Guidelines on Prevention, Diagnosis and Treatment of Infective Endocarditis Executive Summary

The Task Force on Infective Endocarditis of the European Society of Cardiology

Task Force Members, Dieter Horstkotte, Chairperson, (Germany)*, Ferenc Follath, (Switzerland), Erno Gutschik, (Denmark), Maria Lengyel, (Hungary), Ali Oto, (Turkey), Alain Pavie, (France), Jordi Soler-Soler, (Spain), Gaetano Thiene, (Italy) and Alexander von Graevenitz, (Switzerland)

ESC Committee for Practice Guidelines (CPG), Silvia G. Priori, (Chairperson) (Italy), Maria Angeles Alonso Garcia, (Spain), Jean-Jacques Blanc, (France), Andrzej Budaj, (Poland), Martin Cowie, (UK), Veronica Dean, (Greeve), Jaap Deckers, (The Netherlands), Enrique Fernández Burgos, (Spain), John Lekakis, (Greece), Bertil Lindahl, (Sweden), Gianfranco Mazzotta, (Italy), João Morais, (Portugal), Ali Oto, (Turkey) and Otto A. Smiseth, (Norway)

Document Reviewers, John Lekakis, CPG Review Coordinator (Greece), Alec Vahanian, (France), François Delahaye, (France), Alexander Parkhomenko, (Ukraine), Gerasimos Filipatos, (Greece), Jan Aldershvile, (Denmark) and Panos Vardas, (Greece)

* Corresponding author: Chairperson: Dieter Horstkotte, MD, FESC, Professor and Head Department of Cardiology, Heart Center North Rhine-Westphalia, Ruhr University Bochum, Georgstr. 11, D-32545 Bad Oeynhausen, Germany. Tel.: +49-5731-971258; Fax: +49-5731-972194
E-mail address: akohlstaedt{at}hdz-nrw.de

Table of contents

Preamble
Introduction
Definitions, terminology
Prevention of infective endocarditis
    Cardiac condit
    Patient-related non-cardiac conditions
    Predisposing diagnostic and therapeuticinterventions
Prophylactic antibiotic regimens
Diagnosis
    History, symptoms, signs and laboratory tests
    Echocardiography
    Standard blood culture techniques
    Culture-negative endocarditis (CNE)
Treatment and management
    Antimicrobial therapy
    Drug level monitoring
    Empirical therapy
    Special subsets
Management of complications
Surgery for active NVE
Surgery for active PVE
    Postoperative antibiotic treatment
List of Abbreviations
Further Reading

1. Preamble

Guidelines and Expert Consensus documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making.

A great number of Guidelines and Expert Consensus Documents have been issued in recent years by different organizations, the European Society of Cardiology (ESC) and by other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents.

In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined, recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied within the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources.

The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.

Level of recommendations and evidence



Strength ofrecommendation


Definition

Class I Evidence and/or general agreement that a given treatment or a diagnostic approach is beneficial, useful and effective
Class II Conflicting evidence and/or a divergence of opinions about the usefulness/efficacy of a treatment or a diagnostic measure
IIa Weight of evidence/opinion is in favour of usefulness/efficacy
IIb Usefulness/efficacy is less well established by evidence/opinion
Class III

Evidence or general agreement that the treatment/diagnostic measure is not useful/effective and in some cases may be harmful



Level ofevidence


Available evidence

A At least two randomized trials supporting the recommendation
B Single randomized trial and/or a meta-analysis of non-randomized studies supporting the recommendation
C

Consensus opinion of experts based on trials and clinical experience

2. Introduction

If untreated, Infective Endocarditis (IE) is a fatal disease. Major diagnostic (first of all echocardiography) and therapeutic progress (mainly surgery during active IE) have contributed to some prognostic improvement during the last decades. If the diagnosis is delayed or appropriate therapeutic measures postponed, mortality is still high. In this respect, it is of utmost importance that (a) IE is considered early in every patient with fever or septicaemia and cardiac murmurs; (b) echocardiography is applied without delay in suspected IE; (c), cardiologists, microbiologists and cardiac surgeons cooperate closely if IE is suspected or definite.

3. Definitions, terminology

IE is an endovascular, microbial infection of intracardiac structures facing the blood including infections of the large intrathoracic vessels and of intracardiac foreign bodies. The early characteristic lesion is a variably sized vegetation, although destruction, ulceration or abscess formation may be seen earlier by echocardiography.

Terminology (Table 1) should give the following information: (a), activity of the disease and recurrence; (b), diagnostic status; (c), pathogenesis; (d), anatomical site; and (e), microbiology.

