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• Cấy máu

• Huyết thanh học chẩn đoán

• Sinh học phân tử

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• Cấy máu là xét nghiệm chuẩn để xác định căn nguyên gây viêm nội tâm mạc.

• Hiệp hội tim Hoa Kỳ và hội tim châu âu, cấy máu nên cấy ít nhất 3 set từ 3 vị trí chọc ven khác nhau, cách nhau ít nhất 1 tiếng tính từ lần set đầu tiên và set cuối cùng.

• Hội hoá trị liệu Anh: cấy 2 set trong vòng 1 tiếng cho những bệnh

nhân nghi ngờ viêm nội tâm mạc và nhiễm khuẩn huyết cấp và 3 set cách nhau trên 6 tiếng trong trường hợp nghi ngờ viêm nội tâm mạc bán cấp và mạn tính.

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culture sets have been taken, or when infection affects a prosthetic valve or the right side of the heart.10 Recent amendments recognize the role of Q fever, increasing prevalence of staphylococcal infection and widespread use of TOE. The result- ant so-called modified Duke criteria are now recommended.11,12

2.4 The multidisciplinary team

Recommendation 2.10: A cardiologist and infection specialist should be closely involved in the diagnosis, treatment and follow-up of patients with IE. [C]

Recommendation 2.11: Specialist teams managing patients with IE should have rapid access to cardiac surgical services. [C]

There is no evidence to support these recommendations other than a widely held view that this represents good clinical care.

3. Microbiological diagnosis

3.1 Blood cultures

Recommendation 3.1: Blood cultures remain a cornerstone of the diagnosis of IE cases and should be taken prior to starting treatment in all cases. [B]

Recommendation 3.2: Meticulous aseptic technique is required when taking blood cultures, to reduce the risk of contamination with skin commensals, which can lead to misdiag- nosis. Guidelines for best practice should be consulted.13 [B]

Recommendation 3.3: In patients with a chronic or subacute presentation, three sets of optimally filled blood cultures should be taken from peripheral sites with ≥6 h between them prior to commencing antimicrobial therapy. [C]

Clinical suspicion of IE

TTE

Prosthetic valve intracardiac

device

Poor quality

TTE Positive Negative

Clinical suspicion of IE

High TOE

Low TOE Stop

If initial TOE is negative but suspicion for IE remains, repeat TOE within 7–10days

Figure 3. Indications for echocardiography in suspected infective endocarditis. IE, infective endocarditis; TTE, transthoracic echocardiography; TOE, transoesophageal echocardiography. TOE is not mandatory in isolated right-sided native valve IE with good quality TTE examination and unequivocal echocardiographic findings.

Valvular heart disease with stenosis or regurgitation

Valve replacement

Structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialized

Previous infective endocarditis

Hypertrophic cardiomyopathy

•

Figure 2. Cardiac conditions considered to increase a patient’s risk of developing infective endocarditis, i.e. ‘at risk’ heart valve lesions.5

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Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society

for Antimicrobial Chemotherapy

F. 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. Watkin7

1Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, UK;2National Aspergillosis Centre, University Hospital of South Manchester, Manchester, UK;3Department of Microbiology, Queen Elizabeth Hospital, Birmingham, UK;4Department of Microbiology, Papworth Hospital, Cambridge, UK;5Department of Cardiology, John Radcliffe Hospital, Oxford, UK;6Department of Microbiology, Leeds

Teaching Hospitals NHS Trust, Leeds, UK;7Department of Cardiology, Heart of England NHS Foundation Trust, Birmingham, UK

*Corresponding author. Tel:+44-191-223-1248; Fax:+44-191-223-1224; E-mail: kate.gould@nuth.nhs.uk The BSAC guidelines on treatment of infectious endocarditis (IE) were last published in 2004. The guidelines presented here have been updated and extended to reflect developments in diagnostics, new trial data and the availability of new antibiotics. The aim of these guidelines, which cover both native valve and prosthetic valve endocarditis, is to standardize the initial investigation and treatment of IE. An extensive review of the literature using a number of different search criteria has been carried out and cited publications used to support any changes we have made to the existing guidelines. Publications referring toin vitroor animal models have only been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking and therefore a consensus approach has again been adopted for most recommendations; however, we have attempted to grade the evidence, where possible. The guidelines have also been extended by the inclusion of sections on clinical diagnosis, echocardiography and surgery.

