Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most significant pathogens affecting global public health and health care systems. In Canada and the United States, the spread of MRSA is primarily attributed to a single dominant epidemic clone: CMRSA10/USA300. Despite this, the CMRSA7/USA400 epidemic clone has been reported to be the predominate epidemic clone in several Canadian provinces and some parts of the United States. This study examined the epidemiology of CMRSA7/USA400 MRSA in Alberta, Canada, from June 2005 to December 2012. Molecular characterization of CMRSA7/USA400 isolates was done using spa, SCCmec, PVL, and PFGE typing and identified two predominant spa types in Alberta: t128 and t1787. Although closely related, these spa types have distinct geographic distributions. From 2010 to 2012, the number of t128 infections has remained stable while there has been a nearly 3-fold increase in the number of provincial t1787 infections, accompanied by 10-fold increases in t1787 infection rates in some communities. Most t128 and t1787 patients were First Nations or Inuit people, and isolates were usually from skin and soft tissue infections in outpatients. t128 patients were significantly older than t1787 patients. Antimicrobial susceptibility testing showed higher mupirocin resistance in t1787 than in t128 MRSA. Improved strategies to reduce or stabilize t1787 infections in Alberta are needed.
INTRODUCTION
Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that is significantly impacting global human health and has become a major public health burden (1). In the past, MRSA was primarily linked to health care settings and the majority of nosocomial infections were caused by hospital-associated MRSA (HA-MRSA; 2, 3). However, in recent years community-associated MRSA (CA-MRSA) has disseminated into hospitals worldwide (4) and is also affecting otherwise healthy people (5). CA-MRSA strains have caused outbreaks among health care workers (6), prison inmates (7, 8), military personnel (7), athletes (9, 10), tattoo recipients (11), and children (12). In Canada and the United States, the spread of CA-MRSA is mainly attributed to a single dominant epidemic clone, Canadian MRSA 10 (CMRSA10)/USA300 (13, 14), which replaced the previous predominant CA-MRSA epidemic clone: Canadian MRSA 7 (CMRSA7)/USA400 (15, 16). Despite this, the CMRSA7/USA400 epidemic clone was still common from 2005 to 2008 in the Canadian province of Alberta (15) and has been reported to be the predominate epidemic clone in other Canadian provinces such as Saskatchewan (17) and Manitoba (18), in Nunavut (19), and also in southwestern Alaska, United States (20). This report presents the epidemiology of CMRSA7/USA400 MRSA in Alberta over a 7-year period.
MATERIALS AND METHODS
Study population.
Population sizes were obtained from Alberta Health unless indicated otherwise. The province of Alberta is located in western Canada and has one provincial organization which provides health services to a population of approximately 3.9 million. For the purposes of health service delivery, Alberta is divided into five zones (2012 population data shown in Fig. 1): (i) North; (ii) Edmonton; (iii) Central; (iv) Calgary; and (v) South. Edmonton and Calgary are the major cities in the province, and both have populations in excess of one million people. In this study, First Nations status is based on individuals registered with the Alberta Health Care Insurance Plan as either First Nations or Inuit.
FIG 1.
Alberta Health Zones and associated Albertan communities. The population and geographic area of each Alberta Health Zone are shown. Population sizes were current as of 2012.
Bacterial strains.
MRSA was designated a pathogen under public health surveillance by Alberta Health in June 2005, and regional laboratories in the province were required to submit the first clinical MRSA isolates from cases of infection, not colonization, for genotyping to the Provincial Laboratory for Public Health (ProvLab) in Alberta. Isolates included in this study were genotyped using pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome mec (SCCmec), and Panton-Valentine leukocidin (PVL) typing from June 2005 to February 2010 (n = 1,085) and Staphylococcus protein A (spa), SCCmec, PVL, and PFGE typing from March 2010 to December 2012 (n = 1,496). Isolates were classified as duplicates if they were obtained from the same patient within a 12-month period and were excluded from the study.
DNA extraction.
Laboratories submitted confirmed MRSA isolates on swabs which were cultured onto sheep blood agar plates (BAPs; Dalynn Biologicals, Calgary, Alberta, Canada) and grown overnight at 37°C. MRSA isolates from frozen archived cultures were also subcultured onto BAPs. A single colony was picked from the BAP and suspended in 200 μl of rapid lysis buffer (100 mM NaCl, 10 mM Tris-HCl [pH 8.3], 1 mM EDTA [pH 9.0], 1% Triton X). The sample was then frozen at −80°C for 15 min, boiled for 15 min, cooled at room temperature, and centrifuged at 13,000 × g for 15 min (modified from the method of Holland et al. [21]). The resulting supernatant was used as the DNA template for PCR testing.
