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Original Investigation |

Community-Associated Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections at a Public Hospital:  Do Public Housing and Incarceration Amplify Transmission? FREE

Bala Hota, MD, MPH; Charlotte Ellenbogen, MD; Mary K. Hayden, MD; Alla Aroutcheva, MD, PhD; thomas w. Rice, PhD; Robert A. Weinstein, MD
[+] Author Affiliations

Author Affiliations: Division of Infectious Diseases, Department of Medicine, Rush University Medical Center (Drs Hota, Ellenbogen, Hayden, Aroutcheva, and Weinstein) and Division of Infectious Diseases, Department of Medicine, John H. Stroger, Jr Hospital of Cook County (Drs Hota, Aroutcheva, Rice, and Weinstein), Chicago, Ill.


Arch Intern Med. 2007;167(10):1026-1033. doi:10.1001/archinte.167.10.1026.
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Background  Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have emerged among patients without health care–associated risk factors. Understanding the epidemiology of CA-MRSA is critical for developing control measures.

Methods  At a 464-bed public hospital in Chicago and its more than 100 associated clinics, surveillance of soft tissue, abscess fluid, joint fluid, and bone cultures for S aureus was performed. We estimated rates of infection and geographic and other risks for CA-MRSA through laboratory-based surveillance and a case-control study.

Results  The incidence of CA-MRSA skin and soft tissue infections increased from 24.0 cases per 100 000 people in 2000 to 164.2 cases per 100 000 people in 2005 (relative risk, 6.84 [2005 vs 2000]). Risk factors were incarceration (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.00-3.67), African American race/ethnicity (OR, 1.91; 95% CI, 1.28-2.87), and residence at a group of geographically proximate public housing complexes (OR, 2.50; 95% CI, 1.25-4.98); older age was inversely related (OR, 0.89; 95% CI, 0.82-0.96 [for each decade increase]). Of 73 strains tested, 79% were pulsed-field gel electrophoresis type USA300.

Conclusions  Clonal CA-MRSA infection has emerged among Chicago's urban poor. It has occurred in addition to, not in place of, methicillin-susceptible S aureus infection. Epidemiological analysis suggests that control measures could focus initially on core groups that have contributed disproportionately to risk, although CA-MRSA becomes endemic as it disseminates within communities.

Figures in this Article

Since 1998, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have emerged among patient groups with risk factors unassociated with health care, including sports exposure,15 incarceration,610 intravenous drug use,11 overcrowded housing,1216 tattooing,17,18 and poor hygiene.1113,19 An understanding of factors promoting acquisition and emergence of CA-MRSA may aid in the development of prevention strategies. For some infectious diseases, such as sexually transmitted infections, transmission can occur via infected core groups that contribute disproportionately to new cases.20 Surveillance of the geographic distribution and secular trends of CA-MRSA infection may help identify specific high-risk community settings and groups.

We conducted surveillance at a public health care system for patients with CA-MRSA isolated from soft tissue, abscess, joint, or bone specimens. We examined strain clonality, effect of community overcrowding and group housing, and changes in rates and geographic distribution of infection with CA-MRSA during 6 years, and we evaluated risk factors for infection in a nested case-control study.

SETTING

The study was performed at John H. Stroger, Jr Hospital of Cook County (CCH), a 464-bed public hospital in Chicago, Ill, and its more than 100 associated clinics; CCH primarily serves the urban poor (ie, uninsured or indigent individuals) in Cook County. The mean annual patient care volumes from 2001 through 2004 were 749 992 clinic visits, 146 316 emergency department visits, and 23 041 hospital admissions.

The study was reviewed by our institutional review board. The need for informed consent was waived.

CASE DEFINITION

Using a previously validated electronic case definition (κ statistic, 0.97 [100% sensitive and 97% specific for community-associated infection compared with medical record review]),21 we identified individuals without health care exposures with community-onset S aureus infections. Individuals older than 1 year with MRSA or methicillin-susceptible S aureus (MSSA) growing from microbiological cultures of soft tissue, abscess fluid, joint fluid, or bone with (1) culture obtained while an outpatient or within the first 3 days of a hospitalization, (2) no clinical isolate of MRSA in the last 6 months, (3) no hospitalization or surgery within 1 year, and (4) no hemodialysis were designated as having community-associated infection; all other infections were defined as health care–associated infection.22,23 Only the first isolate from a patient within 6 months was counted as CA-MRSA or CA-MSSA.

STUDY DESIGN

Using the electronic case definition, we conducted surveillance from January 1, 2000, through August 31, 2005, among a cohort of individuals infected with community-associated S aureus in clinical cultures of soft tissue, abscess fluid, joint fluid, or bone specimens. Isolates were obtained from patients seen at the CCH emergency department, at affiliated clinics, or on CCH inpatient wards. These clinical infection sites were selected because they account for more than 90% of infections and have a low likelihood of attribution to nosocomial acquisition (ie, from intravenous catheters).

A nested case-control study was conducted using CA-MRSA cases compared with CA-MSSA controls. Cases and controls were identified from September 1, 2001, through August 31, 2004, to ensure complete data for all covariates.

DATA COLLECTION

Data were collected from our clinical data repository.24 Electronic records were queried for presence of diabetes mellitus,25 human immunodeficiency virus, chronic renal insufficiency, and infection relapses within 1 year. Prior antimicrobial use was determined from antimicrobial prescriptions from inpatient or outpatient pharmacies and were categorized as having been given within 1 week or within 1 year to 1 week before the culture date. Exposures to the Cook County Jail within 1 year before positive culture results were obtained from arrest records of the Cook County Department of Corrections. Home addresses were obtained from electronic data; if multiple addresses were available for a patient, the address historically closest to the culture results was used.

