Community-associated methicillin-resistant Staphylococcus aureus and healthcare risk factors.

To determine frequency of methicillin-resistant Staphylococcus aureus infections caused by strains typically associated with community-acquired infections (USA300) among persons with healthcare-related risk factors (HRFs), we evaluated surveillance data. Of patients with HRFs, 18%-28% had a "community-associated" strain, primarily USA300; of patients without HRFs, 26% had a "healthcare-associated" strain, typically USA100.

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In the United States, initial reports of methicillin-resistant Staphylococcus aureus (MRSA) infections among injection drug users in Detroit in 1981 were followed by reports of MRSA associated with the deaths of 4 children in Minnesota and North Dakota in 1997 (1). For the next few years, public health personnel in several states investigated outbreaks of MRSA infections of skin and soft tissue among diverse populations who typically had little or no previous contact with the healthcare system, such as Native Americans (2), sports teams (3), prison inmates (4), and child-care facility attendees (5). These outbreaks were initially associated with a novel MRSA strain known as MW2, or pulsed-field gel electrophoresis (PFGE) type USA400, but were soon replaced by a strain of MRSA belonging to PFGE type USA300 (6). Through 2002, the clinical appearance of cases and the microbiologic characteristics of USA300 and USA400 differed substantially from those associated with strains of MRSA acquired in healthcare settings (7). Increasingly, MRSA strains of community origin are causing healthcare-associated disease (8,9). We evaluated surveillance data from a multisite project to determine the frequency with which infections among patients with healthcare-related risk factors (HRFs) were caused by USA300 or other strains of community origin.

The Study

Active, population-based surveillance for invasive MRSA infections is ongoing in 9 US states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New York, Oregon, and Tennessee) through the Active Bacterial Core Surveillance system in the Emerging Infections Program at the Centers for Disease Control and Prevention (CDC). Personnel in each state actively collect laboratory reports of positive MRSA cultures from normally sterile sites (e.g., blood; cerebrospinal, joint, or pleural fluid) of residents in their catchment areas to identify cases. In 2005, the estimated combined population under surveillance was 16.3 million, according to data from the US Bureau of the Census. To report a case, personnel must link a laboratory report to the patient's medical record. During record reviews, personnel abstract information about the following HRFs: culture obtained >48 hours after admission; presence of an invasive device (e.g., vascular catheter, G-tube); and history of MRSA infection or colonization, surgery, hospitalization, dialysis, or residence in a long-term care facility in the 12 months preceding the culture. Case-patients may have >1 HRF. For this analysis, we used information from the record review to classify cases into 3 mutually exclusive groups: 1) case-patients with classic healthcare-associated infections (HA) whose culture was obtained >48 hours after admission with or without other HRFs; 2) case-patients with HRFs but with community onset (i.e., whose cultures were obtained [less than or equal to]48 hours after admission) (HACO); and 3) case-patients with community-associated (CA) infections without HRFs, according to medical record review.

A subset of isolates from case-patients was collected from laboratories that voluntarily submitted them for microbiologic characterization. Of the isolates received at CDC by October 2005, a sample of 100 was selected for testing as follows. First, isolates were stratified by Emerging Infections Program site; none were available from Maryland. Second, all isolates from tissues other than blood were selected from each Emerging Infections Program site. To ensure 12-13 isolates per site, we selected blood isolates from case-patients classified as CA and obtained the remainder from samples from HA and HACO case-patients. Isolates were tested by PFGE; patterns were analyzed by using BioNumerics (Applied Maths, Austin, TX, USA). Isolates were grouped into PFGE types using Dice coefficients and 80% relatedness (10). We considered isolates with PFGE types USA300, 400, or 1000 to be of community origin and those with types USA100, 200, and 500 to be of healthcare origin as previously described (10).

Statistical analysis consisted of comparisons of proportions between CA and HA and between CA and HACO cases using [chi square] pairwise comparisons. Differences in median age were tested by using Wilcoxon rank sum test.

Of 9,147 cases of invasive MRSA infection investigated from January 2004 through February 2006, 2,535 (28%) were HA, 5,353 (59%) were HACO, and 1,259 (14%) were CA. The median age of case-patients with HA and HACO was significantly higher than that of case-patients with CA (Table 1). CA case-patients were 1) more likely to have pneumonia than HACO but not HA case-patients; 2) more likely to have endocarditis than either HA or HACO case-patients; and 3) less likely to die during this hospital stay than were HA or HACO case-patients.

