Risk factors and mechanisms of in vivo emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae.

Abstract Colistin is one of the last-resort antibiotics for treating carbapenem-resistant Klebsiella pneumoniae (CRKP). However, colistin resistance in CRKP poses a global antimicrobial crisis as therapeutic options are limited. We investigated risk factors for in vivo emergence of colistin resistance in CRKP and explored the underlying resistance mechanisms. We conducted this matched case-control study of patients with sequential CRKP clinical strains at a medical center in Taiwan between October 2016 and June 2019. The case group included patients with an index colistin-resistant CRKP (ColR-CRKP) strain and a previous colistin-susceptible CRKP (ColS-CRKP) counterpart. The control group encompassed patients with both an index and previous ColS-CRKP strain. Cases and controls were matched according to the time at risk, and conditional logistic regression was used to evaluate potential risk factors. Alterations in genes associated with resistance were compared between ColR-CRKP and ColS-CRKP strains. We identified 24 CRKP cases with in vivo emergent colistin resistance, matched in a 1:2 ratio with the controls. Multivariate analysis showed that colistin exposure is the only independent risk factor predisposing to colistin resistance (odds ratio, 19.09; 95% confidence interval, 1.26 to 290.45; P = 0.034). Alteration in mgrB was the predominant mechanism for emergent colistin resistance (17/24, 71%). In conclusion, colistin use is the risk factor for in vivo emergence of colistin resistance in CRKP. Given the lack of a rapid and reliable method to detect colistin resistance in daily practice, physicians should be vigilant for the emergence of resistance during colistin treatment.