PFGE, spa, SCCmec, and PVL typing.
PFGE using the restriction endonuclease SmaI was performed as previously described by Mulvey et al. (22). PCR for spa typing was performed using primers targeting the spa gene as described by Golding et al. (23). PCR products were purified using an Invitrogen ChargeSwitch PCR cleanup kit (Invitrogen, Canada) and sequenced using a BigDye Xterminator purification kit (Applied Biosystems, Canada). SCCmec typing (24) and PVL typing (25) were performed using previously described methods.
Data analysis and PFGE epidemic type assignment.
PFGE data were analyzed using BioNumerics software (version 5.1; Applied Maths), and PFGE epidemic types were assigned based on guidelines published by the National Microbiology Laboratory (NML; [13, 26]). Briefly, isolates genotyped using PFGE were classified as CMRSA7/USA400 if their PFGE fingerprint profile did not differ from that of the NML reference strain by more than seven fingerprint bands. Sequencing results from spa typing were imported and analyzed using BioNumerics and submitted to the online Ridom spa database (http://spaserver.ridom.de/), which was developed by Ridom GmbH and is curated by SeqNet.org (http://www.SeqNet.org), for Ridom spa type designation (27). Ridom repeat successions were also assigned by the Ridom spa database. For isolates genotyped using spa, SCCmec, and PVL typing, the Alberta MRSA typing database (unpublished data) was used to assign PFGE epidemic types based on correlations between spa and PFGE epidemic types (23, 28–30). PFGE was used to confirm the PFGE epidemic type designation of isolates with rare or novel spa types. Infection rates were expressed as numbers of infections per month per 100,000 people. These were calculated by dividing the number of monthly MRSA infections by the population number and multiplying by 100,000. Relative risks (RR), 95% confidence intervals (CI), and corresponding P values were calculated using MedCalc (Version 12.7.5; MedCalc Software, Ostend, Belgium). χ2 values and associated P values, as well as statistical comparisons of means using unpaired two-tailed t tests, were calculated using the online calculator available at the GraphPad QuickCalcs website (GraphPad Software, La Jolla, CA; accessed 22 October 2013). A P value of <0.05 was considered statistically significant.
Antimicrobial susceptibility testing.
Antimicrobial susceptibility and inducible resistance to clindamycin were determined for 50 MRSA isolates (25 t128 isolates and 25 t1787 isolates) at the National Microbiology Laboratory in Winnipeg, Canada, using previously described procedures and MIC breakpoints (31–33). Isolates were selected with the goal of maximizing diversity in isolation year, geography, and infection source. The following antimicrobial agents were included for testing: ampicillin, cefoxitin, ciprofloxacin, clindamycin, erythromycin, fusidic acid, gentamicin, levofloxacin, linezolid, moxifloxacin, mupirocin, nitrofurantoin, penicillin, quinupristin-dalfopristin, rifampin, streptomycin, tetracycline, tigecycline, trimethoprim-sulfamethoxazole, and vancomycin.
Minimum-spanning trees.
Minimum-spanning trees (MST) based on spa types and the duplication, substitution, and indel (DSI) model were created using the spa typing module in BioNumerics with the following parameters: 250% gap creation cost; 50% gap extension, duplicate-creation, and duplicate-extension costs; a maximum of three-repeat duplication; and 1.00% bin grouping distance (34; BioNumerics Manual, version 5.1). Clusters in the minimum-spanning tree were defined as spa types that have a maximum neighbor distance equal to 1.
RESULTS
Incidence and distribution of CMRSA7/USA400 MRSA strains in Alberta.
A total of 2,581 MRSA isolates in Alberta, each representing a unique case of MRSA infection, were classified as PFGE epidemic type CMRSA7/USA400 from June 2005 to December 2012. Both the average number of cases per month and the rates of CMRSA7/USA400 cases increased from 2005 to 2012 (Fig. 2). In 2005, there were 11 cases per month and a rate of 0.32 per 100,000 people compared to 57 cases per month and a rate of 1.44 per 100,000 people in 2012 (Fig. 2).
FIG 2.
Submission frequencies and the rates of infection of CMRSA7/USA400 MRSA isolates in Alberta from June 2005 to December 2012. Data for t1787 and t128 MRSA from March 2010 to December 2012 are plotted. Mar, March; Jun, June; Sep, September; Dec, December; 05, 2005; 06, 2006; 07, 2007; 08, 2008; 09, 2009; 10, 2010; 11, 2011; 12, 2012.
