What drugs are used for combination therapy in enterococcal infections?

Updated: Jun 10, 2021
  • Author: Susan L Fraser, MD; Chief Editor: John L Brusch, MD, FACP  more...
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Combination therapy with a cell wall–active agent (eg, ampicillin, vancomycin) and an aminoglycoside (eg, gentamicin, streptomycin) has long been regarded as the standard of care for E faecalis native valve endocarditis. This combination results in synergistic bactericidal activity against susceptible enterococcal strains. At least 4 weeks of combination therapy is recommended. Six weeks of combination therapy is recommended in patients with symptoms that persisted for more than 3 months before starting therapy, in patients who relapsed after shorter courses of therapy, and in patients with prosthetic valves. In sensitive E faecalis native valve endocarditis treated with ampicillin plus an aminoglycoside, consideration should be given to limiting the aminoglycoside component to 2 weeks in order to avoid nephrotoxic, vestibular, and ototoxic events. However, such limitations are not justified in treating prosthetic valve infections or those that are complicated by large vegetations.

Multiple studies of ceftriaxone plus ampicillin in E faecalis valve endocarditis supported those of smaller earlier ones. Gentamicin has always generated concern because of its significant rates of nephrotoxicity, ototoxicity, and vestibular toxicity, especially among older patients. For individuals at risk for these side effects, intravenous ampicillin 2 g every 4 hours plus intravenous ceftriaxone 2 g every 12 hours appears to provide a reasonable alternative. The combination has been shown to be effective in both gentamicin-resistant and gentamicin-sensitive isolates and in both native and prosthetic valve infections. [33] This therapy is ineffective against E faecium. [34, 35]

However, treatment with ceftriaxone may induce colonization with VRE owing to its high concentration in the bile. [36]

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