Department of Medical Microbiology, Edinburgh University Medical School, Edinburgh EH8 9AG, UK
Sir,
Infection by methicillin-resistant Staphylococcus aureus (MRSA) increased significantly during the 1990s, predominantly due to the epidemic MRSA (EMRSA) strains, EMRSA-15 and EMRSA-16. Vancomycin resistance among these epidemic strains appears to be very rare,1 although a heterogenous intermediate glycopeptide-resistant S. aureus (hetero-GISA) strain has been reported in Bristol.2
We now report the isolation of a homogenous GISA (homo-GISA) from a patient in the Royal Infirmary of Edinburgh. We tested 360 consecutively isolated strains of MRSA to determine whether any of these strains showed reduced susceptibility to vancomycin. The technique used was similar to that described by Woodford et al.1 Test isolates were screened on brainheart infusion (BHI) agar containing 6 mg/L vancomycin. One isolate (G174396) grew confluently on the BHI/vancomycin screening plate indicating that it was a homo-resistant strain and MICs were determined by Etest. MICs of vancomycin and teicoplanin were 8 and 16 mg/L, respectively. This would be classified as resistant when susceptibility categories are assigned according to the BSAC3 but as intermediate according to the NCCLS.4 Resistance was confirmed by the MRSA Reference Laboratory, Stobhill Hospital, Glasgow and also by the Antibiotic Resistance Monitoring and Reference Laboratory, CPHL, Colindale, London. This patient was also colonized by two vancomycin-susceptible strains of MRSA. Phage typing confirmed the vancomycin-resistant strain to be EMRSA-15, whereas the susceptible strains were EMRSA-15 and EMRSA-16.
Before isolation of the GISA, the patient had been an inpatient in this hospital for several months following perforation of the sigmoid colon and localized peritonitis. She had been treated with several antibiotics including two 10 day courses of oral vancomycin for recurrent Clostridium difficile-associated diarrhoea. Other antibiotics used were co-amoxiclav, metronidazole, ciprofloxacin and cefuroxime, all administered iv. The vancomycin-resistant strain was also rifampicin resistant, which is unusual among EMRSA-15 strains. The MRSA reference laboratory in Glasgow report that <1% of EMRSA-15 strains submitted to them are rifampicin resistant (G. Edwards, personal communication). Glycopeptide-resistant strains are extremely rare in the UK. Wilcox & Fawley5 examined 3713 strains of S. aureus of which 39% were MRSA, but none had a vancomycin MIC of >4 mg/L. In a larger study Aucken et al.6 screened c. 26 000 strains and found no isolate with reduced susceptibility to vancomycin.
A search through the patient's record showed no evidence of previous rifampicin therapy. The other EMRSA-15 strains from this patient over the same period show no increased resistance to glycopeptides or rifampicin. It would appear that long-term oral vancomycin therapy may have contributed to the emergence of glycopeptide resistance and this example is a warning that it may be prudent to screen patients on long-term oral vancomycin therapy for the presence of GISA.
Acknowledgements
We are grateful to the MRSA Reference Laboratory, Stobhill Hospital, Glasgow and the Antibiotic Resistance Monitoring and Reference Laboratory, CPHL, Colindale, London for confirmation of resistance and phage typing.
Notes
* Corresponding author. Tel 44-131-651-1396; Fax: 44-131-650-6515; E-mail: rhp{at}srv1.med.ed.ac.uk
References
1
.
Woodford, N., Warner, M. & Aucken, H. M. (2000). Vancomycin resistance among epidemic strains of methicillin-resistant Staphylococcus aureus in England and Wales. Journal of Antimicrobial Chemotherapy 45, 2589.
2 . Howe, R. A., Bowker, K. E., Walsh, T. R., Feest, T. G. & MacGowan, A. P. (1998). Vancomycin-resistant Staphylococcus aureus. Lancet 251, 602.
3
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MacGowan, A. P. & Wise, R. (2001). Establishing MIC breakpoints and the interpretation of in vitro susceptibility tests. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 1728.
4 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFourth Edition: Approved Standard M7-A4. NCCLS, Wayne, PA.
5
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Wilcox, M. & Fawley, W. (2001). Extremely low prevalence of Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Journal of Antimicrobial Chemotherapy 48, 1445.
6
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Aucken, H. M., Warner, M., Ganner, M., Johnson, A. P., Richardson, J. F., Cookson, B. D. et al. (2000). Twenty months of screening for glycopeptide-intermediate Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 46, 63940.