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.
7 Gosbell IB, Barbagiannakos T, Neville SA et al. Non-multiresistantmethicillin-resistant Staphylococcus aureus bacteraemia in Sydney,
Australia: emergence of EMRSA-15, Oceania, Queensland and Western
1 Pearson A, Chronias A, Murray M. Voluntary and mandatory
Australian MRSA strains. Pathology 2006; 38: 239–44.
surveillance for methicillin-resistant Staphylococcus aureus (MRSA)
8 Udo EE, Al-Sweih N, Noronha B. Characterisation of non-multiresistant
and methicillin-susceptible S. aureus (MSSA) bacteraemia in England.
methicillin-resistant Staphylococcus aureus (including EMRSA-15) in
J Antimicrob Chemother 2009; 64 Suppl 1: i11–7.
Kuwait Hospitals. Clin Microbiol Infect 2006; 12: 262–9.
2 Johnson AP, Aucken HM, Cavendish S et al. Dominance of EMRSA-15
9 Hsu LY, Koh TH, Singh K et al. Dissemination of multisusceptible
and -16 among MRSA causing nosocomial bacteraemia in the UK:
methicillin-resistant Staphylococcus aureus in Singapore. J Clin Microbiol
analysis of isolates from the European Antimicrobial Resistance
Surveillance System (EARSS). J Antimicrob Chemother 2001; 48: 143– 4.
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.
clones of Staphylococcus aureus. J Clin Microbiol 2000; 38: 1008–15.
11 Cockfield JD, Pathak S, Edgeworth JD et al. Rapid determination of
hospital-acquired meticillin-resistant Staphylococcus aureus lineages.
obtained from the UK West Midlands region. J Hosp Infect 2008; 70:
12 Milheirico C, Oliveira DC, de Lencastre H. Update to the multiplex PCR
strategy for assignment of mec element types in Staphylococcus aureus.
5 Monnet DL, MacKenzie FM, Lopez-Lozano JM et al. Antimicrobial drug
Antimicrob Agents Chemother 2007; 51: 3374–7.
use and methicillin-resistant Staphylococcus aureus, Aberdeen, 1996–
13 Johnson AP, Sharland M, Goodall C et al. Enhanced surveillance of
2000. Emerg Infect Dis 2004; 10: 1432–41.
methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in
6 Murchan S, Kaufmann ME, Deplano A et al. Harmonization of
children in the UK and Ireland. Arch Dis Child 2009; doi:10.1136/
pulsed-field gel electrophoresis protocols for epidemiological typing of
How long does a hair transplant procedure take? It depends on the number of hair grafts that are transplanted and usual y ranges from 5 to 8 hours. Am I awake during the procedure?Yes. A local anesthetic is used to numb the scalp, al owing you to read, listen to music, watch television or sleep. Is a hair transplant painful?One of the main goals of the TrueHair™ program is to provide excel e
CEREBRAL PALSY Other Common Names • Palsy; Little’s Disease; Infantile Cerebral Paralysis; Static Encephalopathy. Definition/Description • Cerebral Palsy (CP) is an “umbrella term” that covers a group of non-progressive, yet often changing, motor impairment syndromes caused by lesions or anomalies in the brain that arise during the early years (before age 5) of a pers