Management of multidrug-resistant enterococcal infections

Abstract

Enterococci are organisms with a remarkable ability to adapt to the environment and acquire antibiotic resistance determinants. The evolution of antimicrobial resistance in these organisms poses enormous challenges for clinicians when faced with patients affected with severe infections. The increased prevalence and dissemination of multidrug-resistant Enterococcus faecium worldwide has resulted in a major decrease in therapeutic options because the majority of E. faecium isolates are now resistant to ampicillin and vancomycin, and exhibit high-level resistance to aminoglycosides, which are three of the traditionally most useful anti-enterococcal antibiotics. Newer antibiotics such as linezolid, daptomycin and tigecycline have good in vitro activity against enterococcal isolates, although their clinical use may be limited in certain clinical scenarios as a result of reduced rates of success, possible underdosing for enterococci and low serum levels, respectively, and also by the emergence of resistance. The experimental agent oritavancin may offer some hope for the treatment of vancomycin-resistant enterococci but clinical data are still lacking. Thus, optimal therapies for the treatment of multidrug-resistant enterococcal infections continue to be based on empirical observations and extrapolations from in vitro and animal data. Clinical studies evaluating new strategies, including combination therapies, to treat severe vancomycin-resistant E. faecium infections are urgently needed.

FIG. 1

Suggested therapeutic alternatives in severe infections caused by vancomycin-resistant enterococcal infections. (1) In rare cases of β-lactamase-producing isolates, ampicillin-sulbactam (12–24 g/day) is suggested. The use of a continuous infusion is recommended by some experts. (2) Gentamicin or streptomycin. (3) Consider doses of 8–12 mg/kg day. (4) Agents with potential activity include tigecycline [62,63], doxycycline with rifampin or a fluoroquinolone (if susceptible to each agent). (5) Doses to up to 30 g/day could be considered. (6) Quinupristin-dalfopristin or linezolid are listed in the American Heart Association recommendations for the treatment of vancomycin and ampicillin-resistant Enterococcus faecium. Linezolid has been used with success in a few cases of meningitis as a result of vancomycin-resistant enterococci [61,74]. (7) if imipenem MIC < 32 mg/L. HLR, high-level resistance; HD, high-dose.