Keywords:antimicrobial therapy, staphylococci, enterococci,Streptococcusspp., fungal infections

Contents

1. Introduction

2. Clinical assessment and diagnosis 2.1 Clinical features

2.2 Echocardiography

2.3 Diagnostic criteria and their limitations 2.4 The multidisciplinary team 3. Microbiological diagnosis

3.1 Blood cultures 3.2 Susceptibility testing 3.3 Serology

3.4 Investigation of excised heart valves 4. The role of surgery

5. Antibiotic dosing, delivery and monitoring 5.1 Aminoglycosides

5.2 Glycopeptides 5.3b-Lactams

5.4 Alternative antibiotics for patients with penicillin allergy 5.5 Other antibiotics

5.6 Home therapy 5.7 Oral therapy

6. Empirical treatment regimens

7. Staphylococcal endocarditis 7.1 Native valve endocarditis 7.2 Prosthetic valve endocarditis 7.3 Duration of therapy 8. Streptococcal endocarditis 9. Enterococcal endocarditis 10. HACEK endocarditis 11. Q fever

12.Bartonellaendocarditis 13. Other Gram-negative bacteria 14. Fungal endocarditis

14.1Candidaendocarditis 14.2Aspergillusendocarditis 14.3 Endocarditis due to other fungi 14.4 General recommendations

1. Introduction

In 2004 the Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy (BSAC) published updated guidelines for the treatment of streptococcal, enterococcal and staphylococcal endocarditis, as well as HACEK (Haemophilus

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There is no evidence to support the commonly perpetuated view that blood cultures should be taken from different sites.

All skin surfaces are colonized by bacteria and adequate skin disinfection is key to reducing contamination. Taking blood cultures at different times is critical to identifying a constant bacteraemia, a hallmark of endocarditis.

Recommendation 3.4: In patients with suspected IE and severe sepsis or septic shock at the time of presentation, two sets of optimally filled blood cultures should be taken at different times within 1 h prior to commencement of empirical therapy, to avoid undue delay in commencing empirical antimicrobial therapy. [C]

This recommendation reflects recent evidence of improved outcomes in severe infection with rapid instigation of appropriate therapy.14 It is not always appropriate to withhold antimicrobial therapy while three sets of blood cultures are taken over a 12 h period. This recommendation is intended to be pragmatic, allow- ing time to take at least two sets of blood cultures (the minimum for a secure microbiological diagnosis) prior to commencing antimicrobial therapy. Taking three sets of blood cultures within 1 h does not add anything to the diagnostic pathway (which ideally attempts to confirm sustained/persistent bacteraemia).

Although modified Duke criteria specify 1 h between blood cultures, the Working Party did not feel that the evidence to support this criterion was sufficient to justify the inevitable delay in administering antibiotics.

Recommendation 3.5: Bacteraemia is continuous in IE rather than intermittent, so positive results from only one set out of several blood cultures should be regarded with caution. [B]

Recommendation 3.6: Sampling of intravascular lines should be avoided, unless part of paired through-line and peripheral sampling to diagnose concurrent intravascular catheter-related bloodstream infection.15 [B]

Recommendation 3.7: In groin-injecting intravenous drug users, a groin sinus should not be used to sample blood for culture. [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]

Previous ESC guidelines16and the experience of Working Party members indicate that blood cultures may only become positive in partially treated IE after 7–10 days off antibiotic therapy.

Recommendation 3.9: Routine incubation of blood cultures for >7 days is not necessary. [B]

In the previous BSAC guideline,1 the traditional recommendation for extended incubation and terminal subculture was main- tained to increase the yield of fastidious and slow-growing bacteria, although the evidence for this was tenuous in the era of automated continuous-monitoring blood culture systems. In the light of further data and the proven utility of complementary non-culture-based technologies, we feel that the case for extended incubation and blind subculture is not justified and therefore it is not recommended.17–19

Recommendation 3.10: Once a microbiological diagnosis has been made, routine repeat blood cultures are not recommended. [C]

Recommendation 3.11: Blood cultures should be repeated if a patient is still febrile after 7 days of treatment. [C]

3.2 Susceptibility testing

Recommendation 3.12: When the causative microorganism has been isolated, the MIC of the chosen antimicrobial should be established by a standardized laboratory method to ensure susceptibility.20 [C]

Recommendation 3.13: Gradient tests (such as Etest) may be useful for establishing the susceptibility of fastidious or slow-growing bacteria, such as the HACEK group.21 [B]

Recommendation 3.14: Routine measurement of the MBC or serum bactericidal titres is not required. [C]

As documented in previous guidelines, these measurements are affected by a range of technical factors that result in poor intralaboratory reproducibility and there remains a lack of evidence regarding their clinical value.

