Purpose: The aim of this study was to understand the resistance mechanism of ceftazidime/avibactam (CZA) in carbapenem-resistant under antibiotic selection pressure.

Patients And Methods: Four CZA-resistant strains were isolated from two patients, and six CZA-resistant strains that were produced in vitro were screened from 25 carbapenem-resistant strains. The mechanisms of resistance to CZA of these strains were characterized by PCR and Sanger sequencing.

Results: CZA-resistant with different resistance mechanisms (including upregulation of the expression of efflux pumps and KPC variants (KPC-14, KPC-44)) were isolated from the same patient (patient 1). In patient 2, the resistance mechanism of CZA-resistant was the mutation of KPC-2 to KPC-33. In addition, among the CZA-resistant that were produced in vitro, we found 3 new KPC variants: KPC-86 (D179G), KPC-87 (GT241A) and KPC-88 (G523T).

Conclusion: In this study, although the CZA-resistant bacteria originated from only two clinical patients, four different mechanisms of CZA resistance were detected. In the in vitro induction experiment, the mechanisms of resistance to CZA in strains from different patients were also different. The above result implies that the mechanisms of resistance to CZA are generally random and diverse. Therefore, elucidating the mechanism of resistance to CZA can provide a certain theoretical basis for the effective response of CZA-resistant strains and the selection of antibiotics.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394654PMC
http://dx.doi.org/10.2147/IDR.S371285DOI Listing

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