Intestinal co-colonization with different carbapenemase-producing isolates is not a rare event in an OXA-48 endemic area.

Background: The current spread of carbapenemase-producing (CPE) is a great concern.

Methods: We recovered 198 CPE from 162 patients admitted in our Hospital (March 2014-March 2016) during the R-GNOSIS European Project. Microbiological features and plasmid characteristics of CPE recovered from patients co-colonized with multiple CPE were studied.

Findings: Thirty patients (18.5%; CI 95%= 12.5%-24.5%) presented co-colonization with multiple CPE producing the same (CPE-SC) (15.4%) or a different carbapenemase (CPE-DC) (4.3%). OXA-48 (83.3%) was the most frequent carbapenemase, followed by VIM-1 (26.7%), NDM-1 (10%) and KPC-3 (3.3%). CPE-DC-patients had longer admissions [63 days (20-107)] than the other patients. Moreover, hospital stay until CPE detection was lower [9 days (5-14)] ( = 0.0052) in CPE-SC-patients than in those with a single colonization; 56% showed co-colonization in the first positive sample, although most of them had previous admissions and had received multiple antibiotic treatments. CPE were more frequently recovered in clinical samples from co-colonized [CPE-DC (28.6%), CPE-SC (24%)] patients than from patients with a single CPE (15.2%). Among CPE-SC-OXA-48 [80% ( = 0.11)], [88% ( = 0.006)] and [84% ( < 0.001)] were the most frequent species. In 60% of patients, and species were simultaneously recovered, frequently after a single OXA-48- colonization. High-risk clones (ST11, ST15, ST307) were detected in OXA-48- but a higher clonal diversity was found among . A frequent cross-species plasmid transmission was shown, due to a dominant plasmid (IncL-pOXA-48), but also involving related or unrelated -, - and -encoding plasmids.

Interpretation: CPE co-colonization status should be monitored during epidemiological surveillance cultures, as these patients might be at a higher risk for infection.

Funding: European Commission Framework Programme 7 and Instituto de Salud Carlos III, Spain.