3.3 Serology

Failure to culture a causative microorganism in IE is often due to the administration of antimicrobials prior to blood culture, but may also be due to infection caused by fastidious or slow- growing microorganisms.22 Diagnostic methods should include serological investigations where they are available and a system- atic approach is advised, based on the clinical history of the patient and their exposure to possible risk factors.22–26

Recommendation 3.15: In patients with blood culture- negative IE, serological testing for Coxiella and Bartonella should be performed. [B]

Microorganisms that should be considered first include Coxiella burnetii (Q fever) and Bartonella spp. In a large study of 348 cases of blood culture-negative IE in France, the documented aetiological agent was C. burnetii and Bartonella spp.

in 48% and 28% of cases, respectively.26

Recommendation 3.16: In patients with blood culture- negative IE, routine serological testing for Chlamydia, Legion- ella and Mycoplasma should not be performed, but considered if serology in Recommendation 3.15 is negative. [C]

The combined total of infections attributed to Mycoplasma species, Legionella species and Tropheryma whipplei in a recent study amounted to ,1% of all culture-negative cases, and there were no cases in which Chlamydia species were implicated during an 18 year study period.26 IE due to Chlamydia is rarer than previously thought, owing to false-positive Chlamydia serology caused by antibodies to Bartonella.27 Endocarditis caused by these microorganisms is extremely rare and serology has not been shown to be of value. Given their rarity, there is also a significant risk of false-positive serology leading to erroneous therapy.

Recommendation 3.17: Consider Brucella in patients with negative blood cultures and a risk of exposure (dietary, occupational or travel). [C]

The serology of Q fever is considered positive when antiphase I IgG antibody titres are ≥1:800 and for Bartonella when anti- Bartonella quintana or anti-Bartonella henselae IgG antibody titres are ≥1:800.26 Serology may be useful for the diagnosis of IE caused by Brucella species in areas where the clinical history suggests exposure to this agent.24,28

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Baddour et al Infective Endocarditis in Adults 1439

With the guidance of the “diagnostic floor,” a number of these cases were reclassified as rejected for IE.24

Follow-up in these reclassified patients documented the specificity of this diagnostic schema because no patients developed IE during the subsequent 12 weeks of observation.

Thus, on the basis of the weight of clinical evidence involving nearly 2000 patients in the current literature, it appears that patients suspected of having IE should be clini- cally evaluated, with the modified Duke criteria as the primary diagnostic schema. It should be pointed out that the Duke criteria were originally developed to facilitate epidemiological and clinical research efforts so that investigators could com- pare and contrast the clinical features and outcomes of various case series of patients. Extending these criteria to the clinical practice setting has been somewhat more difficult. It should

also be emphasized that full application of the Duke criteria requires detailed clinical, microbiological, radiological, and echocardiographic queries. Because IE is a heterogeneous disease with highly variable clinical presentations, the use of these criteria alone will never suffice. Criteria changes that add sensitivity often do so at the expense of specificity and vice versa. The Duke criteria are meant to be a guide for diag- nosing IE and must not replace clinical judgment. Clinicians may appropriately and wisely decide whether or not to treat an individual patient, regardless of whether the patient meets or fails to meet the criteria for definite or possible IE by the Duke criteria. We believe, however, that the modifications of the Duke criteria (Tables 2 and 3) will help investigators who wish to examine the clinical and epidemiological features of IE and will serve as a guide for clinicians struggling with difficult diagnostic problems. These modifications require further validation among patients who are hospitalized in both community-based and tertiary care hospitals, with particular attention to longer-term follow-up of patients rejected as having IE because they did not meet the minimal floor criteria for possible IE.

