Abstract and Introduction
Abstract
There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. Lipoglycopeptides as a class show excellent in vitro potency. Their long half-lives and complex PKs may preclude these agents being used in critically ill patients. Anti-MRSA cephalosporins provide great promise in the treatment of MRSA. These agents, despite broad-spectrum activity, should be reserved for patients with MRSA infections as it is likely that usage will be associated with increased rates of resistance. Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia. The results of an open-labeled trial to address the superiority of daptomycin compared with vancomycin in reduced vancomycin susceptibility infections are eagerly anticipated. No drug to date has shown superiority to vancomycin in the treatment of MRSA infections with the possible exception of linezolid in hospital-acquired pneumonia (HAP), making linezolid an important option in the treatment of MRSA-proven HAP. Whether these strengths and features are agent or class specific are unclear but will likely be answered with the marketing of tedizolid. There are insufficient data to recommend either quinupristin/dalfopristin or tigecycline, as first line in the treatment of severe MRSA infections. These agents however remain options in patients with no other alternatives.
Introduction
Staphylococcus aureus is a gram-positive bacterium that remains a troublesome pathogen especially within the hospital setting. This bacterium forms a part of the normal human nasal microflora and may cause infections in susceptible individuals especially in health care settings. What makes this bacterium a problem is its propensity to spread, especially in health care settings, and its remarkable capacity to evolve new antibiotic resistance. Not surprisingly therefore, S. aureus has been identified as one of the key "problem" bacteria in addition to Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species; these are the ESKAPE pathogens that urgently require development of new therapies.
The overall burden of antimicrobial-resistant bacteria continues to increase and accounted for approximately 20% of all hospital infections in 2010. These infections in turn are associated with increased patient morbidity and mortality.
The rates of methicillin-resistant S. aureus (MRSA) are dynamic with current United States and European surveillance data suggesting that MRSA incidence has declined by between 27.7 and 54.2% in recent years. Although these MRSA figures are encouraging, the impact of emerging community MRSA clones on health care-related infections is yet to become clear; regardless, MRSA infections are likely to continue to be a significant problem.
The purpose of this review is to explore the possible treatment options available for MRSA including new data related to vancomycin optimization. We will focus on initial therapy and not discuss issues surrounding either maintenance options, which generally following an extended period of parenteral therapy and usually consist of an oral agent, combination treatment or salvage therapy.