4. Prevention of infective endocarditis

For prophylactic reasons, antibiotics should be given before a bacteraemia is expected. If antibiotic prophylaxis is not given prior to this event, antibiotics may help a late clearance if administered intravenously within 2–3h.

4.1. Cardiac conditions/patients at risk
A previous history of IE, the presence of prosthetic heart valves or otherforeign material, surgically created conduits, and complex cyanotic congenital abnormalities are considered high-risk situations. Only patients with high or moderate risk (Table 2) should receive prophylaxis. This is a class I recommendation based on level C evidence.


View this table:
[in this window]
[in a new window]
 
Table 1 Terminology for infective endocarditis (IE). Examples: active mitral valve IE due to Enterococcus faecalis; healed recurrent prosthetic aortic valve endocarditis due to Staphylococcus epidermidis; suspected culture-negative late prosthetic mitral valve endocarditis

 

View this table:
[in this window]
[in a new window]
 
Table 2 Cardiac conditions in which antimicrobial prophylaxis is indicated

 
4.2. Patient-related non-cardiac conditions
Older age, conditions (a), promoting non-bacterial thrombotic vegetation; (b), compromising host defense; (c), compromising local non-immune defence mechanisms; and (d), increased risk/frequency/amount of bacteraemia are considered patient related, non-cardiac risk conditions.

4.3. Predisposing diagnostic and therapeutic interventions
Procedures which may cause bacteraemia and for which antimicrobial prophylaxis is recommended are given in Table 3. Prophylaxis is not recommended for cardiac catheterization.


View this table:
[in this window]
[in a new window]
 
Table 3 Diagnostic and therapeutic interventions likely to produce bacteraemia

 
Dental hygiene is of major importance for the prevention of IE.

5. Prophylactic antibiotic regimens

Prophylaxis aims primarily at viridans streptococci and HACEK organisms before dental, oral, respiratory, and oesophageal procedures, and at enterococci and Streptococcus bovis before gastrointestinal and genitourinary procedures. Despite a lack of convincing evidenceantibiotic prophylaxis (Table 4) is a class I recommendation (based on level C evidence).


View this table:
[in this window]
[in a new window]
 
Table 4 Prophylactic antibiotic regimens

 
6. Diagnosis

6.1. History, symptoms, signs and laboratory tests
The diagnosis of IE is established (definite IE) if during a systemic infection involvement of the endocardium is demonstrated. If, in addition, bacteraemia (positive blood cultures) or bacterial DNA are found, IE is definite and culture/microbiologically positive, otherwise IE is definite but culture/microbiologically negative (Table 5). Duke or modified Duke criteria may be used to make the diagnosis in otherwise unclear cases.


View this table:
[in this window]
[in a new window]
 
Table 5 Criteria that should raise suspicion of IE

 
6.2. Echocardiography
Any patient suspected of having NVE by clinical criteria should be screened by transthoracic echocardiography (TTE). When images are of good quality and prove to be negative and there is only a low clinical suspicion of IE, endocarditis is unlikely and other diagnoses are to be considered. If suspicion of IE is high, transoesophageal echocardiography (TEE) should be performed in all TTE-negative cases, in suspected PVE, and if TTE is positive but complications are suspected or likely and before cardiac surgery during active IE. If TEE remains negative and there is still suspicion, it should be repeated within one week. A repeatedly negative study should virtually exclude the diagnosis (Fig. 1). These class I recommendations are based on level B evidence.



View larger version (23K):
[in this window]
[in a new window]
 
Fig. 1 Algorithm for the use of transthoracic (TTE) and transoesophageal echocardiography (TEE) in suspected IE. N.B. TTE "positive" indicates finding typical of IE (e.g. fresh vegetation or abscess formation)

 
Three echocardiographic findings are considered to be major criteria in the diagnosis of IE: (a), a mobile, echodense mass attached to the valvular or the mural endocardium or to implanted prosthetic material; (b), demonstration of abscesses or fistulas; (c), a new dehiscence of a valve prosthesis, especially when occurring late after implantation.

6.3. Standard blood culture techniques
Three or more blood cultures (BC) should be taken irrespective of body temperature at least 1h apart. If the patient has been on short-term antibiotics, one should wait, if possible, at least for three days after discontinuing antibiotic treatment before new BCs are taken. Blood cultures after long-term antibiotic treatment may not become positive after treatment has been discontinued for 6–7 days.

One BC consists of one aerobic and one anaerobic bottle, each containing approx. 50ml of medium (less in pediatric BC bottles). Venous blood, minimally 5ml and better 10ml in adults and 1–5ml in children should be added to each bottle. Minimum inhibitory concentrations should be determined for the drugs of choice.

