Increased Staphylococcus aureus Nasal Carriage Rates in Rheumatoid Arthritis Patients on Biologic Therapy.
ABSTRACT: BACKGROUND:Rheumatoid arthritis patients are at increased risk for periprosthetic joint infection after arthroplasty. The reason is multifactorial. Nasal colonization with Staphylococcus aureus is a modifiable risk factor; carriage rates in RA patients are unknown. The goal of this study is to determine the S aureus nasal carriage rates of RA patients on biologics, RA patients on traditional disease-modifying anti-rheumatic drugs (DMARDs), and osteoarthritis. METHODS:Consecutive patients with RA on biologics (±DMARDs), RA on non-biologic DMARDs, or OA were prospectively enrolled from April 2017 to May 2018. One hundred twenty-three patients were determined necessary per group to show a difference in carriage rates. Patients underwent a nasal swab and answered questions to identify additional risk factors. S aureus positive swabs were further categorized using spa typing. Logistic regression evaluated the association with S aureus colonization between the groups after controlling for known risk factors. RESULTS:RA patients on biologics, 70% of whom were on DMARDs, had statistically significant increase in S aureus colonization (37%) compared to RA on DMARDs alone (24%), or OA (20%) (P = .01 overall). After controlling for glucocorticoids, antibiotic use, recent hospitalization, and diabetes, RA on biologics had a significant increased risk of S aureus nasal colonization (Odds ratio 1.80, 95% confidence interval 1.00-3.22, P = .047). CONCLUSION:S aureus colonization risk was increased for RA on biologics compared to RA not on biologics and OA. Nasal S aureus carriage increases the risk of surgical site infection; this modifiable risk factor should be addressed prior to total joint arthroplasty for this higher risk patient group.
Project description:Staphylococcus aureus is a human commensal bacterium found in the nasal cavity and other body sites. Identifying risk factors for S. aureus nasal carriage is of interest, as nasal carriage is a risk factor for subsequent invasive infection. We recently investigated the influence of host genetics on S. aureus carriage in Danish middle-aged and elderly twins, which indicated no significant heritability that could account for the observed S. aureus carriage. In the present study, we performed a questionnaire-based study of S. aureus colonization on the same cohort of 2,196 Danish middle-aged and elderly twins to identify specific risk factors for S. aureus nasal colonization, including analyzing the paired twins (n?=?478) that were discordant for S. aureus colonization. We found associations between risk factors and S. aureus nasal colonization among middle-aged and elderly twins, including age, male gender, psoriasis, and atopic diseases. Also, present living on a farm is clearly associated with S. aureus colonization, while smoking had a borderline statistically significant protective effect.
Project description:BACKGROUND:Use of hormonal contraceptives has been associated with Staphylococcus aureus nasal carriage in adult women. However, the role of hormonal contraceptives in S. aureus colonization among adolescents and associations with progestin only contraceptives are unknown. METHODS:We obtained nasal and throat swab samples from 439 girls aged 17-21 years in the population-based Tromsø study Fit Futures, 2012-2013, Norway, with information on lifestyle, health and biomarkers. We used multivariable logistic regression to study the association between use of hormonal contraceptives and Staphylococcus aureus carriage while adjusting for potential confounding factors. RESULTS:Staphylococcus aureus nasal carriage prevalence were 34%, 42%, and 61% among progestin-only users, non-users, and progestin-estrogen combination contraceptive users, respectively (P<0.001). Use of combination contraceptives doubled the odds of nasal carriage (non-users reference; OR = 2.31, 95%CI = 1.43-3.74). The OR of nasal carriage was 0.29 among progestin-only users compared to combination contraceptives users (95% CI = 0.12-0.67). DISCUSSION:In this study, use of combination hormonal contraceptives was associated with higher risk of Staphylococcus aureus nasal carriage in adolescent girls. Experimental design studies are needed to establish the role of exogenous sex steroids in Staphylococcus aureus colonization in women.
Project description:Background: The anterior nares are the main ecological niche for Staphylococcus aureus, an important commensal and opportunistic pathogen. Medical students are frequently colonized by a variety of pathogens. Microbial interactions in the human nose can prevent or favor colonization by pathogens, and individuals colonized by pathogens have increased risk of infection and are the source of transmission to other community members or susceptible individuals. According to recent studies, the microbiome from several anatomic areas of healthy individuals varies across different ethnicities. Although previous studies analyzed the nasal microbiome in association with S. aureus carriage, those studies did not provide information regarding ethnicity of participants. Our aim was to assess S. aureus nasal carriage patterns and prevalence among medical students from Colombia, a country of Hispanic origin, and to investigate possible associations of colonization and nasal microbiome composition (bacterial and fungal) in a subgroup of students with known S. aureus carriage patterns. Methods: Nasal swabs from second-year medical students were used to determine prevalence and patterns of S. aureus nasal carriage. Based on microbiological results, we assigned participants into one of three patterns of S. aureus colonization: persistent, intermittent, and non-carrier. Then, we evaluated the composition of nasal microbial communities (bacterial and fungal) in 5 individuals from each carriage category using 16S rRNA and Internal-Transcribed-Spacer sequencing. Results: Prevalence of S. aureus nasal carriage among medical students was 28%. Carriage of methicillin-resistant strains was 8.4% and of methicillin-sensitive strains was 19.6%. We identified 19.6% persistent carriers, 17.5% intermittent carriers, and 62.9% non-carriers. Conclusions: Analysis of nasal microbiome found that bacterial and fungal diversity was higher in individuals colonized by S. aureus than in non-carriers; however, the difference among the three groups was non-significant. We confirmed that fungi were present within the healthy anterior nares at substantial biomass and richness.
