KEYNOTE Infective Endocarditis (IE)...

Infective Endocarditis (IE)

Jonathan SandoeConsultant Microbiologist

Leeds Teaching Hospitals NHS Trust

BSAC Endocarditis workshop

Introduction

BSAC endocarditis working party has revised the 2004 guidelines in light of new evidence, particularly in relation to diagnosis and new treatment options.

This lecture highlights some changes and explains some more controversial recommendations.

(Thornhill, 2011)©2011 by British Medical Journal Publishing Group


IntroductionThe incidence of IE is increasing

Monthly number of cases of IE. Separate lines for linear trend (Blue line) within 2 standarddeviations (broken lines). Red lines represent moving average figure for number of cases every three months


IntroductionType of IE (%)

Type of IE N America Europe

Native valve 72 74Prosthetic valve 20 20Pacemaker, ICD 8 7

(Murdoch, 2009)

Implantable electronic cardiac device (pacemaker, ICD) infections have their own complexities and are the subject of a separate guideline project.


Clinical Assessment and diagnosis2.1 scenarios

Recommendation 2.1 contains a number of commonscenarios in which IE should be considered andactively investigated.

Justification:• Diagnosing IE remains difficult• Diagnoses often delayed• Speeding up diagnosis may improve outcomes

Notes: “actively investigated” may mean initial bloodcultures or echocardiography or both

Sign %Fevers >38oC 96%

Splinter haemorrhages 8%

Oslers nodes 3%

Janeway lesions 5%

Roth spots 2%

Conjunctival haemorrhages 5%

Splenomegaly 11%

New murmur 48%

(Murdoch, 2009)


Clinical Assessment and diagnosis2.1 scenarios‐ ”classic” signs are now uncommon


Clinical Assessment and diagnosis2.2 Echocardiography

• Echocardiography is a cornerstone of IE diagnosis but is neither 100% sensitive or specific

• TTE (70-80%) is less sensitive than TOE (90-100%)

• Multiple scans may be needed to identify vegetations


Clinical Assessment and diagnosis2.2 Echocardiography

*TOE is not mandatory in isolated right‐sided native valve IE with good quality TTE and unequivocal echocardiographic findings

Recommendation 2.1: Duke criteria can beused to assist in the diagnosis of IE but arenot a substitute for clinical judgment. [C]

• Duke criteria were developed as a research tool• They have high specificity but lower sensitivity


Clinical Assessment and diagnosis2.3 Diagnostic criteria and their limitations


3. Microbiological diagnosis3.1 Blood cultures

Recommendation 3.4• In patients with suspected IE and severe sepsis

or septic shock…two sets of optimally filled blood cultures should be taken at different times within an hour prior to commencement of empirical therapy, to avoid undue delay in commencing empirical antimicrobial therapy. [C]

Recommendation 3.8• If a stable patient has suspected IE but is

already on antibiotic treatment, consideration should be given to stopping treatment and performing three sets of blood cultures off antibiotics.

• Antibiotic therapy may need to be stopped for 7-10 days before blood cultures become positive. [C]


3. Microbiological diagnosis3.1 Blood cultures

Vegetations109 bacteria/g tissue


3. Microbiological diagnosis3.4 Investigation of excised heart valves

Recommendation 3.21Samples of excised heart valve (or tissue from embolectomy) from cases of culture negative IE should be referred for broad range PCR and sequencing. [B]


3. Microbiological diagnosis3.4 Investigation of excised heart valves

Recommendation 3.22A positive broad range PCR result can be reliably usedto identify the cause of endocarditis but cannot beused to infer ongoing presence of infection and shouldnot therefore be used alone to judge the duration ofpost operative antimicrobial therapy. [B]

Recommendation 5.11• IE patients need to be generally suitable…Recommendation 5.12• IE patients who might be considered for OPAT

would include those: who are stable andresponding well to therapy; without signs ofheart failure; without any of the indications forsurgery listed in Table 4; or, uncontrolled extra-cardiac foci of infection. [C]

BSAC Endocarditis workshop5. ANTIBIOTIC DOSING, DELIVERY AND MONITORING5.6 Home/community/outpatient therapy (OPAT)

