Ampicillin plus Ceftriaxone for Enterococcus faecalis Endocarditis

Summary and Comment |
April 10, 2013

Ampicillin plus Ceftriaxone for Enterococcus faecalis Endocarditis

  1. Neil M. Ampel, MD

In an observational multicenter study, outcomes were similar between ampicillin plus ceftriaxone and ampicillin plus gentamicin, but renal dysfunction was significantly more common with the latter.

  1. Neil M. Ampel, MD

Although intravenous therapy with penicillin or ampicillin plus an aminoglycoside has been the standard treatment for infective endocarditis caused by β-lactam– and gentamicin-susceptible enterococci, the combination of ampicillin plus ceftriaxone (AC) has been used in cases caused by Enterococcus faecalis with high-level aminoglycoside resistance (HLAR). In daily practice, however, AC has also been used even in the absence of aminoglycoside resistance.

In an observational, nonrandomized, comparative cohort study involving consecutive adults treated for E. faecalis infective endocarditis (EFIE) at centers in Spain or Italy between 2005 and 2011, researchers compared the safety and efficacy of these treatments. Of 291 EFIE episodes, 159 (55%) were treated with AC, 87 (30%) with ampicillin plus gentamicin (AG), and 45 (15%) with other antimicrobial combinations. Isolates from 72 episodes (25%) showed HLAR. Compared with patients receiving AG, those receiving AC were significantly more likely to have previous chronic renal failure (P=0.004) and to have healthcare-acquired infection (P=0.006).

The rates of death — both during antibiotic therapy and at 3-month follow-up — and of subsequent relapse were similar between treatment groups. However, those on AG were significantly more likely to have their therapy discontinued because of an adverse event (25% vs. 1%; P<0.001), most often new renal failure (23% vs. 0%).


As editorialists note, Enterococcus faecalis, unlike Enterococcus faecium, has generally remained susceptible to ampicillin. Although the impetus to use ampicillin plus ceftriaxone for E. faecalis infective endocarditis originated because of aminoglycoside resistance, the present findings suggest that this regimen may be a reasonable alternative for many patients with EFIE, regardless of high-level aminoglycoside status.


Reader Comments (1)

Marco Andres Bergevin

Ampicillin monotherapy is suboptimal for Enterococcus faecalis endocarditis. However, whether we face high level aminoglycoside resistance or renal toxicity which precludes aminoglycoside use, I believe that Daptomycin should be the drug chosen for combination therapy with ampicillin. It has better in vitro activity against enterococci than ceftriaxone and this combination has the potential to prevent the emergence of drug resistance sometimes encountered during daptomycin monotherapy of enterococcal endocarditis. This combination certainly deserves a randomised trial.

Competing interests: Received honorarium for participating in advisory boards to Sunovion which distributes Daptomycin in Canada.

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