Of the 100 isolates selected for initial testing, 29 were from HA case-patients, 44 were from HACO case-patients (including 1 isolate of a unique PFGE type), and 27 were from CA case-patients (including 1 isolate that could not be typed) (Table 2). Of the HA isolates, 8 (28%) were USA300. Of the HACO isolates, 6 (14%) were USA300, 1 (2%) was USA400, and 1 (2%) was USA1000. Thus, 18%-28% of isolates in patients with HRFs (HA and HACO) had PFGE patterns typical of community strains. Of the 27 isolates from CA case-patients, 5 (19%) were USA100 and 2 (7%) were USA500; thus, 7 (26%) of isolates among CA case-patients were strains typically considered to be of healthcare origin.

Conclusions

MRSA strains such as USA300, which were initially a cause of MRSA infections in the community, have migrated into healthcare settings. The results from this multisite project are consistent with observations from individual facilities, where USA300 isolates caused illness in patients whose infection was healthcare associated (11,12). Although age and frequency of endocarditis still differed between case-patients with HRFs (HA and HACO) and those without HRFs (CA), PFGE testing indicated that 18%-28% of patients with HRFs were infected with a "community-associated" strain of MRSA, primarily USA300. Furthermore, 26% of patients without HRFs had a "healthcare-associated" strain, typically USA 100. Thus, the distinction between healthcare- and community-associated MRSA is rapidly blurring.

Acknowledgments

We are indebted to Rachel Gorwitz and Jeff Hageman for their review of the report and to Roberta Carey, Jean Patel, and Sigrid McAllister for their guidance and contributions to laboratory testing of isolates.

Dr Klevens is a medical epidemiologist at CDC. She is the CDC principal investigator in a multistate project that measures methicillin-resistant Staphylococcus aureus in the population, and she provides epidemiologic support to the National Healthcare Safety Network.

References

(1.) Centers for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus Minnesota and North Dakota, 1997-1999. JAMA. 1999;282:1123-5.

(2.) Baggett HC, Hennessy TW, Rudolph K, Bruden D, Reasonover A, Parkinson A, et al. Community-onset methicillin-resistant Staphylococcus aureus associated with antibiotic use and the cytotoxin Panton-Valentine leukocidin during a furunculosis outbreak in rural Alaska. J Infect Dis. 2004; 189:1565-73.

(3.) Centers for Disease Control and Prevention. Methicillin-resistant Staphylococcus aureus infections among competitive sports participants--Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000-2003. MMWR Morb Mortal Wkly Rep. 2003;52:793-5.

(4.) Centers for Disease Control and Prevention. Public health dispatch: outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections--Los Angeles County, California, 2002-2003. JAMA. 2003;289:1377.

(5.) Adcock PM, Pastor P, Medley F, Patterson JE, Murphy TV. Methicillin-resistant Staphylococcus aureus in two child care centers. J Infect Dis. 1998;178:577-80.

(6.) Yenover FC, McDougal LK, Goering RV, Killgore G, Projan S J, Patel JB, et al. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006;44:108-18.

(7.) Fridkin SK, Hageman JC, Morrison M, Sanza LT, Como-Sabetti K, Jernigan JA, et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med. 2005;352:1436-44. Erratum in: N Engl J Med. 2005;352:2362.

(8.) Healy CM, Hulten KG, Palazzi DL, Campbell JR, Baker CJ. Emergence of new strains of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Clin Infect Dis. 2004;39:1460-6.

(9.) Saiman L, O'Keefe M, Graham PL III, Wu F, Said-Salim B, Kreiswirth B, et al. Hospital transmission of community-acquired methicillin-resistant Staphylococcus aureus among postpartum women. Clin Infect Dis. 2003;37:1313-9.

(10.) McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41:5113-20.

(11.) Seybold U, Kourbatova EV, Johnson JG, Halvosa SJ, Wang YF, King MD, et al. Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis. 2006;42:647-56.

(12.) Huang H, Flynn NM, King JH, Monchaud C, Morita M, Cohen SH. Comparisons of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MSRA infections in Sacramento, California. J Clin Microbiol. 2006; 44:2423-7.

