Clonal expansion of community-associated meticillin-resistant Staphylococcus aureus (MRSA) in people who inject drugs (PWID): prevalence, risk factors and molecular epidemiology, Bristol, United Kingdom, 2012 to 2017

摘要

Background: In 2015, Bristol (South West England) experienced a large increase in cases of meticillin-resistant Staphylococcus aureus (MRSA) infection in people who inject drugs (PWID).Aim: We aimed to characterise and estimate the prevalence of MRSA colonisation among PWID in Bristol and test evidence of a clonal outbreak.Methods: PWID recruited through an unlinked-anonymous community survey during 2016 completed behavioural questionnaires and were screened for MRSA. Univariable logistic regression examined associations with MRSA colonisation. Whole-genome sequencing used lineage-matched MRSA isolates, comparing PWID (screening and retrospective bacteraemia samples from 2012-2017) with non-PWID (Bristol screening) in Bristol and national reference laboratory database samples.Results: The MRSA colonisation prevalence was 8.7% (13/149) and was associated with frequently injecting in public places (odds ratio (OR): 5.5; 95% confidence interval (CI):1.34–22.70), recent healthcare contact (OR: 4.3; 95% CI: 1.34–13.80) and injecting in groups of three or more (OR: 15.8; 95% CI: 2.51–99.28). People reporting any one of: injecting in public places, injection site skin and soft tissue infection or hospital contact accounted for 12/13 MRSA positive cases (sensitivity 92.3%; specificity 51.5%). Phylogenetic analysis identified a dominant clade associated with infection and colonisation among PWID in Bristol belonging to ST5-SCCmecIVg.Conclusions: MRSA colonisation in Bristol PWID is substantially elevated compared with general population estimates and there is evidence of clonal expansion, community-based transmission and increased infection risk related to the colonising strain. Targeted interventions, including community screening and suppression therapy, education and basic infection control are needed to reduce MRSA infections in PWID. Keywords: Meticillin-Resistant Staphylococcus aureus, Staphylococcal epidemiology, Staphylococcal Infections/transmission, MRSA, Sepsis, Injecting drug use, Intravenous, Substance Abuse, Intravenous: complications, Substance Abuse, Intravenous: microbiology, Drug users, Substance-Related Disorders/complications, Substance-Related Disorders/microbiology, Sequence Analysis, DNA, Whole-genome sequencing, United Kingdom, Community acquired infections, Community acquired infections epidemiology, Community acquired infections microbiologyIntroductionMeticillin-resistant Staphylococcus aureus (MRSA) can exist as a harmless commensal or a potentially life-threatening pathogen [1,2]. Clinical presentations range from localised skin and soft tissue infections (SSTIs) to disseminated blood stream infections. These infections are responsible for substantial healthcare costs, morbidity and mortality [2-4]. The United Kingdom (UK) government have adopted a zero tolerance approach to avoidable healthcare associated infections with a focus on MRSA bacteraemia [5,6]. However, this approach is controversial as organisms can be introduced through multiple independent sources [5].MRSA can survive in a range of ecological settings, interact with and colonise the human host and develop antimicrobial resistance via a range of mechanisms [4]. These traits allow MRSA to spread between populations and species exploiting niches and opening up footholds to establish reservoirs within different settings [4]. MRSA was initially thought to be confined to healthcare settings (HA-MRSA) but during the 1980s infections were noticed in the community (CA-MRSA) and in the early 2000s infections were also identified in humans associated with exposure to livestock (LA-MRSA) [1,7]. Colonising MRSA can be transmitted from person-to-person and introduced into the body when host defences are breached [1,8,9]. This is apparent in communities of people who inject drugs (PWID), with outbreaks previously reported in England and the United States (US) resulting in substantial morbidity and mortality [10-12]. Studies in Switzerland (2001), Canada (2006) and the US (2012) have found a high MRSA colonisation prevalence in PWID ranging from 5.7 to 18.6% [10,11,13]. These high prevalence estimates contrast sharply with general population estimates of? ?2.5) and potential for targeting interventions. Factors representing recent MRSA colonisation were excluded. Risk factor combinations were assessed in terms of sensitivity, specificity, receiver operator curve (ROC) and positive predictive value (PPV). A ROC value of 0.70 or above was used as a threshold for inclusion [32].Microbiological testing Trained BDP staff members collected groin and nasal swabs from participants. Swabs were cultured onto Brilliance Staph 24 agar (Oxoid). Presumptive S.aureus were initially identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry MALDI-TOF (Bruker Daltonik GmbH, Germany) and MRSA were identified by antibiotic susceptibility testing using VITEK 2 (software v07.01 and card name AST-P635, bioMérieux). Colonised