6.4. Culture-negative endocarditis (CNE)
The most frequent cause of CNE is previous antimicrobial treatment. If traditional (non-automatic) BC systems are used, longer incubation periods (>6 days) are required when organisms of the HACEK group, Propionibacterium spp., Neisseria spp., Brucella, Abiotrophia spp., or Campylobacter spp. are suspected. Especially in CNE all material excised during cardiac surgery for active IE should also be cultured and examined.

The value of serology has been proven for IE due to Bartonella, Legionella, Chlamydia (immunofluorescence) and Coxiella burnetii.

The use of broad-spectrum polymerase chain reaction (PCR) provides a significant improvement in thecapability to detect difficult-to-culture organisms and even dead bacteria.

7. Treatment and management

7.1. Antimicrobial therapy
For treatment strategies refer to Tables 6–9.


View this table:
[in this window]
[in a new window]
 
Table 6 Decision making for antibiotic treatment of native (NVE) and prosthetic valve endocarditis (PVE) due to streptococci

 

View this table:
[in this window]
[in a new window]
 
Table 7 Decision-making for antibiotic treatment of IE due to enterococci and penicillin-resistant streptococci

 

View this table:
[in this window]
[in a new window]
 
Table 8 Decision-making for antibiotic treatment of IE due to staphylococci

 

View this table:
[in this window]
[in a new window]
 
Table 9 Antimicrobial treatment in CNE or if therapy is urgent and the causative organism unidentified

 
All patients with streptococcal IE should be treated for at least 2 weeks in hospital and observed for cardiac and non-cardiac complications. Patients may then be candidates for outpatient and home parenteral antibiotic therapy. Treatment recommendations for streptococcal IE are based on consistent results of a large number of studies (class I recommendation based on level B evidence).

IE caused by methicillin-resistant S. aureus (MRSA) is a therapeutic challenge as most strains are also resistant to most aminoglycosides. If the clinical course is complicated, treatment should be as for PVE.

Coagulase-negative species (CONS) causing PVE within the first year after valve replacement are usually methicillin-resistant. Therapy of choice is a combination of vancomycin and rifampicin for at least 6 weeks with the addition of gentamicin for the initial 2 weeks.

Despite lacking randomized studies and thus level A evidence, the scientific material available is convincing and allows for a class I recommendation.

Enterococci are generally resistant to a wide range of antimicrobial agents including aminoglycosides (MIC for gentamicin 4–64mg/l). (Table 7)

Duration of treatment should be at least 4 weeks for the combination and at least 6 weeks in complicated cases, in patients having symptoms for more than 3 months, and in patients with PVE. These class IIarecommendations are based on level B evidence.

7.2. Drug level monitoring
Gentamicin trough levels should be less than 0.1mg/l to avoid renal or ototoxic effects.

Optimum vancomycin effects are achieved if serum concentrations are continuously kept at least 2–4 times above the MIC of the causative organism. Trough levels should be at least 10–15mg/l. In patients with normal renal function, drug levels should be controlled once, but 2–3 times weekly if combined with aminoglycosides.

7.3. Empirical therapy
In cases complicated by sepsis, severe valvular dysfunction, conduction disturbances, or embolic events, empirical antimicrobial therapy should be started after three blood cultures have been taken (see standard blood culture techniques section).

Recommendations for empirical antibiotic treatment (before microbiologic test results are available) and CNE are given in Table 9.

7.4. Special subsets
Antimicrobial therapy for infections of permanently implanted pacemakers or ICD leads are based on culture and susceptibility results. Duration of therapy should be 4–6 weeks in most cases. Removal of the entire system is generally recommended.

In intravenous drug abusers (IVDAs), a methicillin-susceptible S. aureus (MSSA) is the causative organism in about 60–70% of cases. The tricuspid valve is affected in more than 70%. The most common organism (S. aureus) must always be covered by the antibiotic regimen. Treatment will include either penicillinase-resistant penicillins or vancomycin, depending on the local prevalence of MRSA. If the patient is a pentazocine addict, an antipseudomonas agent should be added. If IVDAs use brown heroine dissolved in lemon juice, Candida should be considered and antifungal treatment added. In IVDAs with underlying valve lesions and/or left-sided involvement, antibiotic treatment against streptococci and enterococci must be added.

8. Management of Complications

Rapid and effective antimicrobial treatment may help to prevent embolism. If the patient is on long-term oral anticoagulation, coumarin therapy should be discontinued and replaced by heparin immediately after thediagnosis of IE has been established.

