Predominance and clonal spread of CTX-M-15 in cefotaxime-resistant Klebsiella pneumoniae in Korea and their association with plasmid-mediated quinolone resistance determinants

Introduction: β-lactams and fluoroquinolones are extensively used worldwide in the treatment of infections caused by Enterobacterales. In this study, we investigated the prevalence of extended-spectrum β-lactamases (ESBL), their correlation with plasmid-mediated quinolone resistance determinants (PMQR) and clonal distribution among the cefotaxime-resistant K. pneumoniae isolates. Methods: In Korea, a total of 429 K. pneumoniae collected in 2015 were studied. Antimicrobial susceptibility test for cefotaxime, ciprofloxacin and levofloxacin was performed by broth microdilution method. By PCR and/or sequencing, mutations in gyrA and parC genes, PMQR genes and ESBL were identified. Multilocus-sequence-type (MLST) was determined for isolates harboring CTX-M-15. Results: Among the 149 K. pneumoniae showing cefotaxime MICs of >1 μg/ml, 142 (95.3%) isolates were ESBL-producers and CTX-M-15 was predominant (99 isolates). Among the 142 ESBL-producers, mutations in gyrA and parC were found in 112 (78.9%) and 93 isolates (65.5%), respectively. PMQR genes were detected in 141 isolates and the non-susceptibility rate to ciprofloxacin and levofloxacin was 95.1% (135/142) and 82.4% (117/142), respectively. The most frequently found PMQR combination was qnrB-aac(6′)-Ib-cr-oqxAB, (58/142, 40.8%). By MLST, four major STs/CC: ST48, ST392, ST307 and CC15 accounted for 67% of the CTX-M-15 producers and the prevalence of qnrB was significantly higher in these four major STs/CC than other groups (P = 0.004). Of note, we found the additive effect of PMQR genes; the more PMQR genes, the higher ciprofloxacin MICs. Conclusions: CTX-M-15 was predominant among the cefotaxime-resistant K. pneumoniae and co-harboring CTX-M-15 and PMQR genes, especially qnrB, seems to contribute the spread of high risk clones.