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Port Glasgow, United Kingdom

Rao G.G.,North West London Hospitals | Kearns A.M.,Public Health England | Edwards G.F.S.,Scottish MRSA Reference Laboratory
Journal of Hospital Infection | Year: 2011

Epidemic meticillin-resistant Staphylococcus aureus-16, which was widespread throughout the UK and the rest of the world, has declined markedly in recent years. The reasons for this are not clear. © 2011 The Healthcare Infection Society.

Pichon B.,Public Health England | Hill R.,Public Health England | Laurent F.,French Institute of Health and Medical Research | Larsen A.R.,Statens Serum Institute | And 5 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Background: The recent discovery of a mecA homologue (mecALGA251) with a high level of variability between the two gene variants suggested that Staphylococcus aureus harbouring mecALGA251 could be wrongly identified as methicillin-susceptible S. aureus (MSSA), in the absence of antimicrobial susceptibility testing. Methods: In this context we designed a real-time quadruplex PCR assay to distinguish unequivocally between mecA and mecALGA251, alongside the nuc gene (a species-specific marker) and detection of the lukS-PV gene [encoding the Panton-Valentine leucocidin (PVL) toxin]. Results and discussion: The assay was validated using a collection of (i) PVL-positive and PVL-negative MSSA and methicillin-resistant S. aureus (MRSA) and (ii) known MRSA harbouring mecALGA251 from the UK, Denmark and France. When applied to a retrospective collection of oxacillin-non-susceptible, mecA-negative human isolates, three were found to encode mecALGA251, including one from blood, representing the first hitherto recognized case of bacteraemia due to S. aureus possessing the mecALGA251 in England. Finally, the assay was introduced into the routine Staphylococcus Reference Unit (HPA Microbiology Services, London, UK) workflow in August 2011, and, during the first 5 months of use, 10 isolates harbouring the mecA homologue were identified out of 2263 S. aureus tested, suggesting a low but continuous circulation within the human population in England. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Lawes T.,Royal Aberdeen Childrens Hospital | Lopez-Lozano J.-M.,Medicine Preventive Infection Control Team | Nebot C.,Centro Universitario Of La Defensa Cud Of San Javier | Macartney G.,Royal Infirmary | And 4 more authors.
BMJ Open | Year: 2015

Objectives: To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Design: Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Setting: Regional hospital and primary care in a Scottish Health Board. Participants: General adult (N=1 051 993) or intensive care (18 235) admissions and primary care registrations (460 000 inhabitants) between January 1997 and December 2012. Interventions: Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and '4Cs' (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Outcome measures: Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10 000 inhabitant-days). Results: 67% of all clinical MRSA isolates (10 707/15 947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of '4Cs' and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R2=0.63-0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4 days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135-141, and 48-81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. Conclusions: Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts. © 2015, BMJ. All rights reserved.

Ba X.,University of Cambridge | Harrison E.M.,University of Cambridge | Edwards G.F.,Scottish MRSA Reference Laboratory | Holden M.T.G.,Wellcome Trust Sanger Institute | And 8 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is an important global health problem. MRSA resistance to β-lactam antibiotics is mediated by the mecA or mecC genes, which encode an alternative penicillin-binding protein (PBP) 2a that has a low affinity to β-lactam antibiotics. Detection of mec genes or PBP2a is regarded as the gold standard for the diagnosis of MRSA. We identified four MRSA isolates that lacked mecA or mecC genes, but were still phenotypically resistant to pencillinase-resistant β-lactam antibiotics. Methods: The four human S. aureus isolates were investigated by whole genome sequencing and a range of phenotypic assays. Results: We identified a number of amino acid substitutions present in the endogenous PBPs 1, 2 and 3 that were found in the resistant isolates but were absent in closely related susceptible isolates and which may be the basis of resistance. Of particular interest are three identical amino acid substitutions in PBPs 1, 2 and 3, occurring independently in isolates from at least two separate multilocus sequence types. Two different non-conservative substitutions were also present in the same amino acid of PBP1 in two isolates from two different sequence types. Conclusions: This work suggests that phenotypically resistant MRSA could be misdiagnosed using molecular methods alone and provides evidence of alternative mechanisms for β-lactam resistance in MRSA that may need to be considered by diagnostic laboratories. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Skov R.,Statens Serum Institute | Larsen A.R.,Statens Serum Institute | Kearns A.,Public Health England | Holmes M.,University of Cambridge | And 3 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: To investigate the reliability of cefoxitin and oxacillin for the detection of mecC-positive Staphylococcus aureus. Methods: The susceptibility to cefoxitin and oxacillin of 62 mecC-positive S. aureus isolateswas investigated using broth microdilution, agar dilution, Etest and disc diffusion on different types of media. The data were interpreted for the utility of cefoxitin and oxacillin in conjunction with the stated methodologies for the detection of mecC-positive isolates. Results: Cefoxitin with Mueller-Hinton media fromBecton Dickinson and Oxoid detected all mecC-positive isolates when tested by broth microdilution, agar dilution and disc diffusion. By Etest, one isolate was falsely susceptible. Mueller-Hinton agar from bioMérieux was substantially less able to detect these isolates. One isolate was falsely susceptible by agar dilution when using Iso-Sensitest and Columbia agar. Disc diffusion using cefoxitin on Iso- Sensitest agar missed 29% of the isolates. For oxacillin, only agar dilution on Columbia agar+2% NaCl was able to detect all mecC-positive isolates successfully. Conclusions:Cefoxitin used withEUCASTmethodologyandoxacillin used with agardilutiononColumbia agar+2% NaCl detected all mecC-positive isolates. These methods with their concomitant agars should be preferred over Iso-Sensitest, which is recommended by the BSAC. It should be noted that for disc diffusion Mueller-Hinton media from bioMérieux performed poorly, with 26%-47% of mecC isolates being falsely susceptible. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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