The diagnosis of IE must be made as soon as possible to initiate appropriate empirical antibiotic therapy and to iden- tify patients at high risk for complications who may be best managed by early surgery. In cases with a high suspicion of IE based on either the clinical picture or the patient’s risk factor profile such as injection drug use, another focus of cardiovascular infection, including catheter-related bloodstream infections caused by S aureus, or a history of previous IE, the presumption of IE often is made before blood culture results are available. Identification of vegetations and incremental valvular insufficiency with echocardiography often com- pletes the diagnostic criteria for IE and affects the duration of therapy. Although the use of case definitions to establish a diagnosis of IE should not replace clinical judgment,46 the recently modified Duke criteria24 have been useful in both epidemiological and clinical trials and in individual patient management. Clinical, echocardiographic, and microbiological criteria (Tables 2 and 3) are used routinely to support a diagnosis of IE, and they do not rely on histopathological confirmation of resected valvular material or arterial embolus.

If suggestive features are absent, then a negative echocardiogram should prompt a more thorough search for alternative sources of fever and sepsis. In light of these important func- tions, at least 3 sets of blood cultures obtained from separate venipuncture sites should be obtained, with the first and last samples drawn at least 1 hour apart. In addition, echocardiography should be performed expeditiously in patients suspected of having IE.

Recommendations

1. At least 3 sets of blood cultures obtained from dif- ferent venipuncture sites should be obtained, with the first and last samples drawn at least 1 hour apart (Class I; Level of Evidence A).

2. Echocardiography should be performed expedi- tiously in patients suspected of having IE (Class I;

Level of Evidence A).

Table 3. Definition of Terms Used in the Modified Duke Criteria for the Diagnosis of IE*

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 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 (TEE recommended for patients with prosthetic valves, rated at least possible IE by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients) 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; abscess;

or new partial dehiscence of prosthetic valve or new valvular regurgitation (worsening or changing or pre-existing 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 lesions

Immunological phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor

Microbiological evidence: positive blood culture but does not meet a major criterion as noted above (excludes single positive cultures for coagulase- negative staphylococci and organisms that do not cause endocarditis) or serological evidence of active infection with organism consistent with IE Echocardiographic minor criteria eliminated

HACEK indicates Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species; IDU, injection drug use; IE, infective endocarditis; IgG, immunoglobulin G; TEE transesophageal echocardiography; and TTE, transthoracic echocardiography.

Modifications appear in boldface.

*These criteria have been universally accepted and are in current use.

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AHA Scientific Statement

1435

Background—Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today’s myriad healthcare- associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.

Methods and Results—This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations.

Conclusions—Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management. (Circulation. 2015;132:1435-1486. DOI: 10.1161/CIR.0000000000000296.) Key Words: AHA Scientific Statements ◼ anti-infective agents ◼ echocardiography ◼ endocarditis ◼ infection

(Circulation. 2015;132:1435-1486. DOI: 10.1161/CIR.0000000000000296.)

Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0000000000000296

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on May 12, 2015, and the American Heart Association Executive Committee on June 12, 2015. A copy of the document is available at http://my.americanheart.org/statements by selecting either the “By Topic” link or the “By Publication Date” link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.

The American Heart Association requests that this document be cited as follows: Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O’Gara P, Taubert KA; on behalf of the American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435–1486.

Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://my.americanheart.org/statements and select the “Policies and Development” link.

Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright- Permission-Guidelines_UCM_300404_Article.jsp. A link to the “Copyright Permissions Request Form” appears on the right side of the page.

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications

A Scientific Statement for Healthcare Professionals From the American Heart Association

Endorsed by the Infectious Diseases Society of America

Larry M. Baddour, MD, FAHA, Chair; Walter R. Wilson, MD; Arnold S. Bayer, MD;

Vance G. Fowler, Jr, MD, MHS; Imad M. Tleyjeh, MD, MSc;

Michael J. Rybak, PharmD, MPH; Bruno Barsic, MD, PhD; Peter B. Lockhart, DDS;

Michael H. Gewitz, MD, FAHA; Matthew E. Levison, MD; Ann F. Bolger, MD, FAHA;

James M. Steckelberg, MD; Robert S. Baltimore, MD; Anne M. Fink, PhD, RN;

Patrick O’Gara, MD, FAHA; Kathryn A. Taubert, PhD, FAHA; on behalf of the American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on

Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council

Infective endocarditis (IE) is an uncommon infectious disease with an annual incidence ranging from 3 to 7 per 100 000 person-years in the most contemporary population

surveys.1–3 Although relatively rare, IE continues to be char- acterized by increased morbidity and mortality and is now the third or fourth most common life-threatening infection

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drug use (4, 6, 7). Endocarditis associated with prosthetic valves or cardiovascular implantable electronic devices accounts for approximately one-third of cases and is most commonly caused by staphylococci (4, 7). Coagulase-negative staphylococci are more frequent causes of prosthetic versus native valve endocarditis, while viridans group streptococci more commonly cause native than prosthetic valve endocarditis.

