Effectiveness of Measures to Eradicate Staphylococcus aureus Carriage in Patients with Community-Associated Skin and Soft-Tissue Infections: A Randomized Trial

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Infection Control and Hospital Epidemiology (Impact Factor: 4.18). 09/2011; 32(9):872-80. DOI: 10.1086/661285
Source: PubMed


Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft-tissue infection (SSTI).
Compare the effectiveness of 4 regimens for eradicating S. aureus carriage.
Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at 1 and 4 months.
Barnes-Jewish and St. Louis Children's Hospitals, St. Louis, Missouri, 2007-2009.
Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds.
Participants were randomized to receive no therapeutic intervention (control subjects) or one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths.
Among 244 participants with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group, 56% of those in the mupirocin group (P = .03 vs controls), 55% of those in the mupirocin and chlorhexidine group (P = .05), and 63% off those in the mupirocin and bleach group (P = .006). Of 229 participants with 4-month colonization data, eradication rates were 48% in the control group, 56% in the mupirocin only group (P = .40 vs controls), 54% in the mupirocin and chlorhexidine group (P = .51), and 71% in the mupirocin and bleach group (P = .02). At 1 and 4 months, recurrent SSTIs were reported by 20% and 36% of participants, respectively.
An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over a 4-month period. High rates of recurrent SSTI suggest that factors other than endogenous colonization are important determinants of infection. Trial registration. identifier: NCT00513799.