MICROBIOLOGICAL ANALYSIS

Clinical isolates were identified as S aureus using routine methods.26 Antimicrobial resistance was determined by automated broth microdilution (MicroScan; Dade Behring, West Sacramento, Calif). Isolates were considered resistant to methicillin if the oxacillin minimum inhibitory concentration was at least 4 μg/mL. Clindamycin resistance was determined in all periods by automated broth microdilution. Inducible clindamycin resistance was determined by D test27 when requested by clinicians.

Community-associated methicillin-resistant S aureus isolates from patients with cultures performed on or after January 1, 2004, were available for further analysis. Isolates from patients with recent incarceration, with cultures performed in July 2004, or with residence within the borders of 2 specific geographic clusters were studied for pulsed-field gel electrophoresis type, staphylococcal chromosome cassette mec type, and presence of the Panton-Valentine leukocidin genes2831 to assess clonality among isolates clustered geographically, temporally, and with a common exposure (eg, incarceration). Antibiogram data were used to examine isolates before January 1, 2004.

STATISTICAL ANALYSIS

Prevalence (the number of positive culture results divided by the number of cultured patients) and incidence (the number of positive culture results among Cook County patients seen at CCH divided by the CCH catchment population residing in Cook County) of infection with CA-MRSA or CA-MSSA were calculated. The CCH catchment population was calculated from an estimation of the proportion of all Cook County residents who seek care at CCH. This proportion was determined by dividing the number of Cook County residents hospitalized at CCH in 2004 for infections of skin or subcutaneous tissue or erysipelas (International Classification of Diseases, Ninth Revision code 035 or 680-686) by the number with these diagnoses hospitalized at all Cook County hospitals in that year, stratified by ZIP code of residence. Data for all Cook County hospitalizations were obtained from the Illinois Hospital Association; 2004 was chosen because it was the first year available with complete data. The proportion for each ZIP code was then multiplied by the total number of residents in each ZIP code as reported in the most recent US census ZIP code tabulation areas from 2000; these values were summed for all ZIP codes in Cook County to produce an unadjusted estimate of the catchment population for CCH.32 Two hundred nineteen patients with addresses outside of Cook County or without addresses (ie, homeless) were excluded for these calculations.

Addresses were geocoded using commercially available software (Arcview 9.0; ESRI, Redlands, Calif), and these data were entered using SaTScan software version 5.1.33,34 Clusters of cases of CA-MRSA were detected by the Bernoulli method of the spatial scan statistic35; this analysis was stratified into 4 periods because of a temporal trend among cases. The periods, chosen a priori to create approximately equal time frames, were period 1 (January 1, 2000, through June 30, 2001), period 2 (July 1, 2001, through December 31, 2002), period 3 (January 1, 2003, through June 30, 2004), and period 4 (July 1, 2004, through August 31, 2005).

To assess the effect of overcrowding on risk of infection with CA-MRSA, we used the Cook County US Census Bureau 2000 occupancy data (percentage of the population living with >1 person per room36) for the block group of a patient's residence. Strata were created based on quartiles of level of overcrowding after examination of the frequency distribution of persons per room in the cohort. Counts of MRSA cases were compared with counts of MSSA cases and with counts of all patients who had had cultures performed for each strata of overcrowding. The association of public housing and overcrowding with CA-MRSA infection was assessed using the χ2 statistic for univariate analysis.

Logistic regression was used to perform multivariate analysis, with presence or absence of CA-MRSA as the outcome variable. Variables were those with P<.15 on univariate analysis and year of culture. Antimicrobial use was excluded from multivariate analysis because differences were only noted within 1 week of culture, which may have reflected therapy for active infections. Interaction was assessed for comorbidities and recent incarceration, as was collinearity.37 Residence in public housing regardless of period was used in multivariate analysis, and interaction between period and residence was assessed. Public housing units were categorized based on whether they were contained within clusters detected by SaTScan. Variables were eliminated using backward elimination for P>.15. Statistical analyses were performed using SAS software version 8 (SAS institute, Cary, NC).

LABORATORY-BASED SURVEILLANCE

During 6 years (January 1, 2000, through August 31, 2005), soft tissue, abscess fluid, joint fluid, or bone specimens from 2346 (34.0%) of 6894 patients without health care–associated risk factors grew S aureus; 971 (41.4%) and 1375 (58.6%) isolates met our previously defined criteria for CA-MRSA and CA-MSSA, respectively. Community-associated methicillin-resistant S aureus isolates were mostly susceptible to aminoglycosides (95%), fluoroquinolones (76%), and trimethoprim-sulfamethoxazole (99%). Erythromycin resistance steadily increased from 51% in 2000 to 87% in 2004; erythromycin-resistant and clindamycin-susceptible strains accounted for most of this increase (25%, 28%, 54%, 69%, 80%, and 81% of CA-MRSA isolates during 2000, 2001, 2002, 2003, 2004, and 2005, respectively). D test results were available for 47 isolates (performed between 2004 and 2005) and were positive in only 2.

Over time, CA-MRSA skin and soft tissue infections increased 6.84-fold (Figure 1). Based on the estimated CCH catchment population of 212 815, CA-MRSA skin and soft tissue infections increased from 24.0 cases per 100 000 people in 2000 to 164.2 cases per 100 000 people in 2005, while the incidence of CA-MSSA skin and soft tissue infections was 90.7 cases per 100 000 people in 2000 and 121.9 cases per 100 000 people in 2005. During this period, 56% of CA-MRSA infections and 55% of CA-MSSA infections occurred in outpatients or in nonhospitalized emergency department patients, while 44% of CA-MRSA infections and 45% of CA-MSSA infections required hospitalization. There were 5 deaths among CA-MSSA patients and 2 deaths among CA-MRSA patients (mortality rates of 5 per 1000 and 1 per 1000, respectively).

