Methicillin-resistant Staphylococcus aureus. Mechanisms of resistance and implications for treatment.
The frequency of methicillin-resistant Staphylococcus aureus (MRSA) continues to increase steadily, with nosocomial isolates approaching 50% of the total tested. Primarily isolated in hospitals, strains of MRSA have now spread into the community, complicating the management of this sometimes-fatal pathogen. Methicillin resistance in S aureus is mediated by the mecA gene, which encodes for a novel penicillin-binding protein (PBP), PBP-2a. In MRSA, exposure to methicillin inactivates the 4 high-binding-affinity PBPs normally present. PBP-2a, which displays a low affinity for methicillin, takes over the functions of these PBPs, permitting the cell to grow. Regulation of the methicillin-resistant phenotype and production of PBP-2a are influenced by the action of other genes. Two genes located upstream from mecA--mecR1 and mecI--control expression of PBP-2a. Antibiotics with high affinity for PBP-2a have displayed efficacy against MRSA in vivo, but none of these agents has made it beyond the investigational stage. Vancomycin remains the drug of choice for treatment of infections caused by MRSA, although it is intrinsically less active than the antistaphylococcal penicillins. Combinations of vancomycin with ss-lactam antibiotics may be synergistic in vivo against MRSA strains, including those with intermediate susceptibility to vancomycin. Given the increasing prevalence of MRSA in hospitals and in community settings, alternative approaches are needed for treatment of infections caused by MRSA.
Chambers
H F
HF
Division of Infectious Diseases, Department of Medicine, University of California-San Francisco, 3rd and Parnassus Aves., San Francisco, CA 94143, USA. chipc@itsa.ucsf.edu.
D001426:Bacterial Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D046915:Penicillin-Binding Proteins / Q000235:genetics; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D014481:United States / Q000453:epidemiology
D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; C487789:mecA protein, Staphylococcus aureus