After an embolic complication, the risk for recurrent episodes is high. After manifestation of a cerebral embolism, cardiac surgery to prevent a recurrent episode is not contraindicated if performed early (best within 72h) and cerebral haemorrhage has been excluded by cranialcomputed tomography immediately before the operation. If surgery is not performed early it is advisable to be postponed for 3–4 weeks.

9. Surgery for active NVE

The following indications for urgent valve surgery are accepted:

If vegetations are larger than 10mm on the mitral valve or if they are increasing in size despite antibiotic therapy or if they represent mitral kissing vegetations, early surgery should also be considered.

The prognosis of right-sided IE is favourable. Surgery is necessary if tricuspid vegetations are larger than 20mm after recurrent pulmonary emboli.

10. Surgery for active PVE

The following indications are accepted:

10.1. Postoperative antibiotic treatment
A full course of antimicrobial treatment should be completed regardless of the duration of treatment prior to surgery, but at least 7–15 days postoperatively.

11. List of Abbreviations

  1. Atrial septal defect
  2. Blood culture
  3. Culture-negative endocarditis
  4. Coagulase-negative staphylococci
  5. Group of bacteria consistent of Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae
  6. High level resistance
  7. Implantable cardioverter defibrillator
  8. Infective endocarditis
  9. Intravenous drug abuser
  10. Minimal inhibitory concentration
  11. Methicillin-resistant Staphylococcus aureus
  12. Methicillin-sensitive Staphylococcus aureus
  13. Native valve endocarditis
  14. Polymerase chain reaction
  15. Prosthetic valve endocardits
  16. Plural of ‘species’
  17. Transoesophageal echocardiography
  18. Transthoracic echocardiography

