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Acquisition of a Stable and Transferable bla NDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella pneumoniae During Treatment.
Front Cell Infect Microbiol. 2021; 11:658070.FC

Abstract

The emergence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) have drawn worldwide attention. Ceftazidime/avibactam (CAZ/AVI) gives us a valuable alternative strategy to treat CRE infections. Unfortunately, CAZ/AVI resistance could occur during CAZ/AVI treatment. The CAZ/AVI-resistant Carbapenem-resistant Klebsiella pneumoniae (CR-KP) (KP137060) and earlier CAZ/AVI-susceptible isolate (KP135194) from the same hospitalized patient were collected at Fujian Medical University Union Hospital between October and November 2019. In this study, CAZ/AVI MICs of CAZ/AVI-susceptible and -resistant isolates (KP135194 and KP137060) were 4 mg/L and 128 mg/L, respectively; and the two isolates had the same antibiotic resistance pattern to other carbapenems. Two strains were then submitted for whole-genome sequencing and bioinformatic analysis. ompK36 was not detected in two isolates. No mutation was observed in bla KPC-2, ompK35 and ompK37 in this study and there was no significant difference of the expression in bla KPC-2, ompK35 and ompK37 between the two isolates (p>0.05). Two isolates were sequence type 11 and harbored bla KPC-2, bla SHV-182 and bla TEM-1B. Compared with KP135194, KP137060 harbored an additional bla NDM-5 positive plasmid. bla NDM-5 gene could be successfully transferred into E. coli J53 at a conjugation frequency of 1.14×10-4. Plasmid stability testing showed that bla KPC-2- and bla NDM-5-harboring plasmids were still stably maintained in the hosts. Growth assay and growth competition experiments showed there was no significant difference in fitness cost between two CR-KP isolates. Our study described the acquisition of a bla NDM-5-harboring plasmid leading to resistance to ceftazidime/avibactam in KPC-2-producing Klebsiella pneumoniae during treatment. This phenomenon deserves further exploration.

Authors+Show Affiliations

Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.Department of Laboratory Medicine, Fujian Medical University, Fuzhou, China.Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34354959

Citation

Huang, Jiangqing, et al. "Acquisition of a Stable and Transferable Bla NDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella Pneumoniae During Treatment." Frontiers in Cellular and Infection Microbiology, vol. 11, 2021, p. 658070.
Huang J, Zhang S, Zhao Z, et al. Acquisition of a Stable and Transferable bla NDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella pneumoniae During Treatment. Front Cell Infect Microbiol. 2021;11:658070.
Huang, J., Zhang, S., Zhao, Z., Chen, M., Cao, Y., & Li, B. (2021). Acquisition of a Stable and Transferable bla NDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella pneumoniae During Treatment. Frontiers in Cellular and Infection Microbiology, 11, 658070. https://doi.org/10.3389/fcimb.2021.658070
Huang J, et al. Acquisition of a Stable and Transferable Bla NDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella Pneumoniae During Treatment. Front Cell Infect Microbiol. 2021;11:658070. PubMed PMID: 34354959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acquisition of a Stable and Transferable bla NDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella pneumoniae During Treatment. AU - Huang,Jiangqing, AU - Zhang,Shengcen, AU - Zhao,Zhichang, AU - Chen,Min, AU - Cao,Yingping, AU - Li,Bin, Y1 - 2021/07/20/ PY - 2021/01/25/received PY - 2021/06/29/accepted PY - 2021/8/6/entrez PY - 2021/8/7/pubmed PY - 2021/8/18/medline KW - NDM KW - carbapenem-resistant Klebsiella pneumoniae KW - ceftazidime/avibactam KW - fitness cost KW - whole-genome sequencing SP - 658070 EP - 658070 JF - Frontiers in cellular and infection microbiology JO - Front Cell Infect Microbiol VL - 11 N2 - The emergence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) have drawn worldwide attention. Ceftazidime/avibactam (CAZ/AVI) gives us a valuable alternative strategy to treat CRE infections. Unfortunately, CAZ/AVI resistance could occur during CAZ/AVI treatment. The CAZ/AVI-resistant Carbapenem-resistant Klebsiella pneumoniae (CR-KP) (KP137060) and earlier CAZ/AVI-susceptible isolate (KP135194) from the same hospitalized patient were collected at Fujian Medical University Union Hospital between October and November 2019. In this study, CAZ/AVI MICs of CAZ/AVI-susceptible and -resistant isolates (KP135194 and KP137060) were 4 mg/L and 128 mg/L, respectively; and the two isolates had the same antibiotic resistance pattern to other carbapenems. Two strains were then submitted for whole-genome sequencing and bioinformatic analysis. ompK36 was not detected in two isolates. No mutation was observed in bla KPC-2, ompK35 and ompK37 in this study and there was no significant difference of the expression in bla KPC-2, ompK35 and ompK37 between the two isolates (p>0.05). Two isolates were sequence type 11 and harbored bla KPC-2, bla SHV-182 and bla TEM-1B. Compared with KP135194, KP137060 harbored an additional bla NDM-5 positive plasmid. bla NDM-5 gene could be successfully transferred into E. coli J53 at a conjugation frequency of 1.14×10-4. Plasmid stability testing showed that bla KPC-2- and bla NDM-5-harboring plasmids were still stably maintained in the hosts. Growth assay and growth competition experiments showed there was no significant difference in fitness cost between two CR-KP isolates. Our study described the acquisition of a bla NDM-5-harboring plasmid leading to resistance to ceftazidime/avibactam in KPC-2-producing Klebsiella pneumoniae during treatment. This phenomenon deserves further exploration. SN - 2235-2988 UR - https://www.unboundmedicine.com/medline/citation/34354959/Acquisition_of_a_Stable_and_Transferable_bla_NDM_5_Positive_Plasmid_With_Low_Fitness_Cost_Leading_to_Ceftazidime/Avibactam_Resistance_in_KPC_2_Producing_Klebsiella_pneumoniae_During_Treatment_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34354959/ DB - PRIME DP - Unbound Medicine ER -