Serious Infections Caused by Methicillin-Resistant Staphylococcus aureus

Clinical Infectious Diseases, Sep 2010

Although first identified just 14 decades ago, methicillin-resistant Staphylococcus aureus (MRSA) has undergone rapid evolutionary changes and epidemiologic expansion to become a major cause of nosocomial and community-acquired infections worldwide. Increasing resistance to vancomycin among MRSA strains in conjunction with availability of new antibiotics, including daptomycin and linezolid, have increased treatment choices but made clinical treatment decisions more challenging. This article describes the clinical features and management issues of 2 challenging-to-treat manifestations of MRSA infection, bacteremia and/or endocarditis and osteomyelitis. It also presents a brief review of community-associated MRSA infections and preventive strategies directed against MRSA. Micrococcus, which, when limited in extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicaemia and pyaemia, as well as many forms intermediate between the two extremes. Alexander Ogston, on the organism now known as S. aureus [1]

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Serious Infections Caused by Methicillin-Resistant Staphylococcus aureus

0 Mayo Clinic College of Medicine , Rochester, Minnesota 1 tissue, respiratory, bone, joint, and endovascular infec- tions. S. aureus remains, to date, one of the major causes of both health care-associated (HA) and community- associated (CA) infections. With the emergence of drug-resistant strains in the 1960s, primarily methicil- lin-resistant S. aureus (MRSA), this ubiquitous path- ogen has become an even greater therapeutic challenge. At present, MRSA strains account for 150% of all S. aureus strains causing clinical disease in many hospitals [5]. Relatively recently, MRSA has been seen in patients with CA infection, defined as infection in persons with- out health-related risk factors. In a study, CA-MRSA caused 150% of all suppurative skin infections among patients who presented to emergency departments (EDs) in 11 US metropolitan centers [6]. Of concern, serious and potentially lethal manifestations caused by 2 David Geffen School of Medicine at UCLA, Division of Infectious Diseases, Harbor-UCLA Medical Center , Torrance, California 3 Infectious Diseases Fellowship Program, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center , Boston, Massachusetts Although first identified just 14 decades ago, methicillin-resistant Staphylococcus aureus (MRSA) has undergone rapid evolutionary changes and epidemiologic expansion to become a major cause of nosocomial and community-acquired infections worldwide. Increasing resistance to vancomycin among MRSA strains in conjunction with availability of new antibiotics, including daptomycin and linezolid, have increased treatment choices but made clinical treatment decisions more challenging. This article describes the clinical features and management issues of 2 challenging-to-treat manifestations of MRSA infection, bacteremia and/or endocarditis and osteomyelitis. It also presents a brief review of community-associated MRSA infections and preventive strategies directed against MRSA. - Figure 1. Overall rates of Staphylococcus aureus bacteremia, methicillin-susceptible S. aureus bacteremia, and methicillin-susceptible S. aureus at 2 British hospitals from 1997 through 2004. *Slope of line is statistically significant (P ! .01). Reprinted with permission from [21]. Wyllie DH, Crook DW, Peto TE. Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 19972003: cohort study. BMJ 2006; 333:281. CA-MRSA have also been described. These infections have included necrotizing pneumonia [7], necrotizing fasciitis [8], severe sepsis [9], and Waterhouse-Friderichsen syndrome (characterized by petechial rash, coagulopathy, and cardiovascular collapse) [10]. Many of these infections occurred in apparently healthy hosts. These more serious infections are associated with strains of CA-MRSA found to harbor genes for Panton-Valentine leukocidin [11] and with a higher prevalence of genes for a-toxin and staphylococcal enterotoxin B, compared with that associated with HA-MRSA [12]. Of note, strains of CAMRSA that are found in the community have also been found to cause HA infections in among hospitalized patients [1315]. Three known mechanisms account for the resistance of S. aureus to the penicillins: hyperproduction of b-lactamases, modification of the normal penicillin-binding proteins (PBPs), and the presence of an acquired penicillin-binding protein (PBP2a) [16]. Most clinical isolates demonstrate the latter. With this mechanism, when penicillin is bound to normal PBPs, S. aureus strains are unable to properly assemble the cell wall, resulting in lysis and cell death. The unique, inducible, acquired PBP2a proteins produced by MRSA retain some low affinity for b-lactam antibiotics, although they permit antibiotic resistance in the presence of continued biosynthetic function [17]. Traditionally, because of the universal resistance of MRSA to b-lactams and because of the lack of other effective alternatives, the glycopeptide vancomycin became the mainstay of treatment, because it provides in vitro activity against all staphylococci and demonstrates clinical response against MRSA infection [18]. However, in vitro susceptibility of MRSA to vancomycin is no longer universal. A 1997 report of clinical strains of S. aureus with intermediate (minimum inhibitory S184 CID 2010:51 (Suppl 2) Boucher at al concentration [MIC], 816 mg/mL) susceptibility to vancomycin in Japan [19] was soon followed by descriptions of several frankly vancomycin-resistant S. aureus isolates (MIC, 32 mg/mL) in the United States [20]. This article describes the clinical features and management issues related to 2 of the most challenging S. aureus infections, bacteremia and/or endocarditis and osteomyelitis, with special emphasis on MRSA infections. Selected aspects of CA MRSA are also described. BACTEREMIA AND ENDOCARDITIS Among the infections caused by S. aureus, bacteremia is associated with relatively high morbidity and mortality. A study of mortality at 2 (...truncated)


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Helen Boucher, Loren G. Miller, Raymund R. Razonable. Serious Infections Caused by Methicillin-Resistant Staphylococcus aureus, Clinical Infectious Diseases, 2010, pp. S183-S197, 51/Supplement 2, DOI: 10.1086/653519