Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains and Antibiotic Susceptibility Testing
2.2. Detection of Colistin-Heteroresistant Isolates
2.3. Genotyping and Sequence Analysis of Genes Associated with Colistin Resistance
2.4. Time–Kill Assays
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Antibiotics | MIC (mg/L) a, b | ||||||||
---|---|---|---|---|---|---|---|---|---|
S1703-35 | S1703-109 | S1703-112 | |||||||
P | RP1 | RP2 | P | RP1 | RP2 | P | RP1 | RP2 | |
Colistin | 1 (S) | 128 (R) | 64 (R) | 0.25 (S) | 64 (R) | 64 (R) | 1 (S) | 256 (R) | 128 (R) |
Polymyxin B | 1 (S) | 64 (R) | 32 (R) | 0.25 (S) | 64 (R) | 32 (R) | 1 (S) | 64 (R) | 64 (R) |
Meropenem | 0.06 (S) | 0.125 (S) | 0.125 (S) | 0.06 (S) | 0.06 (S) | 0.06 (S) | 4 (R) | 4 (R) | 2 (I) |
Imipenem | 1 (S) | 1 (S) | 0.5 (S) | 0.25 (S) | 0.25 (S) | 0.25 (S) | 2 (I) | 1 (S) | 1 (S) |
Cefotaxime | 0.125 (S) | 0.25 (S) | 0.25 (S) | 0.25 (S) | 0.25 (S) | 0.125 (S) | >128 (R) | >128 (R) | >128 (R) |
Ceftazidime | 0.5 (S) | 1 (S) | 1 (S) | 1 (S) | 1 (S) | 1 (S) | >64 (R) | >64 (R) | >64 (R) |
Cefepime | 0.25 (S) | 1 (S) | 1 (S) | 0.125 (S) | 1 (S) | 1 (S) | >64 (R) | >64 (R) | >64 (R) |
Amikacin | 4 (S) | 4 (S) | 4 (S) | 2 (S) | 2 (S) | 2 (S) | 32 (I) | 32 (I) | 32 (I) |
Gentamicin | 1 (S) | 1 (S) | 1 (S) | 0.5 (S) | 0.5 (S) | 0.5 (S) | 2 (S) | 2 (S) | 1 (S) |
Ciprofloxacin | 0.25 (S) | 0.25 (S) | 0.25 (S) | 0.06 (S) | 0.06 (S) | 0.06 (S) | >64 (R) | >64 (R) | >64 (R) |
Aztreonam | 0.125 (S) | 0.125 (S) | 0.125 (S) | 0.125 (S) | 0.125 (S) | 0.125 (S) | >64 (R) | >64 (R) | >64 (R) |
Tigecycline | 2 (S) | 1 (S) | 1 (S) | 2 (S) | 0.5 (S) | 0.5 (S) | 1 (S) | 1 (S) | 1 (S) |
Piperacillin–tazobactam | 16/4 (S) | 8/4 (S) | 8/4 (S) | 8/4 (S) | 8/4 (S) | 8/4 (S) | >256/4 (R) | >256/4 (R) | >256/4 (R) |
Isolatea | Amino Acid Substitutions in: | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PmrA | PmrB | PhoP | PhoQ | ||||||||||||||||
178 | 203 | 43 | 150 | 163 | 185 | 186 | 198 | 199 | 216 | 152 | 154 | 359 | 414 | 421 | 423 | 429 | 430 | ||
S1703-35 | P | Iso | Arg | Glu | Asp | Arg | Arg | Lys | Arg | Lys | Gln | Asp | Lys | Arg | Leu | Asp | Ala | Val | Phe |
RP1 | Lys | Asn | Leu | Glu | His | Asn | Lys | Arg | Pro | Ala | Val | ||||||||
RP2 | Lys | Asn | Glu | Asn | Lys | Pro | Ala | Val | |||||||||||
S1703-109 | P | Ile | Gly | Arg | Asp | Cys | Thr | Gly | Gly | Cys | Gly | Asp | Ser | Lys | Leu | Gly | Pro | Ala | Val |
RP1 | Phe | Glu | |||||||||||||||||
RP2 | Glu | Asn | |||||||||||||||||
S1703-112 | P | Ile | Arg | Pro | Leu | Glu | Arg | Lys | Arg | Asp | Gln | Lys | Leu | Gly | Pro | Ala | Val | ||
RP1 | Lys | Arg | Arg | Gln | Lys | Arg | |||||||||||||
RP2 | Lys | Arg | Arg | Gln | Lys | Arg | Arg |
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Cheong, H.S.; Kim, S.Y.; Wi, Y.M.; Peck, K.R.; Ko, K.S. Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations. J. Clin. Med. 2019, 8, 1444. https://doi.org/10.3390/jcm8091444
Cheong HS, Kim SY, Wi YM, Peck KR, Ko KS. Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations. Journal of Clinical Medicine. 2019; 8(9):1444. https://doi.org/10.3390/jcm8091444
Chicago/Turabian StyleCheong, Hae Suk, So Yeon Kim, Yu Mi Wi, Kyong Ran Peck, and Kwan Soo Ko. 2019. "Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations" Journal of Clinical Medicine 8, no. 9: 1444. https://doi.org/10.3390/jcm8091444