R. Monina Klevens, * Melissa A. Morrison, * Scott K. Fridkin, * Arthur Reingold, ([dagger]) Susan Petit, ([double dagger]) Ken Gershman, ([section]) Susan Ray, ([paragraph]) Lee H. Harrison, (#) Ruth Lynfield, ** Ghinwa Dumyati, ([dagger])([dagger]) John M. Townes, ([double dagger])([double dagger]) Allen S. Craig, ([subsection]) Gregory Fosheim, * Linda K. McDougal, * and Fred C. Tenover * for the Active Bacterial Core Surveillance of the Emerging Infections Program Network (1)

* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) University of California, Berkeley, California, USA; ([double dagger]) Connecticut Department of Health, Hartford, Connecticut, USA; ([section]) Colorado Emerging Infections Program, Denver, Colorado, USA; ([paragraph]) Grady Memorial Hospital, Atlanta, Georgia, USA; (#) Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; ** Minnesota Department of Health, Minneapolis, Minnesota, USA; ([dagger])([dagger]) University of Rochester, Rochester, New York, USA; ([double dagger])([double dagger]) Oregon Health Science University, Portland, Oregon, USA; and ([subsection]) Tennessee Department of Health, Nashville, Tennessee, USA

(1) Joelle Nadle, Elizabeth Partridge, Pam Daily, Gretchen Rothrock, Steve Burnite, Deborah Aragon, Nicole Haubert, Allison Daniels, Jonathan Schwartz, Jim Hadler, Zack Fraser, Nancy Barrett, Wendy Baughman, Monica Farley, Janine Ladson, James Howgate, Emily McMahan, Laurie Thompson Sanza, Janice Langford, Kathleen Shutt, Kathy Como-Sabetti, Jessica Buckand, Kathy Harriman, Nana Bennett, Anita Gellert, Paul Malpiedi, Michael Emerson, Karen Stefonek, Michelle Barber, Ann Thomas, Brenda Barnes, Terri McMinn, Jane Conners, Melinda Eady, William Schaffner, Chris Van Beneden, Tami Skoff, Carolyn Wright, Emily Weston, Catherine Rebmann, and Robert Pinner

Address for correspondence: R. Monina Klevens, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Mailstop A24, 1600 Clifton Rd NE, Atlanta, GA 30333, USA; email:rmk2@ cdc.gov

Table 1. Selected characteristics among case-patients
with invasive MRSA, by healthcare-related risk factors,
Active Bacterial Core Surveillance, January 2004-February 2006 *

                      With HRFs, no. (%)

Characteristic      Healthcare-associated,
                          n = 2,535

Median age, y        62 ([double dagger])
Pneumonia                 413 (16.3)
Endocarditis      72 (2.8) ([double dagger])
Died             687 (27.1) ([double dagger])

                      With HRFs, no. (%)

Characteristic     Healthcare-associated,
                       community onset,
                          n = 5,353

Median age, y        62 ([double dagger])
Pneumonia        685 (12.8) ([double dagger])
Endocarditis     345 (6.4) ([double dagger])
Died             845 (15.8) ([double dagger])

                    Without HRFs, no. (%)

Characteristic      Community-associated,
                     ([dagger]) n = 1,259

Median age, y                 46
Pneumonia                 190 (15.1)
Endocarditis              158 (12.6)
Died                     131 (10.4)

* MRSA, methicillin-resistant Staphylococcus aureus;
HRFs, healthcare-related risk factors.

([dagger]) Patients with community-associated infections
were those who did not have HRFs; these patients were used
as reference.

([double dagger]) p < 0.05 for [chi square] test for categorical
variables; Wilcoxon rank sum for age.

Table 2. MRSA isolates from invasive sites by healthcare-related
risk factors and PFGE type, Active Bacterial Core Surveillance,
January 2004-February 2006 *

PFGE type      Healthcare     Healthcare      Community      Total,
               associated,    associated,     associated,    no. (%)
                 no. (%)       community      ([dagger])
                             onset, no. (%)     no. (%)

USA100           20 (69)        30 (68)         5 (19)       55 (55)
USA200            1 (3)            0               0          1 (1)
USA300           8 (28)          6 (14)         18 (67)      32 (32)
USA400              0            1 (2)             0          1 (1)
USA500              0            5 (11)          2 (7)        7 (7)
USA1000             0            1 (2)           1 (4)        2 (2)
Unique type         0            1 (2)             0          1 (1)
Not typeable        0              0             1 (4)        1 (1)
Total           29 (100)        44 (100)       27 (100)     100 (100)

* MRSA, methicillin-resistant Staphylococcus aureus; PFGE,
pulsed-field gel electrophoresis,

([dagger]) Patients with community-associated infections were those
who did not have healthcare-related risk factors.