Recommendation 5.13• IE caused by any organism may be appropriate for

OPAT provided the conditions in recommendation 5.12are satisfied, however, Staphylococcus aureus is themicroorganism associated with highest mortality andcomplications and caution is therefore advised wherethis is the cause. [C]

Recommendation 5.15• When patients are managed using OPAT, systems

should be in place to monitor the patient’s clinicalcondition on a daily basis. [C]

BSAC Endocarditis workshop5. ANTIBIOTIC DOSING, DELIVERY AND MONITORING5.6 Home/community/outpatient therapy (OPAT)

Antimicrobial Dose/route Comment 1. NVE – indolent presentation Amoxicillin* AND (optional) gentamicin*

2g 4-hourly IV 1 mg/kg 12 hourly IV

If patient is stable, ideally await blood cultures. Better activity against enterococci and many HACEK microorganisms compared with benzyl penicillin. Use regimen 2. If genuine penicillin allergy.


6. Empirical Therapy - NVE

Most common causes of NVE in non‐IVDU are currently:Staphylococcus aureus (28%), coagulase negative staphylococci (9%), streptococci (35%) and enterococci (11%); 9% are culture negative (Murdoch, 2009).

Antimicrobial Dose/route Comment 2. NVE, severe sepsis (no risk factors for Enterobacteriaceae, Pseudomonas) Vancomycin* AND gentamicin*

dosed according to local guidelines, IV 1 mg/kg 12 hourly IV

In severe sepsis, staphylococci (including meticillin resistant staphylococci) need to be covered. If allergic/intolerant to vancomycin replace with daptomycin 6mg/kg 24 hourly IV If acute kidney injury present, use ciprofloxacin in place of gentamicin

3. NVE, severe sepsis AND risk factors for muti-resistant Enterobacteriaceae, Pseudomonas Vancomycin* AND Meropenem*

dosed according to local guidelines, IV 2g 8 hourly, IV

Will provide cover against staphylococci (including meticillin resistant staphylococci), streptococci, enterococci, HACEK and Enterobacteriaceae and Pseudomonas aeruginosa.


6. Empirical Therapy - NVE

4. Prosthetic valve endocarditis pending blood cultures, or with negative blood cultures. Vancomycin* AND gentamicin* AND rifampicin*

1g 12 hourly IV 1mg/kg 12 hourly IV 300-600mg 12-hourly po/iv

Use lower dose of rifampicin in severe renal impairment.


6. Empirical Therapy ‐ PVE

Recommendation unchanged from previous.

Recommendation 7.2• Gentamicin should not be added to

flucloxacillin for the initial treatment ofnative valve staphylococcal IE. [A]

• Unchanged from previous guidelines• Nephrotoxicity data analysed from daptomycin

vs comparator RCT (Cosgrove, 2009; Fowler, 2006)


7. Staphylococcal endocarditis

Figure 2. Time to a clinically significant decrease in creatinine clearance* (ASP, antistaphylococcal penicillin)

Cosgrove, 2009

*Cr Cl fall to <50ml/min if baseline >50ml/minOr reduction in Cr Cl 10ml/min if baseline <50ml/min

• RCT of daptomycin vs flucloxacillin or vancomycin plus low-dose gentamicin for Staphylococcus aureus bloodstream infection and IE


7. Staphylococcal endocarditis

(Fowler, 2006)


7. Staphylococcal endocarditisOutcomes (success at 42 days) of RCT

Type of IE Daptomycin Standard therapy

Uncomplicated right-sided endocarditis

3/6 1/4

Complicated right-sided endocarditis 5/13 6/12

Left-sided endocarditis¶ 1/9 2/9

(Fowler, 2006)


8. Streptococcal endocarditis

Treatment of streptococci (penicillin MIC >0.125 - ≤0.5)

7 Benzyl Penicillin

AND

Gentamicin

2.4g 4-hourly IV

1mg/kg 12

hourly IV

4-6

2

Preferred regimen,

particularly for patients at risk

of C. difficile.


Treatment - enterococci

Recommendation 9.3• There should be a low threshold for

stopping gentamicin in patients withdeteriorating renal function or other signsof toxicity. [B]


Concluding comments

• New evidence justifies new approaches to diagnosis and treatment of endocarditis

• Changing resistance patterns and microbial aetiology complicate current therapy –particularly among staphylococci.

KEYNOTE Infective Endocarditis (IE)...

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