1 The Endocarditis Working Group of the International Society of ChemotherapyPettersson G, Carbon C. Recommendations for the surgical treatment of endocarditis. Clin Microbiol Infect. 1998;4(Suppl 3):S34–46.[Medline]
2 Renzulli A, Carozza A, Romano G et al. Recurrent infective endocarditis: a multivariate analysis of 21 years of experience. Ann Thorac Surg. 2001;72:39–43.[Abstract/Free Full Text]
3 Karchmer AW, Gibbons GW. Infections of prosthetic heart valves and vascular grafts. Bisno AL, Waldvogel FA. Infections associated with indwelling medical devices. 2nd edn. Washington DC: American Society for Microbiology; 1994. p. 213.
4 Horstkotte D, Piper C, Niehues R et al. Late prosthetic valve endocarditis. Eur Heart J. 1995;16(Suppl B):39–47.[Medline]
5 Selton-Suty Ch, Hoen B, Grentzinger A et al. Clinical and bacteriological characteristics of infective endocarditis in the elderly. Heart. 1997;77:260–263.[Abstract]
6 Durack DT, Towns ML. Diagnosis and management of infective endocarditis. In: Yusuf S, Camm AJ, Cairns JA et al. (eds), Evidence Based Cardiology. BMJ Books 1998:884–904..
7 Lamas CC, Eykyn SJ. Hospital acquired native valve endocarditis: analysis of 22 cases presenting over 11 years. Heart. 1998;79:442–447.[Abstract/Free Full Text]
8 Everett ED, Hirschmann JV. Transient bacteremia and endocarditis prophylaxis. A review. Medicine. 1977;56:61–77.[ISI][Medline]
9 Strom BL, Abrutyn E, Berlin JA et al. Dental and cardiac risk factors for infective endocarditis. Ann Intern Med. 1998;129:761–769.[Abstract/Free Full Text]
10 Durack DT. Prevention of infective endocarditis. N Engl J Med. 1995;332:38–44.[Free Full Text]
11 Horstkotte D, Rosin H, Friedrichs W et al. Contribution for choosing the optimal prophylaxis of bacterial endocarditis. Eur Heart J. 1987;8(Suppl J):379–381.[ISI]
12 Dajani AS, Taubert KA, Wilson W et al. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA. 1997;277:1794–1801.[Abstract]
13 Steckelberg JM, Murphy JG, Ballard D et al. Emboli in infective endocarditis: the prognostic value of echocardiography. Ann Intern Med. 1991;114:635–640.[ISI][Medline]
14 Li W, Somerville J. Infective endocarditis in the grown-up congenital heart (GUCH) population. Eur Heart J. 1998;19:166–173.[Abstract/Free Full Text]
15 Bonow RO, Carabello B, deLeon AC et al. ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 1998;32:1486–1588.[CrossRef][ISI][Medline]
16 The Endocarditis Working Group of the International Society of ChemotherapyLeport C. Antibiotic prophylaxis for infective endocarditis. Clin Microbiol Infect. 1998;4(Suppl 3):S56–S61.[Medline]
17 Grieve DA, Chen SC, Chapuis PH et al. Streptococcus bovis bacteraemia: its significance for the colorectal surgeon. Aust NZ J Surg. 1990;60:550–552.[Medline]
18 Lacassin F, Hoen B, Leport C et al. Procedures associated with infective endocarditis in adults. A case control study. Eur Heart J. 1995;16:1968–1974.[Abstract]
19 Steckelberg JM, Khandheria BK, Anhalt JP et al. Prospective evaluation of the risk of bacteremia associated with transesophageal echocardiography. Circulation. 1991;84:177–180.[Abstract]
20 Ho H, Zuckerman MJ, Wassem C. A prospective controlled study of the risk of bacteremia in emergency sclerotherapy of esophageal varices. Gastroenterology. 1991;101:1642–1648.[Medline]
21 Dajani AS, Bawdon RE, Berry MC. Oral amoxicillin as prophylaxis for endocarditis: what is the optimal dose? Clin Infect Dis. 1994;18:157–160.[Medline]
22 Rouse MS, Steckelberg JM, Brandt CM et al. Efficacy of azithromycin or clarithromycin for the prophylaxis of viridans group streptococcus experimental endocarditis. Antimicrob Agents Chemother. 1997;41:1673–1676.[Abstract]
23 Bayer AS, Nelson RJ, Slama TG. Current concepts in prevention of prosthetic valve endocarditis. Chest. 1990;97:1203–1207.[Medline]
24 Cheitlin MD, Alpert JS, Armstrong WF et al. ACC/AHA guidelines for the clinical application of echocardiography: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 1997;95:1686–1744.[Free Full Text]
25 Mügge A, Daniel WG, Frank G et al. Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol. 1989;14:631–638.[ISI][Medline]
26 Job FP, Franke S, Lethen H et al. Incremental value of biplane and multiplane transesophageal echocardiography for the assessment of active infective endocarditis. Am J Cardiol. 1995;75:1033–1037.[CrossRef][Medline]
27 Vuille C, Nidorf M, Weyman AE et al. Natural history of vegetations during successful medical treatment of endocarditis. Am Heart J. 1994;128:1200–1209.[ISI][Medline]
28 DeCastro S, d’Amati G, Cartoni D et al. Valvular perforation in left-sided infective endocarditis: a prospective echocardiographic evaluation and clinical outcome. Am Heart J. 1997;134:656–664.[Medline]
