Recommended antibiotic regimes to treat infective endocarditis vary between guidelines. In a new review of clinical benefits and harms among different antibiotics, no clear evidence was found to inform which regimen should be used in preference to another, leading to a call for further randomized controlled trials to be conducted. 

The researchers identified four small randomized control trials which met their study criteria. Each trial had to contain participants diagnosed with infective endocarditis according to modified Duke’s criteria, and each trial had to compare an antibiotic therapy with any other active antibiotic treatment at any dose, administration route and duration.

Primary outcomes were defined as 1) all-cause mortality during hospital stay and at 1 year; 2) cure; 3) and adverse events, including treatment-related adverse events. The trials included a total number of 728 patients. 

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Results showed no difference in the primary outcome of all-cause mortality, which was a barometer in just two trials. In one (Fortún, 2001) comparing glycopeptides (vancomycin or teicoplanin) plus gentamicin versus cloxacillin plus gentamicin, there were no recorded deaths. In the other trial, which compared levofloxacin plus standard treatment versus standard treatment alone, there was no conclusive evidence. Twenty-six percent (8/31) of patients died with levofloxacin plus standard treatment compared to 23% (9/39) with standard treatment alone (RR 1.12, 95% CI 0.49 to 2.56).

Similarly, no trial demonstrated superiority of any treatment when it came to a cure. In one trial (Fowler 2006), daptomycin showed a 32% cure rate (9/28), versus low-dose gentamicin, combined with either an anti-staphylococcal penicillins or glycopeptide antibiotics, which had a 36% (9/25) cure rate (RR 0.89, 95% CI 0.42 to 1.89).  Patients given glycopeptide plus gentamicin had a cure rate of 56% (12/23) versus 100% (11/11) for those given cloxacillin plus gentamincin (RR 0.59, 95% CI 0.40 to 0.85), however the evidence was considered very low quality. Another trial comparing ceftriaxone plus gentamicin to cetriaxone monotherapy found inconclusive evidence with regards to cure rates (44% vs. 64%, respectively; very low quality evidence).

Regarding the third primary outcome, treatment related adverse events (TRADs), glycopeptides plus aminoglycoside showed 22% (5/23) versus 0% (0/11) with beta-lactam plus aminoglycoside. However given the small cohort, these findings cannot be deemed significant. The same is true of the trial that compared beta-lactam (ceftriaxone) plus an aminoglycoside (gentamicin) versus a beta-lactam (ceftriaxone) alone, finding that 8.8% (3/34) of the ceftriaxone plus gentamicin group had TRADs compared to 15% (5/33) of thebeta-lactam alone group.  

Each finding is adjudged to have a low quality of evidence by the authors, a main reason why they are calling for further and larger randomized control trials. The factors which influenced the author’s assessment of low quality evidence included, failure to conceal allocation, blinding, and selective outcome reporting of the trials for the main outcomes assessed. Additionally, three of the trials were sponsored by a drug company.

The researchers concluded that “due to the number and quality of included trials, we found no a clear evidence to inform guidelines about which antibiotic regimen should be used in preference to another for the management of infective endocarditis.” They called for the instigation of further randomized controlled trials to assess the use of the antibiotic regimens for treating infective endocarditis.

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