The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis.
ABSTRACT: BACKGROUND:Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials. OBJECTIVES:To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers. METHODS:In this case-control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups. RESULTS:Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR ) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid-derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016). CONCLUSIONS:The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD.
Project description:Topical mupirocin is used widely to treat skin and soft tissue infections and to eradicate nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). Few studies to date have characterized the rates of S. aureus mupirocin resistance in pediatric populations. We retrospectively studied 358 unique S. aureus isolates obtained from 249 children seen in a predominantly outpatient setting by the Division of Pediatric Dermatology at a major academic center in New York City between 1 May 2012 and 17 September 2013. Mupirocin resistance rates and the associated risk factors were determined using a logistic regression analysis. In our patient population, 19.3% of patients had mupirocin-resistant S. aureus isolates at the time of their first culture, and 22.1% of patients with S. aureus infection had a mupirocin-resistant isolate at some time during the study period. Overall, 31.3% of all S. aureus isolates collected during the study period were resistant to mupirocin. Prior mupirocin use was strongly correlated (odds ratio [OR] = 26.5; P = <0.001) with mupirocin resistance. Additional risk factors for mupirocin resistance included methicillin resistance, atopic dermatitis (AD), epidermolysis bullosa (EB), immunosuppression, and residence in northern Manhattan and the Bronx. Resistance to mupirocin is widespread in children with dermatologic complaints in the New York City area, and given the strong association with mupirocin exposure, it is likely that mupirocin use contributes to the increased resistance. Routine mupirocin testing may be important for MRSA decolonization strategies or the treatment of minor skin infections in children.
Project description:It is not well understood why strains of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), a major cause of skin and soft tissue infections, became successful so quickly, overtaking the place of methicillin-sensitive S. aureus (MSSA) in many communities. To evaluate the genetic basis of differences in their virulence traits, 293 S. aureus isolates consisting of three cohorts, genotypically defined clinical CA-MRSA (n = 77), clinical MSSA (n = 103), and nasal carriage MSSA (n = 113), collected over a 19-year period in two Midwestern states in the United States, were (i) extensively genotyped and (ii) screened for 40 known virulence genes which included those for enterotoxins, leukocidins, hemolysins, and surface proteins and several newly identified putative toxin genes from the USA400 lineage of CA-MRSA. Genotypically, nasal carriage and clinical MSSA isolates were much more diverse than was the CA-MRSA group, which was found to be of USA400 lineage only. Virulence gene profiles of the three groups showed that CA-MRSA strains harbored significantly higher percentages (?95%; P value, <0.05) of the sea, sec, sec4, seg2, seh, sek, sel, sel2, ear, ssl1, lpl10, lukSF-PV, lukD, lukE, and clfA genes than did the carriage and the clinical MSSA group (range, 0% to 58%). Genes of the enterotoxin gene cluster, seg, sei, sem, sen, and seo, were present in the clinical and carriage isolates but not in the CA-MRSA group. These results suggest that the presence of additional virulence factors in USA400 CA-MRSA strains compared to the nasal carriage and clinical MSSA strains probably contributed to their enhanced virulence.
Project description:Staphylococcus aureus is a leading cause for clinical infections and food intoxications, causing over 100,000 yearly cases of bacteremia in the United States and 434 food-borne outbreaks in the European Union. Approximately 30% of the population permanently carry S. aureus asymptomatically in their nasal cavity. The risk of infection and transmission to food items or the environment is higher in individuals that are nasally colonized. In addition, S. aureus can acquire various antimicrobial resistances leading to therapeutic failure, additional medical costs, and fatalities. Methicillin-resistant S. aureus (MRSA) cause a considerable burden of disease in humans and animals. MRSA carriage has been associated with animal and in particular livestock contact. Extensive current data on the virulence gene profiles, as well as data on antimicrobial resistance determinants is crucial in developing effective strategies to mitigate the burden of disease. To this end, we screened the anterior nares of 160 test subjects (87 pupils and 73 members of farmer families) in Switzerland for S. aureus carriage. A total of 73 S. aureus isolates were obtained. Factors such as exposure to farm or companion animals and personal medical history were recorded using a questionnaire. Using a DNA microarray, isolates were assigned to clonal complexes (CCs), and virulence and resistance gene profiles were determined. The collected strains were assigned to 20 CCs, among others CC1, CC7, CC8, CC15, CC30, CC45, CC97, and CC398. Two MRSA strains and one multiresistant isolate carrying genes blaZ/I/R, InuA, aadD, tetK, and fosB were isolated from farmers with intensive exposure to animals. Strains carrying pvl, causing severe skin lesions and necrotizing pneumonia, as well as tetracycline, erythromycin, and kanamycin resistance genes were found in individuals that had taken antibiotics during the last year. A variety of superantigenic toxin genes was detected, including among others, the toxic shock syndrome toxin (tst1), and various enterotoxins (sea, sec, sel, and the egc cluster). Contact to chickens was identified as a significant factor contributing to S. aureus colonization.