The distribution of CMRSA7/USA400 MRSA strains across the five Alberta Health Zones is shown in Table 1. Increases in CMRSA7/USA400 infection rates were observed in the North, Edmonton, and Central Health Zones from 2010 to 2012, while little change was seen for the South Health Zone. The North Health Zone had the highest CMRSA7/USA400 infection rate and the greatest infection rate increase during the study period. The Calgary and South Health Zones had the lowest CMRSA7/USA400 infection rates in 2011 and 2012 (Table 1).
TABLE 1.
Infection rates of CMRSA7/USA400 MRSA isolates with spa types t128 and t1787 in Alberta Health Zones from March 2010 to December 2012a
| Health Zone | Avg monthly infection rate, RR (95% CI), or P value per 100,000 |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mar 2010-Dec 2010 |
Jan 2011-Dec 2011 |
Jan 2012-Dec 2012 |
|||||||||||||
| CMRSA7/USA400 | t128 | t1787 | RR (95% CI) | P value | CMRSA7/USA400 | t128 | t1787 | RR (95% CI) | P value | CMRSA7/USA400 | t128 | t1787 | RR (95% CI) | P value | |
| All zones | 0.91 | 0.70 | 0.12 | 5.8 (4.4–7.6) | <0.0001 | 1.04 | 0.63 | 0.22 | 3.9 (3.2–4.6) | <0.0001 | 1.44 | 0.78 | 0.33 | 2.4 (2.1–2.8) | <0.0001 |
| North | 2.11 | 1.09 | 0.88 | 1.2 (0.9–1.7) | 0.1888 | 3.21 | 1.28 | 1.61 | 0.8 (0.6–1.0) | 0.0550 | 4.74 | 1.74 | 2.52 | 0.7 (0.6–0.8) | 0.0002 |
| Edmonton | 0.51 | 0.46 | 0.02 | 26.5 (6.8–103.8) | <0.0001 | 0.78 | 0.52 | 0.04 | 12.5 (5.7–27.5) | <0.0001 | 1.24 | 0.70 | 0.03 | 26. 0 (9.8–69.1) | <0.0001 |
| Central | 1.30 | 0.98 | 0.02 | 44.0 (6.3–308.8) | 0.0001 | 1.70 | 1.17 | 0.02 | 64.0 (9.1–451.7) | <0.0001 | 2.09 | 1.63 | 0.07 | 22.8 (8.6–59.9) | <0.0001 |
| Calgary | 0.85 | 0.78 | 0.01 | 54.0 (13.7–213.6) | <0.0001 | 0.49 | 0.40 | 0.02 | 22.7 (7.4–69.2) | <0.0001 | 0.50 | 0.33 | 0.03 | 11.8 (5.0–28.0) | <0.0001 |
| South | 0.42 | 0.25 | 0.04 | 7.0 (1.0–48.5) | 0.0489 | 0.40 | 0.29 | 0.06 | 5.0 (1.3–18.8) | 0.0173 | 0.65 | 0.53 | 0.00 | 39.0 (2.5–609.8) | 0.0090 |
Relative risk (RR) and 95% confidence interval (CI) calculations are based on t128 and t1787 MRSA data. Jan, January; Mar, March; Dec, December.
Molecular characterization of CMRSA7/USA400 MRSA in Alberta.
During the study, 2,581 MRSA isolates were characterized as CMRSA7/USA400: 1,085 by PFGE (June 2005 to February 2010; 146 isolates were retroactively spa typed) and 1,496 by spa typing (March 2010 to December 2012). There were 94 unique PFGE fingerprint patterns and 45 different spa types observed. The CMRSA7/USA400 spa types identified had a range of 2 to 11 repeat successions, and their relatedness is shown in Fig. 3. A major cluster was observed: cluster 1 (Fig. 3). Cluster 1 included 21 of the 45 spa types seen and 88.7% (n = 1,457/1,642) of the isolates spa typed in this study. Of the most common CMRSA7/USA400 spa types in Alberta (Table 2), only t1508 (no cluster) and t175 (cluster 4) were not a part of cluster 1 (Fig. 3). An additional four small clusters—clusters 2 to 5—were observed that included two to four spa types (Fig. 3). Of the 45 spa types, a total of 13, including t5977, t5978, t5979, t6879, t7347, t8943, t9494, t9668, t9838, t9933, t10280, t11117, and t11672, were novel and had not been previously reported. The novel spa types are closely related to a number of different spa types rather than to a single parent spa type (Fig. 3).
FIG 3.
Minimum-spanning tree of CMRSA7/USA400 spa types in Alberta. Each circle in the tree represents a different spa type. spa types t128 and t1787 are marked with a star and are shaded purple and red, respectively. Novel spa types are shaded green. Similarity values are shown on the connecting lines between spa types. spa type clusters are shaded as indicated in the legend.
