Southampton Public Health Laboratory, Level B, South Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Keywords: MRSA, glycopeptide resistance
Sir,
The epidemiology of teicoplanin resistance in methicillin-resistant Staphylococcus aureus (MRSA) may be changing. In 2000, Aucken et al.1 reported on glycopeptide-intermediate S. aureus (GISA) strains obtained between May 1998 and December 1999 in England and Wales and concluded that it was not a major problem at that time. In the light of that letter, we thought it prudent to highlight our experience with GISA strains. In March 2000, the PHLS reported several isolates of MRSA from Southampton and Portsmouth that were intermediately resistant to teicoplanin and were therefore classified as GISA strains.2 Over a period of 1 year (February 2000 to February 2001), we recovered 75 isolates of MRSA displaying teicoplanin insusceptibility from in-patients at Southampton General Hospital. Subsequent phage typing and pulsed-field gel electrophoresis (PFGE) have shown that these isolates belong to the new UK epidemic strain, EMRSA-17 (Figure 1).
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We compared the breakpoint method and brainheart infusion (BHI) agar screening plates containing 5 and 6 mg/L of vancomycin and teicoplanin. The reference method of agar dilution was compared with Etest (AB Biodisk, Solna, Sweden) at 0.5 and 2.0 McFarland standard.
Of the 75 isolates included in the study, 69 had teicoplanin MICs of 8 mg/L using the agar dilution method. All 69 isolates would be classified as resistant using the British Society for Antimicrobial Chemotherapy (BSAC) interpretative criteria. The vancomycin MICs for most (70/75) isolates were 2 mg/L, although five strains had MICs of 4 mg/L (i.e. vancomycin resistance was not detected).
Using the breakpoint method, 65 isolates had teicoplanin MICs of >4 mg/L. Of the 10 strains with teicoplanin MICs of 4 mg/L, six actually had MICs of 4 mg/L when determined by the reference method of agar dilution. Eleven isolates had breakpoint vancomycin MICs of >4 mg/L.
With the commercially prepared BHI agar, 49/75 isolates had teicoplanin MICs of >6 mg/L at 24 h incubation; only one isolate had a vancomycin MIC of >6 mg/L.
Using Etest at 0.5 McFarland, 68/75 isolates had teicoplanin MICs of 6 mg/L, which is the CDC cut-off for detecting GISA strains. When Etest at 2.0 McFarland standard was used, 72/75 GISA strains (i.e. isolates with teicoplanin
12 mg/L) were detected (AB Biodisk interpretative criteria for a GISA strain when using this method is vancomycin
8 mg/L and teicoplanin
8 mg/L, or teicoplanin
12 mg/L).
Our results suggest that the breakpoint method is the simplest and most cost-effective technique for the detection of GISA strains. This methodology does not increase the workload of a clinical laboratory and allows resistance phenotypes to be detected early.
Although the recent BSAC Working Party report (July 2001)5 stresses that the disc method developed for determining the susceptibility of S. aureus to vancomycin will not detect glycopeptide-intermediate strains, a suitable alternative has yet to be suggested.
In the meantime, breakpoint testing seems an appropriate method of screening for staphylococcal strains with reduced susceptibility to glycopeptides, as the technique was able to detect 65/69 isolates that had raised teicoplanin MICs by the reference method. Although this technique is not widely used in the UK as a susceptibility testing method, it would be possible to include an agar plate containing 4 mg/L of teicoplanin as a method of screening should an outbreak of multi-resistant MRSA occur. If the MIC is >4 mg/L, further testing is warranted using a combination of tests. For example, if Etest at 2.0 McFarland incubated for 48 h is 12 mg/L, the isolate should be referred to the Antibiotic Resistance Monitoring and Reference Laboratory for further work-up.
An alternative approach for the detection of EMRSA-17 strains is to use resistance to other antibiotics such as fucidin and rifampicin as markers for multi-resistance in S. aureus. If resistance to these antibiotics is present, isolates should ideally have vancomycin and teicoplanin Etests performed. We agree with Walsh et al.3 that the CDC recommendation of submitting S. aureus isolates with a vancomycin MIC of 4 mg/L for further study is important for the detection of GISA strains.
In the UK, teicoplanin resistance in S. aureus, as demonstrated by EMRSA-17 strains, is increasing in incidence. The difficulties of diagnosis and glycopeptide insusceptibility severely limit treatment options.6 New agents such as linezolid and synercid, to which all our isolates were susceptible, are of limited use in invasive infections. Clinical laboratories should adopt appropriate methodology to detect such strains and work closely with infection control personnel to contain potential outbreaks.
Note added in proof
During the submission process, Aucken et al.7 published their updated findings on EMRSA-17 isolates from 1997 to 2000, which clearly show the increasing prevalence of multi-resistant MRSA, highlighting the diagnostic and therapeutic difficulties and the need for heightened surveillance.
Footnotes
* Corresponding author. Tel: +44-23-8079-6408; Fax: +44-23-8070-2530; E-mail: rmanuel{at}doctors.org.uk
References
1
.
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.
2 . Anon. (2000). MRSA with intermediate resistance to teicoplanin. Communicable Diseases Report 10, 99102.
3
.
Walsh, T. R., Howe, R. A., Wootton, M., Bennett, P. M. & MacGowan, A. P. (2001). Detection of glycopeptide resistance in Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 47, 3578.
4 . Tenover, F. C. (2000). VRSA, VISA and GISA: the dilemma behind the name game. Clinical Microbiology Newsletter 22, 4953.
5
.
Working Party of the British Society for Antimicrobial Chemotherapy. (2001). BSAC standardized disc susceptibility testing method. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 4357.
6
.
Elsaghier, A. A. F., Aucken, H. M., Hamilton-Miller, J. M., Shaw, S. & Kibbler, C. C. (2002). Resistance to teicoplanin developing during treatment of methicillin-resistant Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 49, 4234.
7
.
Aucken, H. M., Ganner, M., Murchan, S., Cookson, B. D. & Johnson, A. P. (2002). A new UK strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-17) resistant to multiple antibiotics. Journal of Antimicrobial Chemotherapy 50, 1715.