Presence of the epidemic European fusidic acid-resistant impetigo clone (EEFIC) of Staphylococcus aureus in France

Abstract

Sir, Denton et al. recently reported the results of the EPISA study, which compared the susceptibility of Staphylococcus aureus causing community-acquired skin and soft tissue infections (SSTIs) in three European countries. They highlighted in particular that the resistance rate to fusidic acid was significantly lower in French (6.3%) than in Irish (31.4%) or British (24.4%) isolates. This difference was attributed by the authors to the likely spread of a fusidic acid-resistant clone, named the epidemic European fusidic acid-resistant impetigo clone (EEFIC) in the latter two countries. This clone, initially described in Scandinavia, had so far been reported sporadically in the UK. It is characterized by: (i) agr allelic group 4, spa type t171 [or single-locus variants (t408, t659, t874, t875)], sequence type (ST) 123, clonal complex 121; (ii) the presence of the eta (exfoliative toxin A) gene with the majority of strains also carrying the etb (exfoliative toxin B) gene; (iii) resistance to fusidic acid (MIC of 2–8 mg/L) related to the expression of the fusB gene; and (iv) strong association with impetigo. In the same issue, Larsen et al. reported the molecular characterization of all these fusidic acid-resistant isolates (n 1⁄4 136) collected during the EPISA study. The results confirmed that the EEFIC represented 63% (34/54) of fusidic acid-resistant strains in the UK and 49% (34/69) in Ireland, but was not detected in France (0%, 0/13). These results seemed to indicate that the EEFIC was not present in France. We were puzzled by this unexpected and surprising French epidemiology and decided to screen a part of the collection of the French national reference centre for staphylococci (Lyon, France) for the presence of the EEFIC. First, between December 2003 and August 2004, corresponding to the appropriate period of the EPISA study, we identified 19 isolates harbouring agr allelic group 4 and the eta gene, characteristics matching the EEFIC. We then performed a fusidic acid susceptibility test using disc diffusion (using the breakpoint from the BSAC) and fusB PCR on these isolates. Four strains (21%, 4/19) appeared to be resistant and PCR-positive, strongly suggesting that they belonged to the EEFIC. Second, we applied the same screening to all S. aureus isolates collected from October 2000 to November 2003 (before the EPISA study) and from September 2004 to December 2007 (after the EPISA study). The agr allelic group 4 and eta positive strains represented a total of 256 isolates. Forty-four of these isolates were randomly selected to undergo the fusidic acid susceptibility test and fusB PCR. Six isolates (14%, 6/44) were detected as resistant to fusidic acid and positive for fusB PCR. Finally, the fusidic acid MICs (determined by Etest) and spa types were determined for the 10 isolates thus screened. All revealed MICs between 4 and 8 mg/L and belonged to spa type t171 or a related spa type (t171, n 1⁄4 8; t408, n 1⁄4 2) corresponding to ST123, which definitively confirmed that they belonged to the EEFIC. The 10 isolates were collected from eight different hospitals and over a long period (2000–07), confirming the geographical and temporal dissemination of the EEFIC in France. As expected, the clinical data for the 10 patients indicated that impetigo or its generalized form were the motives for consultation. Even if we are not presently able to establish the proportion of the EEFIC within fusidic acid-resistant S. aureus in our collection, because of the design of our screening procedure, these data definitively demonstrated that the EEFIC is present in France and likely represents 15% to 20% of all French S. aureus isolates harbouring exfoliative toxin A. In the EPISA study, the low rate of impetigo in the French patients (12.2%) compared with British patients (33.3%) could partly explain the underrepresentation of the EEFIC in the French data. The low number in the series is probably due to the French practice of consulting a specialist (paediatrician or dermatologist) or hospital emergency wards for impetigo, rather than a general practitioner as would tend to be the case in the UK and Ireland. So, the fact that the EPISA inclusion criterion was ‘patient attending a general practice clinic in the community with SSTIs’, probably introduced a recruitment bias in the French isolates implicated in impetigo and more generally in severe SSTIs. Conversely, the French national reference centre for staphylococci collects S. aureus strains of clinical interest with recruitment from hospitals as well as non-hospital community laboratories, thereby avoiding the bias found in the EPISA study and allowing us to detect the presence of the EEFIC in France in the 2000–07 period.