Risk factors and outcome associated with the acquisition of colistin-resistant Klebsiella pneumoniae: A matched case-control-control study

INTRODUCTION: Carbapenem resistance in Klebsiella pneumoniae (Kp) has led to increased use of colistin-based therapy in the intensive care units (ICUs). Lately however, colistin resistance among K. pneumoniae has been widely reported. This study aims to investigate the prevalence, and the potential risk factors associated with colistin resistant K. pneumoniae (ColRKp) in the intensive care unit (ICU). MATERIALS AND METHODS: All ICU patients, above 18 years of age, with a culture positive blood stream infection were included. A case-control-control design was used. Patients with colistin resistant K. pneumoniae (ColRKp) blood stream infections (BSI) were defined as cases. These were compared to two control populations, Control Group A had Kp infections moderately sensitive to colistin (ColMSKp); and control group B who had other bacterial infections. 50 ColRKp isolates were subjected to whole genome sequencing (WGS). RESULTS: Lungs as the source of infection (13.9 % vs 6.4 %, p ≤ 0.05) and longer hospital stay (26 days vs 22 days, p ≤ 0.05) were the significant risk factors which correlated with acquisition of colistin resistance in Klebsiella pneumoniae. An increased 28-day mortality was noticed in control groups who were given colistin based upon their in vitro sensitivity, (group A, 79 % and group B, 75.8 %) compared to cases (56.9 %). From among the ColRKp isolates subjected to WGS, 72 % (n = 36) carried NDM with OXA-48 like (OXA-181/232) carbapenemases. Mutations were found in pmrA, in pmrB, pmrC and pmrABC gene. None of the isolates had insertion in mgrB gene, all isolates were negative for mcr gene variants. CONCLUSIONS: Both NDM and OXA-48 like carbapenemases were present in ColRKp. Patients receiving colistin therapy based on their in vitro sensitivity had increased risk for developing resistance to colistin and 28-day mortality.