Methicillin-resistant Staphylococcus aureus in Taiwan

We found a virulent closely related clone (Panton-Valentine leukocidin–positive, SCCmec V:ST59) of methicillin-resistant Staphylococcus aureus in inpatients and outpatients in Taiwan. The isolates were found mostly in wounds but were also detected in blood, ear, respiratory, and other specimens; all were susceptible to ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole.

A lthough most methicillin-resistant Staphylococcus aureus (MRSA) illness and death are associated with healthcare facilities (H-MRSA), isolates from communityassociated MRSA (C-MRSA) infections have been obtained with increasing frequency in the last few years in different countries, including Taiwan (1)(2)(3)(4)(5). The changing epidemiology of MRSA has become an important public health concern worldwide (1,4). MRSA arises when S. aureus organisms acquire a large mobile genetic element called staphylococcal cassette chromosome mec (SCCmec) (6). Most H-MRSA strains possess either SCCmec II or III; most C-MRSA strains possess SCCmec IV (7)(8)(9). Recently, a novel type V SCCmec type was characterized and found in a C-MRSA isolate from Australia (10). With the exception of variable resistance to erythromycin, C-MRSA strains are generally susceptible to other non-β-lactam antimicrobial agents, in contrast to most H-MRSA, which are typically resistant to many of the non-βlactam agents (1,4,9). Another characteristic of C-MRSA is the production of Panton-Valentine leukocidin (PVL), an extracelluar cytotoxin involved in primary skin infections and pneumonia (2)(3)(4).
We conducted a study to characterize the molecular epidemiology of selected MRSA isolates from the Taiwan Surveillance of Antimicrobial Resistance (TSAR), a national surveillance program of inpatient and outpatient clinical isolates in Taiwan (11). We describe the finding of a virulent closely related clone of MRSA and its prevalence in Taiwan.

The Study
A total of 398 and 865 nonduplicate S. aureus isolates were collected from March to May 2000 from 21 hospitals and from July to September 2002 from 26 hospitals, respectively, as part of the TSAR collection (11). The proportions of isolates for the 2 years were similar for outpatients (27.5% in 2000 and 28.9% in 2002); the rest of the isolates were from inpatients. The most common specimen type was wound, which accounted for 35. 4%  To obtain an overall understanding of MRSA throughout Taiwan, we first chose 80 MRSA isolates (68 inpatient and 12 outpatient isolates) collected in 2002 from 4 hospitals located in the north, middle, south, and east regions of Taiwan. Pulsed-field gel electrophoresis was performed according to a published protocol (9), and pulsotypes were assigned to clusters of isolates with >80% similarity from the dendrograms. SCCmec typing and PVL gene detection were performed according to published protocols (7,8,10). Multilocus sequence typing (MLST) was performed on randomly selected strains from major pulsotypes, and the sequence type (ST) was assigned by using the MLST database (http://www.mlst.net) (13). Three major clusters (pulsotypes) were found, including 47 (58.8%) pulsotype A, 7 (8.8%) pulsotype B, and 18 (22.5%) pulsotype C (online Appendix Figure 1, available from http://www.cdc.gov/ ncidod/EID/vol11no11/05-0367_app1.htm). All 47 pulsotype A isolates had SCCmec III; 4 isolates tested by MLST had ST239. In addition to being resistant to clindamycin (94%), erythromycin (100%), and tetracycline (100%), all pulsotype A isolates were resistant to ciprofloxacin (CIP), gentamicin (GEN), and trimethoprim/sulfamethoxazole (SXT). The 7 pulsotype B isolates possessed SCCmec IV but were not of the 4 known IV subtypes (IV not a-d); all were CIP-and SXT-susceptible but GEN-resistant. Seventeen of the 18 isolates in pulsotype C possessed SCCmec V; the other had SCCmec IVa; all 18 were CIP/GEN/SXT-susceptible. Of the 10 isolates tested by MLST from pulsotype B (3 isolates) and pulsotype C (7 isolates), all had ST59. Only pulsotype C isolates were PVL-positive.
The reason for the high prevalence of this virulent clone (pulsotype C:ST59, SCCmec V, PVL-positive) of MRSA in Taiwan in both inpatients and outpatients is not known. Data on the prevalence of SCCmec V are still limited, and ST59 has been described infrequently. A recent longitudinal study of MRSA isolates in the San Francisco area found that the ST59-SCCmec IV has increased steadily from 1999 to become 1 of the 4 major clones associated with C-MRSA (14).
Production of the PVL cytotoxin is considered a genetic marker for C-MRSA, and although PVL-positive MRSA have usually been associated with skin and soft tissue infections, severe and fatal infections, such as necrotizing pneumonia, have been reported (2)(3)(4). Thus, PVL may confer an additional virulence advantage for this particular clone of MRSA in Taiwan. Other possible explanations are that the less resistant C-MRSA can grow faster than multidrug-resistant H-MRSA and that SCCmec IV and V carried by C-MRSA may have the advantage over SCCmec I-III carried by H-MRSA because they are smaller and more transferable; both of these putative advantages may contribute to their propagation (10,15).
The close relatedness and high prevalence of this virulent pathogen argue for a clonal expansion advantage of this particular clone. Outbreaks of C-MRSA infections caused by SCCmec IV (IVa) have been reported in several countries (4). Since our genotyping results showed that MRSA isolates possessing SCCmec V and PVL in Taiwan are clonally related, we cannot rule out the possibility of outbreaks due to this particular clone in some areas. However, our isolates came from multiple hospitals throughout the 4 geographic regions of Taiwan. Our data also showed that this particular clone was already present in 2000. In addition, this particular clone was found not only in outpatients but also in ICU and non-ICU inpatients, including in hospital-acquired infections. These findings indicate that this clone has migrated into the hospital environment; moreover, it can cause more severe infections, as shown by its presence in blood, respiratory, ear, and other specimens.

Conclusions
Our analysis of MRSA isolates collected in 2000 and 2002 indicated that a virulent clone of MRSA (pulsotype C:ST59, SCCmec V and PVL-positive), which caused wound infections primarily but also other potentially more serious infections, is highly prevalent in Taiwan inpatient and outpatient settings. Recognition of this clone can be facilitated by its antimicrobial susceptibility profile. Because the resistance pattern of these isolates differs from that of traditional H-MRSA strains, the antimicrobial susceptibility profile has important implications for treatment. Understanding the roles these strains play in MRSA epidemiology helps physicians choose the most appropriate treatment. Prompt and judicious management and infection control measures should help deter further spread of this virulent pathogen.