Molecular epidemiology of carbapenem resistant klebsiella pneumoniae in bloodstream infections

Carbapenem resistant Klebsiella pneumoniae (CRKP) has become a clinically important pathogen causing worldwide nosocomial infections that are associated with high rates of mortality. High risk clones of CRKP carrying KPC, NDM and OXA-48-like carbapenemases have spread worldwide. Resistance to carbapenem has limited the effective and safe treatment options, thus causing increased patient fatality. In this study, our aim was to describe molecular epidemiology of CRKP bacteremia in Turkey and to evaluate the effect of carbapenemase producing high risk clones on mortality. A total of 254 CRKP bacteremia isolates from 13 tertiary care centers in Turkey were collected between June 2018 and June 2019. The 30-day mortality of the patients was recorded. Meropenem, colistin, and ceftazidime/avibactam minimum inhibitory concentrations were determined by meropenem Etest and broth microdilution methods. Carbapenemase genes (blaOXA-48-like, blaKPC-2, blaNDM-1) were detected by multiplex PCR. For genotyping of the isolates pulsed field gel electrophoresis and multilocus sequence typing were performed. All analyses were performed using STATA software version 16.0. The ST2096 constituted the largest clonal type with 62 isolates (30%) followed by ST101 with 36 isolates (18%) and ST14 with 27 isolates (13%) in the CRKP group. Fifty-one of 254 isolates were detected as meropenem susceptible and classified as carbapenem susceptible Klebsiella pneumoniae. The OXA-48-like carbapenemases comprised the largest carbapenemase group with 171 isolates (91%), NDM-1 was detected in 40 isolates (21%). OXA-48-like carbapenemases were mainly carried on ST2096 in 61 isolates and on ST101 in 35 isolates. The number of OXA-48-like and NDM-1 co-producer was 30 (16%) and 19 of them (63%) belonged to the ST14 clone. Overall colistin susceptibility was found as 38%. The ST101 and ST2096 clonal types had high colistin resistance rates with 83% and 81%, respectively. Overall ceftazidime-avibactam was the most active antibiotic with 84% susceptibility rate but the isolates belonging to ST14 had the lowest susceptibility rate (22%). The 30-day all-cause mortality was 40% for all patients. Mortality rates in infections with the ST2096, ST14 and ST101 clonal groups were 50%, 53%, and 41%, respectively. ST2096 (P=0.02) and ST14 (P=0.002) clonal types were found to be associated with high mortality. In conclusion, the emerging CRKP ST2096 clone possessing OXA-48-like is now the predominating clonal type in Turkish hospitals. Epidemiology of carbapenemases is shifting towards MBL and non-MBL co-producers. High colistin resistance and mortality rates in clones of CRKP ST14 and ST2096 indicates successful adaptation and severe disease production capacity of these clones. High ceftazidime/avibactam resistance in MBL producer ST14 clone demonstrates an urgent need for new antibiotics that are active not only against OXA-48-like producers but also against MBL producers.