Comparison of livestock-associated and community-associated Staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection.
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ABSTRACT:
SUBMITTER: Randad PR
PROVIDER: S-EPMC6494861 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
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Comparison of livestock-associated and community-associated Staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection.
Randad Pranay R PR Dillen Carly A CA Ortines Roger V RV Mohr David D Aziz Maliha M Price Lance B LB Kaya Hülya H Larsen Jesper J Carroll Karen C KC Smith Tara C TC Miller Lloyd S LS Heaney Christopher D CD
Scientific reports 20190501 1
Industrial hog operation (IHO) workers are at increased risk of carrying Staphylococcus aureus in their nares, particularly strains that are livestock-associated (LA) and multidrug-resistant. The pathogenicity of LA-S. aureus strains remains unclear, with some prior studies suggesting reduced transmission and virulence in humans compared to community-associated methicillin-resistant (CA-MRSA) S. aureus. The objective of this study was to determine the degree to which LA-S. aureus strains contrac ...[more]
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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.
| S-EPMC5112983 | biostudies-literature
Project description:BackgroundStaphylococcus aureus is a major pathogen causing significant morbidity and mortality worldwide. The emergence of MDR S. aureus strains in the community setting has major implications in disease management. However, data regarding the occurrence and patterns of MDR community-associated S. aureus sub-clones is limited.ObjectivesTo use whole-genome sequences to describe the diversity and distribution of resistance mechanisms among community-associated S. aureus isolates.MethodsS. aureus isolates from skin and soft tissue infections (SSTIs) and nasal colonization were collected from patients within 10 primary care clinics from 2007 to 2015. The Illumina Miseq platform was used to determine the genome sequences for 144 S. aureus isolates. Phylogenetic and bioinformatics analyses were performed using in silico tools. The resistome was assembled and compared with the phenotypically derived antibiogram.ResultsApproximately one-third of S. aureus isolates in the South Texas primary care setting were MDR. A higher proportion of SSTI isolates were MDR in comparison with nasal colonization isolates. Individuals with MDR S. aureus SSTIs were more likely to be African American and obese. Furthermore, S. aureus populations are able to acquire and lose antimicrobial resistance genes. USA300 strains were differentiated by a stable chromosomal mutation in gyrA conferring quinolone resistance. The resistomes were highly predictive of antimicrobial resistance phenotypes.ConclusionsThese findings highlight the high prevalence and epidemiological factors associated with MDR S. aureus strains in the community setting and demonstrate the utility of next-generation sequencing to potentially quicken antimicrobial resistance detection and surveillance for targeted interventions.
| S-EPMC5890715 | biostudies-literature
Project description:ObjectiveDetermine the prevalence and relatedness of Staphylococcus aureus anterior nares colonization in individuals with community-associated staphylococcal skin and soft-tissue infection (SSTI).DesignObservational cohort.SettingUS Army soldiers undergoing infantry training.ParticipantsTrainees who developed SSTI from May 2010 to January 2012.MethodsParticipants underwent anterior nares culture at the time of presentation for purulent SSTI. We determined the prevalence of S. aureus nasal colonization and strain relatedness between colonizing and clinical isolates with pulsed-field gel electrophoresis (PFGE).ResultsWe enrolled 1,203 SSTI participants, of whom 508 had culture-confirmed S. aureus SSTI. Overall, 70% (357/508) were colonized with S. aureus. Phenotypically, concordant colonization was more common with methicillin-susceptible S. aureus (MSSA; 56%; 122/218) than methicillin-resistant S. aureus (MRSA) SSTI (41%; 118/290; P < .01). With PFGE, 48% (121 of 254) of clinical-colonizing pairs were indistinguishable, and concordant colonization was more common with MRSA (53%; 92/173) than MSSA SSTI (36%; 29/81; P < .01). Restricting analysis to concomitant MRSA-MRSA or MSSA-MSSA pairs, 92% (92/100) of MRSA SSTI were indistinguishable, and 40% (29/72) MSSA SSTI were indistinguishable (P < .01). All 92 MRSA pairs were USA300.ConclusionsOn the phenotypic level, concordant anterior nares colonization with incident staphylococcal SSTI is more common in MSSA than MRSA; however, the opposite is observed when accounting for molecular typing, and MRSA SSTI displays greater concordance. USA300 was responsible for strain concordance with MRSA SSTI. Studies are needed to examine the roles of nasal and extra-nasal carriage, colonization preceding infection, and increased virulence in the pathogenesis of MRSA SSTI.Trial registrationClinicalTrials.gov identifier: NCT01105767.