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Figure 1.

Counts and incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-associated methicillin-susceptible S aureus (CA-MSSA) skin and soft tissue infections among patients at John H. Stroger, Jr Hospital of Cook County (Illinois) from January 1, 2000, through August 31, 2005.

Graphic Jump Location
GEOGRAPHIC ANALYSIS

Geographic analysis revealed 4 clusters of CA-MRSA infections (Figure 2). Cluster 1 (July 1, 2001, through December 31, 2002) had 15 patients with CA-MRSA (10.7% of that period's cases). Cluster 2 (January 1, 2003, through June 30, 2004) had 17 patients with CA-MRSA (6.4% of cases). Cluster 3 (January 1, 2003, through June 30, 2004) had 44 patients with CA-MRSA (15.0% of cases). Within the borders of cluster 3 were 5 high-rise public housing complexes; 8 (18.2%) of 44 patients within cluster 3 were residents of this housing. Cluster 4 (July 1, 2004, through August 31, 2005) included a region with its center near CCH and a perimeter that included the geographic area with the highest CCH use in CookCounty; 185 patients with CA-MRSA (47.1% of cases) were within this cluster.

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Figure 2.

John H. Stroger, Jr Hospital of Cook County (CCH) catchment by ZIP code tabulation area (ZCTA). Clusters of methicillin-resistant Staphylococcus aureus skin and soft tissue infections in Cook County (Illinois) from January 1, 2000, through August 31, 2005, identified by SaTScan. Cluster 1, P = .004; cluster 2, P = .03; cluster 3, P = .06; and cluster 4, P = .004. See the “Geographic Analysis” subsection of the “Methods” section for explanation of cluster groups.

Graphic Jump Location
RISKS OF PUBLIC HOUSING, INCARCERATION, AND OVERCROWDING

The proportion of community-associated S aureus skin and soft tissue isolates that was methicillin resistant was higher among residents who lived in public housing complexes in cluster 3 (55.4%) than among non–public housing residents (41.6%). Public housing residents in cluster 3 had a higher prevalence of CA-MRSA from 2000 through 2005, which was statistically significant in 2005 (P<.001) (Figure 3).

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Figure 3.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as a proportion of all community-associated S aureus skin and soft tissue infections in relation to public housing from January 1, 2000, through August 31, 2005. CI indicates confidence interval. See the “Geographic Analysis” subsection of the “Methods” section for explanation of cluster groups.

Graphic Jump Location

We found no association between case status and overcrowding; patients with S aureus infections from census block groups that were more overcrowded were not more likely to be infected with CA-MRSA. Similarly, we found no association between high-occupancy block groups and CA-MRSA infection regardless of whether the comparison group was patients with CA-MSSA infections or all patients from whom cultures were obtained, nor did we find an association when occupancy was stratified by race/ethnicity or by year of culture.

NESTED CASE-CONTROL STUDY

On univariate analysis, the following variables were associated with CA-MRSA skin and soft tissue infections: younger age, incarceration within 1 year, African American race/ethnicity, and human immunodeficiency virus infection (Table 1). More patients with CA-MRSA received an antibiotic within 1 week before cultures were performed (9% vs 6%, P =.03), and 44% of patients with CA-MRSA infections received inadequate therapy with a β-lactam antibiotic following culture (no differences in deaths or readmissions were noted as a result of inadequate therapy). Residence in the 5 public housing complexes within cluster 3 during any period was associated with CA-MRSA skin and soft tissue infections on univariate analysis, while residence in public housing developments outside of cluster 3 was not.

Table Graphic Jump LocationTable 1. Univariate Analysis of Demographic and Clinical Characteristics of Patients With Community-Associated Staphylococcus aureus Skin and Soft Tissue Infections From September 1, 2001, Through August 31, 2004*
MULTIVARIATE ANALYSIS

On multivariate analysis (Table 2), year of culture showed a strong secular trend. Residence in the public housing complexes within cluster 3 was also a risk factor for MRSA skin and soft tissue infections (odds ratio, 2.50; 95% confidence interval, 1.25-4.98) regardless of year of culture, as was recent incarceration (odds ratio, 1.92; 95% confidence interval, 1.00-3.67). African American race/ethnicity increased the risk of CA-MRSA infection, and older age and Hispanic race/ethnicity were protective. Human immunodeficiency virus status and recent incarceration exhibited interaction and resulted in decreased risk when both were present.

Table Graphic Jump LocationTable 2. Multivariate Analysis of Risk Factors for Community-Associated Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections
MICROBIOLOGICAL ANALYSIS

Community-associated methicillin-resistant S aureus isolates tested were predominantly pulsed-field gel electrophoresis type USA300 (ie, 10 of 11 isolates from recently incarcerated subjects, 8 of 11 isolates from cluster 2, 16 of 23 isolates from cluster 3, and 24 of 28 isolates obtained in July 2004). USA300 isolates were erythromycin resistant, did not carry inducible clindamycin resistance, and were positive for staphylococcal chromosome cassette mec type IV and Panton-Valentine leukocidin genes. USA400 strains were found in 6 infections. Regardless of pulsed-field gel electrophoresis type, most isolates from all groups were positive for staphylococcal chromosome cassette mec type IV (67 of 73) and Panton-Valentine leukocidin genes (65 of 73).