Although the majority of endocarditis cases are community acquired, health care- associated endocarditis is increasing and now accounts for approximately one-third of endocarditis cases in North America (4). S. aureus, coagulase-negative Staphylococcus species, and enterococci are most frequently detected in health care-associated cases.

Organisms acquired in health care settings are notable for being increasingly resistant to antibacterial agents; methicillin-resistant S. aureus, for example, is more frequently associated with health care-acquired than community-acquired endocarditis, and most cases of endocarditis caused by non-HACEK Gram-negative bacilli are health care associated (8).

ROLE OF BLOOD CULTURES IN DIAGNOSIS OF INFECTIVE ENDOCARDITIS

Endocarditis is an endovascular infection associated with the persistent presence of infecting microorganisms in blood. For this reason, blood cultures are the standard test to determine the microbiologic etiology of infective endocarditis. Routine blood cultures incubated on modern automated, continuous-monitoring blood culture systems allow recovery of almost all easily cultivable agents of endocarditis without additional specialized testing, such as prolonged incubation or terminal subculture. Recommen- dations regarding the number and timing of blood cultures differ by guideline set. The American Heart Association and the European Society of Cardiology recommend at least three sets of blood cultures collected from different venipuncture sites, with at least 1 h between the first and last draw (1, 6). The British Society for Antimicrobial Chemotherapy (BSAC) recommends collection of two sets of blood cultures within 1 h of each other in patients with suspected endocarditis and acute sepsis and three sets of blood cultures spaced !6 h apart in cases of suspected subacute or chronic endocarditis (9). Conventionally, three sets of blood cultures, with each set including one aerobic and one anaerobic bottle, are collected. Alternatively, two sets may be collected, with two aerobic and one anaerobic bottle per set (i.e., a total of six blood culture bottles) (10). Yield of blood cultures is directly related to volume of blood cultured, with properly filled blood culture bottles (i.e., 10 ml of blood per Bactec or BacT/Alert bottle) being essential. Most, if not all, blood cultures from patients with endocarditis caused by microorganisms able to grow in blood culture systems should be positive, provided that blood cultures are appropriately collected and drawn prior to the administration of antimicrobial therapy; a single positive blood culture does not typically represent an endocarditis pathogen. Although the concept of spacing blood culture draws to detect continuous bacteremia is promulgated in the above-referenced guidelines, separation of blood culture draws over time is not the norm for routine blood culture draws. We are not aware of evidence supporting the value of spaced blood culture draws for etiologic diagnosis of endocarditis; for these reasons, we do not recommend routinely spacing blood culture draws in cases of suspected endocarditis.

Standard blood culture incubation times of 5 days are adequate for recovery of almost all cultivable causes of endocarditis, including Candida species. The HACEK organisms were classically considered challenging to detect in blood cultures due to their fastidious nature; accordantly, in the past, prolonged incubation times were advised. With current blood culture systems, extended incubation (and terminal blind subculture) is unnecessary for recovery of these organisms, as they are easily grown and detected within the standard 5-day incubation period (11, 12). Current blood culture systems also contain sufficient supplements to support growth of Abiotrophia and Granulicatella species (nutritionally variant streptococci). Brucella species are infrequent causes of endocarditis in the United States, and detection in routine blood cultures is typically achieved within the standard 5-day incubation period (13); notably, serologic testing may be helpful if exposures are suggestive of Brucella endocarditis. Cutibacte-

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Laboratory Diagnosis of Infective Endocarditis

Rachael M. Liesman,aBobbi S. Pritt,a,b,cJoseph J. Maleszewski,cRobin Patela,b Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology,aDivision of Infectious Diseases, Department of Medicine,band Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology,cMayo Clinic, Rochester, Minnesota, USA

ABSTRACT Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing, Tropheryma whippleiPCR) may be ap- plied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis.

