Antibiotic therapy for 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 may be required. Antibiotics are medicines that treat infections and the cornerstone of treatment for infective endocarditis. Despite this, there are surprising differences between guidelines in their recommendations for antibiotic therapy. Furthermore, because of the dose and length of time that antibiotics must be given for, the antibiotics given can have serious side effects, such as kidney and ear damage, and allergic reactions.

Study characteristics

We identified only four studies that compared different antibiotic regimens. They included a limited number of people. Each trial investigated different types and doses of antibiotics. These studies were published between 1998 and 2006 and were conducted in the USA, Spain and Finland. The evidence is up to date as of 30 April 2015.

Key results

One study showed imprecise results on all-cause mortality (dead from any cause). One study suggested that one antibiotic regimen was superior to another (cloxacillin plus gentamycin was superior to either vancomycin or teicoplanin plus gentamycin). Two studies did not show any difference between the antibiotic regimens. In terms of the need for cardiac surgery, uncontrolled infection or relapse from endocarditis the knowledge is imprecise. No trials assessed septic embolic complications (when infection travels around the body and causes infection in other areas, such as the spine, eyes or lungs) or quality of life. We do not know how safe these medicines are.

Quality of evidence

The confidence in the results of this review is very low. Current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis. The studies had limitations in the way they were designed and performed, and three 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: 

Limited and very low quality evidence suggested that there were no conclusive differences between antibiotic regimens in terms of cure rates or other relevant clinical outcomes. However, because of the very low quality evidence, this needs confirmation. The conclusion of this Cochrane review was based on randomised controlled trials with high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for 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 their use is not standardised, due to the differences in presentation, populations affected and the wide variety of micro-organisms that can be responsible.

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 on 30 April 2015. 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 assessing the effects of antibiotic regimens for treating possible 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: 

Three 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 studies. We described the included studies narratively.

Main results: 

Four small randomised controlled trials involving 728 allocated/224 analysed participants met our inclusion criteria. These trials had a high risk of bias. Drug companies sponsored two of the trials. We were unable to pool the data due to the heterogeneity in outcome definitions and the different antibiotics used.

The included trials compared the following antibiotic schedules. The first trial compared quinolone (levofloxacin) plus standard treatment (anti-staphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin) and rifampicin) versus standard treatment alone reporting uncertain effects on all-cause mortality (8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; RR 1.12, 95% CI 0.49 to 2.56, very low quality evidence). The second trial compared daptomycin versus low-dose gentamicin plus an anti-staphylococcal penicillin (nafcillin, oxacillin or flucloxacillin) or vancomycin. This showed uncertain effects in terms of cure rates (9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus anti-staphylococcal penicillin or vancomycin, RR 0.89 95% CI 0.42 to 1.89; very low quality evidence). The third trial compared cloxacillin plus gentamicin with a glycopeptide (vancomycin or teicoplanin) plus gentamicin. In participants receiving gentamycin plus glycopeptide only 13/23 (56%) were cured versus 11/11 (100%) receiving cloxacillin plus gentamicin (RR 0.59, 95% CI 0.40 to 0.85; very low quality evidence). The fourth trial compared ceftriaxone plus gentamicin versus ceftriaxone alone and found no conclusive differences in terms of cure (15/34 (44%) with ceftriaxone plus gentamicin versus 21/33 (64%) with ceftriaxone alone, RR 0.69, 95% CI 0.44 to 1.10; very low quality evidence).

The trials reported adverse events, need for cardiac surgical interventions, uncontrolled infection and relapse of endocarditis and found no conclusive differences between comparison groups (very low quality evidence). No trials assessed septic emboli or quality of life.

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