In the major public safety net health care system of Cook County, we noted a 6.84-fold increase in the risk of skin and soft tissue infections with CA-MRSA from 2000 through 2005. This increase occurred in addition to a stable rate of CA-MSSA infections. Although at the start of the surveillance period our incidence of CA-MRSA infections was similar to that found in a recent multicity population-based study,23 by 2005 it was higher, which may reflect our high-risk patient population (62% African American, 5% recent incarceration, and 6% public housing residents).

African American race/ethnicity and recent incarceration were risk factors for CA-MRSA skin and soft tissue infections; Hispanic race/ethnicity was protective, a finding consistent with the results of prior studies.610,23,38 Residence in specific public housing complexes was also a risk factor and increased the odds of CA-MRSA infection almost 3-fold (Table 2), even after adjustment for the countywide secular increase.

Why CA-MRSA has emerged at such a rapid pace remains unclear. Cross-sectional studies38,39 examining other community populations have found MRSA colonization rates far below those of MSSA, generally not exceeding 4% for CA-MRSA compared with 30% for CA-MSSA. Despite the apparently lower prevalence of MRSA colonization, infection rates are approaching or exceeding those of CA-MSSA. Potential host or pathogen explanations for this discordance include CA-MRSA colonization at sites not tested (eg, skin, gastrointestinal tract, or deeper than the anterior nares), greater risk of person-to-person spread from infected patients or of spread from contaminated fomites (eg, towels in locker rooms),3,40 virulence factors (eg, Panton-Valentine leukocidin genes) that trump the traditional colonization before infection sequence (ie, “hit-and-run” infections),41 or yet-to-be-measured increasing rates of CA-MRSA colonization.42

An additional explanation for rapid emergence of CA-MRSA is that some community settings may promote cross-transmission. Hospitals and long-term care facilities have long been considered “epicenters” for antimicrobial resistance, housing colonized and noncolonized individuals in close proximity, and offering the opportunity for cross-transmission. Hartley et al43 suggested that prisons, with their large at-risk populations and long lengths of stay, can be sources of MRSA-colonized individuals at rates comparable to those of hospitals. Other community settings such as public housing and halfway houses may amplify CA-MRSA spread; for example, the geographic clusters of CA-MRSA detected in our study that were not related to public housing may represent foci of increased cross-transmission.

The concept of a “core group” of colonized or infected individuals that is responsible for many new infections is basic to the epidemiology of sexually transmitted and some viral infections (eg, severe acute respiratory syndrome)20,44; geographically disparate clusters of infection may represent networks of individuals who transmit infection through person-to-person contact, with further spread by individuals who bridge these networks.44 In the case of CA-MRSA, geographically closed community foci (eg, prisons) may be promoting spread, while other settings or factors (eg, athletics or intravenous drug use) act as bridges for transmission.

Public housing also may represent a bridge between high-risk individuals in Chicago. Since the late 1990s, demolition of high-rise public housing complexes and widespread relocation of public housing residents have occurred as part of the HOPE VI plan.45 In 2003, 62% of relocated families were moved to other Chicago public housing complexes,45 potentially contributing to overcrowding not measured by census data. In addition, public housing residents are part of a network associated with inmates; in a 2002 study,46 29% of respondents reported that they had been incarcerated or were expecting a resident to arrive from jail or prison. Public housing may also house individuals with severe drug problems, and squatters (or nonlease tenants) may transiently reside in nondemolished public housing between episodes of homelessness.45 Triangulation of risks for CA-MRSA transmission47 may occur in the public housing complexes identified in cluster 3, with personal contacts or contaminated fomites promoting cross-transmission among susceptible host populations. However, whether and what interactions among these populations have contributed to CA-MRSA dissemination require further study.

Strain typing by pulsed-field gel electrophoresis did not discriminate between the various populations assessed in our study; however, it confirmed that most isolates tested were strain type USA300, whether or not related to incarceration or public housing exposure. These findings are consistent with those of a 3½-month laboratory-based survey from Atlanta, Ga,48 and a cross-sectional study49 among emergency department patients in which most CA-MRSA skin and soft tissue infections were caused by USA300.

Because of a lack of historical isolates available for typing, we were unable to ascertain if USA300 replaced other CA-MRSA strains in the community. Prior work examining CA-MRSA among Chicago children found clonality in one instance: 69 (78.4%) of 88 clindamycin-susceptible CA-MRSA isolates obtained from 1987 to 2000 were USA400, 70% were erythromycin-susceptible, and D test results were positive in 31 of 33 isolates with discordant erythromycin and clindamycin susceptibilities.50 Prior work examining CA-MRSA among Chicago children in one instance found clonality: 69 (78%) of 88 clindamycin-susceptible CA-MRSA isolates obtained from 1987 to 2000 were USA-400, 70% were erythromycin-susceptible, and D-test results were positive for 31 of 33 isolates with discordant erythromycin and clindamycin susceptiblities.50 In another instance, however, polyclonal infection was described.51 Given the rapid increases among our patients in prevalence of clindamycin-susceptible, erythromycin-resistant isolates and the low rate of inducible clindamycin-resistance, replacement of another CA-MRSA strain (possibly USA400) by USA300 as the major cause of CA-MRSA infection seems to have occurred between 2000 and 2006 in our patients.

Our data should be interpreted in light of several epidemiological limitations. First, geographic clustering among cases may have been because of the differences between cases and controls in the use of CCH unrelated to infection status. The stability of MSSA rates over time argues against systematic changes in health care use, and Figure 3 shows that public housing complexes in cluster 3 consistently exhibited higher rates of MRSA isolation than other areas, suggesting a true and disproportionate secular trend.