Project description:INTRODUCTION:Staphylococcal infections can cause significant morbidity in patients undergoing dialysis. This study evaluated the effects of HIV infection on nasal carriage of Staphylococcus aureus, staphylococcal peritonitis, and catheter infection rates in patients with end-stage renal failure managed with continuous ambulatory peritoneal dialysis (CAPD). METHODS:Sixty HIV-positive and 59 HIV-negative CAPD patients were enrolled and followed up for up to 18 months. S. aureus nasal carriage (detected by nasal swab culture), Staphylococcal peritonitis (diagnosed by clinical presentation, and CAPD effluent Staphylococcal culture and white blood cell count ≥100 cells/µL), and catheter infections (including exit site and tunnel infections) were assessed monthly. RESULTS:At 18 months, S. aureus nasal carriage rates were 43.3% and 30.5% (p = 0.147) and the methicillin-resistant S. aureus (MRSA) nasal carriage rates were 31.7% and 13.6% (p = 0.018) for the HIV-positive and HIV-negative cohorts, respectively. The HIV-positive cohort was associated with increased hazards for staphylococcal peritonitis, (adjusted hazard ratio [AHR] 2.85, 95% confidence interval [CI] 1.19-6.84, p = 0.019) due to increased coagulase-negative staphylococcal (CNS) peritonitis rate in the HIV-positive cohort compared with the HIV-negative cohort (0.435 vs. 0.089 episodes/person-years; AHR 7.64, CI 2.18-26.82, p = 0.001). On multivariable analysis, CD4+ cell count <200 cells/µL, diabetes, and S. aureus nasal carriage were found to be independent predictors of S. aureus peritonitis. CONCLUSIONS:These findings suggest that HIV infection may be a risk factor for MRSA nasal colonization and may increase the risks of CNS peritonitis, while a CD4+ cell count <200 cells/µL and S. aureus nasal carriage may be important predictors of S. aureus peritonitis.
Project description:Objectives:The role of inflammation in OA is controversial and it is unclear whether suppressing inflammation with conventional or biologic DMARDs is effective. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare DMARDs with placebo in participants with symptomatic OA. Methods:Databases (Medline, Embase, Allied and Complementary Medicine Database, Web of Science and Cochrane Library), conference abstracts and ClinicalTrials.gov were searched to end of November 2017 for placebo-controlled RCTs of DMARDs, including biologics, in symptomatic OA. Pain data at treatment peak time point were extracted and combined using a random-effects meta-analysis. Markers of inflammation and adverse events were extracted and reviewed. Risk of bias assessment was conducted using Cochrane's tool. Results:Eleven RCTs (1205 participants) were meta-analysed, including six for conventional DMARDs (757 participants) and five for biologics (448 participants). Overall, DMARDs were statistically superior to placebo [effect size (ES) = 0.18, 95% CI: 0.03, 0.34], although the difference was not clinically significant (0.5 ES threshold). Furthermore, no statistically significant differences were observed in sub-analysis of high-quality trials (ES = 0.11, 95% CI : -0.06, 0.28), biologics (ES = 0.16, 95% CI: -0.02, 0.34) or conventional DMARDs (ES = 0.24, 95% CI: -0.05, 0.54). No difference was found between erosive vs non-erosive hand OA, hand vs knee OA or anti-IL1 vs anti-TNF biologics. Conclusion:DMARDs did not offer clinically significant pain relief above placebo in OA. This poor efficacy indicates that inflammation may not be a prime driver for OA pain.
Project description:Medical laboratory staff are a high-risk population for colonization of Staphylococcus aureus (S. aureus) due to direct and dense contact with the pathogens; however, there is limited information about this colonization. This study sought to determine the prevalence and molecular characteristics of nasal colonization by S. aureus in medical laboratory staff in Guangzhou, southern China, and to compare the differences between microbiological laboratory (MLS) and non-microbiological laboratory (NMLS) staff.S. aureus colonization was assessed by nasal swab cultures from 434 subjects, including 130 MLSs and 304 NMLSs from 33 hospitals in Guangzhou. All S. aureus isolates underwent the antimicrobial susceptibility test, virulence gene detection and molecular typing.The overall prevalence of S. aureus carriage was 20.1% (87/434), which was higher in MLSs than in NMLSs (26.2% vs. 17.4%, P?<?0.05), while the prevalence of Methicillin-resistant S. aureus (MRSA) was similar. Living with hospital staff was associated with S. aureus carriage. The majority of the isolates harboured various virulence genes, and those in MLSs appeared less resistant to antibiotics and more virulent than their counterparts. A total of 37 different spa types were detected; among these, t338, t437, t189 and t701 were the most frequently encountered types. T338 was the main spa type contributing to nasal colonization Methicillin-sensitive S. aureus (MSSA) (13.0%), and t437-SCCmec IV was predominant in MRSA isolates (40%).These findings provide insight into the risk factors, molecular epidemiology and virulence gene profiles of S. aureus nasal carriage among the medical laboratory staff in Guangzhou.