| S-EPMC5824647 | biostudies-literature
Project description:Adult community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-susceptible S. aureus (CA-MSSA) skin and soft tissue infection (SSTI) in China is not well described. A prospective cohort of adults with SSTI was established between January 2009 and August 2010 at 4 hospitals in Beijing. Susceptibility testing and molecular typing, including multilocus sequence typing, spa, agr typing, and toxin detection were assessed for all S. aureus isolates. Overall, 501 SSTI patients were enrolled. Cutaneous abscess (40.7%) was the most common infection, followed by impetigo (6.8%) and cellulitis (4.8%). S. aureus accounted for 32.7% (164/501) of SSTIs. Five isolates (5/164, 3.0%) were CA-MRSA. The most dominant ST in CA-MSSA was ST398 (17.6%). The prevalence of Panton-Valentine Leukocidin (pvl) gene was 41.5% (66/159) in MSSA. Female, younger patients and infections requiring incision or drainage were more commonly associated with pvl-positive S. aureus (P<0.03); sec gene was more often identified in CC5 (P<0.03); seh gene was more prevalent in CC1 (P = 0.001). Importantly, ST59 isolates showed more resistance to erythromycin, clindamycin and tetracycline, and needed more surgical intervention. In conclusion, CA-MRSA infections were rare among adult SSTI patients in Beijing. Six major MSSA clones were identified and associated with unique antimicrobial susceptibility, toxin profiles, and agr types. A high prevalence of livestock ST398 clone (17.1% of all S. aureus infections) was found with no apparent association to animal contact.
| S-EPMC3368899 | biostudies-other
Project description:BackgroundDevising effective, targeted approaches to prevent recurrent meticillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection requires an understanding of factors driving MRSA acquisition. We comprehensively defined household longitudinal, strain-level S aureus transmission dynamics in households of children with community-associated MRSA skin and soft tissue infection.MethodsFrom 2012-15, otherwise healthy paediatric patients with culture-confirmed, community-onset MRSA infections were recruited for the Household Observation of MRSA in the Environment (HOME) prospective cohort study from hospitals and community practices in metropolitan St Louis (MO, USA). Children with health-care-related risk factors were excluded, as determined by evidence of recent hospital admission, an invasive medical device, or residence in a long-term care facility. Household contacts (individuals sleeping in the home ?four nights per week) and indoor dogs and cats were also enrolled. A baseline visit took place at the index patient's primary home, followed by four quarterly visits over 12 months. At each visit, interviews were done and serial cultures were collected, to detect S aureus from three anatomic sites of household members, two anatomic sites on dogs and cats, and 21 environmental surfaces. Molecular typing was done by repetitive-sequence PCR to define distinct S aureus strains within each household. Longitudinal, multivariable generalised mixed-effects logistic regression models identified factors associated with S aureus acquisition.FindingsAcross household members, pets, and environmental surfaces, 1267 strain acquisition events were observed. Acquisitions were driven equally by 510 introductions of novel strains into households and 602 transmissions within households, each associated with distinct factors. Frequent handwashing decreased the likelihood of novel strain introduction into the household (odds ratio [OR] 0·86, credible interval [CrI] 0·74-1·01). Transmission recipients were less likely to own their homes (OR 0·77, CrI 0·63-0·94) and were more likely to share bedrooms with strain-colonised individuals (OR 1·33, CrI 1·12-1·58), live in homes with higher environmental S aureus contamination burden (OR 3·97, CrI 1·96-8·20), and report interval skin and soft tissue infection (OR 1·32, CrI 1·07-1·64). Transmission sources were more likely to share bath towels (OR 1·25, CrI 1·01-1·57). Pets were often transmission recipients, but rarely the sole transmission source.InterpretationThe household environment plays a key role in transmission, a factor associated with skin and soft tissue infection. Future interventions should inclusively target household members and the environment, focusing on straightforward changes in hand hygiene and household sharing behaviours.FundingNational Institutes of Health, Agency for Healthcare Research and Quality, Children's Discovery Institute, Burroughs Wellcome Foundation, Defense Advanced Research Projects Agency.