Second, we may be missing data that explain our findings further. For example, the interaction of recent incarceration and human immunodeficiency virus positivity that reduced the risk of CA-MRSA could be explained by prescription of trimethoprim-sulfamethoxazole prophylaxis to patients with AIDS in the jail.52

Third, we relied on electronic records for defining health care exposure. In a prospective study by Furuno et al,52 an electronic rule did not always reliably detect health care exposures. However, a distinction of our data set is that CCH is the county's largest provider of indigent care and likely sees a “loyal” population of patients. Validation of our rule found only a 3% misclassification rate,21 in contrast to 29% demonstrated by Furuno et al.53

In conclusion, among CCH patients, the rate of CA-MRSA skin and soft tissue infections increased rapidly between 2000 and 2005, adding significantly to the overall burden of staphylococcal disease. Incarceration and residence at some public housing complexes increased the chance of infection with CA-MRSA, perhaps as a consequence of the “epidemiological weight”43 of these locations. Whether strategies directed at prevention of transmission in these settings will be effective in slowing the emergence of CA-MRSA remains to be determined.

Correspondence: Bala Hota, MD, MPH, Rush University Medical Center and John H. Stroger, Jr Hospital of Cook County, 637 S Wood St, Chicago, IL 60612 (bhota@rush.edu).

Accepted for Publication: January 23, 2007.

Author Contributions: Dr Hota had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hota, Hayden, Aroutcheva, and Weinstein. Acquisition of data: Hota, Ellenbogen, Aroutcheva, and Rice. Analysis and interpretation of data: Hota, Rice, and Weinstein. Drafting of the manuscript: Hota and Aroutcheva. Critical revision of the manuscript for important intellectual content: Hota, Ellenbogen, Hayden, Rice, and Weinstein. Statistical analysis: Hota. Obtained funding: Weinstein. Administrative, technical, and material support: Ellenbogen, Aroutcheva, Rice, and Weinstein. Study supervision: Weinstein.

Financial Disclosure: None reported.

Previous Presentation: This study was presented in part at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; December 14, 2005; Washington, DC (abstract L-142).

Acknowledgment: Control strains for staphylococcal chromosome cassette mec types and subtypes, Panton-Valentine leukocidin genes, and pulsed-field gel electrophoresis were received from the Network for Antimicrobial Resistance in S aureus repository and from colleagues. Cook County admission diagnosis information was obtained through the assistance of the Illinois Hospital Association. We appreciate the assistance of Ellen Holfels in the preparation of the manuscript.

This article was corrected for typographical errors on 5/28/2007.

