Synergistic effects of length of stay and prior MDRO carriage on the colonization and co-colonization of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and carbapenemase-producing Enterobacterales across healthcare settings

To characterize the epidemiology of methicillin-resistant (MRSA), vancomycin-resistant enterococci (VRE), and carbapenemase-producing Enterobacterales (CPE) co-colonization and to compare risk factors between healthcare facility types. We conducted a 3-year cross-sectional study among patients admitted to an acute-care hospital (ACH) and its 6 closely affiliated intermediate- and long-term care facilities (ILTCFs) in Singapore in June and July of 2014-2016. Specimens were concurrently collected from nares, axillae, and groins for MRSA detection, and from rectum or stool for VRE and CPE detection. Co-colonization was defined as having >1 positive culture of MRSA/VRE/CPE. Multinomial logistic regression was performed to determine predictors of co-colonization. Of 5,456 patients recruited, 176 (3.2%) were co-colonized, with higher prevalence among patients in ITCFs (53 of 1,255, 4.2%) and the ACH (120 of 3,044, 3.9%) than LTCFs (3 of 1,157, 0.3%). MRSA/VRE was the most common type of co-colonization (162 of 5,456, 3.0%). Independent risk factors for co-colonization included male sex (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.37-2.80), prior antibiotic therapy of 1-3 days (OR, 10.39; 95% CI, 2.08-51.96), 4-7 days (OR, 4.89; 95% CI, 1.01-23.68), >7 days (OR, 11.72; 95% CI, 2.81-48.85), and having an open wound (OR, 2.34; 95% CI, 1.66-3.29). Additionally, we detected the synergistic interaction of length of stay >14 days and prior multidrug-resistant organism (MDRO) carriage on co-colonization. Having an emergency surgery was a significant predictor of co-colonization in ACH patients, and we detected a dose-response association between duration of antibiotic therapy and co-colonization in ILTCF patients. We observed common and differential risk factors for MDRO co-colonization across healthcare settings. This study has identified at-risk groups that merit intensive interventions, particularly patients with prior MDRO carriage and longer length of stay.