Project description:Investigations regarding Staphylococcus aureus carriage among Brazilian children are scarce. We evaluated the determinants of S. aureus and methicillin-resistant S. aureus (MRSA) nasal carriage in infants attending day care centers (DCCs) and the molecular features of the MRSA strains. A total of 1,192 children aged 2 months to 5 years attending 62 DCCs were screened for S. aureus and MRSA nasal carriage. MRSA isolates were characterized by pulsed-field gel electrophoresis, multilocus sequence typing, spa typing, staphylococcal cassette chromosome (SCC) mec typing and the presence of the Panton-Valentine leukocidin gene. Logistic regression was performed to determine risk factors associated with S. aureus and MRSA colonization. S. aureus and MRSA carriage were detected in 371 (31.1%) and 14 (1.2%) children, respectively. Variables found to be independently associated with an increased risk for S. aureus carriage included being older than 24 months (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3 to 2.6) and previous DCC attendance (OR, 1.5; 95% CI, 1.0 to 2.2). Having a mother with a high level of education was a protective factor for nasal colonization (OR, 0.4; 95% CI, 0.2 to 0.8). Moreover, we observed that more children carrying MRSA had younger siblings than children not colonized by MRSA. Among the 14 MRSA strains, three SCCmec types (IIIA, IV, and V) were detected, together with a multidrug-resistant dominant MRSA lineage sharing 82.7% genetic similarity with the Brazilian clone (ST239-MRSA-IIIA; ST indicates the sequence type determined by multilocus sequence typing). Although SCCmec type V was recovered from one healthy child who had been exposed to known risk factors for hospital-associated MRSA, its genetic background was compatible with community-related MRSA. Our data suggest that DCC attendees could be contributing to MRSA cross-transmission between health care and community settings.
Project description:Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonization in AD patients. ClfB is a key adhesion molecule for the interaction of S. aureus with AD corneocytes and represents a target for intervention.
Project description:Staphylococcus aureus nasal carriage increases infection risk. However, few studies have investigated S. aureus acquisition/loss over >1 year, and fewer still used molecular typing.1123 adults attending five Oxfordshire general practices had nasal swabs taken. 571 were re-swabbed after one month then every two months for median two years. All S. aureus isolates were spa-typed. Risk factors were collected from interviews and medical records.32% carried S. aureus at recruitment (<1% MRSA). Rates of spa-type acquisition were similar in participants S. aureus positive (1.4%/month) and negative (1.8%/month, P = 0.13) at recruitment. Rates were faster in those carrying clonal complex (CC)15 (adjusted (a)P = 0.03) or CC8 (including USA300) (aP = 0.001) at recruitment versus other CCs. 157/274 (57%) participants S. aureus positive at recruitment returning ? 12 swabs carried S. aureus consistently, of whom 135 carried the same spa-type. CC22 (including EMRSA-15) was more prevalent in long-term than intermittent spa-type carriers (aP = 0.03). Antibiotics transiently reduced carriage, but no other modifiable risk factors were found.Both transient and longer-term carriage exist; however, the approximately constant rates of S. aureus gain and loss suggest that 'never' or truly 'persistent' carriage are rare. Long-term carriage varies by strain, offering new explanations for the success of certain S. aureus clones.
Project description:Staphylococcus aureus is a colonizing opportunistic pathogen and a leading cause of bloodstream infection with high morbidity and mortality. S. aureus carriage frequency is reportedly between 20 and 40?% among healthy adults, with S. aureus colonization considered to be a risk factor for S. aureus bacteraemia. It is unknown whether a genetic component of the bacterium is associated with S. aureus bacteraemia in comparison to nasal carriage strains. Previous association studies primarily focusing on the clinical outcome of an S. aureus infection have produced conflicting results, often limited by study design challenged by sample collections and the clonal diversity of S. aureus. To date, no study has investigated whether genomic features separate nasal carriage isolates from S. aureus bacteraemia isolates within a single clonal lineage. Here we have investigated whether genomic features, including single-nucleotide polymorphisms (SNPs), genes, or kmers, distinguish S. aureus nasal carriage isolates from bacteraemia isolates that all belong to the same clonal lineage [clonal complex 45 (CC45)] using whole-genome sequencing (WGS) and a genome-wide association (GWA) approach. From CC45, 100 isolates (50 bacteraemia and 50 nasal carriage, geographically and temporally matched) from Denmark were whole-genome sequenced and subjected to GWA analyses involving gene copy number variation, SNPs, gene content, kmers and gene combinations, while correcting for lineage effects. No statistically significant association involving SNPs, specific genes, gene variants, gene copy number variation, or a combination of genes was identified that could distinguish bacteraemia isolates from nasal carriage isolates. The presented results suggest that all S. aureus nasal CC45 isolates carry the potential to cause invasive disease, as no core or accessory genome content or variations were statistically associated with invasiveness.
