J Antimicrob Chemother 2010; 65: 446 – 448doi:10.1093/jac/dkp448 Advance publication 24 December 2009 Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between Matthew J. Ellington*, Russell Hope, David M. Livermore, Angela M. Kearns, Katherine Henderson, Barry D. Cookson, Andrew Pearson and Alan P. Johnson Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK *Corresponding author. Present address: Health Protection Agency Cambridge Microbiology and Public Health Laboratory, Addenbrookes Hospital, Cambridge, UK. Tel: þ44-1223-257036; Fax: þ44-1223-242775. E-mail: [email protected]
Received 11 November 2009; returned 16 November 2009; revised 16 November 2009; accepted 17 November 2009 Objectives: Between 1998 and 2000, 95.6% of methicillin-resistant Staphylococcus aureus (MRSA) bacterae-mias in the UK were due to two epidemic strains, namely EMRSA-15 or EMRSA-16 (60.2% and 35.4%, respect-ively). We sought to determine the proportions of these strains before and after the general decline in MRSAbacteraemia that began around 2004.
Methods: Consecutive MRSA isolates collected in 2001, 2003, 2005 and 2007 by the BSAC Bacteraemia Surveil-lance Programme were categorized to multilocus sequence typing (MLST) clonal complex and to SCCmec typeby PCR. MICs were determined by the BSAC method. Data trends were tested for significance using a general-ized linear regression model.
Results: Collectively, EMRSA-15 and EMRSA-16 consistently accounted for 95% of MRSA studied between2001 and 2007, but the proportions of EMRSA-16 declined from 21.4% in 2001 to 9% in 2007 (P, 0.05),whilst the proportion of EMRSA-15 rose commensurately, accounting for 85% of MRSA in 2007. Ciprofloxacinand erythromycin resistance were common amongst both EMRSA-15 and EMRSA-16.
Conclusions: EMRSA-15 and EMRSA-16 remain the main MRSA strains in bacteraemia in the UK, but the pro-portion of EMRSA-16 declined from the late 1990s, thus preceding the general decline in MRSA bacteraemiasthat began in the middle of the present decade.
Keywords: MRSA, surveillance, bloodstream infections whereas EMRSA-16 typically has SCCmecII.4 They may differ inresistance profile too, but both lineages are usually resistant to Methicillin-resistant Staphylococcus aureus (MRSA) emerged in fluoroquinolones and macrolides, and the use of these antibiotics 1961 and became dramatically more prevalent as agents of has been described as a risk factor for colonization or infection.5 bacteraemia in the UK in the mid-1990s in England, Wales and Since its first emergence in the UK, EMRSA-15 has become dissemi- Northern Ireland. By the end of the 1990s, .40% of all nated in Europe,6 Australia,7 the Middle East8 and the Far East;9 S. aureus bacteraemias were due to MRSA, though this proportion EMRSA-16 has been reported widely, in- and outside of the UK, (and the total number) of MRSA bacteraemias has since declined but it is not perceived to be as successful as EMRSA-15.
and stood at 20% in 2008.1 The rise of MRSA in the 1990s and Here, we report trends for EMRSA-15 and EMRSA-16 among early 2000s correlated with the emergence and spread of two MRSA isolated as part of the BSAC Bacteraemia Surveillance epidemic strains, designated EMRSA-15 and EMRSA-16, which, in 1999 –2000, accounted for 95.6% of all UK MRSA bacterae-mias; with 60.2% due to EMRSA-15 and 35.4% to EMRSA-16.2 EMRSA-15 and EMRSA-16 differ genetically, belonging to distinct multilocus sequence type (MLST) clonal complexes (CCs), namelyCC22 (ST22) for EMRSA-15 and CC30 (ST36) for EMRSA-16.3 They Bacterial isolates and collecting centres also differ in their staphylococcal cassette chromosome mec The methods for the BSAC Bacteraemia Surveillance Programme (http:// (SCCmec) types, with EMRSA-15 typically harbouring SCCmecIV www.bsacsurv.org) have been described previously.10 In brief, 25 clinical # The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