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Available from: Jonathan Louis Dukes, Nov 11, 2014
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    • "Each agent in the model is in one of three disease states at any time: colonized (denoted by C), uncolonized (denoted by U), or infected (denoted by I). Individuals transition between these states, and individuals return to being susceptible after an infection or colonization, consistent with the observed frequency of repeat infections [29]. Figure 3 summarizes the disease states and transitions. "
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    ABSTRACT: Background Methicillin-resistant Staphylococcus aureus (MRSA) has been a deadly pathogen in healthcare settings since the 1960s, but MRSA epidemiology changed since 1990 with new genetically distinct strain types circulating among previously healthy people outside healthcare settings. Community-associated (CA) MRSA strains primarily cause skin and soft tissue infections, but may also cause life-threatening invasive infections. First seen in Australia and the U.S., it is a growing problem around the world. The U.S. has had the most widespread CA-MRSA epidemic, with strain type USA300 causing the great majority of infections. Individuals with either asymptomatic colonization or infection may transmit CA-MRSA to others, largely by skin-to-skin contact. Control measures have focused on hospital transmission. Limited public health education has focused on care for skin infections. Methods We developed a fine-grained agent-based model for Chicago to identify where to target interventions to reduce CA-MRSA transmission. An agent-based model allows us to represent heterogeneity in population behavior, locations and contact patterns that are highly relevant for CA-MRSA transmission and control. Drawing on nationally representative survey data, the model represents variation in sociodemographics, locations, behaviors, and physical contact patterns. Transmission probabilities are based on a comprehensive literature review. Results Over multiple 10-year runs with one-hour ticks, our model generates temporal and geographic trends in CA-MRSA incidence similar to Chicago from 2001 to 2010. On average, a majority of transmission events occurred in households, and colonized rather than infected agents were the source of the great majority (over 95%) of transmission events. The key findings are that infected people are not the primary source of spread. Rather, the far greater number of colonized individuals must be targeted to reduce transmission. Conclusions Our findings suggest that current paradigms in MRSA control in the United States cannot be very effective in reducing the incidence of CA-MRSA infections. Furthermore, the control measures that have focused on hospitals are unlikely to have much population-wide impact on CA-MRSA rates. New strategies need to be developed, as the incidence of CA-MRSA is likely to continue to grow around the world.
    Journal of Translational Medicine 05/2014; 12(1):124. DOI:10.1186/1479-5876-12-124 · 3.93 Impact Factor
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    • "Clinical strains from multiple body site sources (blood, sputum, and wound) were collected through the Centers for Disease Control and Prevention Active Bacterial Core Surveillance system of the Emerging Infections Program: A nationwide S. aureus surveillance program at the University of Iowa Carver College of Medicine, and Emory University Hospital in Atlanta (Klevens et al. 2007; Limbago et al. 2009; Satola et al. 2009, 2011; Richter et al. 2011). The nasal colonization strain was collected as part of a decolonization study by the Washington University School of Medicine in St. Louis (Fritz et al. 2011). Etest MICs were determined using a 0.5 McFarland standard inoculum on Mueller–Hinton Agar plates (Remel, Lenexa, KS) and vancomycin Etest strips (bioMérieux, Durham, NC) according to the manufacturer’s instructions. "
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    ABSTRACT: Vancomycin intermediate Staphylococcus aureus (VISA) is currently defined as having MIC (minimal inhibitory concentration) of 4-8 μg/ml. VISA evolves through changes in multiple genetic loci with at least 16 candidate genes identified in clinical and in vitro-selected VISA strains. We report a whole genome comparative analysis of 49 vancomycin sensitive S. aureus (VSSA) and 26 VISA strains. Resistance to vancomycin was determined by broth microdilution, Etest and PAP-AUC (population analysis profile-area under the curve). Genome-wide association studies (GWAS) of 55,977 SNPs identified in one or more strains found one highly significant association (P = 8.78E-08) between a nonsynonymous mutation at codon 481 (H481) of the rpoB gene and increased vancomycin MIC. Additionally, we used a database of public S. aureus genome sequences to identify rare mutations in candidate genes associated with VISA. Based on these data, we proposed a preliminary model called ECM+RMCG for the VISA phenotype as a benchmark for future efforts. The model predicted VISA based on the presence of a rare mutation in a set of candidate genes (walKR, vraSR, graSR, agrA), and/or three previously experimentally verified mutations (including the rpoB H481 locus) with an accuracy of 81% and a sensitivity of 73%. Further, the level of resistance measured by both Etest and PAP-AUC regressed positively with the number of mutations present in a strain. This study demonstrated (i) the power of GWAS for identifying common genetic variants associated with antibiotic resistance in bacteria and (ii) that rare mutations in candidate gene, identified using large genomic datasets, can also be associated with resistance phenotypes.
    Genome Biology and Evolution 04/2014; 6(5). DOI:10.1093/gbe/evu092 · 4.23 Impact Factor
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    • "USA300 accounted for the majority of these infections. The limited success of decolonization strategies to prevent recurrent infections in households has also raised concern regarding the role of environmental contamination in these infections [22], [23]. "
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    ABSTRACT: Background The household is a recognized community reservoir for Staphylococcus aureus. This study investigated potential risk factors for intra-household S. aureus transmission, including the contribution of environmental contamination. Methods We investigated intra-household S. aureus transmission using a sample of multiple member households from a community-based case-control study examining risk factors for CA-MRSA infection conducted in Northern Manhattan. During a home visit, index subjects completed a questionnaire. All consenting household members were swabbed, as were standardized environmental household items. Swabs were cultured for S. aureus. Positive isolates underwent further molecular characterization. Intra-household transmission was defined as having identical strains among two or more household members. Multiple logistic regression was used to identify independent risk factors for transmission. Results We enrolled 291 households: 146 index cases, 145 index controls and 687 of their household contacts. The majority of indexes were Hispanic (85%), low income (74%), and female (67%), with a mean age of 31 (range 1–79). The average size of case and control households was 4 people. S. aureus colonized individuals in 62% of households and contaminated the environment in 54% of households. USA300 was the predominant clinical infection, colonizing and environmental strain. Eighty-one households had evidence of intra-household transmission: 55 (38%) case and 26 (18%) control households (P<.01). Environmental contamination with a colonizing or clinical infection strain (aOR: 5.4 [2.9–10.3] P<.01) and the presence of a child under 5 (aOR: 2.3 [1.2–4.5] P = .02) were independently associated with transmission. In separate multivariable models, environmental contamination was associated with transmission among case (aOR 3.3, p<.01) and control households (aOR 27.2, p<.01). Conclusions Environmental contamination with a colonizing or clinical infection strain was significantly and independently associated with transmission in a large community-based sample. Environmental contamination should be considered when treating S. aureus infections, particularly among households with multiple infected members.
    PLoS ONE 11/2012; 7(11):e49900. DOI:10.1371/journal.pone.0049900 · 3.23 Impact Factor
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