Ampicillin/ceftriaxone vs. β-lactam/aminoglycoside combination therapy for Enterococcus faecalis infective endocarditis: a systematic review and meta-analysis.

Authors

Yui Sugimoto, Ryosuke Sasaki, Mayu Tominaga, Ryuka Hirai, Takayuki Mihara, Rina Shimamura, Maiko Yoshikawa, Shintaro Ikegami, Sora Shimada, Ayu Tsubouchi, Yuko Okamoto, Yuki Igarashi, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto

Published in

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. Aug 12, 2026. Epub Aug 12, 2026.

Abstract

Enterococcus faecalis infective endocarditis (EFIE) remains a formidable infection requiring prolonged antimicrobial therapy. Although β-lactam/aminoglycoside (BL + AG) combination therapy has long been regarded as the standard treatment, AG-associated toxicities pose a major clinical dilemma. Recently, dual β-lactam therapy with ampicillin/ceftriaxone (A + C) has become an established treatment option. This systematic review and meta-analysis aimed to compare the efficacy and safety of A + C versus BL + AG therapy in patients with EFIE.
A literature search was conducted using PubMed, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Clinical studies comparing A + C versus BL + AG for EFIE were included. Primary outcomes were mortality and relapse rates. Secondary outcomes included overall adverse events, renal adverse events, ototoxicity/vestibular toxicity, skin rash, Clostridioides difficile diarrhea, and regimen changes or discontinuation. Pooled ORs and 95% CIs were estimated utilizing random-effects models.
Six studies involving 619 patients with EFIE were included. Cumulative mortality (OR 1.10, 95% CI: 0.73-1.65) and relapse rates (OR 1.08, 95% CI: 0.39-3.01) did not differ significantly between A + C and BL + AG. However, A + C was associated with significantly lower incidences of total adverse events (OR 0.20, 95% CI: 0.08-0.53), renal adverse events (OR 0.34, 95% CI: 0.19-0.58), ototoxicity/vestibular toxicity (OR 0.07, 95% CI: 0.01-0.37), and antibiotic regimen change (OR 0.20, 95% CI: 0.10-0.39) or discontinuation (OR 0.17, 95% CI: 0.05-0.56).
A + C therapy was associated with a more favorable safety profile than BL + AG therapy, with no significant differences in efficacy, mortality, or relapse in patients with EFIE. These findings support the use of A + C as an important therapeutic option for patients at increased risk of AG-associated toxicity.

PMID:
42581256
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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