Loss of mecA gene in Staphylococcus epidermidis after prolonged therapy with vancomycin

Parham Sendi*, Peter Graber and Werner Zimmerli

Division of Infectious Diseases, Basel University Medical Clinic, Rheinstrasse 26, CH-4410 Liestal, Switzerland


* Corresponding author. Tel: +41-61-925-34-19; Fax: +41-61-925-28-04; E-mail: sendi-pa{at}magnet.ch

Keywords: methicillin resistance , S. epidermidis , gene loss , glycopeptides

Sir,

The most commonly cultured microorganisms in prosthetic-joint infections are coagulase-negative staphylococci.1 Resistance to ß-lactam antibiotics is encoded by the mecA gene; this gene is carried on a mobile genetic element, the staphylococcal chromosome cassette mec (SCCmec). Loss or deletion of the mecA gene rarely occurs, mainly due to factors affecting the stability of SCCmec. Vancomycin may induce deletion of the mecA gene in Staphylococcus aureus, as reported in this journal last year.2 We report the case of an implant-associated infection due to a methicillin-resistant Staphylococcus epidermidis which lost the mecA gene after prolonged treatment with glycopeptides.

An 82-year-old man was admitted to our hospital because of a prosthetic-joint associated infection with a sinus tract, 4 months after implantation of a total hip prosthesis. S. epidermidis resistant to oxacillin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, clindamycin, erythromycin, fusidic acid and rifampicin, but susceptible to tetracycline, teicoplanin and vancomycin grew in biopsies from periprosthetic tissue. Species identification was made using API ID 32 Staph system (bioMérieux, La Balme les Grottes, Montalieu Vercieu, France); the MIC of vancomycin was 2 mg/L determined by Etest (AB Biodisk, Solna, Sweden) in Mueller–Hinton (MH) agar. A spacer-free, two-stage exchange of the prosthesis with an 8 week interval was performed and antimicrobial chemotherapy was administered during the first 6 weeks.1 The patient was treated with a 5.5 week course of vancomycin (1 g twice daily), followed by teicoplanin (400 mg once daily) for the remaining 4 days, after removal of the central venous catheter. On reimplantation, biopsies from periprosthetic tissue were obtained and vancomycin (1 g twice daily) was given for another 2 weeks, until cultures were reported to be negative.

Unfortunately, relapse occurred 4 months after reimplantation. Again, S. epidermidis was isolated, but showed two different phenotypes in susceptibility tests. While one strain was indistinguishable from the pathogen causing the primary infection, the second type was susceptible to oxacillin, but otherwise there was no difference in the resistance pattern. Both strains showed no increase in MIC of vancomycin, as revealed by Etest in MH agar. PCR for the mecA gene was negative in the second type, but positive in the original isolate. Interestingly, pulsed-field gel electrophoresis (PFGE) after SmaI digestion revealed only a slight difference between the two strains. The distance between two bands at ~140 kb and at ~160 kb was narrower in the mecA-positive strain (Figure 1), probably representing the location of the mecA gene. Vancomycin (1 g twice daily for 6 weeks) was administered during the implant-free-interval, and a complete recovery was made.



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Figure 1. PFGE after SmaI digest: the distance between two bands at ~140 kb and at ~160 kb is shorter in the mecA-positive strain (arrow).

 
To our knowledge, in vivo loss of mecA gene in S. epidermidis after treatment has only been published in abstract form, without reporting any further details about antimicrobial agents and duration of therapy.3 Acquiring methicillin resistance is attributed to intra- and interspecies transfer of SCCmec,4 but little is known about the loss or deletion of the mecA gene. Long-term storage, high temperatures and UV radiation have been described to be factors influencing the stability of SSCmec in vitro.2 Moreover, experiments have shown that coagulase-negative staphylococci exposed to glycopeptides may lose high-level resistance to oxacillin, without loss of the mecA gene.5 Recently published findings indicate that the acquisition and/or loss of SCCmec in S. epidermidis, may occur in the region of the orfX gene.6 Our case illustrates that the mecA complex may lose its stability after prolonged antimicrobial treatment.

Transparency declarations

None of the authors has a conflict of interest regarding this case report. No funding was available.

Acknowledgements

We thank Reno Frei, MD and Professor Brigitte Berger-Bächi, PhD for their discussions regarding this case.

References

1 Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. New Engl J Med 2004; 351: 1645–54.[Free Full Text]

2 Adhikari RP, Scales GC, Kobayashi K et al. Vancomycin-induced deletion of the methicillin resistance gene mecA in Staphylococcus aureus. J Antimicrob Chemother 2004; 54: 360–3.[Abstract/Free Full Text]

3 Strandén A, Frei R, Widmer AF. In vivo deletion of the mec region in S. epidermidis in implant-associated infection. In: Abstracts of the Forty-second Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002. Abstract K-588, p. 313. American Society for Microbiology, Washington, DC, USA.

4 Wisplinghoff H, Rosato A, Enright MC et al. Related clones containing SSCmec type IV predominate among clinically significant Staphylococcus epidermidis isolates. Antimicrob Agents Chemother 2003; 47: 3574–9.[Abstract/Free Full Text]

5 Domaracki BE, Evans A, Preston KE et al. Increased oxacillin activity associated with glycopeptides in coagulase-negative staphylococci. Eur J Clin Microbiol Infect Dis 1998; 17: 143–50.[ISI][Medline]

6 Miragaia M, Couto I, de Lencastre H. Genetic diversity among methicillin-resistant Staphylococcus epidermidis (MRSE). Microb Drug Resist 2005; 11: 83–93.[CrossRef][ISI][Medline]





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