Project description:Staphylococcus aureus is a common human and animal opportunistic pathogen. In humans nasal carriage of S. aureus is a risk factor for various infections. Methicillin-resistant S. aureus ST398 is highly prevalent in pigs in Europe and North America. The mechanism of successful pig colonization by MRSA ST398 is poorly understood. Previously, we developed a nasal colonization model of porcine nasal mucosa explants to identify molecular traits involved in nasal MRSA colonization of pigs. Here, we report the analysis of the transcriptome of MRSA ST398 strain S0462 during colonization on the explant epithelium. Major regulated genes were encoding metabolic processes and regulation of these genes represents metabolic adaptation to nasal mucosa explants. Colonization was not accompanied by significant changes in transcripts of main virulence associated genes or known human colonization factors. Here, we document regulation of two genes which have potential influence on S. aureus colonization; cysteine extracellular proteinase (scpA) and von Willebrand factor-binding protein (vwbp, located on SaPIbov5). Colonization with isogenic-deletion strains (Δvwbp and ΔscpA) did not alter the nasal S. aureus colonization compared to wild type. Our results suggest that nasal colonization with MRSA ST398 is a complex event that is accompanied with changes in bacterial gene expression regulation and metabolic adaptation. Number of the samples: 5 (timepoint 0 min, 30 min, 60 min, 90 min and 180 min) in 4 replicates. 4 control samples
Project description:The natural history of contemporary Staphylococcus aureus nasal colonization was evaluated in community children during a 1-year period. Methicillin-susceptible S. aureus nasal carriage was more persistent than methicillin-resistant S. aureus nasal carriage, which was usually self-limited. Children with persistent staphylococcal colonization often carried identical strains. Identification of persistent methicillin-resistant S. aureus carriers might inform strategies for decolonization and reduction of staphylococcal transmission.
Project description:Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate.We used MarketScan® databases (2011-2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics. The date of first prescription was defined as the cohort entry. The therapy was considered effective if all of the following criteria from a claims-based algorithm were achieved at the first year of follow-up: high adherence, no biologic or tofacitinib switch or addition, no DMARD switch or addition, no increase in dose or frequency of index drug, no more than one glucocorticoid joint injection, and no new/increased oral glucocorticoid dose. The safety outcome was serious infections requiring hospitalization. Non-TNF biologics comprised the reference group.We included 21,832 patients with RA, including 0.8% treated with tofacitinib, 24.7% treated with other DMARDs, 61.2% who had started therapy with TNFi, and 13.3% treated with non-TNF biologics. The rates of therapy effectiveness were 15.4% for tofacitinib, 11.1% for DMARDs, 18.6% for TNFi, and 19.8% for non-TNF biologics. In adjusted analyses, tofacitinib and non-TNF biologics appeared to have similar effectiveness rates, whereas DMARD initiators were less effective than non-TNF biologics. We could not clearly establish if tofacitinib was associated with a higher rate of serious infections.In patients with RA previously treated with methotrexate, our comparisons of tofacitinib with non-TNF biologics, though not definitive, did not demonstrate differences with respect to hospitalized infections or effectiveness.
Project description:<h4>Background</h4>Nasal colonization by Staphylococcus aureus is a key risk factor for bacteremia. The objective of this study is to identify genomic modifications occurring in nasal carriage strains of S. aureus as they progress to bacteremia in a cohort of hospitalized patients.<h4>Methods</h4>Eight patients with S. aureus bacteremia were identified. Genomic sequences of the bloodstream isolates were compared with 57 nasal isolates collected longitudinally prior to the occurrence of bacteremia, which covered a timespan of up to 326 days before bacteremia.<h4>Results</h4>Within each subject, nasal colonizing strains were closely related to bacteremia strains. Within a subject, the number of single nucleotide polymorphisms (SNPs) observed between time points was greater than within a single time point. Co-colonization and strain replacement were observed in one case. In all cases colonization progressed to bacteremia without addition of new virulence genes. In one case, a mutation in the accessory gene regulator gene caused abrogation of agr function.<h4>Conclusion</h4>S. aureus evolves in the human nares at a variable rate. Progression of S. aureus nasal colonization to nosocomial infection is seldom associated with acquisition of new virulence determinants. Mutation in the agr gene with abrogation of function was associated with progression to bacteremia in one case.