TABLE 2.
Distribution of CMRSA7/USA400 spa types in Albertaa
| spa type | Ridom repeat succession | Count |
|---|---|---|
| t128 | 07-23-23-21-16-34-33-13 | 1,007 |
| t1787 | 26-23-23-21-16-34-33-13 | 332 |
| t1508 | 15-16-34-33-13 | 134 |
| t127 | 07-23-21-16-34-33-13 | 34 |
| t1788 | 07-23-23-21-34-33-13 | 34 |
| t1909 | 07-23-23-16-34-33-13 | 13 |
| t555 | 07-23-23-23-21-16-34-33-13 | 13 |
| t175 | 07-23-21-16-16-33-21-16-33-13 | 8 |
| t4671 | 07-23-23-21-16-34-33-16-34-33-13 | 6 |
| Other | Not applicable | 61 |
| Total | 1,642 |
spa types observed at a frequency of five or fewer are grouped collectively into the spa type “Other.”
Over 81% of the spa-typed isolates were t128 (n = 1,007; 61.3%) or t1787 (n = 332; 20.2%; Table 2), and both types belong to cluster 1 (Fig. 3). Each of spa types t128 (Ridom repeat succession: 07-23-23-21-16-34-33-13) and t1787 (Ridom repeat succession: 26-23-23-21-16-34-33-13) has eight repeat successions in the spa region, and the two types are closely related, differing by a single nucleotide in the first repeat block (cytosine in t128; alanine in t1787). All t128 and t1787 isolates were SCCmec type IV. The majority of t128 isolates (n = 821/1007; 81.5%) were PVL positive. All but two of the t1787 isolates (n = 330/332; 99.4%) were PVL positive. PFGE data from 51 t128 isolates showed 31 unique PFGE patterns. In comparison, only four PFGE patterns were seen from 33 t1787 isolates, all of which were also observed in t128 MRSA.
Antimicrobial susceptibility testing of t128 and t1787 MRSA in Alberta.
The antimicrobial resistance profiles of 25 t128 and 25 t1787 MRSA was determined. Both t128 MRSA and t1787 MRSA had no resistance to chloramphenicol, daptomycin, gentamicin, linezolid, nitrofurantoin, quinupristin-dalfopristin, rifampin, streptomycin, tetracycline, tigecycline, trimethoprim-sulfamethoxazole, or vancomycin. Additionally, t128 MRSA had no resistance to clindamycin. Inducible clindamycin resistance was observed in four (16.0%) of the t128 and nine (36.0%) of the t1787 isolates tested—however, this difference was not statistically significant (χ2 = 2.599; P = 0.1069). Nearly all of the t128 isolates tested were also sensitive to ciprofloxacin (n = 24/25; 96.0%), fusidic acid (n = 24/25; 96.0%), levofloxacin (n = 24/25; 96.0%), moxifloxacin (n = 24/25; 96.0%), and erythromycin (n = 21/25; 84.0%). Similarly, t1787 MRSA had no resistance to ciproflaxin, levofloxacin, and moxifloxacin. Of the 25 t1787 isolates tested, 1 (4.0%) was resistant to clindamycin and 1 (4.0%) was resistant to fusidic acid. t1787 isolates were significantly more resistant to mupirocin than t128 isolates (χ2 = 17.568; P < 0.0001). There were 12 (48.0%) mupirocin-resistant t128 isolates; of these isolates, 1 (4.0%) was also resistant to fusidic acid. In comparison, all t1787 isolates tested were resistant to mupirocin: 10 (40.0%) were also resistant to erythromycin and had clindamycin resistance/inducible clindamycin resistance; and 1 (4.0%) was also resistant to fusidic acid.
Distribution of t128 and t1787 MRSA in Alberta.
