We studied S. aureus isolates collected over 10 years (2005–2014) at Shanghai Renji Hospital, Shanghai, China, a large teaching hospital at which ≈10,000 patients from the entire Shanghai metropolitan area are admitted each day. We obtained 2,048 infectious S. aureus isolates and characterized them by multilocus sequence and spa typing, antibiotic resistance profiling, determination of the staphylococcal cassette chromosome (SCC) mec type (encoding methicillin resistance), and analytical PCR to determine presence of the lukSF genes encoding PVL. For isolates obtained during 2005–2010, we investigated randomly selected subsets (100 isolates/year); for isolates obtained during 2011, 2012, and 2014, we investigated all isolates. No isolates were collected in 2013. CA–S. aureus was defined as an isolate obtained from either an outpatient or an inpatient (including from general and urgent care and emergency rooms) <24 h after hospital admission, who lacked risk factors (contact with the hospital environment in the 6 months preceding the culture, S. aureus infection history, residence in a long-term care facility in the 12 months before culture, presence of a central vascular catheter at the time of infection, or recent use of antimicrobial drugs). These data were obtained by a review of medical records. The study was approved by the ethics committee of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (protocol RJ-H-2015–0221).

Figure

Figure. Epidemiology of MRSA in Shanghai, 2005–2014. Of infectious Staphylococcus aureus isolates obtained during 2005–2010, a random selection of 100 from each year were analyzed; of those obtained during 2001, 2012, and...

The percentage of methicillin resistance in the S. aureus infectious isolates was high, as is generally reported for China (13), and remained stable (at ≈70%) over the past 10 years (Table; Figure, panel A). In contrast, during the same time, resistance among CA–S. aureus infections rose considerably, from 21% to 43% (p = 0.0108, Fisher exact test). While the percentage of HA-MRSA infections slightly decreased and that of CA–methicillin-sensitive S. aureus infections remained stable, CA-MRSA infections increased significantly, from 2.4% (12/500 total S. aureus infections) during 2005–2010 to 7.4% (35/470) in 2014 (p = 0.0003, Fisher exact test) (Table; Figure, panel A). ST59 dominated among CA-MRSA infections; increasing relative frequency reached a level of 71.4% in 2014 (Table; Figure, panel A). This finding links the observed surge in the CA-MRSA infection rate nearly exclusively to the ST59 lineage.

Of the 56 ST59 CA-MRSA infections, most (34 [61%]) were skin and soft tissue infections (i.e., spontaneous pyogenic skin abscesses), but a considerable number were respiratory (10 [18%]) or blood (9 [16%]) infections. The percentage of invasive infections (as defined by isolation from an otherwise sterile site, such as primary skin and soft tissue infection, with subsequent isolation from the blood, lung, or other otherwise sterile body fluids) among ST59 CA-MRSA patients was high at 62.5% (35/56). Fatality rate was 14% (5/35) among patients with invasive infections. Multidrug resistance was frequent. In addition to being resistant to β-lactams, most of the recently (2014) isolated ST59 CA-MRSA was also resistant to erythromycin (23/25; 92%), clindamycin (23/25; 92%), gentamicin (2/25; 8%), levofloxacin (3/25; 12%), trimethoprim/sulfamethoxazole (4/25; 16%), fosfomycin (3/25; 12%), or rifampin (5/25; 20%). None was resistant to tetracycline, linezolid, or vancomycin.

The ST59 CA-MRSA isolates were genetically heterogeneous and belonged to 7 spa types, predominantly t437 (31/56; 55%), t216 (12/56; 21%), and t441 (6/56; 11%). This finding is in contrast to the scenario described for USA300 CA-MRSA isolates, which are closely related (14), and suggests independent acquisition of SCCmec elements by genetically divergent parental ST59 methicillin-sensitive S. aureus strains.

Of note, only 20 (36%) of the 56 ST59 CA-MRSA isolates that we obtained contained the lukSF genes encoding PVL (Figure, panel B), and presence of the PVL genes was not correlated with more severe (i.e., invasive) infection (Figure, panel C). The PVL-positive Taiwan clone (spa types t437/t441, lukSF⁺, SCCmec V) was responsible for only 20% of cases (Figure, panel D). Moreover, while the percentage of PVL-positive ST59 CA-MRSA isolates and those belonging to the Taiwan clone increased in 2012, probably because of dissemination of the Taiwan clone into China, those numbers recently declined, indicating that PVL and the Taiwan clone are not main driving forces explaining the increase and current high percentage of CA-MRSA infections in Shanghai (Figure, panel B). Also, these subsets were not correlated with a specific infection type (Figure, panels C,D). Last, the Taiwan clone was not more frequently involved with invasive infections than were other ST59 CA-MRSA isolates (Figure, panel D).

CA-MRSA infections caused by a non-USA300 clone increased significantly in a highly populated area in China. Whether our findings are representative of all of China and adjacent countries remains to be addressed. Our findings do not support the previously indicated correlation of the PVL-positive ST59 subset (Taiwan clone) with infection (11,12). Thus, our study provides epidemiologic evidence challenging the widespread notion about a significant role of PVL in CA-MRSA dissemination in the ST59 lineage and in general. Inasmuch as our findings underscore the idea that the development of CA-MRSA clones is less limited to specific genetic backgrounds than previously thought, they underscore that novel successful CA-MRSA clones will probably continue to emerge.