Comparison of subsequent infection in methicillin-resistant Staphylococcus aureus nasal carriers between ST72 community-genotype and hospital genotypes: a retrospective cohort study

A retrospective cohort study was performed at Samsung Medical Center (Seoul, Republic of Korea), a university-affiliated tertiary care hospital with 1983 patient beds. We identified patients who were newly-detected MRSA nasal carriers between January 1, 2007 and March 31, 2010 from the previous study [12]. MRSA nasal screening was performed in selected newly-admitted patients according to the active surveillance policy for infection prevention purpose of the hospital. The indications for screening included the referral patients from the other hospitals or the chronic care facilities, the patients scheduled for operations in the departments of orthopedic surgery, neurosurgery, thoracic surgery and general surgery, the patients receiving hemodialysis or peritoneal dialysis, MRSA isolation from clinical specimens and carriage of vancomycin-resistant Enterococcus (VRE). Conventional culture methods were used for screening and confirmation of nasal carrier status of MRSA. The MRSA isolates were collected and stocked in the Asian Bacterial Bank (Seoul, Republic of Korea). Patients were excluded from the study if nasal MRSA carriage had been already known prior to the study period.

The patients carrying MRSA belonging to the sequence types other than ST72, ST5 and ST239 were excluded. We also excluded the patients who could not be followed up at least 6 months and had not developed subsequent MRSA infection until that time point (Fig. 1). Cohort 1 included the patients carrying MRSA with community-genotype, ST72, and cohort 2 included those who carried MRSA with hospital-genotypes, ST5 or ST239. If the patients developed MRSA infection multiple times, the first episode was only included in the analysis. This study was approved by the Institute Review Board of Samsung Medical Center.

Demographic and clinical characteristics, laboratory data, and outcome data were collected from the electronic medical records. The McCabe classification was used to categorize the severity of the underlying medical condition as non-fatal, ultimately fatal, or rapidly fatal [13]. Outcome variables included the rates of subsequent MRSA infection within six months after new detection of MRSA nasal colonization, overall mortality rates at six months, and time to development of subsequent MRSA infection. The type of infections was also described.

The Vitek 2 automated system (bioMerieux, Marcy l’Etoile, France) was used for microbiological identification and antimicrobial susceptibility testing. The MICs were determined according to the standards established by the Clinical and Laboratory Standards Institute (CLSI) [14]. Multilocus sequence typing (MLST) was carried out using PCR amplification and sequencing of seven housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi, and yqiL), as previously described [15]. The allelic profiles and sequence types (STs) were assigned according to the MLST web site (http//saureus.mlst.​net/).

All tests of significance were two-tailed. P-values <0.05 were considered statistically significant. Categorical variables were compared between the groups using Chi-square test or Fisher’s exact test. Continuous variables were compared using the Mann–Whitney U test. Multivariate logistic regression analysis was used to determine the risk factors of subsequent MRSA infection. Stepwise model comparison was used to determine the best model using the PASW version 18.0 (SPSS Inc., Chicago, IL, USA). Times to development of subsequent MRSA infection during the follow-up period were calculated by the Kaplan-Meier method and compared between the cohorts using the log-rank test. Stata version 11.2 (StataCorp, College Station, TX, USA) was used for this analysis.

We identified 1118 patients with nasal MRSA colonization during the study period. Among those patients, 592 known MRSA carriers revisiting the hospital were excluded. The patients carrying MRSA strains belonging to ST72, ST5 or ST239 who were followed up for at least 6 months were included in this study. A total of 354 patients carrying MRSA were included (Fig. 1). Among those MRSA isolates, the most frequent sequence type was ST72 (55.9%). ST5 and ST239 accounted for 23.8% and 5.4%, respectively. The most frequent reasons for nasal MRSA screening were transfer from other hospital (36.2%) and pre-operative screening (33.6%). Other reasons included MRSA isolation from clinical specimens (9.0%), carriage of VRE (6.5%), and undergoing hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) (4.2%). Among the MRSA isolates from nasal carriers who were screened for pre-operative screening, ST72 (67.2%) was more frequent than ST5 or ST239 (Table 1).

The demographic and clinical characteristics of MRSA nasal carriers were compared between ST72 cohort and ST5 / ST239 cohort (Table 1). The most frequent comorbidity in ST72 cohort was solid tumor (24.2%), followed by cardiovascular disease, diabetes mellitus, liver disease, neurologic disease, and chronic kidney disease. Solid tumor was more frequent in ST72 cohort than in ST5 / ST239 cohort, whereas hematologic malignancy was more frequent in ST5 / ST239 cohort.

The median duration of follow-up after detection of nasal MRSA carriage was 1058 days (range 11–2441 days) in ST72 cohort and 774.5 days (range 13–2515 days) in ST5 / ST239 cohort (P = 0.555). Among MRSA carriers of ST72 cohort, 13.1% developed subsequent MRSA infection similar to the rate in ST5 / ST239 cohort (12.8%) (P = 0.931). The median time to development of subsequent MRSA infection following new detection of nasal carriage was 27 days in ST72 cohort, which was not a statistically significant difference compared to ST5 / ST239 cohort (88 days). The Kaplan-Meier method was used to calculate the cumulative rate of being free of subsequent MRSA infection, and no significant difference was observed between two cohorts (P = 0.9209) (Fig. 2). Overall mortality rates did not differ between two cohorts (1.5% vs. 1.9%) (P = 1.000).

The most frequent type of subsequent MRSA infections was pneumonia (50%), followed by urinary tract infection (13.0%), primary bacteremia (10.9%), surgical site infection (8.7%), intra-abdominal infection (8.7%), and skin and soft tissue infection (6.5%). There was no difference in distribution of infection types between two cohorts. Among 26 cases of subsequent MRSA infections in ST72 cohort, 19 (73.1%) were hospital-onset.

Multivariate analysis showed that the nasal carriers who also had MRSA isolated from culture of clinical specimens had 33-fold increased risk of subsequent MRSA infection (Table 2). Chronic lung disease and transfer from another hospital were also the risk factors for subsequent MRSA infection (O.R. 4.870 and O.R. 2.375, respectively).

Multivariate analysis showed that predictive factors for ST72 MRSA among MRSA nasal carriage were pre-operative screening for MRSA nasal carriage (odds ratio 1.828; 95% CI 1.127–2.967; P = 0.015) and solid tumor (odds ratio 1.747; 95% CI 1.004–3.040; P = 0.048).