Optimizing Therapy for Vancomycin-resistant Enterococcal Bacteremia in Children

Pranita D. Tamma; Alice J. Hsu

Disclosures

Curr Opin Infect Dis. 2014;27(6):517-527. 

In This Article

Abstract and Introduction

Abstract

Purpose of review Uncertainties exist regarding the optimal treatment for vancomycin-resistant enterococcal (VRE) bloodstream infections, particularly in settings in which ampicillin cannot be used.

Recent findings Quinupristin-dalfopristin, linezolid, and daptomycin, all approved between 1999 and 2003, represent the mainstays of therapy for VRE bacteremia, although only linezolid has been specifically approved by the United States Food and Drug Administration for this indication. The main objective of this review is to compare the relative efficacies, dosing strategies, and side-effect profiles of quinupristin-dalfopristin, linezolid, and daptomycin for VRE bacteremia in the pediatric population. A brief description of recently approved broad-spectrum Gram-positive agents that may have a role in the management of VRE bacteremia in upcoming years is also provided.

Summary Linezolid, despite its bacteriostatic activity against VRE, may be the most versatile of the available drugs. It has activity against both Enterococcus faecalis and E. faecium, can be administered orally, and resistance appears to be less of a concern with linezolid compared with the other agents. Additionally, the results of two recent meta-analyses demonstrate more favorable outcomes with linezolid compared with daptomycin for the treatment of VRE bacteremia. The clinical pharmacokinetics of linezolid have been well described in children. The most notable concern with linezolid, however, is toxicities associated with prolonged use. Until more prospective data are available, we favor linezolid as first-line therapy for the treatment of VRE bacteremia in children.

Introduction

The preferred treatment for vancomycin-resistant enterococci (VRE) bacteremia is ampicillin if the isolate is susceptible to this agent. However, the majority of vancomycin-resistant Enterococcus faecium isolates (80–95%) are resistant to ampicillin.[1,2] In contrast, vancomycin-resistant E. faecalis are usually susceptible to ampicillin, as are E. gallinarum and E. casseliflavus, both of which are intrinsically resistant to vancomycin.

The optimal therapy for VRE bacteremia in the setting of ampicillin resistance is unclear. Quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline, all approved between 1999 and 2005, represent the mainstays of therapy for invasive VRE infections, although only linezolid has been specifically approved by the United States Food and Drug Administration (FDA) for this indication. Given concerns regarding the achievement of adequate tigecycline serum drug concentrations,[3] we do not recommend tigecycline for the treatment of VRE bacteremia. The main objective of this review is to compare the relative efficacies and side-effect profiles of quinupristin-dalfopristin, linezolid, and daptomycin for VRE bacteremia in the pediatric population.

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