| Title | Detection of colistin-resistant populations prior to antibiotic exposure in KPC-2-producing Klebsiella pneumoniae clinical isolates |
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| Author | Jungyu Seo1, Yu Mi Wi2, Jong Min Kim3, Yae-Jean Kim4, and Kwan Soo Ko1 |
| Address | 1Department of Microbiology and Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea, 2Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea, 3Department of Pediatrics, Myongji Hospital, Goyang 10475, Republic of Korea, 4Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea |
| Bibliography | Journal of Microbiology, 59(6),590–597, 2021, |
| DOI | 10.1007/s12275-021-0610-1 |
| Key Words | Klebsiella pneumoniae, colistin, heteroresistance |
| Abstract | Although colistin is frequently regarded as the antibiotic of last resort in treating carbapenem-resistant Klebsiella pneumoniae, colistin heteroresistance may in part be associated with antibiotic treatment failure. However, we do not know how widespread the colistin heteroresistance is in carbapenem- resistant K. pneumoniae isolates. In this study, we performed colistin disc diffusion assays, E-tests, and population analysis profiling for KPC-2-producing K. pneumoniae isolates to identify colistin heteroresistance. Although no colistin- resistant colonies were detected by the disc diffusion test and E-test, a colistin-resistant subpopulation was identified in population analysis profiling in all colistin-susceptible, KPC-2-producing K. pneumoniae isolates. Colistin-resistant subpopulations were also identified even when isolates had no colistin exposure. The ratio of colistin-resistant subpopulations to the total population increased as the exposure concentration of colistin increased. In in vitro time-kill assays, regrowth was observed in all isolates after 2 h upon exposure to colistin. We identified common amino acid alterations in PhoQ, PhoP, and PmrB in colistin-resistant subpopulations from some isolates, but no substitutions were found in most resistant subpopulations from other isolates. In all colistin-resistant subpopulations, overexpression of PhoQ and PbgP was observed. In this study, we demonstrated that colistin heteroresistance may be common in KPC-2-producing K. pneumoniae isolates, which could not be detected in the disc diffusion method and E-test. Colistin heteroresistance may cause colistin treatment failure in part and may evolve into resistance. Thus, development of more reliable diagnostic methods is required to detect colistin heteroresistance. |