Therapeutic Options for Resistant Gram Positives

Abstract

Vancomycin remains the current gold standard for treatment of serious MRSA (methicillin resistant Staphylococcus aureus) infections despite uncertainties about rates of toxicity and the optimal dosing strategy. The only alternative for bloodstream infections (BSI) based on prospective randomised controlled trial data is daptomycin. However, higher doses should be implemented to prevent resistance emerging. Although linezolid and ceftaroline have been shown to be effective BSI treatment in retrospective cohort studies, there is no prospective randomised comparative data with vancomycin. These agents should thus be considered as salvage therapy options. In the treatment of MRSA cSSSIs (complicated skin and skin structure infections), daptomycin, linezolid, ceftaroline and telavancin have all been shown to be equally effective to vancomycin and thus the choice of agent is dependent on the side effect profile and patient setting. In the treatment of nosocomial MRSA pneumonia, both linezolid and telavancin have been shown to be non-inferior to vancomycin. Linezolid was shown to have improved microbiological and clinical cure rates compared with vancomycin, but with no mortality benefit in a randomised controlled trial by Wunderink et al., [1, 2]. Debate still exists, however, as to whether these studies, in the absence of a mortality benefit, provide sufficient evidence to recommend linezolid or telavancin above vancomycin in the treatment of MRSA pneumonia. For the treatment of VRE (Vancomycin Resistant Enterococci) BSI, prospective data is lacking and recommendations are based upon in vitro activity and cohort studies. Quinupristin-dalfopristin is limited by its side effect profile and the need for a central line. As such the first line agents include daptomycin and linezolid. Although two recent meta-analyses suggest improved outcomes with linezolid over daptomycin, this may reflect suboptimal daptomycin dosing rather than linezolid superiority. Tigecycline, although active against VRE, has been shown to be inferior in eradication rates compared with linezolid [3]. Combination therapy for MRSA or VRE infections cannot currently be endorsed and thus should be limited to settings where no other alternative is available.