The CMRSA7/USA400 infection rates in Alberta have steadily increased from June 2005 to December 2012 (Fig. 2 and Table 1). Despite this, t128 infection rates have remained stable since March 2010 (Table 1). t128 MRSA isolates were collected throughout the province—most commonly in the North and Central Health Zones. In 2012, Alberta communities A (53.94 infections/100,000 people), B (12.23 infections/100,000 people), C (49.46/100,000 people), D (9.20 infections/100,000 people), and J (32.36 infections/100,000 people) had the highest monthly t128 infection rates (Fig. 1 and Table 3). From 2010 to 2012, communities A and B had the biggest declines in t128 infection rates while community J had the biggest increase. In contrast to t128, the monthly infection rates for t1787 MRSA in Alberta increased from 0.12 infections per 100,000 in 2010 (RR = 0.17, P < 0.0001) to 0.33 infections per 100,000 people in 2012 (RR = 0.42, P < 0.0001; Table 1). Infections from t1787 were more concentrated in the North Health Zone (2.52 infections/100,000 people per month in 2012) than in the other health zones (0.00 to 0.07 infections/100,000 people per month in 2012; Table 1). Small communities (population ≤ 10,000 people) in the North Health Zone had the highest monthly t1787 infection rates in 2012. These included communities D (165.56 infections/100,000 people), E (181.65 infections/100,000 people), F (139.66 infections/100,000 people), H (45.00 infections/100,000 people), I (22.25 infections/100,000 people), and J (80.91 infections/100,000 people) (Fig. 1 and Table 3). Substantial t1787 infection rate increases were observed in communities D, H, and J. Communities D to J are in close geographic proximity, and all fall within an area spanning approximately 38,800 km2. Areas with high t128 infection rates typically had low t1787 infection rates and vice versa (with the exception of community J).
TABLE 3.
Infection rates of CMRSA7/USA400 isolates with spa types t128 and t1787 in Alberta communities from March 2010 to December 2012a
| Community (population) | Avg monthly infection rate, RR (95% CI), or P value per 100,000 |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mar 2010-Dec 2010 |
Jan 2011-Dec 2011 |
Jan 2012-Dec 2012 |
|||||||||||||
| CMRSA7/USA400 | t128 | t1787 | RR (95% CI) | P value | CMRSA7/USA400 | t128 | t1787 | RR (95% CI) | P value | CMRSA7/USA400 | t128 | t1787 | RR (95% CI) | P value | |
| Edmonton (881,200) | 0.47 | 0.41 | 0.02 | 17.0 (4.4–65.9) | <0.0001 | 0.88 | 0.53 | 0.06 | 9.0 (4.1–19.9) | <0.0001 | 1.43 | 0.73 | 0.03 | 25.7 (8.3–79.6) | <0.0001 |
| Calgary (1,221,500) | 0.29 | 0.24 | 0.00 | 55.0 (3.5–865.7) | 0.0044 | 0.19 | 0.13 | 0.01 | 9.0 (2.3–35.1) | 0.0015 | 0.25 | 0.13 | 0.02 | 6.3 (2.1–19.5) | 0.0013 |
| A (3,700) | 99.45 | 99.45 | 0.00 | 73.0 (4.7–1145.7) | 0.0023 | 48.44 | 48.44 | 0.00 | 43.0 (2.8–666.6) | 0.0072 | 56.18 | 53.94 | 0.00 | 49.0 (3.1–764.0) | 0.0055 |
| B (2,700) | 75.27 | 75.27 | 0.00 | 41.0 (2.7–634.6) | 0.0079 | 43.52 | 43.52 | 0.00 | 29.0 (1.9–443.3) | 0.0155 | 12.23 | 12.23 | 0.00 | 9.0 (0.6–126.9) | 0.1036 |
| C (9,400) | 21.56 | 14.01 | 1.08 | 13.0 (1.9–90.2) | 0.0095 | 51.00 | 33.10 | 0.89 | 37.0 (5.3–260.6) | 0.0003 | 59.18 | 49.46 | 0.00 | 113.0 (7.1–1792.1) | 0.0008 |
| D (900) | 0.00 | 0.00 | 0.00 | 1.0 (0.06–16.0) | 1.0000 | 57.08 | 0.00 | 57.08 | 0.08 (0.005–1.1) | 0.0606 | 174.76 | 9.20 | 165.56 | 0.06 (0.008–0.4) | 0.003 |
| E (700) | 145.99 | 0.00 | 145.99 | 0.05 (0.003–0.7) | 0.0277 | 261.16 | 0.00 | 261.20 | 0.02 (0.001–0.3) | 0.0065 | 181.65 | 0.00 | 181.65 | 0.03 (0.002–0.5) | 0.0121 |
| F (400) | 146.20 | 0.00 | 116.96 | 0.1 (0.008–1.6) | 0.1099 | 144.93 | 0.00 | 144.90 | 0.08 (0.005–1.1) | 0.0606 | 139.66 | 0.00 | 139.66 | 0.08 (0.005–1.1) | 0.0606 |
| G (10,100) | 8.20 | 1.02 | 7.17 | 0.1 (0.02–0.9) | 0.0395 | 6.68 | 0.83 | 5.84 | 0.1 (0.02–0.9) | 0.0395 | 11.51 | 1.64 | 9.86 | 0.2 (0.05–0.6) | 0.0069 |
| H (900) | 0.00 | 0.00 | 0.00 | 1.0 (0.06–16.0) | 1.0000 | 64.24 | 0.00 | 64.24 | 0.07 (0.005–1.0) | 0.0485 | 45.00 | 0.00 | 45.00 | 0.1 (0.006–1.3) | 0.0778 |
| I (5,200) | 25.51 | 3.92 | 19.62 | 0.2 (0.05–0.7) | 0.016 | 12.83 | 3.21 | 9.62 | 0.3 (0.09–1.2) | 0.0888 | 25.43 | 1.59 | 22.25 | 0.07 (0.01–0.5) | 0.0067 |
| J (4,100) | 12.33 | 4.93 | 7.40 | 0.7 (0.2–2.4) | 0.5379 | 30.50 | 6.10 | 22.37 | 0.3 (0.1–0.8) | 0.016 | 119.34 | 32.36 | 80.91 | 0.4 (0.3–0.6) | 0.0001 |
Population sizes rounded to the nearest hundred are given in parentheses and were current as of 2012. Relative risk (RR) and 95% confidence interval (CI) calculations are based on t128 and t1787 MRSA data.
