Emergence of mupirocin resistance in multiresistant Staphylococcus aureus clinical isolates belonging to Brazilian epidemic clone III::B:A.
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Mupirocin is a topical antimicrobial agent that has been successfully used to eradicate methicillin-resistant Staphylococcus aureus from the anterior nares and other sites of patients and health care personnel. This report describes the acquisition of a novel mupirocin resistance gene (ileS) by an epidemic MRSA clone that is geographically widespread in Brazil. (+info)
Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus.
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Mupirocin has been widely used for the clearance of nasal methicillin-resistant Staphylococcus aureus (MRSA) carriage during outbreaks, but no placebo-controlled trial has evaluated its value for eradicating MRSA carriage at multiple body sites in settings where MRSA is not epidemic. In a 1,500-bed teaching hospital with endemic MRSA, 102 patients colonized with MRSA were randomized into a double-blind, placebo-controlled trial and treated with either mupirocin (group M) or placebo (group P) applied to the anterior nares for 5 days; both groups used chlorhexidine soap for body washing. Follow-up screening, susceptibility testing, and genotyping were performed to evaluate treatment success, mupirocin or chlorhexidine resistance, and exogenous recolonization. At baseline, MRSA carriage was 60% in the nares, 38% in the groin, and 62% in other sites (skin lesions, urine). The MRSA eradication rate (all body sites) was 25% in group M (12 of 48 patients), compared to 18% in group P (9 of 50 patients; relative risk [RR], 0.72; 95% confidence interval [CI95], 0.33 to 1.55). At the end of follow-up, 44% of patients (19 of 43) were free of nasal MRSA in group M, compared to 23% (11 of 44) in group P (RR, 0.57; CI95, 0.31 to 1.04). Ten patients developed MRSA infections (three in group M and seven in group P). One mupirocin treatment failure was due to exogenous MRSA recolonization. No MRSA isolate showed chlorhexidine resistance or high-level mupirocin resistance; however, we observed an association (P = 0.003) between low-level mupirocin resistance at study entry (prevalence, 23%) and subsequent treatment failure in both study arms. These results suggest that nasal mupirocin is only marginally effective in the eradication of multisite MRSA carriage in a setting where MRSA is endemic. (+info)
The antifungal activity of mupirocin.
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The antibacterial agent mupirocin (pseudomonic acid A) is used as a topical agent in the treatment of superficial infections by Gram-positive bacteria, particularly Staphylococcus aureus. However, we demonstrate here that the compound also inhibits the growth of a number of pathogenic fungi in vitro, including a range of dermatophytes and Pityrosporum spp. It inhibited the incorporation of amino acids and precursors of RNA, but not that of acetate, by Trichophyton mentagrophytes. It also inhibited the isoleucyl-tRNA synthetase from Candida albicans, indicating a mechanism of action similar to that in bacteria. When administered topically, mupirocin was efficacious in a T. mentagrophytes ringworm model in guinea pigs. These results suggest that mupirocin could have clinical utility for superficial infections caused by dermatophytes. (+info)
Cost-effectiveness of prophylactic nasal mupirocin in patients undergoing peritoneal dialysis based on a randomized, placebo-controlled trial.
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The study objective was to measure the benefits of elimination of nasal carriage of Staphylococcus aureus by calcium mupirocin ointment in patients undergoing continuous ambulatory peritoneal dialysis. The design was a prospective, placebo-controlled, randomized clinical trial. The subjects were 267 patients recruited from nine renal units in Belgium, France and the UK. The main outcome measures were the rate of catheter exit site infection (ESI), rates of other infections and healthcare costs from the perspective of a hospital budget-holder. The rate of ESI caused by S. aureus was significantly reduced from one in 28.1 patient months to one in 99.3 patient months (P = 0.006) and there were also non-significant trends towards lower rates of ESI caused by any organism and peritonitis caused by S. aureus. In comparison with the placebo group, patients in the mupirocin group with ESI had lower antibiotic (P = 0.02) and hospitalization costs (P = 0.065). However, overall costs of antibiotic treatment, for all infections combined, were not significantly different (P = 0.2) and total antibiotic costs (including mupirocin) were significantly higher in the mupirocin group (P = 0.001). Mupirocin prophylaxis would have been cost-neutral if the rate of ESI increased to >75% in the placebo group, or if all healthcare costs increased by 40%, or if the cost of screening was reduced from Pound Sterling 15 to Pound Sterling 3 per patient, or if the cost of mupirocin treatment was reduced from Pound Sterling 93 to Pound Sterling 40 per patient year. In conclusion, savings in healthcare costs are unlikely to be sufficiently great to offset the cost of mupirocin and screening for nasal carriage of S. aureus. The decision about whether or not to implement mupirocin should depend on a local analysis of the value of preventing ESIs caused by S. aureus. (+info)
A randomized clinical trial of mupirocin in the eradication of Staphylococcus aureus nasal carriage in human immunodeficiency virus disease.
