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

Clin Res Cardiol. 2022 Oct;111(10):1077-1086. doi: 10.1007/s00392-021-01971-3. Epub 2021 Nov 9.

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.

Keywords: Ampicillin; Cardiology; Ceftriaxone; Endocarditis; Enterococcus; Gentamicin; Meta-analysis.

Publication types

  • Meta-Analysis

MeSH terms

  • Amoxicillin / pharmacology
  • Amoxicillin / therapeutic use
  • Ampicillin / adverse effects
  • Anti-Bacterial Agents / adverse effects
  • Ceftriaxone / adverse effects
  • Drug Therapy, Combination
  • Endocarditis*
  • Endocarditis, Bacterial* / drug therapy
  • Endocarditis, Bacterial* / epidemiology
  • Enterococcus faecalis
  • Gentamicins / adverse effects
  • Gram-Positive Bacterial Infections* / chemically induced
  • Gram-Positive Bacterial Infections* / drug therapy
  • Heart Diseases* / drug therapy
  • Humans
  • Renal Insufficiency* / drug therapy

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Ceftriaxone
  • Ampicillin
  • Amoxicillin