These data represent a very large collection of MRSA isolates associated with invasive disease from geographically distinct areas of the United States; analysis suggests that among these, there is minimal genetic diversity among USA300 strains. This affirms the conclusions of smaller studies of MRSA isolates, suggesting relatively recent evolution and national expansion of USA300 (20
USA100 was the most common strain type isolated in this study, most commonly from patients with health care risk factors. This is not surprising; USA100 has a long history as a common health care-associated MRSA strain (24
), and the diversity of PFGE patterns observed in this strain is consistent with its longevity as a pathogen (10
). Nearly three-quarters of the USA100 isolates tested in this study were PCR positive for SED, which is higher than the percentage reported by Diep and colleagues (14%) in 2006 (8
). The significance of this finding for invasive MRSA disease is unknown.
As expected (24
), the majority of CA-MRSA isolates were USA300, although USA300 was also a common isolate from patients with health care-associated infections (12% of all USA300 isolates were identified among HO-MRSA cases and 47% were among HACO-MRSA cases). USA500 was more common than USA300 at one site and was less geographically represented than other strain types, although USA500 was the third most commonly observed strain type. PVL, present in 96.5% of USA300 isolates, was the only toxin we tested for that was commonly found among USA300 isolates. Although USA400 and USA1100 were rare in this collection, the prevalences of PVL in these strains (66.7% and 75.0%, respectively) found in this study are similar to those observed in the CDC's larger database of more than 5,000 characterized MRSA isolates received over the past decade (G.E. Fosheim, personal communication).
Resistance to erythromycin, levofloxacin, and clindamycin was common in this collection of isolates. This is likely because of the high proportion of USA100 isolates, although more than half of USA300 isolates in our collection were resistant to levofloxacin. Fluoroquinolone resistance among USA300 isolates was previously reported to be uncommon, but several recent reports, including this one, suggest that fluoroquinolone resistance is increasing among USA300 isolates (16
). Six percent of isolates demonstrated vancomycin MICs of 2 μg/ml. This might be because of acceptable variation in the reference broth microdilution method (4
), but of note is that most of these isolates were USA100 and health care associated (HO- or HACO-MRSA), as was the single isolate with a vancomycin MIC of 4 μg/ml.
Although no interpretive criteria currently exist for mupirocin MICs for S. aureus
, there is increasing evidence that isolates with very high MICs for mupirocin, mediated by mupA
, are associated with decolonization failure (19
). Only 45 (2.3%) isolates in this study demonstrated mupirocin MICs of ≥128 μg/ml; 42 (93.3%) of these were from patients with health care risk factors. These isolates were nearly equally distributed between USA100 and USA300 and were not limited to any geographic region. As hospitals increasingly implement active surveillance and decolonization for MRSA, it may be important to monitor MICs for this agent.
We attempted to correlate strain characteristics to presenting syndrome; however, PFGE type was so closely tied to presence of toxin gene that we were only able to evaluate the relationship between PFGE type and presenting syndrome in a valid manner. Although our data are limited to invasive disease, an absence of documented health care exposures was the strongest predictor of strain type, although the clinical syndromes commonly thought of as presenting among outpatients are also predictive (e.g., endocarditis, soft-tissue infections, pneumonia, and osteomyelitis).
MRSA isolates belonging to strain types USA100, USA200, and USA500 have been associated primarily with health care-associated disease, while strains USA300, USA400, USA1000, and USA1100 were associated most often with CA-MRSA disease (9
). Recently, however, the association between strain type and epidemiologic class of disease has become less distinct, as strains historically associated with community disease enter and spread within health care institutions (21
). Skin abscesses, cellulitis, and necrotizing pneumonia are the clinical presentations most often associated with CA-MRSA infections (1
). Therefore, our finding that soft tissue infection (AOR = 6.9) and invasive pneumonia or empyema (AOR = 2.3) were associated with infection by USA300, rather than USA100, is not especially surprising. Our data also quantify the magnitude of the association between USA300 and epidemiologic classification, where CA-MRSA patients were 10-fold more likely, and HACO-MRSA patients were 6-fold more likely, to be infected with USA300 than with hospital onset strains. The fact that this association for HACO-MRSA cases is so high suggests that many HACO-MRSA patients, despite documented contacts with health care delivery, are often infected with USA300.
Both endocarditis and osteomyelitis were also found more frequently among patients with USA300 infections than among those with USA100 infections. With the exception of intravenous drug users, patients who develop endocarditis often have health care risk factors, such as indwelling lines, history of surgery, or underlying disease, such as diabetes (12
). Recent reports suggest that CA-MRSA infectious endocarditis cases could be increasing (11
), and more than 30% of the CA-MRSA patients described in that report had recent or concurrent skin infections. In this study, 15.4% of CA-MRSA endocarditis patients and 14.8% of USA300 endocarditis patients had concurrent or underlying skin or soft tissue infections, compared to 8.1% of USA100 endocarditis patients.
The association between USA300 and osteomyelitis is also unclear. Hematogenous osteomyelitis in children is relatively common, but isolates from pediatric patients were infrequent in our collection, and only 5.4% of osteomyelitis patients in this study were under 15 years of age. There are only a few reports of osteomyelitis in adults caused by CA-MRSA, defined either by epidemiology or by strain characteristics in the literature, and these are very closely linked to a history of boils or other skin infections (13
). In this study, less than one-third of USA100 and USA300 isolates associated with osteomyelitis came from patients with documented concurrent or historic skin infection (i.e., abscess or cellulitis) (25.5% or 30.9%, respectively). The presence of decubiti or other ulcers was also common among patients with osteomyelitis, occurring in 34.5% of patients infected with USA100 and 10.3% of patients infected with USA300.
A limitation of this study is the sample of isolates available for evaluation. Isolates were collected as a convenience sample of patients with invasive MRSA. However, the patients from which our sample was obtained have characteristics similar to those of all patients reported to the surveillance system (22
). Second, our analysis was limited to only those MRSA isolates recovered from a normally sterile site, usually blood. This limits the interpretation of the findings, in that isolates associated with some clinical syndromes (e.g., pneumonia and cellulitis) were limited to bacteremic cases and might not reflect the full spectrum of those diseases. For instance, there might be greater variability in strain characteristics among strains recovered from skin abscesses or lung tissue than are described in this paper. Finally, this study relies upon retrospective chart review by surveillance personnel and those diagnoses documented in the patient's chart. The clinical syndrome data presented here have not been validated in comparison with clinical observations made by treating physicians.
Despite these limitations, these data confirm that MRSA with PFGE type USA300 associated with invasive disease has limited molecular diversity in the United States and is still strongly associated with disease from patients having no documented exposures to health care facilities. These data also serve as a baseline for tracking changes in susceptibility to antistaphylococcal agents as emerging resistance among USA300 or all MRSA isolates is monitored through this and other systems.