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Antist aphyloco cc al Agents
Howard S. Gold, MD*, Satish K. Pillai, MD
KEYWORDS  Staphylococcus aureus  b-Lactam drugs  Methicillin-resistant S aureus  Vancomycin-intermediate S aureus

These are interesting times in the treatment of infections caused by Staphylococcus aureus, with shifting epidemiology of antibiotic resistance; changing prevalence of clinical syndromes (probablyreflecting changes in virulence of circulating strains); and the recent availability of a variety of new agents with activity against multidrugresistant gram-positive cocci. In the wake of the well-documented explosion in methicillin resistance in S aureus, one can confidently predict more limited use for currently approved b-lactam drugs for the treatment of S aureus infections, although severalinvestigational b-lactams have clinically useful activity against methicillin-resistant S aureus (MRSA). Despite initial reports showing general susceptibility to non–blactam drugs (with the exception of erythromycin), it has become increasingly apparent that at least some community-associated MRSA (CA-MRSA) have become multidrug resistant and this trend is almost certain to continue as these clones causemore infections and are exposed to more courses of various non–b-lactam drugs.1 After 40 years of vancomycin use for treatment of MRSA infections and for methicillin-susceptible S aureus (MSSA) in b-lactam–allergic patients, there is gathering evidence hinting at reduced efficacy of that drug. Clearly, there are isolated reports of vancomycin-resistant S aureus (VRSA) and vancomycin-intermediateS aureus (VISA), but some experts have begun to debate the efficacy of vancomycin even against isolates that test susceptible to vancomycin using the updated Clinical and Laboratory Standards Institute (CLSI) breakpoint for susceptibility of 2 mg/mL.2–4 The magnitude of this evidence has perhaps been amplified by the efforts of pharmaceutical companies to position newer Food and DrugAdministration (FDA)–approved and premarket branded agents. However, it is impossible to ignore reports of rising vancomycin minimum inhibitory concentrations (MICs), despite the fact that this has not been a universal finding,5,6 and the effect that higher vancomycin MICs within the susceptible range seem to have on treatment outcomes in some retrospective

Silverman Institute for Health Care Quality andSafety, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, LMOB-6A, Boston, MA 02215, USA * Corresponding author. E-mail address: (H.S. Gold). Infect Dis Clin N Am 23 (2009) 99–131 doi:10.1016/j.idc.2008.10.008 0891-5520/08/$ – see front matter ª 2009 Elsevier Inc. All rights reserved.


Gold & Pillaiseries7 and one prospective observational study,8 not to mention the observations of increased vancomycin toxicity at currently used higher trough concentrations.9 The abundance of riches in new drugs for the multidrug-resistant gram-positive space is timely, and these agents show great potential, but as yet have incompletely tested durability and comparative efficacy. This article reviews theadvantages and disadvantages of the variety of antistaphylococcal agents by providing basic information including mechanism of action; mechanisms of resistance; clinical use (including dosing for and data supporting common indications); drug toxicities; and major drug interactions.

The family of b-lactam antibiotics is a large and diverse group of drugs that have variable degrees ofactivity against S aureus. A detailed review of these agents is encyclopedic and beyond the scope of this article, but can be found in various standard texts.10–13 Thus, we will limit our consideration to agents that are currently available in the United States, focusing on common themes, common usage of these drugs for staphylococcal infection, and notable exceptions. b-lactams act by binding to...
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