Guidelines for the diagnosis and antibiotic treatment of ...

1 Guidelines for the diagnosis and antibiotic treatment of endocarditisin adults: a report of the Working Party of the British Societyfor Antimicrobial ChemotherapyF. Kate Gould1*, David W. Denning2, Tom S. J. Elliott3, Juliet Foweraker4, John D. Perry1, Bernard D. Prendergast5,Jonathan A. T. Sandoe6, Michael J. Spry1and Richard W. Watkin71 Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, UK;2 National Aspergillosis Centre, University Hospital of SouthManchester, Manchester, UK;3 Department of Microbiology, Queen Elizabeth Hospital, Birmingham, UK;4 Department of Microbiology,Papworth Hospital, Cambridge, UK;5 Department of Cardiology, John Radcliffe Hospital, Oxford, UK;6 Department of Microbiology, LeedsTeaching Hospitals NHS Trust, Leeds, UK;7 Department of Cardiology, Heart of England NHS Foundation Trust, Birmingham, UK*Corresponding author. Tel:+44-191-223-1248; Fax:+44-191-223-1224; E-mail: BSAC Guidelines on treatment of infectious endocarditis (IE) were last published in 2004.

2 The guidelinespresented here have been updated and extended to reflect developments in diagnostics, new trial data andthe availability of new antibiotics. The aim of these Guidelines , which cover both native valve and prostheticvalve endocarditis, is to standardize the initial investigation and treatment of IE. An extensive review of the lit-erature using a number of different search criteria has been carried out and cited publications used to supportany changes we have made to the existing Guidelines . Publications referring toin vitroor animal models haveonly been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the de-velopment of evidenced-based Guidelines in this area are still lacking and therefore a consensus approach hasagain been adopted for most recommendations; however, we have attempted to grade the evidence, wherepossible. The Guidelines have also been extended by the inclusion of sections on clinical diagnosis , echocardi-ography and :antimicrobial therapy, staphylococci, enterococci,Streptococcusspp.

3 , fungal infectionsContents1. Introduction2. Clinical assessment and Clinical Diagnostic criteria and their The multidisciplinary team3. Microbiological Blood Susceptibility Investigation of excised heart valves4. The role of surgery5. antibiotic dosing, delivery and Alternative antibiotics for patients with penicillin Other Home Oral therapy6. Empirical treatment regimens7. Staphylococcal Native valve Prosthetic valve Duration of therapy8. Streptococcal endocarditis9. Enterococcal endocarditis10. HACEK endocarditis11. Q Other Gram-negative bacteria14. Fungal Endocarditis due to other General recommendations1. IntroductionIn 2004 the Endocarditis Working Party of the British Societyfor Antimicrobial Chemotherapy (BSAC) published updatedguidelines for the treatment of streptococcal, enterococcal andstaphylococcal endocarditis, as well as HACEK (Haemophilus#The Author 2011.)

4 Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights Permissions, please e-mail: Antimicrob Chemother2012;67: 269 289 Advance Access publication 14 November 2011269 at Newcomb Library, Homerton Hospital on January 10, 2012 from spp.,Aggregatibacter actinomycetemcomitans,Cardiobacteriumhom inis,Eikenellaspp. andKingellaspp.), Q fever the light of the introduction of new antibiotic agents, develop-ments in diagnostics and new trial data, the existing guidelineshave been revised. In addition to considering the microbiologicaland therapeutic aspects of infective endocarditis (IE), we havenow included sections on clinical diagnosis , echocardiographyand surgery . The Guidelines include native valve endocarditis(NVE) and prosthetic valve endocarditis (PVE). For the purposesof these Guidelines , PVE includes prosthetic valves of all types,annuloplasty rings, intracardiac patches and shunts.

5 We haveexcluded IE where it is related to pacemakers, defibrillators orventricular-assist devices, which are the subject of a separateBSAC Working Party review. The aim of these Guidelines is tostandardize the initial investigation and treatment of IE;however, it is well recognized that patients can developadverse drug reactions to the recommended regimens and/orfail to respond to initial antimicrobial therapy and may requirea change in therapy. Several treatment options are thereforeprovided for most such as these have, in the past, received criticismfor not being evidence based. We appreciate that clinical guide-lines should ideally be based on high-quality, prospective, rando-mized controlled trials; however, few such trials have beenperformed to assess the benefit of antibiotic regimens in thetreatment of endocarditis. Since the last Guidelines were pub-lished, there has been at least one randomized controlled trialthat included patients with endocarditis.