t128 and t1787 MRSA patient demographics in Alberta.
The mean ages of patients with CMRSA7/USA400 and t128 infections were not significantly different at 28.3 years and 27.3 years, respectively (P value = 0.1796; Table 4). In comparison, the mean t1787 patient age of 21.0 years was lower than those for CMRSA7/USA400 (P value < 0.0001) and t128 (P value < 0.0001) patients. The majority of patients with CMRSA7/USA400 (n = 1,919; 74.35%), t128 (n = 762; 75.67%), and t1787 (n = 272; 81.93%) infections were outpatients, and no significant gender difference was observed (Table 4). Most CMRSA7/USA400 (n = 2,344; 90.82%), t128 (n = 922; 91.56%), and t1787 (n = 313; 94.28%) isolates were from skin and soft tissue infections (SSTIs), although some were also isolated from other sources (Table 4). The most common anatomic infection site for t128 SSTIs was the abdomen (n = 94; 9.33%). Abdomen infections were also seen for t1787 MRSA (n = 23; 6.93%); however, the most common anatomic infection site for t1787 MRSA was the buttocks (n = 52; 15.66%), which was a significantly less common infection site for t128 MRSA (n = 72; 7.15%; RR = 0.46, P < 0.0001). More than half of the CMRSA7/USA400 infections (n = 1,681; 65.13%) were those of First Nations or Inuit people (Table 4). The observed difference was more prominent for t1787 MRSA (n = 277; 83.43%) than for t128 MRSA (n = 705; 70.01%; RR = 1.19, P < 0.0001).
TABLE 4.
Demographics of CMRSA7/USA400 isolates with spa types t128 and t1787 in Albertaa
| Characteristic | No. (%) of isolates |
P value | |||
|---|---|---|---|---|---|
| CMRSA7/USA400 (n = 2,581) | t128 (n = 1,007) | t1787 (n = 332) | RR (95% CI)b | ||
| Age (yrs) | |||||
| <1 | 95 (3.68) | 38 (3.77) | 13 (3.92) | 1.0 (0.5–1.8) | 0.9066 |
| 1–4 | 271 (10.50) | 104 (10.32) | 58 (17.47) | 0.6 (0.4–0.8) | 0.5912 |
| 5–9 | 201 (7.79) | 77 (7.64) | 41 (12.35) | 0.6 (0.4–0.9) | 0.0087 |
| 10–19 | 387 (14.99) | 161 (15.97) | 56 (16.87) | 1.0 (0.7–1.3) | 0.7054 |
| 20–29 | 515 (19.95) | 219 (21.73) | 71 (21.39) | 1.0 (0.8–1.3) | 0.8896 |
| 30–39 | 378 (14.65) | 156 (15.48) | 39 (11.75) | 1.3 (1.0–1.8) | 0.0985 |
| 40–49 | 314 (12.17) | 107 (10.62) | 35 (10.54) | 1.0 (0.7–1.5) | 0.9658 |
| 50–59 | 218 (8.45) | 67 (6.65) | 11 (3.31) | 2.0 (1.1–3.8) | 0.0289 |
| 60–69 | 97 (3.76) | 40 (3.97) | 5 (1.51) | 2.6 (1.1–6.6) | 0.0391 |
| 70+ | 96 (3.72) | 33 (3.27) | 3 (0.90) | 3.6 (1.1–11.8) | 0.0317 |
| Unknown | 9 (0.35) | 5 (0.60) | 0 (0.00) | ||
| Mean | 28.3 | 27.3 | 21.0 | ||
| Sex | |||||
