Antibiotic therapy for the treatment of infective endocarditis

Review question

We aimed to assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis.

Background

Infective endocarditis is an infection of the inner lining of the heart. It is a serious infection that is frequently fatal, and cardiac surgery is often required. Antibiotics are medicines that treat infections and are the cornerstone of treatment for infective endocarditis. Treatment of patients with infective endocarditis is nosocomial (in-hospital). Despite this, there are surprising differences between guidelines in their recommendations for antibiotic therapy. Furthermore, due to the dose and length of time that antibiotics must be given for, the antibiotics can have serious side effects, such as kidney and ear damage, and cause allergic reactions.

Study characteristics

We identified only six randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) that compared different antibiotic regimens, which included a limited number of participants. Each trial investigated different types and doses of antibiotics. The included studies were published between 1998 and 2019 and were conducted in the USA, Spain, Finland, and Denmark. The evidence is up-to-date as of 6 January 2020.

Key results

This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few randomised controlled trials with a high risk of bias. Accordingly, the current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

Quality of evidence

The confidence in the results of this review is low to very low. The included studies had limitations in the way they were designed and performed, and three studies were sponsored by the manufacturer of the medicine that was assessed. Moreover, the limited number of people included in the studies led to uncertain results. Larger studies are required to provide more information about the best antibiotic regimens to treat people with infective endocarditis.

Authors' conclusions: 

This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

Read the full abstract...
Background: 

Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016.

Objectives: 

To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions.

Selection criteria: 

We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women.

Data collection and analysis: 

Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively.

Main results: 

Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled.

The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size.

The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31).

The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55).

The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life.

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