Project description:This study aimed to evaluate the persistence of nasal carriage of Staphylococcus aureus, methicillin-resistant S. aureus and multidrug-resistant S. aureus over 14?days of follow-up among industrial hog operation workers in North Carolina.Workers anticipating at least 24?h away from work were enrolled June-August 2012. Participants self-collected a nasal swab and completed a study journal on the evening of day 1, and each morning and evening on days 2-7 and 14 of the study. S. aureus isolated from nasal swabs were assessed for antibiotic susceptibility, spa type and absence of the scn gene. Livestock association was defined by absence of scn.Twenty-two workers provided 327 samples. S. aureus carriage end points did not change with time away from work (mean 49?h; range >0-96?h). Ten workers were persistent and six were intermittent carriers of livestock-associated S. aureus. Six workers were persistent and three intermittent carriers of livestock-associated multidrug-resistant S. aureus. One worker persistently carried livestock-associated methicillin-resistant S. aureus. Six workers were non-carriers of livestock-associated S. aureus. Eighty-two per cent of livestock-associated S. aureus demonstrated resistance to tetracycline. A majority of livestock-associated S. aureus isolates (n=169) were CC398 (68%) while 31% were CC9. No CC398 and one CC9 isolate was detected among scn-positive isolates.Nasal carriage of livestock-associated S. aureus, multidrug-resistant S. aureus and methicillin-resistant S. aureus can persist among industrial hog operation workers over a 14-day period, which included up to 96?h away from work.
Project description:Staphylococcus aureus is an important cause of infection, and brings additional concern with methicillin resistance. In addition, nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization rates among health care workers are higher than that for general population. To determine the prevalence rate and risk factors for the colonization of S. aureus, including MRSA, among janitors working in hospitals in northern Taiwan, we conducted this study.Between June and August, 2014, a total of 186 janitors, 111 working in hospitals and 75 working in non-medical institutions, were recruited. Specimens were obtained from the nares of the subjects for the detection of S. aureus, with a questionnaire completed for each subject. All the S. aureus isolates, including MRSA and methicillin-susceptible S. aureus (MSSA), were further molecularly characterized.The nasal carriage rate of S. aureus was 15.3% for hospital janitors and 13.3% for non-medical janitors. The carriage rate of MRSA was 3.6% for hospital janitors and 1.3% for non-medical janitors. No statistically significant difference was found in the nasal carriage rate of S. aureus (p = 0.707) and MRSA (p = 0.65) between hospital janitors and non-medical janitors. Hospital janitors working in hospital more than 6 years and cleaning microbiologic laboratories were significantly associated with nasal S. aureus colonization. All 5 MRSA isolates carried either staphylococcal cassette chromosome type IV or V and three of them belonged to sequence type (ST) 59, the community clone prevailing in Taiwan. Of the 22 MSSA isolates, six pulsotypes were identified, with one major type for 14 isolates (shared by five STs) and another type for 4 isolates (all belonged to ST 188).Exposure to the hospital environment may not increase the nasal carriage rate of S. aureus, including MRSA, among janitors in hospitals in Taiwan. However, for janitors in the hospital setting, working for more than six years in hospital and cleaning laboratories may be risks factors for carrying S. aureus.
Project description:Swine production work is a risk factor for nasal carriage of livestock-associated (LA-) Staphylococcus aureus and also for skin and soft tissue infection (SSTI). However, whether LA-S. aureus nasal carriage is associated with increased risk of SSTI remains unclear. We aimed to examine S. aureus nasal carriage and recent (?3 months prior to enrollment) SSTI symptoms among industrial hog operation (IHO) workers and their household contacts. IHO workers and their household contacts provided a nasal swab and responded to a questionnaire assessing self-reported personal and occupational exposures and recent SSTI symptoms. Nasal swabs were analyzed for S. aureus, including methicillin-resistant S. aureus (MRSA), multidrug-resistant-S. aureus (MDRSA), absence of scn (livestock association), and spa type. S. aureus with at least one indicator of LA was observed among 19% of 103 IHO workers and 6% of 80 household members. Prevalence of recent SSTI was 6% among IHO workers and 11% among 54 minor household members (0/26 adult household members reported SSTI). Among IHO workers, nasal carriers of MDRSA and scn-negative S. aureus were 8.8 (95% CI: 1.8, 43.9) and 5.1 (95% CI: 1.2, 22.2) times as likely to report recent SSTI as non-carriers, respectively. In one household, both an IHO worker and child reported recent SSTI and carried the same S. aureus spa type (t4976) intranasally. Prevalence of scn-negative S. aureus (PR: 5.0, 95% CI: 1.2, 21.4) was elevated among IHO workers who reported never versus always wearing a face mask at work. Although few SSTI were reported, this study of IHO workers and their household contacts is the first to characterize a relation between nasal carriage of antibiotic-resistant LA-S. aureus and SSTI. The direction and temporality of this relation and IHO workers' use of face masks to prevent nasal carriage of these bacteria warrant further investigation.