| Male | 1,346 (52.15) | 489 (48.56) | 171 (51.50) | 0.9 (0.8–1.1) | 0.3449 |
| Female | 1,234 (47.81) | 517 (51.34) | 161 (48.49) | 1.1 (0.9–1.2) | 0.3753 |
| Unknown | 1 (0.04) | 1 (0.10) | 0 (0.00) | ||
| Patient location | |||||
| Clinic | 3 (0.12) | 0 (0.00) | 0 (0.00) | 0.3 (0.01–16.6) | 0.5795 |
| Hospital | 2 (0.08) | 1 (0.10) | 0 (0.00) | 1.0 (0.04–24.3) | 0.9956 |
| Emergency department | 53 (2.05) | 16 (1.59) | 11 (3.31) | 0.5 (0.2–1.0) | 0.0573 |
| Inpatient | 428 (16.58) | 165 (16.39) | 25 (7.53) | 2.2 (1.5–3.3) | 0.0001 |
| Outpatient | 1,919 (74.35) | 762 (75.67) | 272 (81.93) | 0.9 (0.9–1.0) | 0.0113 |
| Home care | 1 (0.04) | 0 (0.00) | 0 (0.00) | 0.3 (0.01–16.6) | 0.5795 |
| Long-term care | 7 (0.27) | 2 (0.20) | 0 (0.00) | 1.7 (0.08–34.3) | 0.7458 |
| Correctional center | 39 (1.51) | 6 (0.60) | 0 (0.00) | 4.3 (0.2–76.0) | 0.3202 |
| IV therapy | 2 (0.08) | 2 (0.20) | 0 (0.00) | 1.7 (0.08–34.3) | 0.7458 |
| Other | 11 (0.43) | 5 (0.50) | 1 (0.30) | 1.7 (0.2–14.1) | 0.6476 |
| Unknown | 116 (4.49) | 48 (4.77) | 23 (6.93) | ||
| Patient residence | |||||
| Urban | 1,108 (42.93) | 419 (41.61) | 66 (19.88) | 2.1 (1.7–2.6) | <0.0001 |
| Rural | 1,285 (49.79) | 538 (53.43) | 261 (78.61) | 0.7 (0.6–0.7) | <0.0001 |
| Unknown | 188 (7.28) | 50 (4.96) | 5 (1.51) | ||
| Source | |||||
| Blood | 27 (1.05) | 7 (0.70) | 2 (0.60) | 1.2 (0.2–5.5) | 0.8578 |
| Device | 2 (0.08) | 2 (0.20) | 0 (0.00) | 1.7 (0.08–34.3) | 0.7458 |
| Respiratory specimen | 42 (1.63) | 16 (1.59) | 2 (0.60) | 2.6 (0.6–11.4) | 0.1944 |
| Urine specimen | 27(1.05) | 6 (0.60) | 2 (0.60) | 1.0 (0.2–4.9) | 0.9892 |
| Sterile | 6 (0.23) | 4 (0.40) | 0 (0.00) | 3.0 (0.2–55.1) | 0.4644 |
| SSTIc | 2,344 (90.82) | 922 (91.56) | 313 (94.28) | 1.0 (0.9–1.0) | 0.0774 |
| Abdomen | 94 (9.33) | 23 (6.93) | 1.4 (0.9–2.1) | 0.1828 | |
| Buttocks | 72 (7.15) | 52 (15.66) | 0.5 (0.3–0.6) | <0.0001 | |
| Legs | 71 (7.05) | 35 (10.54) | 0.7 (0.5–1.0) | 0.0407 | |
| Other | 90 (3.49) | 38 (3.77) | 7 (2.11) | 1.8 (0.8–4.0) | 0.1521 |
| Unknown | 43 (1.67) | 10 (0.99) | 6 (1.81) | ||
| First Nations status | |||||
| First Nations or Inuit | 1,681 (65.13) | 705 (70.01) | 277 (83.43) | 0.8 (0.8–0.9) | <0.0001 |
| Non-First Nations or Inuit | 839 (32.51) | 287 (28.50) | 54 (16.27) | 1.8 (1.4–2.3) | <0.0001 |
| Unknown | 61 (2.36) | 15 (1.49) | 1 (0.30) | ||
The percentage of total isolates is given in brackets.
Relative risk (RR) and 95% confidence interval (CI) calculations are based on t128 and t1787 MRSA data.
SSTI, skin and soft tissue infection.
