Dynamic evolution of ceftazidime-avibactam resistance due to interchanges between blaKPC-2 and blaKPC-145 during treatment of Klebsiella pneumoniae infection.
Front Cell Infect Microbiol
; 13: 1244511, 2023.
Article
in En
| MEDLINE
| ID: mdl-37671146
ABSTRACT
Background:
The emergence of ceftazidime-avibactam (CZA) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is of major concern due to limited therapeutic options.Methods:
In this study, 10 CRKP strains were isolated from different samples of a patient with CRKP infection receiving CZA treatment. Whole-genome sequencing (WGS) and conjugation experiments were performed to determine the transferability of the carbapenem resistance gene.Results:
This infection began with a KPC-2-producing K. pneumoniae (CZA MIC = 2 µg/mL, imipenem MIC ≥ 16 µg/mL). After 20 days of CZA treatment, the strains switched to the amino acid substitution of T263A caused by a novel KPC-producing gene, blaKPC-145, which restored carbapenem susceptibility but showed CZA resistance (CZA MIC ≥ 256 µg/mL, imipenem MIC = 1 µg/mL). The blaKPC-145 gene was located on a 148,185-bp untransformable IncFII-type plasmid. The subsequent use of carbapenem against KPC-145-producing K. pneumoniae infection led to a reversion of KPC-2 production (CZA MIC = 2 µg/mL, imipenem MIC ≥ 16 µg/mL). WGS analysis showed that all isolates belonged to ST11-KL47, and the number of SNPs was 14. This implied that these blaKPC-positive K. pneumoniae isolates might originate from a single clone and have been colonized for a long time during the 120-day treatment period.Conclusion:
This is the first report of CZA resistance caused by blaKPC-145, which emerged during the treatment with CZA against blaKPC-2-positive K. pneumoniae-associated infection in China. These findings indicated that routine testing for antibiotic susceptibility and carbapenemase genotype is essential during CZA treatment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Klebsiella Infections
/
Drug Resistance, Bacterial
/
Carbapenem-Resistant Enterobacteriaceae
/
Klebsiella pneumoniae
Limits:
Humans
Language:
En
Journal:
Front Cell Infect Microbiol
Year:
2023
Document type:
Article
Affiliation country:
China