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Seventy-six human immunodeficiency virus (HIV)-infected patients with Staphylococcus aureus nasal carriage were randomized to treatment groups receiving intranasal mupirocin or placebo twice daily for 5 days. Nasal cultures for S. aureus were obtained at 1, 2, 6, and 10 weeks after therapy. At 1 week, 88% of mupirocin-treated patients had negative nasal cultures compared with 8% in placebo patients (P<.001). The percentage of mupirocin-treated patients with persistently negative nasal cultures decreased over time (63%, 45%, and 29% at 2, 6, and 10 weeks, respectively) but remained significantly greater than the placebo group (3% at 2, 6, and 10 weeks). In mupirocin-treated patients, most (16/19) instances of nasal recolonization were with pretreatment strains (determined by means of by pulsed field gel electrophoresis); mupirocin resistance was not observed. Five days of treatment with mupirocin eliminated S. aureus nasal carriage in HIV-infected patients for several weeks; however, since the effect waned over time, intermittent dosing regimens should be considered for long-term eradication. (+info)
Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin.
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Isoleucyl-transfer RNA (tRNA) synthetase (IleRS) joins Ile to tRNA(Ile) at its synthetic active site and hydrolyzes incorrectly acylated amino acids at its editing active site. The 2.2 angstrom resolution crystal structure of Staphylococcus aureus IleRS complexed with tRNA(Ile) and Mupirocin shows the acceptor strand of the tRNA(Ile) in the continuously stacked, A-form conformation with the 3' terminal nucleotide in the editing active site. To position the 3' terminus in the synthetic active site, the acceptor strand must adopt the hairpinned conformation seen in tRNA(Gln) complexed with its synthetase. The amino acid editing activity of the IleRS may result from the incorrect products shuttling between the synthetic and editing active sites, which is reminiscent of the editing mechanism of DNA polymerases. (+info)
Outbreak of mupirocin-resistant staphylococci in a hospital in Warsaw, Poland, due to plasmid transmission and clonal spread of several strains.
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An outbreak of mupirocin-resistant (MuR) staphylococci was investigated in two wards of a large hospital in Warsaw, Poland. Fifty-three MuR isolates of Staphylococcus aureus, S. epidermidis, S. haemolyticus, S. xylosus, and S. capitis were identified over a 17-month survey which was carried out after introduction of the drug for the treatment of skin infections. The isolates were collected from patients with infections, environmental samples, and carriers; they constituted 19.5% of all staphylococcal isolates identified in the two wards during that time. Almost all the MuR isolates were also resistant to methicillin (methicillin-resistant S. aureus and methicillin-resistant coagulase-negative staphylococci). Seven of the outbreak isolates expressed a low-level-resistance phenotype (MuL), whereas the remaining majority of isolates were found to be highly resistant to mupirocin (MuH). The mupA gene, responsible for the MuH phenotype, has been assigned to three different polymorphic loci among the strains in the collection analyzed. The predominant polymorph, polymorph I (characterized by a mupA-containing EcoRI DNA fragment of about 16 kb), was located on a specific plasmid which was widely distributed among the entire staphylococcal population. All MuR S. aureus isolates were found to represent a single epidemic strain, which was clonally disseminated in both wards. The S. epidermidis population was much more diverse; however, at least four clusters of closely related isolates were identified, which suggested that some strains of this species were also clonally spread in the hospital environment. Six isolates of S. epidermidis were demonstrated to express the MuL and MuH resistance mechanisms simultaneously, and this is the first identification of such dual MuR phenotype-bearing strains. The outbreak was attributed to a high level and inappropriate use of mupirocin, and as a result the dermatological formulation of the drug has been removed from the hospital formulary. (+info)
Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections.
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A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin against S. pyogenes but superior against S. aureus (P < 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream against S. aureus but was significantly superior against S. pyogenes (P < 0.01). A hamster impetigo model infected with S. aureus was also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections. (+info)