To the Editor—Infections due to methicillin-resistant Staphylococcus aureus (MRSA) strains are a common clinical problem that causes a high burden of disease and that often requires long-term treatment.Reference Weis, Kaasch and Rieg ¹ MRSA rates vary in different countries, with rates being high in the United States, Middle and Far Eastern countries, and Southern Europe but relatively low in, for example, Northern Europe.

Encoded by different alleles of the mecA gene, an alternate penicillin-binding protein (PBP2a) is expressed in MRSA conferring resistance to β-lactam antibiotics (except ceftaroline and ceftobiprole).Reference Monecke, Muller and Schwarz ² mecA is situated on a mobile genetic element named staphylococcal cassette chromosome mec (SCCmec). Currently, this mobile element occurs as 12 different types in S. aureus as well as in other clinically relevant staphylococci such as S. haemolyticus and S. epidermidis.Reference Garcia-Alvarez, Holden and Lindsay ^{3 ,} Reference Shore, Deasy and Slickers ⁴

In 2011, a divergent mecA homologue was discovered and subsequently designated mecC. mecC MRSA has been isolated from patients from Western and Central Europe.Reference Garcia-Alvarez, Holden and Lindsay ^{3 –} Reference Paterson, Larsen and Robb ⁵ It has also been detected in different domestic and wild animals including cattle, sheep, hedgehogs, storks, and fox.Reference Monecke, Gavier-Widen and Hotzel ⁶ The reservoir of mecC strains is still unknown, although zoonotic transmission from cows or sheep is believed to play a major role.

The mecC gene was detected in various rare lineages of S. aureus in multilocus sequence type (MLST) clonal complexes (CC) 49, 130, 425, 599, and 1943.Reference Becker, Ballhausen and Köck ⁷ The amino acid identity between mecC- and mecA-encoded PBP2a is only 63%. While the mecC gene itself does not mediate resistance to penicillin, it is frequently accompanied by the β-lactamase blaZ, which is part of the SCCmec XI element that does confer resistance to penicillin.Reference Ba, Harrison and Lovering ⁸ Previous studies found that mecC also mediates resistance to oxacillin and cefoxitin.Reference Ballhausen, Kriegeskorte and Schleimer ⁹

We report a 59-year-old male patient with a postthrombotic ulcer on his right lower leg measuring 3 × 3 cm. This patient had no other concomitant disease and no prior hospital admission. The bacterial culture of the wound swab was analysed with Vitek 2 (bioMérieux, Nürtingen, Germany) and broth microdilution according to EUCAST break points. The isolate was further analyzed using the S. aureus Genotyping Kit 2.0 (Alere Technologies, Jena, Germany).

After repetitive wound debridement, bacterial culture of a wound swab revealed an S. aureus isolate resistant to benzylpenicillin, oxacillin, and cefoxitin in the routine susceptibility test. Other tested antibiotics typically used for treatment of S. aureus (eg, glycopeptides and chinolones) were found to be susceptible.

The MRSA isolate carried the mecC gene was negative for Panton-Valentine leukocidin (PVL) and was assigned to the CC130 lineage. The isolate belonged to agr group III and capsule type 8, and the mecC gene was present as a part of the SCCmec XI element together with the distinct blaZ. Despite the association of the mecC gene to zoonotic transmission, the patient reported no contact with livestock or any other potential animal source.

The patient was admitted to the hospital for treatment of the leg ulcer and was simultaneously MRSA sanitized according to the German guidelines on 5 consecutive days with an octenidin-containing wound compresses for 20 minutes per day, mupirocin nasal ointment, throat flushing with chlorhexidine, and skin washing with octenidin. After waiting for 3 days, control swabs were taken on 3 consecutive days from the nose, throat, skin, and wound. None of these 12 swabs were positive for S. aureus, which was interpreted as evidence for successful sanitization exclusively with topical treatment. During the following 2 years, all 10 swabs taken for diagnostic and screening purposes remained negative for S. aureus.

The prevalence of mecC in humans and animals is still low: the value reported in a meta-analysis was 0.009% (95% confidence interval = 0.055–0.013%) of MRSA,Reference Diaz, Ramalheira and Afreixo ¹⁰ which corresponds to an order of magnitude range of 1:100 to 1:1000 of typed MRSA.Reference Paterson, Larsen and Robb ⁵ While mecC strains in humans do not appear to be particularly virulent, cohort studies are missing and case reports are sparse.

Currently, there is no recommendation on treatment of mecC MRSA. With regard to treatment options, minimum inhibitory concentrations (MICs) for methicillin and cefoxitin are usually lower than in conventional MRSA, but these compounds might not be effective. Penicillin is an inhibitor for the mecC gene product, but because mecC is accompanied by a specific penicillinase (also carried on the SCCmec XI element), monotherapy is not a treatment option. However, in vitro and in vivo models have shown an effective combination with a β-lactamase inhibitor.Reference Ba, Harrison and Lovering ⁸ The patient was treated as an mecA MRSA case to overcome the risk of treatment failures in case of susceptible or intermediate oxacillin MICs.

The current setup to diagnose mecA/mecC of MRSA is multifaceted and time-consuming. Because of its divergent sequence, mecC and its gene product cannot be detected by all assays designed to identify mecA/PBP2a,Reference Shore, Deasy and Slickers ⁴ and it has been suggested that mecC is largely underreported. The discrepancy between phenotypic resistance and mecA-negative molecular or protein-based confirmatory tests might delay reporting to the physician and, thus, also delay the administration of an appropriate treatment. Hence, the discovery of mecC has resulted in the recognition of the need to redesign diagnostic tests.

In summary, clinicians and microbiologists should be aware of the changing facets of MRSA infections, particularly the emergence of mecC MRSA-conferred resistance against oxacillin. MRSA resistance warrants further investigation, especially in cases of discrepant testing results. Because the clinical experience is limited to case reports (probably due to the underreporting of mecC MRSA), a mecC MRSA infection should be treated as an mecA MRSA infection to avoid treatment failure.