grow slowly ) Haemophilus Haemophilus

parainfluenzaeparainfluenzae, , H H aphrophilusaphrophilus, , H H paraphrophilusparaphrophilus, , H H influenzaeinfluenzae, , Actinobacillus Actinobacillus actinomycetemcomitansactinomycetemcomitans, , Cardiobacterium hominisCardiobacterium hominis, , Eikenella corrodensEikenella corrodens, , Kingella kingaeKingella kingae, and , and K K denitrificansdenitrificans

5%-10% of native valve 5%-10% of native valve community-acquired IE in community-acquired IE in non IDUsnon IDUs

hold blood cultures for 2 hold blood cultures for 2 wks in patients suspected of wks in patients suspected of having IE. having IE.

ß-lactamase–producing ß-lactamase–producing strains increasing strains increasing

should be considered should be considered ampicillin resistantampicillin resistant

susceptible to susceptible to ceftriaxone,ceftriaxone, ampicillin- ampicillin-sulbactam, and sulbactam, and fluoroquinolones. fluoroquinolones.

limited published clinical limited published clinical data data

duration of therapy for duration of therapy for native valve infection native valve infection should be 4 weeksshould be 4 weeks

prosthetic valve 6 weeksprosthetic valve 6 weeks bacteremia caused by bacteremia caused by

HACEK is highly HACEK is highly suggestive of endocarditissuggestive of endocarditis

Other Gram-negativesOther Gram-negatives IDU, prosthetic valve, and cirrhosis IDU, prosthetic valve, and cirrhosis

are risk factorsare risk factors EnterobacteriaceaeEnterobacteriaceae

SalmonellaSalmonella species have an species have an affinity for abnormal cardiac affinity for abnormal cardiac valvesvalves

Valvular perforation, atrial Valvular perforation, atrial thrombi, myocarditis, and thrombi, myocarditis, and pericarditis are commonpericarditis are common

SalmonellaeSalmonellae also may produce also may produce endarteritis in aneurysms of endarteritis in aneurysms of major vessels. Other major vessels. Other Enterobacteriaceae, including Enterobacteriaceae, including

E coliE coli and and Serratia marcescensSerratia marcescens, , may rarely cause endocarditis may rarely cause endocarditis

S marcescensS marcescens endocarditis endocarditis typically develops in IDUs. typically develops in IDUs.

Left-sided disease, large Left-sided disease, large vegetations, and vegetations, and involvement of normal involvement of normal valves valves

mortality rates are 70%. mortality rates are 70%.

Cardiac surgery is a Cardiac surgery is a cornerstone of treatment cornerstone of treatment

Combinations of pens/cephs Combinations of pens/cephs and aminoglycosides have and aminoglycosides have been shown to be synergistic been shown to be synergistic

E. coliE. coli or or Proteus mirabilisProteus mirabilis, a , a combination of either combination of either ampicillin or penicillin or a ampicillin or penicillin or a broad-spectrum ceph + broad-spectrum ceph + aminoglycoside, usually gentaminoglycoside, usually gent

Endovascular Endovascular SalmonellaSalmonella infections also may respond infections also may respond to third-generation to third-generation cephalosporins.cephalosporins.

combination of a third-combination of a third-generation cephalosporin generation cephalosporin and an aminoglycoside and an aminoglycoside (either gentamicin or (either gentamicin or amikacin) is recommended amikacin) is recommended for for KlebsiellaKlebsiella endocarditis. endocarditis.

PseudomonasPseudomonas Nearly all IDUsNearly all IDUs Associated with tripelennamine Associated with tripelennamine

and pentazocine ("T’s and and pentazocine ("T’s and blues") blues")

mean age 30 years mean age 30 years affects normal valves affects normal valves Major embolic phenomena, Major embolic phenomena,

inability to sterilize valves, inability to sterilize valves, neurol complications (53%), ring neurol complications (53%), ring and annular abscesses, splenic and annular abscesses, splenic abscesses, bacteremic relapses, abscesses, bacteremic relapses, and rapidly progressive CHF are and rapidly progressive CHF are common. common.

many authorities recommend many authorities recommend early surgery for left-sided early surgery for left-sided PseudomonasPseudomonas endocarditis endocarditis

High-dose regimens of High-dose regimens of antipseudomonal penicillins antipseudomonal penicillins combined with aminoglycosides combined with aminoglycosides are used minimum 6 weeksare used minimum 6 weeks

Medical therapy works in Medical therapy works in P P aeruginosaaeruginosa IE involving the right IE involving the right side of the heart in 50% to 75%side of the heart in 50% to 75%

partial tricuspid valvulectomy or partial tricuspid valvulectomy or "vegetectomy“ if failure"vegetectomy“ if failure

quinolones (in combination quinolones (in combination with an aminoglycoside) with an aminoglycoside) appear promising, based on appear promising, based on favorable results in animal favorable results in animal models and humans, but models and humans, but development of stepwise development of stepwise resistance during therapy resistance during therapy may limit the efficacy may limit the efficacy

ceftazidime-tobramycin is ceftazidime-tobramycin is preferred over aztreonam-preferred over aztreonam-tobramycintobramycin

7 cases of 7 cases of P aeruginosaP aeruginosa endocarditis have been endocarditis have been successfully treated with successfully treated with imipenem plus an imipenem plus an aminoglycosideaminoglycoside

potential for the potential for the development of resistance development of resistance exists with any of these exists with any of these regimens.regimens.

Culture-negative IECulture-negative IE Why?Why?

Antibiotics priorAntibiotics prior Cover your bases i.e. Staph, Strep, enterococcusCover your bases i.e. Staph, Strep, enterococcus

Fastidious organism (Rocephin + gent +doxy)Fastidious organism (Rocephin + gent +doxy) BartonellaBartonella BrucellaBrucella Q feverQ fever Whipple’sWhipple’s ChlamydiaChlamydia

Not infectiousNot infectious MaranticMarantic AutoimmuneAutoimmune NeoplasticNeoplastic

Fungal IEFungal IE often a complication of often a complication of

medical and surgical medical and surgical advancesadvances

usually have multiple usually have multiple predisposing conditions predisposing conditions (cardiovascular devices, (cardiovascular devices, prosthetic cardiac valves prosthetic cardiac valves and central venous and central venous catheters) catheters)

mortality rates for fungal mortality rates for fungal endocarditis are very high. endocarditis are very high.

survival rate for patients survival rate for patients with mold-related with mold-related endocarditis is <20%. endocarditis is <20%.

CandidaCandida and and AspergillusAspergillus species account for the large species account for the large majoritymajority

Historically, is an Historically, is an indication for surgical indication for surgical replacement of an infected replacement of an infected valve. valve.

amphotericin B, a amphotericin B, a fungicidal agent, is the fungicidal agent, is the drug of choicedrug of choice

antifungal therapy usually antifungal therapy usually is given for 6 weeks. is given for 6 weeks.

long-term (lifelong) long-term (lifelong) suppressive therapy with suppressive therapy with an oral azole an oral azole

Predisposing Conditions in FE From:   Pierrotti: Chest, Volume 122(1).July 2002.302-310

Complications of FE

From:   Pierrotti: Chest, Volume 122(1).July 2002.302-310

Complications of IEComplications of IE CardiovascularCardiovascular

CHFCHF MIMI Mycotic aneurysmsMycotic aneurysms

EmbolicEmbolic CVACVA PeripheralPeripheral OrganOrgan

BowelBowel Peripheral arteriesPeripheral arteries spleenspleen