Eradication of S aureus Carriage

Rates of S. aureus infection are higher in carriers than in non-carriers in a range of clinical settings (Weinstein 1959; Yu etal. 1986; Luzar etal. 1990; Weinke etal. 1992). This is consistent with the finding that individuals are usually infected with their own carriage isolate (Yu etal. 1986; Luzar etal. 1990; Nguyen etal. 1999; von Eiff etal. 2001b). Temporary eradication of carriage has been reported to result in a reduction in nosocomial infection in several patient groups and has been the focus of much recent interest and research. Eradication of S. aureus carriage is usually achieved by the topical application of antibiotic to the anterior nose. The most common agent in use is mupirocin, which has also been applied to exit sites of prosthetic devices such as intravenous and peritoneal dialysis catheters. A potentially promising agent currently under trial is lysostaphin, a peptidoglycan hydrolase secreted by Staphylococcus simulans that cleaves the polyglycine interpeptide bridges of the S. aureus cell wall. This agent is undergoing evaluation in both treatment and carriage eradication trials. Lysostaphin has been shown to have efficacy in the treatment of experimental S. aureus keratitis (Dajcs etal. 2000) and endocarditis (Climo etal. 1998; Patron etal. 1999). A single application of 0.5% lysostaphin formulated in a petrolatum-based cream eradicates S. aureus nasal colonization in 93% of animals in a cotton rat model. A single dose of lysostaphin cream was more effective than a single dose of mupirocin ointment at eradicating S. aureus nasal colonization in this animal model (Kokai-Kun etal. 2003). Exposure of S. aureus to lysostaphin alone results in the emergence of lysostaphin-resistant mutants in vitro and in vivo (Climo, Ehlert and Archer 2001), but it is unclear whether this will prove to be a limiting factor in clinical practice. Publication of study data pertaining to human use is awaited.

Many studies have been conducted to examine the effect of temporary carriage eradication, most of which have been in the dialysis population. Eradication of carriage by topical application of mupirocin to the nose in a cohort of haemodialysis patients led to a reduction in the number of episodes of S. aureus infection per patient year (Boelaert etal. 1989, 1993; Holton etal. 1991; Kluytmans etal. 1996). Efficacy of nasal S. aureus carriage eradication has also been evaluated for patients received peritoneal dialysis, but the evidence for efficacy of nasal mupirocin in preventing morbidity in CAPD patients is not convincing. Topical application of mupirocin to the peritoneal dialysis catheter exit site has been shown to reduce exit-site infection and peritonitis (Bernardini etal. 1996; Thodis etal. 1998). However, routine application of mupirocin to the exit site of all patients is likely to result in the rapid emergence of drug resistance. A double-blind, placebo-controlled trial of patients undergoing surgery was conducted to assess the effect of mupirocin on rates of postoperative S. aureus infection. Mupirocin did not significantly reduce the rate of S. aureus surgical-site infections overall, but it did significantly decrease the rate of all nosocomial S. aureus infections among patients who were S. aureus carriers (Perl etal. 2002). An evidence-based review has been performed to examine the efficacy of intranasal mupirocin in the eradication of S. aureus nasal carriage and in the prophylaxis of infection. Sixteen randomized, controlled trials were appraised, of which seven assessed the reduction in the rate of infection and nine trials assessed eradication of colonization as a primary outcome measure. Mupirocin was highly effective at eradication of nasal carriage in the short term, although 2-14-day courses did not result in long-term eradication. This did not convert into clinical benefit overall, although subgroup analyses and several small studies revealed lower rates of S. aureus infection among selected populations of patients with nasal carriage treated with mupirocin (Laupland and Conly 2003). The authors concluded that the available literature does not support routine use of topical intranasal mupirocin to prevent subsequent infections, but suggested that there are some patient groups who would benefit, particularly those with acute disease (cardiac surgery and head injury). Further studies are required to clarify this area. A Cochrane review has also been performed to examine the effects of topical and systemic antimicrobial agents on nasal and extranasal MRSA carriage, adverse events and incidence of subsequent MRSA infections. This study concluded that there is insufficient evidence to support the use of topical or systemic antimicrobial therapy for eradicating nasal or extranasal MRSA (Loeb etal. 2003).

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