29 Erbel R, Liu F, Ge J, Rohmann S et al. Identification of high-risk subgroups in infective endocarditis and the role of echocardiography. Eur Heart J. 1995;16:588–602.[Abstract]
30 Leung DY, Cranney GB, Hopkins AP et al. Role of transesophageal echocardiography in the diagnosis and management of aortic root abscess. Br Heart J. 1994;72:175–181.[Abstract]
31 Choussat R, Thomas D, Isnard R et al. Perivalvular abscesses associated with endocarditis. Clinical features and prognostic factors of overall survival in a series of 233 cases. Eur Heart J. 1999;20:232–241.[Abstract/Free Full Text]
32 Piper C, Hetzer R, Körfer F et al. The importance of secondary mitral valve involvement in primary aortic valve endocarditis: The mitral kissing vegetation. Eur Heart J. 2002;23:79–86.[Abstract/Free Full Text]
33 Freedberg RS, Goodkin GM, Perez JL et al. Valve strands are strongly associated with systemic embolizaton: A transesophageal echocardiographic study. J Am Coll Cardiol. 1995;26:1709–1712.[CrossRef][ISI][Medline]
34 Vilacosta I, Sarriá C, San Román JA et al. Usefulness of transesophageal echocardiography for diagnosis of infected transvenous permanent pacemakers. Circulation. 1994;89:2684–2687.[Abstract]
35 Victor F, De Place C, Camus C et al. Pacemaker lead infection: echocardiographic features, management, and outcome. Heart. 1999;81:82–87.[Abstract/Free Full Text]
36 Reimer LG, Wilson ML, Weinstein MP. Update on detection of bacteremia and fungemia. Clin Microbiol Rev. 1997;10:444–465.[Abstract]
37 Pazin GJ, Saul S, Thompson E. Blood culture positivity. Suppression by outpatient antibiotic therapy in patients with bacterial endocarditis. Arch Int Med. 1982;142:263–268.[CrossRef]
38 The Endocarditis Working Group of the International Society of ChemotherapyGutschik E. Microbiological recommendations for the diagnosis and follow-up of infective endocarditis. Clin Microbiol Infect. 1998;4(Suppl 3):S10–S16.[Medline]
39 Von Reyn CF, Levy BS, Arbeit RD et al. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med. 1981;94:505–518.[ISI][Medline]
40 The Duke Endocarditis ServiceDurack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings. Am J Med. 1994;96:200–209.[ISI][Medline]
41 Bayer AS, Ward JI, Ginzton LE et al. Evaluation of new clinical criteria for the diagnosis of infective endocarditis. Am J Med. 1994;96:211–219.[ISI][Medline]
42 Habib G, Derumeaux G, Avierinos JF et al. Value and limitations of the Duke criteria for the diagnosis of infective endocarditis. J Am Coll Cardiol. 1999;33:2023–2029.[CrossRef][ISI][Medline]
43 Li JS, Sexton DJ, Mick N et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633–638.[CrossRef][ISI][Medline]
44 Wilson ML, Mirrett S, Reller LB et al. Recovery of clinically important microorganisms from in the BacT/Alert blood culture system does not require testing for seven days. Diagn Microbiol Infect Dis. 1993;16:31–34.[CrossRef][Medline]
45 Burnie JP, Clark I. Immunoblotting in the diagnosis of culture negative endocarditis caused by streptococci and enterococci. J Clin Pathol. 1995;48:1130–1136.[Abstract]
46 Siegman-Igra Y, Kaufman O, Keysary A et al. Q fever endocarditis in Israel and a worldwide review. Scand J Infect Dis. 1997;29:41–49.[ISI][Medline]
47 Woods GL, Wood RP, Shaw BW Jr. Aspergillus endocarditis in patients without prior cardiovascular surgery: report of a case in a liver transplant recipient and review. Rev Infect Dis. 1989;11:263–272.[Medline]
48 Goldenberger D, Künzli A, Vogt P et al. Molecular diagnosis of bacterial endocarditis using broad-range PCR amplification and direct sequencing. J Clin Microbiol. 1997;35:2733–2739.[Abstract]
49 Climo MW, Patron RL, Archer GL. Combinations of vancomycin and ß-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin. Antimicrob Agents Chemother. 1999;43:1747–1753.[Abstract/Free Full Text]
50 Kim WJ, Weinstein RA, Hayden MK. The changing molecular epidemiology and establishment of endemicity of vancomycin resistance in enterococci at one hospital over a 6-year period. J Infect Dis. 1999;179:163–171.[CrossRef][ISI][Medline]
51 Working Party of the British Society for Antimicrobial Chemotherapy. Antibiotic treatment of streptococcal, enterococcal, and staphylococcal endocarditis. Heart. 1998;79:207–210.[Free Full Text]
52 Shanson DC. New guidelines for the antibiotic treatment of streptococcal, enterococcal and staphylococcal endocarditis. J Antimicrob Chemother. 1998;42:292–296.[Free Full Text]
53 The Endocarditis Working Group of the International Society for ChemotherapyWilson WR. Antibiotic treatment of infective endocarditis due to viridans streptococci, enterococci, and other streptococci. Clin Microbiol Infect. 1998;4(Suppl 3):S17–S26.[Medline]
