The role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis: a meta-analysis of comparative trials.
BACKGROUND
The addition of an aminoglycoside to a beta-lactam for the treatment of patients with infective endocarditis has been supported by data from laboratory and animal studies.


OBJECTIVE
We sought to review the evidence from the available comparative clinical trials regarding the role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis caused by Gram-positive cocci.


METHODS
The studies for our meta-analysis were retrieved from searches of the PubMed and Cochrane Central Register of Controlled Trials databases, as well as from the references cited in relevant articles. No limits were set regarding the language and date of publication of the studies.


METHODS
Included studies were prospective studies that provided comparative data regarding the effectiveness of the treatment and/or mortality in patients receiving monotherapy with a beta-lactam or beta-lactam/aminoglycoside combination therapy.


METHODS
Two independent reviewers performed the literature search, study selection and extraction of data from relevant studies.


RESULTS
No clinical trial comparing beta-lactam monotherapy with beta-lactam/aminoglycoside combination therapy for the treatment of enterococcal endocarditis was found. We performed a meta-analysis of five available comparative trials [four randomized controlled trials (RCTs) and one comparative prospective trial], which included 261 patients with bacterial endocarditis in native valves due to Staphylococcus aureus (four studies) or streptococci of the viridans group (one study). There was no statistically significant difference between beta-lactam monotherapy and beta-lactam/aminoglycoside combination therapy regarding mortality [odds ratio (OR) = 0.59, 95% confidence interval (95% CI) = 0.21-1.66], treatment success (OR = 1.25, 95% CI = 0.49-3.05), treatment success without surgery (OR = 1.66, 95% CI = 0.64-4.30) or relapse of endocarditis (OR = 0.79, 95% CI = 0.15-4.29). Nephrotoxicity was less common in the beta-lactam monotherapy arm than in the beta-lactam/aminoglycoside combination therapy arm (OR = 0.38, 95% CI = 0.16-0.88, P = 0.024). No difference between the two treatment arms was found in subanalyses of the four studies that included only patients with staphylococcal infections in terms of mortality (OR = 0.69, 95% CI = 0.26-1.86, fixed effects model), treatment success (OR = 1.27, 95% CI = 0.47-3.43, fixed effects model) or relapse (OR = 0.76, 95% CI = 0.12-4.92, fixed effects model).


CONCLUSIONS
The relatively small number of available comparative trials was the major limitation of this meta-analysis.


CONCLUSIONS
The limited evidence from the available prospective comparative studies does not offer support for the addition of an aminoglycoside to beta-lactam treatment of patients with endocarditis caused by Gram-positive cocci. A large multicentre RCT is necessary to reach a definitive conclusion on this issue.
Falagas
Matthew E
ME
Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece. m.falagas@aibs.gr
Matthaiou
Dimitrios K
DK
Bliziotis
Ioannis A
IA
D000617:Aminoglycosides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D016896:Treatment Outcome; D047090:beta-Lactams / Q000627:therapeutic use*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D047090:beta-Lactams