Time to abandon ampicillin plus gentamicin in favour of ampicillin plus ceftriaxone in Enterococcus faecalis infective endocarditis? A meta-analysis of comparative trials

Abstract

Abstract Background Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events. Objectives To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events. Methods In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel–Haenszel method, the Sidik–Jonkman estimator for τ2 and the Hartung–Knapp adjustment. Results Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26–0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03–0.46], p = 0.0160) than AG. Conclusions Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE. Graphical abstract