A comparison of different antibiotic regimens for the treatment of infective endocarditis

Arturo J Martí‐Carvajal, Mark Dayer, Lucieni O Conterno, Alejandro G Gonzalez Garay, Cristina Elena Martí‐Amarista, Daniel Simancas‐Racines

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