54 Bugnon D, Potel G, Xiong YQ et al. In vivo antibacterial effects of simulated human serum profiles of once-daily versus thrice-daily dosing of amikacin in a Serratia marcescens endocarditis experimental model. Antimicrob Agents Chemother. 1996;40:1164–1169.[Abstract]
55 Sexton DJ, Tenenbaum MJ, Wilson WR et al. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group. Clin Infect Dis. 1998;27:1470–1474.[ISI][Medline]
56 Hessen MT, Pitsakis PG, Levison ME. Postantibiotic effect of penicillin plus gentamicin versus Enterococcus faecalis in vitro and in vivo. Antimicrob Agents Chemother. 1989;33:608–611.[ISI][Medline]
57 Renneberg J, Niemann LL, Gutschik E. Antimicrobial susceptibilityof 278 streptococcal blood isolates to seven antimicrobial agents. J Antimicrob Chemother. 1997;39:135–140.[Abstract]
58 Moellering RCJ. Treatment of endocarditis caused by resistant streptococci. Horstkotte D, Bodnar E. Infective Endocarditis. 2nd edn. Aylesburay, Bucks, England: ICR Publishers; 1991. p. 102–109.
59 On behalf of the OHPAT UK WorkshopNathwani D, Conlon C. Outpatient and home parenteral antibiotic therapy (OHPAT) in the UK: a consensus statement by a working party. Clin Microbiol Infect. 1998;4:537–551.
60 The Endocarditis Working Group of the International Society for ChemotherapyFrancioli PB, Stamboulian D. Outpatient treatment of infective endocarditis. Clin Microbiol Infect. 1998;4(Suppl 3):S47–S55.[Medline]
61 Piper C, Wiemer M, Schulte HD et al. Stroke is not a contraindication for urgent valve replacement in acute infective endocarditis. J Heart Valve Dis. 2001;10:703–711.[Medline]
62 Roder BL, Wandall DA, Frimodt-Moller N et al. Clinical featues of Staphylococcus aureus endocarditis: a 10-year experience in Denmark. Arch Intern Med. 1999;159:462–469.[Abstract/Free Full Text]
63 Tornos P, Almirante B, Mirabet S et al. Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy. Arch Intern Med. 1999;159:473–475.[Abstract/Free Full Text]
64 Bonow RO, Carabello B, de Leon AC Jr. et al. Guidelines for the management of patients with valvular heart disease: executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation 1998;98:1949–84.
65 Etienne J, Eykin SJ. Increase in native valve endocardiits caused by coagulase-negative staphylococci. An Anglo-French clinical and microbiological study. Br Heart J. 1990;64:381–384.[Abstract]
66 Wilson WR, Karchmer AW, Dajani AS et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. JAMA. 1995;274:1706–1713.[Abstract]
67 Gutschik E. New developments in the treatment of infective endocarditis and infective cardiovasculitis. Int J Antimicrobial Agents. 1999;13:79–83.[CrossRef][Medline]
68 Ellis M. Fungal endocarditis. J Infect. 1997;35:99–103.[CrossRef][Medline]
69 Piper C, Körfer R, Horstkotte D. Prosthetic valve endocarditis. Heart. 2001;85:590–593.[Free Full Text]
70 Lutwick LI, Vaghjimal A, Connolly MW. Postcardiac surgery infections. Crit Care Clin. 1998;14:221–250.[ISI][Medline]
71 Smart FW, Naftel DC, Constanzo MR et al. Risk factors for early cumulative and fatal infections after heart transplantation: A multiinstitutional study. J Heart Lung Transplant. 1996;15:329–341.[Medline]
72 Mull DH, Wait MA, Page RL et al. Importance of complete system removal of infected cardioverter-defibrillators. Ann Thorac Surg. 1995;60:704–706.[Abstract/Free Full Text]
73 Fischer SA, Trenholme GW, Costanzo MR et al. Infectious complications in left ventricular assist device recipients. Clin Infect Dis. 1997;24:18–23.[ISI][Medline]
74 McCarthy PM, Schmitt SK, Vargo RL et al. Implantable LVAD infections: Implications for permanent use of the device. Ann Thorac Surg. 1996;61:359–373.[Abstract/Free Full Text]
75 Cherubin CE, Sapira JD. The medical complications of drug addiction and the medical assessment of the intravenous drug user: 25 years later. Ann Intern Med. 1993;119:1017–1028.[Abstract/Free Full Text]
76 Bisbe J, Miró JM, Latorre X et al. Disseminated candidiasis in addicts who use brown heroin. Report of 83 cases and review. Clin Infect Dis. 1992;15:910–923.[Medline]
77 Carbon C and the Endocarditis Working Group of the International Society of ChemotherapyRubinstein E. Staphylococcal endocarditis—recommendations for therapy. Clin Microbiol Infect. 1998;4(Suppl 3):S27–S33.
78 Ribera E, Gomez-Jimenez J, Cortes E et al. Effectiveness of cloxacillin with or without gentamicin in short-term therapy for right-sided Staphylococcus aureus endocarditis. A randomized, controlled trial. Ann Intern Med. 1996;125:969–974.[Abstract/Free Full Text]
79 Elkayam U. Pregnancy and cardiovascular disease. Braunwald E. Heart Disease. 5th edn. Philadelphia: Saunders; 1997. p. 1843–1864.
80 Loebstein R, Lalkin A, Koren G. Pharmacokinetic changes during pregnancy and their clinical relevance. Clin Pharmacokin. 1997;33:328–343.[ISI][Medline]
