Canada Communicable Disease Report

August 2008

Volume 34

Number 08

Monthly Report

Epidemiology of community associated methicillin-resistant Staphylococcus aureus

KA Simmonds, MSc (1), DC Dover, MSc (1), M Louie, MD (2,3), G Keays, MD (4)

1. Surveillance and Environmental Health, Alberta Health and Wellness, Edmonton, Alberta, Canada
2. Provincial Laboratory for Public Health, Calgary, Alberta, Canada
3. University of Calgary, Calgary, Alberta, Canada
4. Office of the Chief Medical Officer of Health, Alberta Health and Wellness, Edmonton, Alberta, Canada

Introduction

Traditionally, infections with methicillin-resistant Staphylococcus aureus (MRSA) have been hospital associated. Recently, outbreaks of community-associated MRSA (CAMRSA) infections have become more frequent(1) ; they take place commonly among individuals with no association with the health care setting and are more often associated with skin and soft tissue infections. Transmission is thought to occur primarily through direct person-to-person contact with a colonized or infected individual. In some cases, the unique toxins and virulence factors associated with CA-MRSA are thought to play a role in severe infections, such as septic shock, invasive soft tissue infections and necrotizing pneumonia(2) .

Environmental factors (e.g. living in overcrowded conditions), social factors (e.g. belonging to specific drug-using networks, having limited health care access) and behavioural factors (e.g. sharing drug paraphernalia) may contribute to the transmission of CA-MRSA. Recently reported CA-MRSA outbreaks have occurred in various settings, including sports teams and correctional facilities, among the homeless and military personnel, and in daycare and other institutional centres^(3,4) .

Since 1995, Canada has identified 10 different MRSA epidemic clones using pulsed-field gel electrophoresis (PFGE): CMRSA 1 to CMRSA 10, representing over 80% of all MRSA in Canada⁽⁵⁾ . CMRSA strains 1 to 6, 8 and 9 are typical hospital-associated strains with multidrug-resistant phenotypes. Strains identified as CMRSA 7 and CMRSA 10, also known as USA 400 and USA 300 respectively, are typically community-associated. CMRSA 10 has previously been associated with community outbreaks in the United States⁽⁶⁾. In 2004, the first Canadian outbreak of CMRSA 10 occurred in a marginalized urban population with a history of homelessness, drug use and incarceration⁽⁷⁾ . This outbreak prompted provincial public health officials in Alberta to initiate a province wide outbreak investigation in June 2005 to determine the epidemiology of MRSA. One objective of the investigation was to determine and describe the epidemiology of community-associated CMRSA 10 in Alberta.

Methods

Alberta is a province in western Canada with a population of approximately 3.2 million. The province is divided into nine Regional Health Authorities responsible for the administration and delivery of health care. There are two main urban centres, Calgary and Edmonton, which account for approximately two-thirds of the population and are located in Region 3 and Region 6 respectively. The remaining regions have populations ranging from 75,000 to 300,000 people.

The Provincial Health Officer placed MRSA under provincial surveillance on 1 June, 2005, requiring all regional laboratories to submit the first confirmed clinical (not screening) MRSA isolate to the Alberta Provincial Laboratory of Public Health (PLPH) for typing by PFGE. The isolate would be typed if no other isolate had been received for the same case within the previous year and if the isolate was not from a screening specimen. PFGE was performed following the national standardized protocol, and patterns were assigned using the National Microbiology Laboratory nomenclature⁽⁸⁾. The results were communicated electronically within 1 week of receipt to the submitting laboratories, the Medical Officers of Health, and Alberta Health and Wellness.

The outbreak investigation was focused on CMRSA 10 infections that were acquired in the community. Those isolates identified as CMRSA 10 were then followed up by public health departments in the regions. A case report form was completed to collect risk factor information. Public health made several attempts to contact each individual, first by telephone (three attempts) and then by contacting the ordering physician and occasionally by letter. The outbreak investigation was completed on 28 February, 2006.