Herold  BCImmergluck  LCMaranan  MC  et al.  Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998;279593- 598
PubMed
Begier  EMFrenette  KBarrett  NL  et al.  A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis 2004;391446- 1453
PubMed
Kazakova  SVHageman  JCMatava  M  et al.  A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med 2005;352468- 475
PubMed
Lindenmayer  JMSchoenfeld  SO’Grady  RCarney  JK Methicillin-resistant Staphylococcus aureus in a high school wrestling team and the surrounding community. Arch Intern Med 1998;158895- 899
PubMed
Stacey  AREndersby  KEChan  PCMarples  RR An outbreak of methicillin resistant Staphylococcus aureus infection in a rugby football team. Br J Sports Med 1998;32153- 154
PubMed
Centers for Disease Control and Prevention (CDC), Methicillin-resistant Staphylococcus aureus skin or soft tissue infections in a state prison: Mississippi, 2000. MMWR Morb Mortal Wkly Rep 2001;50919- 922
PubMed
Centers for Disease Control and Prevention (CDC), Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections: Los Angeles County, California, 2002-2003. MMWR Morb Mortal Wkly Rep 2003;5288
PubMed
Centers for Disease Control and Prevention (CDC), Methicillin-resistant Staphylococcus aureus infections in correctional facilities: Georgia, California, and Texas, 2001-2003. MMWR Morb Mortal Wkly Rep 2003;52992- 996
PubMed
Baillargeon  JKelley  MFLeach  CTBaillargeon  GPollock  BH Methicillin-resistant Staphylococcus aureus infection in the Texas prison system. Clin Infect Dis 2004;38e92- e95
PubMed
Pan  ESDiep  BACarleton  HA  et al.  Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails. Clin Infect Dis 2003;371384- 1388
PubMed
Charlebois  EDBangsberg  DRMoss  NJ  et al.  Population-based community prevalence of methicillin-resistant Staphylococcus aureus in the urban poor of San Francisco. Clin Infect Dis 2002;34425- 433
PubMed
Groom  AVWolsey  DHNaimi  TS  et al.  Community-acquired methicillin-resistant Staphylococcus aureus in a rural American Indian community. JAMA 2001;2861201- 1205
PubMed
Shukla  SKStemper  MERamaswamy  SV  et al.  Molecular characteristics of nosocomial and Native American community-associated methicillin-resistant Staphylococcus aureus clones from rural Wisconsin. J Clin Microbiol 2004;423752- 3757
PubMed
Campbell  KMVaughn  AFRussell  KL  et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. J Clin Microbiol 2004;424050- 4053
PubMed
Zinderman  CEConner  BMalakooti  MALaMar  JEArmstrong  ABohnker  BK Community-acquired methicillin-resistant Staphylococcus aureus among military recruits. Emerg Infect Dis 2004;10941- 944
PubMed
Ellis  MWHospenthal  DRDooley  DPGray  PJMurray  CK Natural history of community-acquired methicillin-resistant Staphylococcus aureus colonization and infection in soldiers. Clin Infect Dis 2004;39971- 979
PubMed
Stemper  MEBrady  JMQutaishat  SS  et al.  Shift in Staphylococcus aureus clone linked to an infected tattoo. Emerg Infect Dis 2006;121444- 1446
PubMed
Centers for Disease Control and Prevention (CDC), Methicillin-resistant Staphylococcus aureus skin infections among tattoo recipients: Ohio, Kentucky, and Vermont, 2004-2005. MMWR Morb Mortal Wkly Rep 2006;55677- 679
PubMed
Naimi  TSLeDell  KHBoxrud  DJ  et al.  Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota, 1996-1998. Clin Infect Dis 2001;33990- 996
PubMed
Lloyd-Smith  JOSchreiber  SJKopp  PEGetz  WM Superspreading and the effect of individual variation on disease emergence. Nature 2005;438355- 359
PubMed
Hota  BWeinstein  RA Performance of an electronic rule (eRule) for surveillance of community-acquired (CA) methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) Staphylococcus aureus. Emerg Infect Dis 2006;121469- 1471
PubMed
Naimi  TSLeDell  KHComo-Sabetti  K  et al.  Comparison of community- and health care–associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003;2902976- 2984
PubMed
Fridkin  SKHageman  JCMorrison  M  et al.  Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med 2005;3521436- 1444
PubMed
Wisniewski  MFKieszkowski  PZagorski  BMTrick  WESommers  MWeinstein  RA Development of a clinical data warehouse for hospital infection control. J Am Med Inform Assoc 2003;10454- 462
PubMed
Morris  ADBoyle  DIMacAlpine  R  et al.  The Diabetes Audit and Research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register: DARTS/MEMO Collaboration. BMJ 1997;315524- 528
PubMed
Kloos  WEBannerman  TL Staphylococcus and Micrococcus. Murray  PRBaron  EJPfaller  MATenover  FCYolken  RHManual of Clinical Microbiology. 7th ed. Washington, DC American Society for Microbiology1999;264- 282
Fiebelkorn  KRCrawford  SAMcElmeel  MLJorgensen  JH Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol 2003;414740- 4744
PubMed
Oliveira  DCde Lencastre  H Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2002;462155- 2161
PubMed
Okuma  KIwakawa  KTurnidge  JD  et al.  Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol 2002;404289- 4294
PubMed
Lina  GPiemont  YGodail-Gamot  F  et al.  Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 1999;291128- 1132
PubMed
Matushek  MGBonten  MJHayden  MK Rapid preparation of bacterial DNA for pulsed-field gel electrophoresis. J Clin Microbiol 1996;342598- 2600
PubMed
Harvard School of Public Health.,The Public Health Disparities Geocoding Project Monograph. http://www.hsph.harvard.edu/thegeocodingproject/webpage/monograph/methods.htm. Accessed February 27, 2007
Kulldorff  MSaTScan: Software for the Spatial, Temporal, and Space-Time Scan Statistics Version 7.0.1. October 12, 2006. http://www.satscan.org. Accessed February 27, 2007
Kulldorff  MHeffernan  RHartman  JAssuncao  RMostashari  FA Space-time permutation scan statistic for disease outbreak detection. PLoS Med 2005;2e59
PubMed
Kulldorff  M A spatial scan statistic. Communications Stat Theory Methods 1997;261481- 1496
Myers  DBaer  WCChoi  SY The changing problem of overcrowded housing. J Am Plann Assoc 1996;6266- 84
Kleinbaum  DGKleinbaum  DG Applied Regression Analysis and Other Multivariable Methods. 3rd ed. Pacific Grove, Calif Duxbury Press1998;
Graham  PL  IIILin  SXLarson  ELA US population–based survey of Staphylococcus aureus colonization. Ann Intern Med 2006;144318- 325
PubMed
Salgado  CDFarr  BMCalfee  DP Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis 2003;36131- 139
PubMed
Faden  HFerguson  S Community-acquired methicillin-resistant Staphylococcus aureus and intrafamily spread of pustular disease. Pediatr Infect Dis J 2001;20554- 555
PubMed
Moellering  RC  Jr The growing menace of community-acquired methicillin-resistant Staphylococcus aureus. Ann Intern Med 2006;144368- 370
PubMed
Creech  CB  IIKernodle  DSAlsentzer  AWilson  CEdwards  KM Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus in healthy children. Pediatr Infect Dis J 2005;24617- 621
PubMed
Hartley  DMFuruno  JPWright  MOSmith  DLPerencevich  EN The role of institutional epidemiologic weight in guiding infection surveillance and control in community and hospital populations. Infect Control Hosp Epidemiol 2006;27170- 174
PubMed
Wylie  JLCabral  TJolly  AM Identification of networks of sexually transmitted infection: a molecular, geographic, and social network analysis. J Infect Dis 2005;191899- 906
PubMed
Venkatesh  SACelimli  IMiller  DMurphy  ACenter for Urban Research and Policy. Working paper: Chicago public housing transformation: a research report. February 2004. http://www.curp.columbia.edu/publications2/PH_Transformation_Report.pdf. Accessed February 27, 2006
Venkatesh  SAThe Robert Taylor Homes Relocation Study: a research report from the Center for Urban Research and Policy. September 2002. http://www.curp.columbia.edu/publications2/robert_taylor.pdf. Accessed February 27, 2006
Shukla  SK CA-MRSA triangulation: virulent strains, susceptible hosts, and contaminated environments. WMJ 2006;10521- 23
PubMed
King  MDHumphrey  BJWang  YFKourbatova  EVRay  SMBlumberg  HM Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med 2006;144309- 317
PubMed
Moran  GJKrishnadasan  AGorwitz  RJ  et al.  Methicillin-resistant S aureus infections among patients in the emergency department. N Engl J Med 2006;355666- 674
PubMed
Abi-Hanna  PFrank  ALQuinn  JP  et al.  Clonal features of community-acquired methicillin-resistant Staphylococcus aureus in children. Clin Infect Dis 2000;30630- 631
PubMed
Hussain  FMBoyle-Vavra  SBethel  CDDaum  RS Current trends in community-acquired methicillin-resistant Staphylococcus aureus at a tertiary care pediatric facility. Pediatr Infect Dis J 2000;191163- 1166
PubMed
Lee  NETaylor  MMBancroft  E  et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men. Clin Infect Dis 2005;401529- 1534
PubMed
Furuno  JPHarris  ADWright  MO  et al.  Prediction rules to identify patients with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci upon hospital admission. Am J Infect Control 2004;32436- 440
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Counts and incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-associated methicillin-susceptible S aureus (CA-MSSA) skin and soft tissue infections among patients at John H. Stroger, Jr Hospital of Cook County (Illinois) from January 1, 2000, through August 31, 2005.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

