Carbapenemases producing Klebsiella pneumoniae: a survey and a longitudinal study of the acquisition and the evolution of colonized and infected patients admitted to an Italian teaching hospital from January 1, 2016 to June 30, 2019

BACKGROUND: The worldwide dissemination of carbapenemases-producing Enterobacteriaceae (CPE) is a major threat to healthcare settings, because of their high associated mortality rate and of the few effective treatment options available. In the era of antibiotic resistance, Klebsiella pneumoniae (KP) represents one of the most concerning pathogen involved with high resistant rates to a broader range of antimicrobials. In Italy 30% of KP is carbapenem resistant compared to 7% of the European countries. The increasing frequency of colistin resistant strains detection represents a further challenge for the clinicians. AIM: The aim of the study was to retrospectively analyze the spread of carbapenemases producing Klebsiella pneumoniae (CPKP) in patients (pts) admitted to a highly accessed tertiary level hospital; subsequently a longitudinal analysis of positive pts was performed to evaluate the possible evolution from colonization to infection. Finally, we focused on the switch of colistin-sensitive strains (CoS) to colistin-resistant strains (CoR). PATIENTS AND METHODS: we enrolled 721 pts selected for the detection of a CPKP strain collected in the clinical samples (CS) and in the surveillance rectal swabs (SRS) during an hospital stay from January 1, 2016 to June 30, 2019 in three different clinical settings: medical department (MD), surgical department (SD) and intensive care unit (ICU), with three different surveillance strategies applied. Only the first isolated strain from each patient was included. After incubation on a selective chromogenic screening medium for the detection of CPE (BD BBLTM CHROMagarTM CPE), microbial identification was performed by using MALDI-TOF and carbapenemases were detected using a validated in-house PCR method. RESULTS: A total of 721 consecutive non-replicated strains of CPKP were collected as first isolate: 522 (72.4%) from SRS, 199 (24.6%) from CS. The relative percentage of SRS and CS were comparable during the study-period and the proportion of CS ranged from 20.5% to 32.2%. The highest number of samples was detected in SD where the relative frequency of SRS increased over time. In MD the first CPKP was most frequently identified in CS than in SRS, reflecting an important focus of transmission of CPKP probably due to a different surveillance strategy. KPC-type carbapenemases was the most commonly detected (89.7%). Regarding to the longitudinal analysis of the colonized pts, 23.9% developed an infection with a median interval of evolution of 8 days; respiratory tract infections were the most frequent, followed by bacteremia (40.1% and 21.6%, respectively). In addition, 37.4% of colonized pts showed no other cultures after the first one while 38.7% maintained GI colonization. Urinary tract was the most common site of infection (36.7%) in patients who presented CKPK first clinical manifestation. A bacteremia developed in 61.1% of patients with CPKP spread in multiple sites. The percentage of CoR strains at first detection (both SRS and CS) raised from 20.8% in 2016 to 30.8% in 2018 (p=0.02) and to 26% in the first six months of 2019. One hundred and seventeen of the 161 resistant strains (72.7%) were identified in SRS, suggesting a potential clinical risk to develop a disease with few treatment options. Thirty-one pts (10.2%) had a colistin resistant strain identified after a previous colistin sensitive detected: the median interval of the switch was 26 days. In 74% of subjects SRS was the site of the first CoS isolation. Of note, the subsequent CoR strain was detected in CS in most cases (87.1%). CONCLUSIONS: The application of infection control measures such as active surveillance remains the best approach for CPKP management and it should be implemented in MD. In a complex and endemic scenario we would sensitize health care workers in order to limit infection spread.