81 Dashe JS, Gilstrap LC. Antibiotic use in pregnancy. Obstet Gynecol Clin North Am. 1997;24:617–629.[Medline]
82 Shotan A, Widerhorn J, Hurst A et al. Risks of angiotensin-converting enzyme inhibition during pregnancy: Experimental and clinical evidence, potential mechanisms, and recommendations for use. Am J Med. 1994;96:451–456.[ISI][Medline]
83 Blumberg EA, Robbins N, Adimora A et al. Persistent fever in association with infective endocarditis. Clin Infect Dis. 1992;15:983–990.[ISI][Medline]
84 Conlon PJ, Jefferies F, Krigman HR et al. Predictors of prognosis and risk of acute renal failure in bacterial endocarditis. Clin Nephrol. 1998;49:96–101.[ISI][Medline]
85 Hart RG, Foster JW, Luther MF et al. Stroke in infective endocarditis. Stroke. 1990;21:695–700.[Abstract]
86 DiSalvo G, Habib G, Pergola V et al. Echocardiography predicts embolic events in infective endocarditis. J Am Coll Cardiol. 2001;37:1069–1076.[CrossRef][ISI][Medline]
87 Tischler MD, Vaitkus PT. The ability of vegetation size on echocardiography to predict clinical complications: a meta-analysis. J Am Soc Echocardiogr. 1997;10:562–568.[ISI][Medline]
88 De Castro S, Magni G, Beni S et al. Role of transthoracic and transesophageal echocardiography in predicting embolic events in patients with active infective endocarditis involving native cardiac valves. Am J Cardiol. 1997;80:1030–1034.[CrossRef][ISI][Medline]
89 Kupferwasser LI, Yeaman MR, Shapiro SM et al. Acetylsalicylic acid reduces vegetation bacterial density, hematologenous bacterial dissemination and frequency of embolic events in experimental Staphylococcus aureus endocarditis through antiplatelet and antibacterial effects. Circulation. 1999;99:2791–2797.[Abstract/Free Full Text]
90 Parrino PE, Kron IL, Ross SD et al. Does a focal neurologic deficit contraindicate opertation in a patient with endocarditis? Ann Thorac Surg. 1999;67:59–64.[Abstract/Free Full Text]
91 Moon MR, Stinson EB, Miller DC. Surgical treatment of endocarditis. Progr Cardiovasc Dis. 1997;40:239–264.[ISI][Medline]
92 Horstkotte D, Schulte HD, Niehues R et al. Diagnostic and therapeutic considerations in acute, severe mitral regurgitation: experience in 42 consecutive patients entering the intensive care unit with pulmonary edema. J Heart Valve Dis. 1993;2:512–522.[Medline]
93 Arbulu A, Asfaw I. Tricuspid valvulectomy without prosthetic replacement. Ten years of clinical experience. J Thorac Cardiovasc Surg. 1981;82:684–691.[Medline]
94 Korman TM, Spelman DW, Perry GJ et al. Acute glomerulonephritis associated with acute Q fever: Case report and review of the renal complications of Coxiella burnetii infections. Clin Infect Dis. 1998;26:359–364.[Medline]
95 DiNubile MJ. Heart block during bacterial endocarditis:a review of the literature and guidelines for surgical intervention. Am J Med Sci. 1984;287:30–32.[Medline]
96 Mansur AJ, Dal Bo CM, Fukushima JT et al. Relapses, recurrences, valve replacements, and mortality during the long-term follow-up after infective endocarditis. Am Heart J. 2001;141:78–86.[CrossRef][Medline]
97 Pansini S, di Summa M, Patane F et al. Risk of recurrence after reoperation for prosthetic valve endocarditis. J Heart Valve Dis. 1997;6:84–87.[Medline]
98 Verheul H, Van den Brink RB, van Vreeland T et al. Effects of changes in management of active infective endocarditis on outcome in a 25-year period. Am J Cardiol. 1993;72:682–687.[Medline]
99 Tornos MP, Permanyer-Miralda G, Olona M et al. Long term complications of native valve infective endocarditis in non addicts. A 15-year follow-up study. Ann Intern Med. 1992;117:567–572.[ISI][Medline]
100 Edwards MB, Ratnatunga CP, Dore CJ et al. Thirty-day mortality and long-term survival following surgery for prosthetic endocarditis: a study from the UK heart valve registry. Eur J Cardiothorac Surg. 1998;14:156–164.[CrossRef][Medline]
101 Trouillet JL, Hoen B, Battik R et al. Splenic involvement in infectious endocarditis. Association for the Study and Prevention of Infectious Endocarditis. Rev Med Interne. 1999;20:258–263.[Medline]
102 David TE. Surgical management of aortic root abscess. J Card Surg. 1997;12:262–269.[Medline]
103 Prat A, Fabre OH, Vincentelli A et al. Ross operation and mitral homograft for aortic and tricuspid valve endocarditis. Ann Thorac Surg. 1998;65:1450–1452.[Abstract/Free Full Text]
104 Guerra JM, Tornos MP, Parmanyer-Miralda G et al. Long term results of mechanical prostheses for treatment of active infective endocarditis. Heart. 2001;86:63–68.[Abstract/Free Full Text]
105 Klug D, Lacroix D, Savoye C et al. Systemic infection related to endocarditis on pacemaker leads: clinical presentation and management. Circulation. 1997;95:2098–2107.[Abstract/Free Full Text]