John H. Stroger, Jr Hospital of Cook County (CCH) catchment by ZIP code tabulation area (ZCTA). Clusters of methicillin-resistant Staphylococcus aureus skin and soft tissue infections in Cook County (Illinois) from January 1, 2000, through August 31, 2005, identified by SaTScan. Cluster 1, P = .004; cluster 2, P = .03; cluster 3, P = .06; and cluster 4, P = .004. See the “Geographic Analysis” subsection of the “Methods” section for explanation of cluster groups.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as a proportion of all community-associated S aureus skin and soft tissue infections in relation to public housing from January 1, 2000, through August 31, 2005. CI indicates confidence interval. See the “Geographic Analysis” subsection of the “Methods” section for explanation of cluster groups.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Univariate Analysis of Demographic and Clinical Characteristics of Patients With Community-Associated Staphylococcus aureus Skin and Soft Tissue Infections From September 1, 2001, Through August 31, 2004*
Table Graphic Jump LocationTable 2. Multivariate Analysis of Risk Factors for Community-Associated Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections

References

Herold  BCImmergluck  LCMaranan  MC  et al.  Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998;279593- 598
PubMed
Begier  EMFrenette  KBarrett  NL  et al.  A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis 2004;391446- 1453
PubMed
Kazakova  SVHageman  JCMatava  M  et al.  A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med 2005;352468- 475
PubMed
Lindenmayer  JMSchoenfeld  SO’Grady  RCarney  JK Methicillin-resistant Staphylococcus aureus in a high school wrestling team and the surrounding community. Arch Intern Med 1998;158895- 899
PubMed
Stacey  AREndersby  KEChan  PCMarples  RR An outbreak of methicillin resistant Staphylococcus aureus infection in a rugby football team. Br J Sports Med 1998;32153- 154
PubMed
Centers for Disease Control and Prevention (CDC), Methicillin-resistant Staphylococcus aureus skin or soft tissue infections in a state prison: Mississippi, 2000. MMWR Morb Mortal Wkly Rep 2001;50919- 922
PubMed
Centers for Disease Control and Prevention (CDC), Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections: Los Angeles County, California, 2002-2003. MMWR Morb Mortal Wkly Rep 2003;5288
PubMed
Centers for Disease Control and Prevention (CDC), Methicillin-resistant Staphylococcus aureus infections in correctional facilities: Georgia, California, and Texas, 2001-2003. MMWR Morb Mortal Wkly Rep 2003;52992- 996
PubMed
Baillargeon  JKelley  MFLeach  CTBaillargeon  GPollock  BH Methicillin-resistant Staphylococcus aureus infection in the Texas prison system. Clin Infect Dis 2004;38e92- e95
PubMed
Pan  ESDiep  BACarleton  HA  et al.  Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails. Clin Infect Dis 2003;371384- 1388
PubMed
Charlebois  EDBangsberg  DRMoss  NJ  et al.  Population-based community prevalence of methicillin-resistant Staphylococcus aureus in the urban poor of San Francisco. Clin Infect Dis 2002;34425- 433
PubMed
Groom  AVWolsey  DHNaimi  TS  et al.  Community-acquired methicillin-resistant Staphylococcus aureus in a rural American Indian community. JAMA 2001;2861201- 1205
PubMed
Shukla  SKStemper  MERamaswamy  SV  et al.  Molecular characteristics of nosocomial and Native American community-associated methicillin-resistant Staphylococcus aureus clones from rural Wisconsin. J Clin Microbiol 2004;423752- 3757
PubMed
Campbell  KMVaughn  AFRussell  KL  et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. J Clin Microbiol 2004;424050- 4053
PubMed
Zinderman  CEConner  BMalakooti  MALaMar  JEArmstrong  ABohnker  BK Community-acquired methicillin-resistant Staphylococcus aureus among military recruits. Emerg Infect Dis 2004;10941- 944
PubMed
Ellis  MWHospenthal  DRDooley  DPGray  PJMurray  CK Natural history of community-acquired methicillin-resistant Staphylococcus aureus colonization and infection in soldiers. Clin Infect Dis 2004;39971- 979
PubMed
Stemper  MEBrady  JMQutaishat  SS  et al.  Shift in Staphylococcus aureus clone linked to an infected tattoo. Emerg Infect Dis 2006;121444- 1446
PubMed
Centers for Disease Control and Prevention (CDC), Methicillin-resistant Staphylococcus aureus skin infections among tattoo recipients: Ohio, Kentucky, and Vermont, 2004-2005. MMWR Morb Mortal Wkly Rep 2006;55677- 679
PubMed
Naimi  TSLeDell  KHBoxrud  DJ  et al.  Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota, 1996-1998. Clin Infect Dis 2001;33990- 996
PubMed
Lloyd-Smith  JOSchreiber  SJKopp  PEGetz  WM Superspreading and the effect of individual variation on disease emergence. Nature 2005;438355- 359
PubMed
Hota  BWeinstein  RA Performance of an electronic rule (eRule) for surveillance of community-acquired (CA) methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) Staphylococcus aureus. Emerg Infect Dis 2006;121469- 1471
PubMed
Naimi  TSLeDell  KHComo-Sabetti  K  et al.  Comparison of community- and health care–associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003;2902976- 2984