An individual was considered a case of CA-CMRSA 10 if the clinical isolate was positive for CMRSA 10 and if it had been obtained from a community laboratory specimen or a hospital specimen submitted within 72 hours of admission. Excluded were any cases with a known risk factor for hospital-associated MRSA, defined as a hospital transfer, residence in a long-term care facility, a positive MRSA isolate within the previous 12 months or hospitalization within the previous 12 months. A conservative case definition was used to ensure that there was high specificity for community-associated cases.

Data from case report forms were entered into an Access 2003 database. The data collection and entry were verified by the project manager. Data were then analyzed using SPSS (Statistical Package for the Social Sciences) software. Proportions were compared using the chi-squared test, and means were compared using analysis of variance. Crude rates are presented in the Results section, as age-adjustment had no effect on the rates. The denominator is based on 9 months (study length) of the 2006 Alberta mid-year population.

Results

Between 1 June, 2005, and 28 February, 2006, there were 1,321 individuals identified as MRSA positive, of whom 1,282 (97%) were Alberta residents. The majority of Alberta residents infected with MRSA were infected with either CMRSA 2 (38.5%) or CMRSA 10 (36.7%) (Table 1).

Table 1. Distribution of MRSA strain type in Alberta

Of the 471 individuals identified as infected with CMRSA 10, 176 (37.4%) were classified as CA-MRSA 10, 88 (18.7%) were excluded because of hospital-associated MRSA risk factors, 204 (43.3%) were lost to follow up, and for three (0.6%) there was incomplete information. The primary reason for exclusion associated with hospital-associated risk factors was hospitalization prior to infection (64 cases, 72.7%), followed by previous identification as positive for MRSA (14 cases, 15.9%).

Data collected for all individuals infected with CMRSA 10 are presented in Table 2. There was no significant difference in age at time of diagnosis or proportion of males between the community-associated, hospital-associated or lost to follow-up groups. The proportion of skin and soft tissue infections was significantly higher among CA-CMRSA 10 and those who were lost to follow-up than among hospital-associated cases. There was no significant difference in post-infection hospitalization between the two groups. All of the hospitalizations for both the hospital- and community-associated cases occurred at or after diagnosis.

Table 2. Characteristics of CMRSA 10 community acquired, hospital acquired and lost to follow-up (n = 468)

One hundred and twelve cases were male (63.6%). The risk of CA-CMRSA 10 infection was 1.8 times greater among males than females (95% confidence interval: 1.3 to 2.4). The mean age at diagnosis was 36.2 years (age range: 11 months to 83 years) and was not significantly different between the males and females.

The annual crude provincial rate of CA-CMRSA 10 was 7.1 cases per 100,000 population (Table 3). The rates range from 0.0 to 15.9 cases per 100,000, the rural regions generally having lower rates than the urban regions. The rate of CMRSA 10 infection was highest in Region 9 (nine cases, 15.9 per 100,000) followed by the two urban regions, Region 3 (80 cases, 8.8 per 100,000) and Region 6 (63 cases, 8.2 per 100,000). Figure 1 shows the distribution of communityassociated CMRSA 10 by region.

Table 3. Rates of community acquired CMRSA 10 in Alberta by region (n = 176)

Figure 1. Rates of community acquired CMRSA 10 by region, June 1, 2005 - February 28, 2006

Risk factor information for all CA-CMRSA 10 cases is summarized in Table 4. The data were aggregated into three regions, Region 3, Region 6 and the Rural Regions (all other regions). The seven rural regions were combined, as they are similar in terms of risk factor distribution and the small case counts in each region. There were 59 individuals (33.5%) who responded "No" to all of the risk factor questions. Among those with no known risk factors and those with risk factors, there was no difference in age at diagnosis or sex.

The three most common risk factors were a history of illicit drug use (27.3%), incarceration (21.0%) and recent antibiotic use (19.9%). Eighty-six CA-CMRSA 10 cases (48.9%) had at least two known risk factors. In addition, there were 35 CA-CMRSA 10 cases (19.9%) that had at least two of the following risk factors: drug treatment (detoxification), history of illicit drug use, homelessness and history of incarceration. Of these 35 cases, 23 (65.7%) were from Region 3.

Table 4. Distribution of risk factors among CA-CMRSA 10 cases, by region

For several risk factors there was variability among Region 3, the rural regions and Region 6: incarceration and illicit drug use were both significantly less likely in Region 6; patients with no risk factors identified were most common in Region 6.

