1 Laboratory of Hospital Infection and 2 Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, Colindale, London NW9 5HT, UK
Received 21 January 2002; returned 5 March 2002; revised 24 April 2002; accepted 16 May 2002
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Abstract |
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Introduction |
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In the early 1980s, the first UK epidemic MRSA (EMRSA) strain, now known as EMRSA-1, was recognized in and around London.5 Subsequently, characterization of MRSA isolates collected during a 6-month national survey resulted in the identification of a further 13 multi-hospital MRSA, which were designated EMRSA-2 to -14.6 However, only EMRSA-3 and EMRSA-12 affected more than 10 hospitals each. In the early 1990s, EMRSA-15 was identified in south-east England and the Midlands,7 while EMRSA-16 emerged via a hospital outbreak a year or so later,8 and both have since spread widely.9
Early in 2000, the Reference Service was asked to examine highly multi-resistant isolates from a major outbreak at a hospital on the south coast of England. The isolates appeared closely related to others that had been received sporadically from other hospitals in the same region since 1996, as judged by phage typing and PFGE, and a warning about the new strain was placed in the PHLS Communicable Disease Report.10 Since isolates of the same type had been received from a number of hospitals in the south of England, a study was undertaken to investigate what appeared to be a new UK EMRSA strain.
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Materials and methods |
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The database of S. aureus isolates sent to the PHLS Laboratory of Hospital Infection for epidemiological typing from 1997 to 2000 was searched for those with the characteristic phage patterns (see Results) associated with the outbreak strain from the south coast hospital. Sixty-nine isolates were selected for detailed investigation and maintained on nutrient agar slopes at room temperature. Their identification was confirmed by coagulase testing using rabbit plasma broth and repeat phage typing with the 23 phages of the international set plus four additional UK phages.11
Strain characterization
PFGE profiles were obtained by macro-restriction of chromosomal DNA with SmaI and a run time of 30 h with pulse switch times of 180 s. Isolates were tested for urease production using Christensens urea slopes incubated for 5 days at 37°C. The genes coding for staphylococcal enterotoxins AE (seasee) and GJ (segsej), toxic shock syndrome toxin (tst) and exfoliative toxins A and B (eta and etb) were detected using three multiplex PCRs, as described previously.12 Susceptibility to a range of antimicrobial agents was determined by the agar dilution method using Isosensitest agar supplemented with 2% lysed blood and incubated at 37°C, except for plates containing methicillin, which were incubated at 30°C.
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Results |
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The 69 isolates selected for study were from 19 hospitals. By phage typing, 62 of the isolates appeared similar, showing reactions with phages 29, 77 and 932, with variable reactions with phages 75, 84, 90 and 83C. The remaining seven isolates also reacted with this core panel of phages, but showed a broader reaction pattern, being sensitive to an additional seven phages (47, 53, 54, 79, 85, 88A and 90) (Table 1).
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Sixty-two of the 63 isolates with PFGE profiles F1F6 were positive for the staphylococcal enterotoxin A gene, sea (Table 3). Five of the 62 were positive for seg and sei in addition to sea, and two of these also had tst. One isolate of the F1 profile was negative for all 12 toxin genes tested. Of the six isolates with non-F profiles, three were positive for sea alone and three had unique gene combinations (Table 3).
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All 63 isolates exhibiting PFGE profiles F1F6 were resistant to multiple antibiotics (Table 4), including methicillin (MIC > 32 mg/L), ciprofloxacin (MIC > 16 mg/L), fusidic acid (MIC > 16 mg/L), rifampicin (MIC > 16 mg/L), gentamicin (MIC > 32 mg/L), kanamycin (MIC > 128 mg/L), streptomycin (MIC > 128 mg/L) and tetracycline (MIC > 16 mg/L). Sixty-two of the 63 isolates were also resistant to erythromycin (MIC > 16 mg/L). Four exhibited high-level resistance to mupirocin (MIC > 512 mg/L) and a further 11 had low-level resistance (MIC 64 mg/L). MICs of vancomycin were 24 mg/L, whereas MICs of teicoplanin varied between 4 and 8 mg/L on repeated testing, suggesting borderline resistance.
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Geographical distribution
The 63 isolates producing PFGE profiles F1F6 were from 13 hospitals, seven of which were along, or close to, the south coast, and four in, or near, London. The other two source hospitals were in the Midlands and the north of England, respectively. The isolates exhibiting the commonest PFGE profile, F1, had been referred from 11 hospitals, all of which were in southern England. The four isolates with the F2 profile were from the same Midlands hospital, while the single isolate of profile F3 was from the hospital in the north. The three isolates of profiles F4, F5 and F6 had each been referred from hospitals in the south that had also referred isolates of profile F1. In contrast, the six non-F isolates came from three hospitals in Northern Ireland, one in Wales, one in the north of England and one in the south-west.
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Discussion |
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The emergence of EMRSA-17 is worrying, as the strain is much more resistant than any of the previous UK EMRSA strains.14 For example, while EMRSA-15 is resistant to ciprofloxacin and variably resistant to erythromycin, and EMRSA-16 is resistant to ciprofloxacin and erythromycin and variably resistant to aminoglycosides,14 isolates of EMRSA-17 seen to date have been resistant to all these agents, together with fusidic acid, rifampicin, tetracycline and occasionally to high levels of mupirocin. EMRSA-17 also shows borderline resistance to teicoplanin. As emergence of frank resistance to teicoplanin has been seen in isolates of EMRSA-15 obtained from patients receiving this agent,15 there is concern that resistance may similarly arise in this strain. As low-level resistance to glycopeptides is not readily detected by disc testing, it is suggested that MICs of teicoplanin (and vancomycin) be determined either by agar dilution or by Etest.16
At present, the distribution of EMRSA-17 strains varies across England. Clearly, continued surveillance of the spread of this highly multi-resistant strain will be required.
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Acknowledgements |
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Footnotes |
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Corresponding author. Tel: +44-20-8200-4400, ext. 4237; Fax: +44-20-8358-3292; E-mail: ajohnson{at}phls.org.uk
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References |
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