Risk factors for colonization with multiple species of extended-spectrum beta-lactamase producing Enterobacterales: a case-case-control study.

BACKGROUND Approximately 11% of patients colonized with extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) are colonized with more than one ESBL-producing species. We investigated risk factors associated with colonization with multiple ESBL-PE species. METHODS We performed a case-case-control study at the University Hospital Basel, Switzerland, including hospitalized patients colonized with ESBL-PE between 01/2008 and 12/2018. Patients colonized with multiple species of ESBL-PE during the same hospitalization were assigned to group 1. Group 2 consisted of patients with ESBL-PE and a newly acquired ESBL-PE-species identified during subsequent hospitalization. Controls (i.e., group 3) were patients with only one species of ESBL-PE identified over multiple hospitalizations. Controls were frequency-matched 3:1 to group 2 cases according to time-at-risk (i.e., days between ESBL-PE detection during first and subsequent hospitalizations) to standardize the duration of colonization. ESBL was identified with phenotypic assay and the presence of ESBL genes was confirmed by whole genome sequencing. RESULTS Among 1559 inpatients, 154 cases met eligibility criteria (67 in group 1, 22 in group 2, 65 in group 3). International travel within the previous 12 months (OR 12.57, 95% CI 3.48-45.45, p < 0.001) and antibiotic exposure within the previous 3 months (OR 2.96, 95% CI 1.37-6.41, p = 0.006) were independently associated with co-colonization with multiple ESBL-PE species. Admission from another acute-care facility was the only predictor of replacement of one ESBL-PE species with another during subsequent hospitalizations (OR 6.02, 95% CI 1.15-31.49, p = 0.003). CONCLUSION These findings point to strain-related factors being the main drivers of co-colonization with different ESBL-PE and may support stratification of infection prevention and control measures according to ESBL-PE species/strains.