DISCUSSION
High rates of CMRSA7/USA400 infections have been recently observed in regions around Alberta, Canada, particularly in northern communities (17–19). We report the epidemiology of CMRSA7/USA400 MRSA isolated in Alberta from June 2005 to December 2012. Although PFGE typing was more discriminatory, spa typing provided a more definitive method of molecular characterization for CMRSA7/USA400 MRSA. Many spa types were associated with CMRSA7/USA400, but t128 and t1787 were most common in Alberta. spa type t128 has been previously reported in Alberta (35) and Saskatchewan (17) and is common in many other countries (http://spaserver.ridom.de/); spa type t1787 is rare worldwide (http://spaserver.ridom.de/), has not been seen in Alberta, and has been previously reported only in general practice patients in the Netherlands (36). Although the two spa types are closely related, the geographic distributions of t128 and t1787 MRSA in Alberta are distinct: t128 is generally distributed throughout the province whereas t1787 is mostly concentrated in the North Health Zone. The overall CMRSA7/USA400 infection rate in 2012 (1.44/100,000 people per month) was higher than that in Alberta previously reported by Kim et al. (15) but lower than the rate observed in Saskatchewan, Canada (17). Although most Alberta Health Zones saw an increase in CMRSA7/USA400 infection rates from 2010 to 2012, the rate in the North Health Zone increased most dramatically. This was largely due to a nearly 3-fold increase in t1787 infection rates in the North Health Zone and is contrary to previous reports that CMRSA7/USA400 MRSA is found mostly in southern Alberta (15). In contrast, the overall infection rate of t128 MRSA has remained constant from 2010 to 2012. The high t1787 infection rate in the North Health Zone and the absence of t1787 MRSA in all other Alberta Health Zones could be due to a greater prevalence of reported risk factors in this area, including overcrowding, poor hygiene, previous antibiotic administration, limited access to health care facilities, and inadequate health education (37), although no studies have been done to investigate this possibility. The emergence of t1787 MRSA could also be a recent occurrence that will spread throughout the province given time. This hypothesis is supported by the dramatic increase in t1787 infection rates from 2010 to 2012 in Albertan communities that previously had no reports of t1787 infections. Furthermore, the communities that are most affected by t1787 MRSA are geographically clustered, promoting transmission between subpopulations. The introduction of t1787 MRSA to northern Alberta could be the result of clonal expansion and diversification of t128 MRSA that caused previous outbreaks in Alberta and neighboring provinces (17, 35).
The patient demographics and molecular characteristics for t128 and t1787 MRSA isolates were similar to previous reports for CMRSA7/USA400 (2, 3): they were all SCCmec type IV and mostly PVL positive; they affected a younger population; there was no gender difference; and most isolates were from SSTIs. As well, the majority of patients with CMRSA7/USA400 infections were First Nations or Inuit people. However, several key differences between t128 MRSA and t1787 MRSA were observed. The majority of t1787 patients were 19 years of age or younger, which is significantly lower than the proportion of t128 patients, and a greater proportion of all t1787 infections were from First Nations or Inuit people. As well, the most common anatomic infection site for t1787 is the buttocks soft tissue, which is different from t128 MRSA, where abdominal soft tissue infections are most frequent. The differences observed in patient age and anatomic infection sites could reflect differing colonization efficiencies for t128 and t1787 MRSA. This was previously shown in a study that reported that below-the-waist SSTI infections in children were often caused by rectal CA-MRSA colonization (38). Another key difference between t1787 and t128 MRSA is that t1787 isolates were significantly more resistant to mupirocin than t128 isolates. The level of mupirocin resistance for t1787 MRSA is much higher than that previously reported for CMRSA7/USA400 (15, 39). One limitation of this study is that a low number of isolates were tested for antimicrobial susceptibility. Testing of additional isolates would give more-definitive resistance profiles for the two strains. Despite this, both t128 MRSA and t1787 MRSA were shown to be susceptible to a number of antimicrobials.
Educational tools, promotion of hygiene, appropriate use of antibiotics, and early detection and treatment are all strategies that have been effective in combating the spread of MRSA (40). These strategies could reduce the number of CMRSA7/USA400 infections, particularly t1787 MRSA infections, in northern Alberta communities. If the spread of t1787 MRSA in the North Health Zone is attributable to differences in colonization efficiency, then targeted strategies may be needed to prevent infection, particularly in children. Continued surveillance in Alberta is essential to understanding the changing epidemiology of MRSA and identifying emerging MRSA clones that impact public health.
ACKNOWLEDGMENTS
We thank Alberta MicroNet laboratories for their support and the submission of MRSA isolates used in this study; Jennifer Campbell for her assistance in interpreting spa typing data; and the Bacterial Typing Unit and Molecular Diagnostics at ProvLab for their technical support. We also thank Alberta Health Services and Alberta Health for their support for this research.
Footnotes
Published ahead of print 30 April 2014
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