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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 13 - 2023 | doi: 10.3389/fcimb.2023.1023948

Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections or Lower respiratory tract Infections Caused by extensively drug-resistance or pan drug-resistance (XDR/PDR) Pseudomonas aeruginosa

Yixin Kang1, 2,  Lu Xie3, Jiyong Yang4 and  Junchang Cui5*
  • 1Department of Respiratory Diseases, The first Medical Center, Chinese People’s Liberation Army General Hospital, China
  • 2Medical School of Chinese People's Liberation Army (PLA), 100853, China
  • 3Research Center for Micro-Ecological Agent Engineering and Technology of Guangdong Province, China
  • 4Department of Laboratory, The first Medical Center, Chinese People’s Liberation Army General Hospital, China
  • 5College of Pulmonary & Critical Care Medicine, 8th Medical Center, Chinese People's Liberation Army General Hospital, 100193, China

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Abstract
Objective: To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - causing extensively drug-resistance or pan drug-resistance (XDR/PDR) Pseudomonas aeruginosa.
Method: The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR P. aeruginosa. Whole-genome sequencing was used to analyze the resistant determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimen via traditional infusion (TI)/optimized two-step-administration therapy (OTAT).
Results: P. aeruginosa isolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/ L. All isolates which produced IND-6 plus other serine β-lactamases exhibited high-level resistance to CZA/AZA (MICs ≥64 mg/L). All simulated dosing regimens of CZA /AZA against BSIs-causing XDR/PDR P. aeruginosa achieved a PTA of 100% when the MIC was ≤32 mg/L.
Conclusion: AZA was considered as an option for the treatment of infections caused by XDR/PDR P. aeruginosa producing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposures may be an optimal treatment option for XDR/PDR P. aeruginosa with a high-level MIC of CZA/AZA.

Keywords: Extensively drug resistance, Pseudomonas aeruginosa, Ceftazidime-avibactam, Aztreonam-avibactam, Whole-genome sequencing

Received: 20 Aug 2022; Accepted: 15 Mar 2023.

Copyright: © 2023 Kang, Xie, Yang and Cui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Junchang Cui, College of Pulmonary & Critical Care Medicine, 8th Medical Center, Chinese People's Liberation Army General Hospital, 100193, Beijing, China