Background
Based primarily on in vitro and animal models, with little data directly addressing patient outcomes, current guidelines recommend treating staphylococcal prosthetic valve endocarditis (PVE) with antibiotic combinations including gentamicin and rifampin. Here, we synthesize the clinical data on adjunctive rifampin and gentamicin in staphylococcal PVE.
Methods
We conducted a systematic review and meta-analysis of PubMed- and Cochrane-indexed studies reporting outcomes of staphylococcal PVE treated with adjunctive rifampin, gentamicin, both agents, or neither (i.e., glycopeptide or beta-lactam monotherapy). We recorded outcomes including mortality, relapsed infection, length of stay, nephrotoxicity, hepatotoxicity, and important drug-drug interactions (DDIs).
Results
Four relevant studies were identified. Two studies (n = 117) suggested adding gentamicin to rifampin-containing regimens did not reduce clinical failure (OR 0.98; 95% CI 0.39-2.46), and two studies (n = 201) suggested adding rifampin to gentamicin-containing regimens did not reduce clinical failure (OR 1.29; 95% CI 0.71-2.33). Neither gentamicin nor rifampin was associated with reduced infection relapse; one study found rifampin treatment associated with longer hospitalizations (mean 31.3 vs 42.3 days, p < 0.001). Comparative safety outcomes were rarely reported, but one study found rifampin associated with hepatoxicity, nephrotoxicity, and DDIs, leading to treatment discontinuation in 31% of patients.
Conclusion
The existing clinical data do not suggest a benefit of either adjunctive gentamicin or rifampin in staphylococcal PVE. Given other studies also suggest these agents add nephrotoxicity, hepatoxicity, and risk DDIs without benefit in staphylococcal endovascular infections, we suggest recommendations for gentamicin and rifampin in PVE be downgraded and they primarily be used within the context of clinical trials.