Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant and Isolates from Henan Province, China: A Multicenter Study.

PURPOSE

To evaluate polymyxin-resistant and prevalence and characteristics in the Henan province, China.

MATERIALS AND METHODS

A total of 2301 bacterial isolates collected at six hospitals were assessed. Their response to polymyxin was evaluated by minimum inhibitory concentration (MIC) analysis, and the mobilized colistin resistance (mcr) and carbapenemase gene were explored. Mutations on , and in polymyxin-resistant were detected by PCR. , and transcriptional levels were quantified by RT-qPCR. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were performed to determine the phylogenetic relationship between the polymyxin-resistant isolates.

RESULTS

Of the and isolates identified, 0.3% and 1.4% were polymyxin-resistant, respectively, with MICs of 4-64 μg/mL. All polymyxin-resistant isolates were susceptible to tigecycline. Four isolates were -positive and one was carbapenem-resistant, carrying and . One isolate was -positive and nine were carbapenem-resistant (PRCRKP), carrying but not . The five isolates belonged to four sequence types (ST2, ST132, ST632, and ST983). All PRCRKP isolates belonged to ST11. However, all 16 isolates belonged to different PFGE types with <95% genetic similarity. Insertion sequences in were detected in nine (81.8%) polymyxin-resistant samples. Colistin resistance was linked with operon upregulation, with , and being overexpressed in all but one of the polymyxin-resistant samples. Furthermore, 33.3% of patients carrying polymyxin-resistant isolates had previously used polymyxin, and 66.7% patients displayed good clinical outcomes.

CONCLUSION

The polymyxin resistance rate was slightly higher than that of and was more common in than in . Moreover, the insertion of ISkpn14 into may be the main contributor to polymyxin-resistance in in Henan.