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The NOSE study (nasal ointment for Staphylococcus aureus eradication): a randomized controlled trial of monthly mupirocin in HIV-infected individuals.

ABSTRACT: BACKGROUND:HIV-positive patients at HELP/PSI, Inc, an in-patient drug rehabilitation center, had a high baseline prevalence of Staphylococcus aureus colonization (49%) and incidence of infection (17%) in a previous year-long study. METHODS:A randomized, double-blinded, placebo-controlled study was conducted to determine whether repeated nasal application of mupirocin ointment would decrease the odds of S. aureus nasal colonization in 100 HELP/PSI patients over an 8-month period. A 5-day course of study drug was given monthly, and colonization was assessed at baseline and 1 month after each treatment. S. aureus infection was a secondary outcome. RESULTS:In repeated-measures analysis, mupirocin reduced the odds of monthly S. aureus nasal colonization by 83% compared with placebo [adjusted odds ratio (ORadj) = 0.17; P < 0.0001]. Subjects colonized at study entry had a 91% reduction in subsequent colonization (ORadj = 0.09; P < 0.0001). Mupirocin also suppressed S. aureus colonization in subjects not colonized at baseline (ORadj = 0.23; P = 0.006). There was no difference in infection rates between the mupirocin and placebo groups (hazard ratio = 0.49, P = 0.29). CONCLUSIONS:Monthly application of nasal mupirocin significantly decreased S. aureus colonization in HIV patients in residential drug rehabilitation. Monthly mupirocin application has a potential role in long-term care settings or in HIV-positive patients with high rates of S. aureus colonization and infection.

SUBMITTER: Gordon RJ

PROVIDER: S-EPMC2974816 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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The NOSE study (nasal ointment for Staphylococcus aureus eradication): a randomized controlled trial of monthly mupirocin in HIV-infected individuals.

Gordon Rachel J RJ Chez Nancy N Jia Haomiao H Zeller Barbara B Sobieszczyk Magda M Brennan Caitlin C Hisert Katherine B KB Lee Mei-Ho MH Vavagiakis Peter P Lowy Franklin D FD

Journal of acquired immune deficiency syndromes (1999) 20101201 4

<h4>Background</h4>HIV-positive patients at HELP/PSI, Inc, an in-patient drug rehabilitation center, had a high baseline prevalence of Staphylococcus aureus colonization (49%) and incidence of infection (17%) in a previous year-long study.<h4>Methods</h4>A randomized, double-blinded, placebo-controlled study was conducted to determine whether repeated nasal application of mupirocin ointment would decrease the odds of S. aureus nasal colonization in 100 HELP/PSI patients over an 8-month period. A ...[more]

PMID: 20686410

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Project description:In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. To identify proteins with an altered synthesis pattern in response to mupirocin treatment we used the highly sensitive 2-dimensional gel electrophoresis technique in combination with mass spectrometry. Obtained results were complemented by DNA-microarray, Northern blot and metabolome analysis. Whereas expression of genes involved in nucleotide biosynthesis, DNA metabolism, energy metabolism and translation was significantly down-regulated, expression of the isoleucyl-tRNA synthetase, the branched chain amino acids pathway, genes with functions in oxidative stress resistance (ahpC, katA), putative roles in stress protection (SACOL1759, SACOL2131, SACOL0815) and transport processes was increased. Of particular interest were the differences in the transcription of genes encoding virulence associated regulators (i.e. arlRS, saeRS, sarA, sarR, sarS) as well as genes directly involved in the virulence of S. aureus (i.e. fnbA, epiE, epiG, seb). In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. In total four independent hybridization experiments with each representing a biological replicate including a control and a treated sample were carried out. To account for the dye bias two of the four replicates were dye swapped.

Dataset Information

The NOSE study (nasal ointment for Staphylococcus aureus eradication): a randomized controlled trial of monthly mupirocin in HIV-infected individuals.

Publications

The NOSE study (nasal ointment for Staphylococcus aureus eradication): a randomized controlled trial of monthly mupirocin in HIV-infected individuals.

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