Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with substantial morbidity and mortality. Vancomycin (VAN) has been used as the gold standard treatment for invasive MRSA infections for decades but, unfortunately, the reliance of VAN as the primary treatment option against these infections has led to a reduction in VAN susceptibility in MRSA isolates. Although daptomycin (DAP) is another common treatment option against invasive MRSA infections, it has been shown that the development of VAN resistance can lead to DAP nonsusceptibility. VAN or DAP backbone regimens in combination with other antibiotics has been advocated as an alternative approach to improve patient outcomes in VAN/DAP-susceptible infections, enhance outcomes in infections caused by isolates with reduced VAN/DAP susceptibility, and/or prevent the emergence of VAN/DAP resistance or further resistance. A peer-reviewed literature search was conducted using Medline, Google Scholar and PubMed databases. The primary purpose of this review is to describe the mechanisms and epidemiology of MRSA isolates with a reduction in VAN and/or DAP susceptibility, evaluate in vitro and in vivo literature describing combination therapy (CT) against MRSA isolates with reduced VAN and/or DAP susceptibility and describe studies involving the clinical outcomes of patients treated with CT against invasive MRSA infections.

Highlights

  • Methicillin-resistant Staphylococcus aureus (MRSA) is a predominant pathogen that causes human infections in both community and hospital settings [1]

  • We focus on in vitro and in vivo studies evaluating the impact of combination therapy (CT) on these resistant phenotypes and conclude with an evaluation of health outcomes studies analyzing CT against MRSA ( not all MRSA outcomes studies were evaluated against organisms with increased resistance to VAN and/or DAP and clinically relevant studies evaluating methicillin-susceptible S. aureus (MSSA) will be described)

  • Invasive MRSA infections lead to significant morbidity and mortality

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Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is a predominant pathogen that causes human infections in both community and hospital settings [1]. Vancomycin (VAN) is the most commonly used antibiotic to treat invasive MRSA infections, increased utilization of this antimicrobial has led to the emergence of clinical MRSA isolates with reduced susceptibility to VAN [1]. In addition to VAN, there are some viable alternative antimicrobial agents with in vitro activity against MRSA, such as daptomycin (DAP), teicoplanin, linezolid, ceftaroline (CPT), trimethoprim/sulfamethoxazole (TMP/SMX), tigecycline and quinupristin/dalfopristin [4]. These alternative agents have not proven to be superior to VAN in invasive MRSA infections.

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