Henri A. Verbrugh

Staphylococcus aureus has long been recognized as an important pathogen in human disease. Due to an increasing number of infections caused by methicillin-resistant S. aureus (MRSA) strains, therapy has become problematic. Therefore, prevention of staphylococcal infections has become more important. Carriage of S. aureus appears to play a key role in the epidemiology and pathogenesis of infection. The ecological niches of S. aureus are the anterior nares. In healthy subjects, over time, three patterns of carriage can be distinguished: about 20% of people are persistent carriers, 60% are intermittent carriers, and approximately 20% almost never carry S. aureus. The molecular basis of the carrier state remains to be elucidated. In patients who repeatedly puncture the skin (e.g., hemodialysis or continuous ambulatory peritoneal dialysis [CAPD] patients and intravenous drug addicts) and patients with human immunodeficiency virus (HIV) infection, increased carriage rates are found. Carriage has been identified as an important risk factor for infection in patients undergoing surgery, those on hemodialysis or CAPD, those with HIV infection and AIDS, those with intravascular devices, and those colonized with MRSA. Elimination of carriage has been found to reduce the infection rates in surgical patients and those on hemodialysis and CAPD. Elimination of carriage appears to be an attractive preventive strategy in patients at risk. Further studies are needed to optimize this strategy and to define the groups at risk.

BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. METHODS: In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. RESULTS: From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005). CONCLUSIONS: The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.)

Short-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneous. SSRs are encountered in many different branches of the prokaryote kingdom. They are found in genes encoding products as diverse as microbial surface components recognizing adhesive matrix molecules and specific bacterial virulence factors such as lipopolysaccharide-modifying enzymes or adhesins. SSRs enable genetic and consequently phenotypic flexibility. SSRs function at various levels of gene expression regulation. Variations in the number of repeat units per locus or changes in the nature of the individual repeat sequences may result from recombination processes or polymerase inadequacy such as slipped-strand mispairing (SSM), either alone or in combination with DNA repair deficiencies. These rather complex phenomena can occur with relative ease, with SSM approaching a frequency of 10(-4) per bacterial cell division and allowing high-frequency genetic switching. Bacteria use this random strategy to adapt their genetic repertoire in response to selective environmental pressure. SSR-mediated variation has important implications for bacterial pathogenesis and evolutionary fitness. Molecular analysis of changes in SSRs allows epidemiological studies on the spread of pathogenic bacteria. The occurrence, evolution and function of SSRs, and the molecular methods used to analyze them are discussed in the context of responsiveness to environmental factors, bacterial pathogenicity, epidemiology, and the availability of full-genome sequences for increasing numbers of microorganisms, especially those that are medically relevant.