| S-EPMC6995751 | biostudies-literature
Project description:BackgroundStaphylococcus aureus causes various infections, including skin and soft tissue infections (SSTIs). In this study, methicillin-susceptible S. aureus (MSSA) from SSTIs among patients in three tertiary-care hospitals in Greece were studied in terms of antimicrobial resistance, clonal distribution, toxin and adhesin genes carriage.ResultsDuring a five-year period (2014-2018), 6145 S. aureus were recovered from 13,244 patients with SSTIs and tested for antimicrobial susceptibility. MSSA were 4806 (78.21 %) including 1484 isolates with mupirocin minimum inhibitory concentration (MIC) > 64 mg/L (30.88 %). Two hundred and sixty representative mupirocin-resistant MSSA were analyzed for genes encoding Panton-Valentine leukocidin (PVL, lukS/lukF-PV), exfoliative toxins (eta, etb), adhesin FnbA (fnbA) and resistance genes mupA (high-level resistance to mupirocin), fusB (fusidic acid), aminoglycosides' modifying enzymes, ermA, ermC and msrA (macrolides/lincosamides) by PCRs. Strains were classified into clones by PFGE and MLST. All mupirocin-resistant MSSA were penicillin-resistant; 92.7 % expressed resistance to fusidic acid and 88.9 % to tobramycin. All 260 molecularly analyzed isolates were mupA-positive; all fusidic acid-resistant (241/260) carried fusB whereas, the tobramycin-resistant ones (230), ant(4')-Ia. The majority carried eta (93.85 %), etb (98.08 %) and fnbA (88.85 %). PFGE typing revealed a mostly unvarying population; 260 MSSA were grouped into three types. One major eta/etb-positive clone comprising of 258/260 strains (99.2 %), PFGE type 1, was classified as ST121, including nine strains co-carrying PVL. Another PVL-positive strain was identified as ST1, and one toxins-negative as ST21.ConclusionsA mupirocin-resistant MSSA clone, ST121, carrying resistance, exfoliative toxins and adhesin genes, was spread and predominated in SSTIs from patients in Greece during the five-year studied period.
| S-EPMC8254358 | biostudies-literature
Project description:BackgroundThe antibacterial activities of aqueous leaf extracts of Moringa oleifera, Vernonia amygdalina, Azadirachta indica and Acalypha wilkesiana against multidrug resistance (MDR) Staphylococcus aureus associated with skin and soft tissue infections were investigated.MethodsStaphylococcus aureus (n = 183) from the skin and soft tissue infections with evidence of purulent pus, effusions from aspirates, wounds, and otorrhea were biotyped, and evaluated for biofilm production. The phenotypic antibiotic resistance and MDR strains susceptibility to plant leaves extract were determined using disc diffusion and micro-broth dilution assays respectively. The correlation of plant extract bioactive components with inhibitory activities was determined.ResultsHigh occurrence rate of S. aureus were recorded among infant and adult age groups and 13.2% mild biofilm producers from the wound (p < 0.05). Of 60.2% MDR strains with overall significant MARI of more than 0.85 (p < 0.05), high resistant rates to linozidine (92.7%; 95% CI:7.27-10.52), ofloxacin (94.2%; 95% CI:6.09-8.15), chloramphenicol (91.2%; 95% CI:6.11-8.32), gentamicin (97.3%; 95% CI:6.20-8.22), ciprofloxacin (92.7%; 95% CI: 5.28-7.99) and vancomycin (86.6%; 95% CI:6.81-9.59) were observed. Vernonia amygdalina and Azadirachta indica showed significant antimicrobial activity at 100 mg/ml and 75 mg/ml, with low susceptibility of less than 10% to 25 mg/ml, 50 mg/ml, and 75 mg/ml Moringa oleifera. Alkaloids, saponin and terpenoids were significant in Moringa oleifera, Acalypha wilkesiana, Azadirachta indica and Vernonia amygdalina leaves extracts (p < 0.05). High inhibitory concentrations at IC50; 3.23, 3.75 and 4.80 mg/ml (p = 0.02, CI: - 0.08 - 11.52) and IC90; 12.9, 7.5, and 9.6 mg/ml (p = 0.028, CI: 2.72-23.38) were shown by Acalypha wilkesiana, Vernonia amygdalina and Moringa oleifera respectively. Comparative outcome of the plant extracts showed Acalypha wilkesiana, Vernonia amygdalina and Moringa oleifera to exhibit significant inhibition activities (p < 0.05) compared