Discussion

This large-scale, province-wide, population-based outbreak investigation was the first population-based epidemiologic study of CA-CMRSA 10 in North America. This investigation provides information characterizing those infected with CA-CMRSA 10, including the geographic distribution of cases in Alberta.

The map of Alberta (Figure 1) shows higher rates in Region 9, the most northern region. There is considerable industrial development in selected communities in the region, and the population is young and highly mobile. This makes determining the likely source of infection nearly impossible. It is not clear from the small number of CA-CMRSA 10 cases in this region whether the individuals infected are long-term or temporary residents, or where the likely acquisition point may be.

The most common risk factors were illicit drug use followed by recent incarceration. There were several risk factors that were significantly different between the urban and the rural regions. The rate of contact with a health care facility (excluding admission) was low overall in the province but was higher in Region 3. The cause for this is unknown, as there is no reported transmission of CMRSA 10 among patients, staff or visitors in the hospitals in this region. For all those individuals with contact with a health care facility, no other single risk factor was found, though illicit drug use as a risk factor was highest in Region 3. The frequency with which illicit drug users access ambulatory care services to obtain primary care may account for the high proportion of cases in Region 3 that reported contact with a health care facility.

The proportion of CA-CMRSA 10 cases with a recent previous exposure to an antibiotic was not significantly different between the rural and urban regions and was found in 19.9% of all CA-CMRSA 10 cases. These were self-reported data, and information on the class of antibiotic and duration of exposure was not collected during the investigation. This is an area that warrants further study.

The high proportion of skin and soft tissue infections was expected⁽⁶⁾. The reason for the significant difference between hospital- and community-associated infections in this regard is not clear. The hospital-associated cases did report a greater proportion of blood isolates submitted, and this may be an indication of more invasive infection among hospitalassociated cases. A history of illicit drug use was reported by over a quarter of individuals infected with CA-CMRSA 10. The lifestyle associated with drug use may lend itself to the transmission of MRSA and soft tissue infections. Many of the individuals with a history of illicit drug use also reported a history of incarceration and homelessness.

In Region 3, where the previous outbreak had been reported, many of the reported risk factors were those common in marginalized populations, such as illicit drug use, incarceration and drug treatment. Incarceration may be a risk factor or it may be a confounder of another risk factor for CA-CMRSA 10 acquisition that has yet to be determined.

Previous outbreaks have identified several groups at risk of CA-MRSA⁽⁹⁾ : children < 2 years, adults > 65 years, athletes, injection drug users, men who have sex with men (MSM) and residents in group settings, including shelters and correctional facilities. This investigation identified some of the previously reported risk factors, but many, including young children, athletes and MSM, were not overrepresented among CAMRSA cases. The lack of identified risk factors indicates that there are risk factors yet to be identified.

This population-based surveillance was similar to that reported by Fridkin et al.⁽¹⁰⁾ . In Atlanta and Baltimore, a range of 18.0 to 25.7 CA-MRSA cases per 100,000 was reported. This includes both infection and colonization, and all strain types. In the present study the rate of CA-CMRSA 10 infections was 7.1 in Alberta, ranging from 0 to 15.9 cases per 100,000 across regions. Both studies had a significant number of cases that were lost to follow up.

Conclusions

The potential exists for the rates of CA-MRSA in Alberta to increase, as did those reported by Fridkin et al. The rate of CMRSA 10 in Alberta has increased each month since the study period and continues to do so⁽¹¹⁾ . Many CAMRSA infected individuals report no known risk factors, suggesting that this pathogen is now broadly distributed in the population. The information collected from this investigation is important in developing appropriate public health action and guiding future research in the area of CA-MRSA.

Acknowledgements

This work would not have been possible without the support and collaboration of all the regional laboratories (Alberta MicroNet) in submitting characterized MRSA isolates to the PLPH. We acknowledge the staff in the Bacteriology and Molecular Diagnostics sections at the PLPH for providing the molecular typing data; Linda Chui for her expertise; and the tremendous effort and time invested by the communicable disease nurses in the province who did the case follow-up. We would like to thank Agnes Honish and Bernice Heinrichs for their expertise, and Liz Hare for data management.

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