AUTHOR=Chen Yili , Yang Runshi , Guo Penghao , Liu Pingjuan , Deng Jiankai , Wu Zhongwen , Wu Qingping , Huang Junqi , Liao Kang 

TITLE=Dynamic evolution of ceftazidime–avibactam resistance due to interchanges between blaKPC-2 and blaKPC-145 during treatment of Klebsiella pneumoniae infection

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1244511

DOI=10.3389/fcimb.2023.1244511

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>The emergence of ceftazidime–avibactam (CZA) resistance among carbapenem-resistant <italic>Klebsiella pneumoniae</italic> (CRKP) is of major concern due to limited therapeutic options.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>This infection began with a KPC-2-producing <italic>K. pneumoniae</italic> (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<italic>-</italic>producing gene, <italic>bla</italic><sub>KPC-145</sub>, which restored carbapenem susceptibility but showed CZA resistance (CZA MIC ≥ 256 μg/mL, imipenem MIC = 1 μg/mL). The <italic>bla</italic><sub>KPC-145</sub> gene was located on a 148,185-bp untransformable IncFII-type plasmid. The subsequent use of carbapenem against KPC-145-producing <italic>K. pneumoniae</italic> 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 <italic>bla</italic><sub>KPC</sub>-positive <italic>K. pneumoniae</italic> isolates might originate from a single clone and have been colonized for a long time during the 120-day treatment period.</p></sec><sec><title>Conclusion</title><p>This is the first report of CZA resistance caused by <italic>bla</italic><sub>KPC-145</sub>, which emerged during the treatment with CZA against <italic>bla</italic><sub>KPC-2</sub>-positive <italic>K. pneumoniae</italic>-associated infection in China. These findings indicated that routine testing for antibiotic susceptibility and carbapenemase genotype is essential during CZA treatment.</p></sec>