to other extracts. Significant median inhibitory concentration (15.3 mg/ml) of Azadirachta indica were observed (p < 0.01) and strong associations of phytochemical compounds of Azadirachta indica (eta = 0.527,p = 0.017), Vernonia amygdalina (eta = 0.123,p = 0.032) and Acalypha wilkesiana (eta = 0.492,p = 0.012) with their respective inhibitory values.ConclusionObserved high occurrence rate of skin and soft tissue infections caused by biofilm-producing MDR S. aureus requires alternative novel herbal formulations with rich bioactive compounds from Moringa oleifera, Acalypha wilkesiana, Azadirachta indica and Vernonia amygdalina as skin therapeutic agents.
| S-EPMC8862250 | biostudies-literature
Project description:ImportanceThe longitudinal association among persistent Staphylococcus aureus colonization, household environmental contamination, and recurrent skin and soft tissue infection (SSTI) is largely unexplored to date.ObjectivesTo identify factors associated with persistent S aureus colonization and recurrent SSTI in households with children with community-associated methicillin-resistant S aureus (MRSA) SSTI.Design, setting, and participantsThis 12-month prospective cohort study included 150 children with community-associated MRSA SSTI, 542 household contacts, and 154 pets enrolled from January 3, 2012, through October 20, 2015. A total of 5 quarterly home visits were made to 150 households in the St Louis, Missouri, region. Statistical analysis was performed from September 18, 2018, to January 7, 2020.ExposuresCovariates used in S aureus strain persistence and interval SSTI models included S aureus colonization and contamination measures, personal hygiene and sharing habits, health history, activities external to the home, and household characteristics (eg, cleanliness, crowding, home ownership, and pets). Serial samples to detect S aureus were collected from household members at 3 anatomic sites, from pets at 2 anatomic sites, and from environmental surfaces at 21 sites.Main outcomes and measuresMolecular epidemiologic findings of S aureus isolates were assessed via repetitive-sequence polymerase chain reaction. Individual persistent colonization was defined as colonization by an identical strain for 2 consecutive samplings. Longitudinal, multivariable generalized mixed-effects logistic regression models were used to assess factors associated with persistent S aureus personal colonization, environmental contamination, and interval SSTI.ResultsAmong 692 household members in 150 households, 326 (47%) were male and 366 (53%) were female, with a median age of 14.82 years (range, 0.05-82.25 years). Of 540 participants completing all 5 samplings, 213 (39%) were persistently colonized with S aureus, most often in the nares and with the strain infecting the index patient at enrollment. Nine pets (8%) were persistently colonized with S aureus. Participants reporting interval intranasal mupirocin application were less likely to experience persistent colonization (odds ratio [OR], 0.44; 95% credible interval [CrI], 0.30-0.66), whereas increasing strain-specific environmental contamination pressure was associated with increased individual persistent colonization (OR, 1.17; 95% CrI, 1.06-1.30). Strains with higher colonization pressure (OR, 1.47; 95% CrI, 1.25-1.71) and MRSA strains (OR, 1.57; 95% CrI, 1.16-2.19) were more likely to persist. Seventy-six index patients (53%) and 101 household contacts (19%) reported interval SSTIs. Individuals persistently colonized with MRSA (OR, 1.56; 95% CrI, 1.17-2.11), those with a history of SSTI (OR, 2.55; 95% CrI, 1.88-3.47), and index patients (OR, 1.54; 95% CrI, 1.07-2.23) were more likely to report an interval SSTI.Conclusions and relevanceThe study findings suggest that recurrent SSTI is associated with persistent MRSA colonization of household members and contamination of environmental surfaces. Future studies may elucidate the effectiveness of specific combinations of personal decolonization and environmental decontamination efforts in eradicating persistent strains and mitigating recurrent SSTIs.