KEYWORDS clinical microbiology, endocarditis

Despite recent advances in diagnostic and therapeutic strategies, the mortality of infective endocarditis remains high, with more than one-third of patients affected dying within a year following diagnosis (1, 2). Identification of the specific underlying microbial etiology is essential for optimal patient management; delays in microbial diagnosis may contribute to late initiation of effective antimicrobial therapy, influenc- ing morbidity and mortality. The modified Duke criteria provide a basic scheme for diagnosis and definition of endocarditis and rely on detection of infecting microorganisms in addition to echocardiographic and clinical findings (1, 3). The finding of two (or more) blood cultures positive for a typical microorganism consistent with infective endocarditis is a major criterion for infective endocarditis as is positive Q fever serology (anti-phase I IgG titer of!1:800). Echocardiographic findings are also considered but are beyond the scope of the manuscript.

The epidemiology of endocarditis, which has shifted in recent years, should guide diagnostic testing. Today, staphylococci and streptococci combined cause!80% of cases.Staphylococcus aureusremains the dominant pathogen, associated with!25% to

!30% of cases, while coagulase-negative staphylococci account for!11% of cases (4, 5). Streptococci, primarily viridans group streptococci, cause !30% of cases, with Streptococcus gallolyticus (a Streptococcus bovis group member) being involved in

!20% to !50% of streptococcal cases (4, 5). Enterococci, especially Enterococcus faecalis, account for!10% of cases (4, 5). Gram-negative bacilli account for!5% of cases and include the HACEK group organisms (Haemophilus,Aggregatibacter,Cardio- bacterium, Eikenella, and Kingella species) and, less commonly, non-HACEK Gram- negative bacilli, such as the Enterobacteriaceae and nonfermenting Gram-negative bacilli. Fungi are rare endocarditis causes, with Candida species being the most common. A number of uncultivable or challenging to cultivate organisms cause endocarditis, the most common of which areCoxiella burnetii,Bartonellaspecies, and Tropheryma whipplei.

Endocarditis most often involves the aortic or mitral valves, with tricuspid valve involvement accounting for fewer than 10% of cases often in association with injection

Accepted manuscript posted online28 June 2017

CitationLiesman RM, Pritt BS, Maleszewski JJ, Patel R. 2017. Laboratory diagnosis of infective endocarditis. J Clin Microbiol 55:2599 –2608.

https://doi.org/10.1128/JCM.00635-17.

Address correspondence to Robin Patel, patel.robin@mayo.edu.

MINIREVIEW

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Laboratory Diagnosis of Infective Endocarditis

ABSTRACT Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing,Tropheryma whipplei PCR) may be ap- plied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis.

KEYWORDS clinical microbiology, endocarditis

Endocarditis most often involves the aortic or mitral valves, with tricuspid valve involvement accounting for fewer than 10% of cases often in association with injection

Accepted manuscript posted online28 June 2017

CitationLiesman RM, Pritt BS, Maleszewski JJ, Patel R. 2017. Laboratory diagnosis of infective endocarditis. J Clin Microbiol 55:2599 –2608. https://doi.org/10.1128/JCM.00635-17. EditorColleen Suzanne Kraft, Emory University Copyright© 2017 American Society for Microbiology.All Rights Reserved. Address correspondence to Robin Patel, patel.robin@mayo.edu.

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Laboratory Diagnosis of Infective Endocarditis

ABSTRACT Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing, Tropheryma whipplei PCR) may be ap- plied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis.

KEYWORDS clinical microbiology, endocarditis

The epidemiology of endocarditis, which has shifted in recent years, should guide diagnostic testing. Today, staphylococci and streptococci combined cause !80% of cases.Staphylococcus aureusremains the dominant pathogen, associated with!25% to

!20% to !50% of streptococcal cases (4, 5). Enterococci, especially Enterococcus faecalis, account for !10% of cases (4, 5). Gram-negative bacilli account for!5% of cases and include the HACEK group organisms (Haemophilus,Aggregatibacter,Cardio- bacterium, Eikenella, and Kingella species) and, less commonly, non-HACEK Gram- negative bacilli, such as the Enterobacteriaceae and nonfermenting Gram-negative bacilli. Fungi are rare endocarditis causes, with Candida species being the most common. A number of uncultivable or challenging to cultivate organisms cause endocarditis, the most common of which areCoxiella burnetii,Bartonellaspecies, and Tropheryma whipplei.

Endocarditis most often involves the aortic or mitral valves, with tricuspid valve involvement accounting for fewer than 10% of cases often in association with injection

Accepted manuscript posted online28 June 2017

MINIREVIEW

crossm

September 2017 Volume 55 Issue 9 Journal of Clinical Microbiology jcm.asm.org 2599

on February 13, 2020 by guesthttp://jcm.asm.org/Downloaded from