For Permissions, please e-mail: [email protected] Table 1. EMRSA-15, EMRSA-16 and other strains amongst BSAC MRSA Bacteraemia Surveillance Programme isolates collected in 2001, 2003, 2005and 2007 laboratories in the UK and Ireland, serving a wide range of urban and this trend. Consideration of previous (phage-type based) data rural areas with a range of social deprivation scores, contributed for isolates collected between 1998 and 2000 under the aegis isolates in each year. A total of 29 centres participated during 4 study of the European Antimicrobial Resistance Surveillance Study years (2001, 2003, 2005 and 2007) and 17 of these submitted isolates indicated a 14% decline in EMRSA-16, from 35.4% seen in in all 4 years; the remainder either joined or left the programme 1998– 20002 to the present start point of 21.4% in 2001, and between 2001 and 2007. All MRSA isolates collected in the 4 years a subsequent decline to 9% in 2007. Whilst these data span (n ¼103 from 2001, n¼95 from 2003, n¼87 from 2005 and n ¼89 different collections and methods, they support the view that from 2007) were investigated. To match with MRSA mandatory surveillance data, some analyses considered only the isolates collected the relative and absolute decline of EMRSA-16 began before in hospitals in England. These comprised 85 in 2001, 76 in 2003, 71 in the plateau and decline in total MRSA bacteraemias seen 2005 and 70 in 2007, from a total of 23 centres, of which 15 participated through the results of the mandatory surveillance system.1 in all 4 years of the study. The mandatory MRSA bacteraemia surveillance As noted previously, the majority of both EMRSA-15 and system, which applies to England only, was first introduced in 2001 and EMRSA-16 isolates were resistant to macrolides (74% and 85%, respectively) and fluoroquinolones (97% and 95%, respectively),whilst gentamicin resistance was noted in 3% and 24%, respect-ively. Resistance to tetracyclines was rarer (3% in both strains).
Susceptibility to mupirocin was determined only from 2007.
MICs were determined on Iso-Sensitest agar (Oxoid, Basingstoke, UK), Among subsequent isolates, we found 1/8 (13%) EMRSA-16 according to the BSAC method.3 The antimicrobial agents tested were In summary, the trends observed here suggest that Molecular detection of CC and SCCmec cassette type EMRSA-15 and EMRSA-16 have followed different epidemiccurves, with EMRSA-16 having peaked and declined earlier than Previously described PCRs were used to detect the SCCmec type11,12 and EMRSA-15, and with each then contributing differentially to the the S. aureus CC-specific marker hsdR,11 thus differentiating CC22- total MRSA bacteraemia rate, which peaked in 2004 and declined MRSA-SCCmecIV (corresponding to EMRSA-15) and CC30-MRSA-SCCmecII thereafter. Whilst the reason(s) for the selective decline of EMRSA-16 are not known, various factors, and possible combi-nations, warrant consideration, including antibiotic prescribing patterns, infection control measures and various possible biologi- Regression analysis using the generalized linear model with Poisson cal drivers, such as bacteriophage epidemics. It remains to be distribution was performed via STATA version 10.1 (Statacorp, 2008).
seen whether the downward trajectory of EMRSA-16 will con-tinue and if EMRSA-15 will remain the dominant MRSA lineageassociated with invasive disease in hospitals in the UK.
A total of 374 MRSA were analysed, and throughout the years2001, 2003, 2005 and 2007, 95% of the isolates were foundto be either EMRSA-15 or EMRSA-16. Among the 29 centres that submitted isolates, all submitted EMRSA-15, whilst 22/29 We wish to thank Rosy Reynolds, the BSAC and participants in the annual submitted EMRSA-16, illustrating geographic dissemination of BSAC Bacteraemia Surveillance Programme for the provision of isolates.
both strains. Nevertheless, the proportion of EMRSA-16 declinedfrom 21.4% in 2001 to 9% in 2007, whilst an increase occurredin the proportion of EMRSA-15, from 75.7% in 2001 to 85.4% in2007 (P ¼ 0.014) (Table 1). These data corroborate previous localand national observations of a general decline in EMRSA-16,4,13 but do not preclude the possibility of localized variance from This work was supported by the Health Protection Agency.
strains of methicillin-resistant Staphylococcus aureus: a single approach developed by consensus in 10 European laboratories and its application A. P. J. is Editor-in-Chief of JAC, but took no part in, and did not influence, for tracing the spread of related strains. J Clin Microbiol 2003; 41: the editorial process. Other authors: none to declare.
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10 Reynolds R, Hope R, Williams L. Survey, laboratory and statistical 3 Enright MC, Day NP, Davies CE et al. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible J Antimicrob Chemother 2008; 62 Suppl 2: ii15–28.
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11 Cockfield JD, Pathak S, Edgeworth JD et al. Rapid determination of hospital-acquired meticillin-resistant Staphylococcus aureus lineages.
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