| S-EPMC7105954 | biostudies-literature
Project description:ObjectivesTo describe the pharmacokinetic/pharmacodynamic (PK/PD) modelling and microbiological data that were used to support the recent European approval of ceftaroline fosamil 600 mg q8h by 2 h intravenous (iv) infusion for patients with complicated skin and soft tissue infections (cSSTIs) caused by Staphylococcus aureus with ceftaroline MICs of 2 or 4 mg/L, and the associated EUCAST MIC breakpoint update for q8h dosing (intermediate = 2 mg/L and resistant >2 mg/L).MethodsA population PK model for ceftaroline and ceftaroline fosamil was developed using PK data from 21 clinical studies. The final model was used to simulate PTA in patients with cSSTI receiving ceftaroline fosamil 600 mg q12h by 1 h iv infusion or 600 mg q8h by 2 h iv infusion. PTA was calculated by MIC for S. aureus PK/PD targets derived from preclinical studies (27% fT>MIC for stasis, 31% fT>MIC for 1 log10 kill and 35% fT>MIC for 2 log10 kill) and compared with S. aureus ceftaroline MIC distributions from a 2013 global surveillance study.ResultsThe final population PK model based on 951 subjects adequately described ceftaroline and ceftaroline fosamil PK. High PTA (>90%) was predicted for the ceftaroline fosamil 600 mg q12h dosage regimen against S. aureus isolates with ceftaroline MICs ≤2 mg/L. Greater than 90% PTA was predicted for the ceftaroline fosamil 600 mg q8h dosage regimen against S. aureus with ceftaroline MICs ≤4 mg/L.ConclusionsThe approved ceftaroline fosamil dosage regimens for adults and adolescents with cSSTI achieve high PTA against S. aureus at the associated EUCAST breakpoints.
| S-EPMC6337900 | biostudies-literature
Project description:UnlabelledThe importance of livestock as a source of bacterial pathogens with the potential for epidemic spread in human populations is unclear. In recent years, there has been a global increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections of healthy humans, but an understanding of the different evolutionary origins of CA-MRSA clones and the basis for their recent expansion is lacking. Here, using a high-resolution phylogenetic approach, we report the discovery of two emergent clones of human epidemic CA-MRSA which resulted from independent livestock-to-human host jumps by the major bovine S. aureus complex, CC97. Of note, one of the new clones was isolated from human infections on four continents, demonstrating its global dissemination since the host jump occurred over 40 years ago. The emergence of both human S. aureus clones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, consistent with an important role for these genetic events in the capacity to survive and transmit among human populations. In conclusion, we provide evidence that livestock represent a reservoir for the emergence of new human-pathogenic S. aureus clones with the capacity for pandemic spread. These findings have major public health implications highlighting the importance of surveillance for early identification of emergent clones and improved transmission control measures at the human-livestock interface.ImportanceAnimals are the major source of new pathogens affecting humans. However, the potential for pathogenic bacteria that originally were found in animals to switch hosts and become widely established in human populations is not clear. Here, we report the discovery of emergent clones of methicillin-resistant Staphylococcus aureus (MRSA) that originated in livestock and switched to humans, followed by host-adaptive evolution and epidemic spread in global human populations. Our findings demonstrate that livestock can act as a reservoir for the emergence of new human bacterial clones with potential for pandemic spread, highlighting the potential role of surveillance and biosecurity measures in the agricultural setting for preventing the emergence of new human pathogens.
| S-EPMC3747577 | biostudies-literature