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)