6 Therefore, for the firsttime we have graded the evidence for our recommendations,although the majority remain based on clarity, recommendations are presented in bold text, andthroughout this document we have inserted identifying lettersafter recommendations to identify their provenance. Theseletters are: A, high-quality randomized controlled trials andmeta-analysis of randomized controlled trials; B, observationaldata and non-randomized trials; and C, expert opinion orWorking Party extensive review of the literature using a number ofdifferent search methods incorporating a range of criteria( endocarditis, staphylococci) has been carried out and citedpublications used to support any changes we have made to theexisting Guidelines . Publications referring toin vitroor animalmodels have only been cited if appropriate clinical data are notavailable. The text has been largely confined to justification forchanges to previous recommendations and differences fromEuropean Society for Cardiology (ESC) Clinical assessment and Clinical featuresRecommendation : IE should be considered and activelyinvestigated in patients with any of the criteria shown inFigure1.

7 [B/C]The diverse nature and evolving epidemiological profile of IEensure it remains a diagnostic challenge and delayed ormissed diagnoses continue to be a this reasonwe have attempted to highlight key clinical scenarios where IEshould be considered. Initial investigation in this context mayinvolve appropriate blood culture or echocardiography or both,depending on the index of suspicion or the clinical presentation is highly variable, according tothe causative microorganism, the presence or absence ofpre-existing cardiac disease, and the presence of co-morbiditiesand risk factors for the development of IE. It may present asan acute, rapidly progressive infection, but also as a subacuteor chronic disease, with low-grade fever and non-specific symp-toms that may thwart or confuse initial assessment. Patientspresent to a variety of specialists who may consider a range ofalternative diagnoses, including chronic infection, rheumato-logical and autoimmune disease or malignancy.

8 The early andongoing involvement of a cardiologist and an infection specialistto guide investigation and management is highly majority ( 90%) of patientspresent with fever, often asso-ciated with systemic symptoms of chills, poor appetite and weightloss. Heart murmurs are found in up to 85% and new murmurshave been recently reported in 48%.3A pre-existing heartmurmur is frequently indicative of a pre-existing at risk valvularpathology and should heighten awareness of the possibility ofIE, while new valvular regurgitation is more specific for a diagnosisof IE in an appropriate clinical setting. Classic textbook signs maystill be seen in the developing world, but peripheral stigmata of IEare increasingly uncommon elsewhere, because patients general-ly present at an early stage of the disease. Immunologicalphenomena, such as splinter haemorrhages, Roth spots andglomerulonephritis, are now less common,3but emboli to brain,lung or spleen occur in 30% of patients and are often the present-ing feature.

9 A high index of suspicion and low threshold forinvestigation to exclude IE are therefore essential in at-riskgroups (see Figure2). Laboratory signs of infection, such as ele-vated C-reactive protein or erythrocyte sedimentation rate, leuco-cytosis, anaemia and microscopic haematuria, may be presentin patients with IE but are non-specific findings. Atypical presenta-tion ( absence of fever) is more common in the elderly,after antibiotic pre- treatment , in the immunocompromisedpatient4and in IE involving less virulent or atypical diagnosis of IE should also be considered in patients whopresent with a stroke or transient ischaemic attack and a EchocardiographyRecommendation : Echocardiography must be performedas soon as possible (ideally within 24 h) in all patients withsuspected IE. [C]Recommendation : Transthoracic echocardiography (TTE)is the initial investigation of choice (Figure3).

10 [C]Recommendation : In cases with an initially negativeTTE/transoesophageal echocardiography (TOE) examination,repeat TTE/TOE should be performed 7 10 days later if theclinical suspicion of IE remains high. [C]Recommendation : All patients withStaphylococcusaureusbacteraemia or candidaemia require echocardiography(ideally within the first week of treatment or within 24 h ifthere is other evidence to suggest IE). [B]Recommendation : TTE is recommended at completionof antibiotic therapy for evaluation of cardiac and valvemorphology and function. [C]Recommendation : Follow-up echocardiography shouldbe performed if there is evidence of cardiac complications orReview270 at Newcomb Library, Homerton Hospital on January 10, 2012 from a suboptimal response to treatment the timing and mode ofassessment (TTE or TOE) is a clinical decision. [B]6 Recommendation : Routine repeat echocardiographywhile in therapy is not required.