PubMed
Fridkin  SKHageman  JCMorrison  M  et al.  Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med 2005;3521436- 1444
PubMed
Wisniewski  MFKieszkowski  PZagorski  BMTrick  WESommers  MWeinstein  RA Development of a clinical data warehouse for hospital infection control. J Am Med Inform Assoc 2003;10454- 462
PubMed
Morris  ADBoyle  DIMacAlpine  R  et al.  The Diabetes Audit and Research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register: DARTS/MEMO Collaboration. BMJ 1997;315524- 528
PubMed
Kloos  WEBannerman  TL Staphylococcus and Micrococcus. Murray  PRBaron  EJPfaller  MATenover  FCYolken  RHManual of Clinical Microbiology. 7th ed. Washington, DC American Society for Microbiology1999;264- 282
Fiebelkorn  KRCrawford  SAMcElmeel  MLJorgensen  JH Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol 2003;414740- 4744
PubMed
Oliveira  DCde Lencastre  H Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2002;462155- 2161
PubMed
Okuma  KIwakawa  KTurnidge  JD  et al.  Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol 2002;404289- 4294
PubMed
Lina  GPiemont  YGodail-Gamot  F  et al.  Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 1999;291128- 1132
PubMed
Matushek  MGBonten  MJHayden  MK Rapid preparation of bacterial DNA for pulsed-field gel electrophoresis. J Clin Microbiol 1996;342598- 2600
PubMed
Harvard School of Public Health.,The Public Health Disparities Geocoding Project Monograph. http://www.hsph.harvard.edu/thegeocodingproject/webpage/monograph/methods.htm. Accessed February 27, 2007
Kulldorff  MSaTScan: Software for the Spatial, Temporal, and Space-Time Scan Statistics Version 7.0.1. October 12, 2006. http://www.satscan.org. Accessed February 27, 2007
Kulldorff  MHeffernan  RHartman  JAssuncao  RMostashari  FA Space-time permutation scan statistic for disease outbreak detection. PLoS Med 2005;2e59
PubMed
Kulldorff  M A spatial scan statistic. Communications Stat Theory Methods 1997;261481- 1496
Myers  DBaer  WCChoi  SY The changing problem of overcrowded housing. J Am Plann Assoc 1996;6266- 84
Kleinbaum  DGKleinbaum  DG Applied Regression Analysis and Other Multivariable Methods. 3rd ed. Pacific Grove, Calif Duxbury Press1998;
Graham  PL  IIILin  SXLarson  ELA US population–based survey of Staphylococcus aureus colonization. Ann Intern Med 2006;144318- 325
PubMed
Salgado  CDFarr  BMCalfee  DP Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis 2003;36131- 139
PubMed
Faden  HFerguson  S Community-acquired methicillin-resistant Staphylococcus aureus and intrafamily spread of pustular disease. Pediatr Infect Dis J 2001;20554- 555
PubMed
Moellering  RC  Jr The growing menace of community-acquired methicillin-resistant Staphylococcus aureus. Ann Intern Med 2006;144368- 370
PubMed
Creech  CB  IIKernodle  DSAlsentzer  AWilson  CEdwards  KM Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus in healthy children. Pediatr Infect Dis J 2005;24617- 621
PubMed
Hartley  DMFuruno  JPWright  MOSmith  DLPerencevich  EN The role of institutional epidemiologic weight in guiding infection surveillance and control in community and hospital populations. Infect Control Hosp Epidemiol 2006;27170- 174
PubMed
Wylie  JLCabral  TJolly  AM Identification of networks of sexually transmitted infection: a molecular, geographic, and social network analysis. J Infect Dis 2005;191899- 906
PubMed
Venkatesh  SACelimli  IMiller  DMurphy  ACenter for Urban Research and Policy. Working paper: Chicago public housing transformation: a research report. February 2004. http://www.curp.columbia.edu/publications2/PH_Transformation_Report.pdf. Accessed February 27, 2006
Venkatesh  SAThe Robert Taylor Homes Relocation Study: a research report from the Center for Urban Research and Policy. September 2002. http://www.curp.columbia.edu/publications2/robert_taylor.pdf. Accessed February 27, 2006
Shukla  SK CA-MRSA triangulation: virulent strains, susceptible hosts, and contaminated environments. WMJ 2006;10521- 23
PubMed
King  MDHumphrey  BJWang  YFKourbatova  EVRay  SMBlumberg  HM Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med 2006;144309- 317
PubMed
Moran  GJKrishnadasan  AGorwitz  RJ  et al.  Methicillin-resistant S aureus infections among patients in the emergency department. N Engl J Med 2006;355666- 674
PubMed
Abi-Hanna  PFrank  ALQuinn  JP  et al.  Clonal features of community-acquired methicillin-resistant Staphylococcus aureus in children. Clin Infect Dis 2000;30630- 631
PubMed
Hussain  FMBoyle-Vavra  SBethel  CDDaum  RS Current trends in community-acquired methicillin-resistant Staphylococcus aureus at a tertiary care pediatric facility. Pediatr Infect Dis J 2000;191163- 1166
PubMed
Lee  NETaylor  MMBancroft  E  et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men. Clin Infect Dis 2005;401529- 1534
PubMed
Furuno  JPHarris  ADWright  MO  et al.  Prediction rules to identify patients with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci upon hospital admission. Am J Infect Control 2004;32436- 440
PubMed

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