Optimal treatment of ceftazidime-avibactam and aztreonam-avibactam against bloodstream infections or lower respiratory tract infections caused by extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa

• Published in: Frontiers in cellular and infection microbiology Vol. 13; p. 1023948
• Main Authors: Kang, Yixin, Xie, Lu, Yang, Jiyong, Cui, Junchang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.06.2023
• Subjects: 173 aztreonam-avibactam; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Aztreonam - pharmacology; beta-Lactamases; ceftazidime-avibactam; Cellular and Infection Microbiology; Drug Combinations; extensively drug-resistant Pseudomonas aeruginosa; Humans; Microbial Sensitivity Tests; pan drug-resistant Pseudomonas aeruginosa; Pharmaceutical Preparations; Pseudomonas aeruginosa; Pseudomonas Infections - drug therapy; Respiratory Tract Infections - drug therapy; Sepsis - drug therapy; whole-genome sequencing; extensively drug-resistant Pseudomonas aeruginosa; ceftazidime-avibactam; pan drug-resistant Pseudomonas aeruginosa; whole-genome sequencing; 173 aztreonam-avibactam
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2023.1023948

To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - caused by extensive drug-resistant or pan drug-resistant (XDR/PDR) The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR . Whole-genome sequencing was used to analyze the resistance 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 traditional infusion (TI)/optimized two-step-administration therapy (OTAT). We found that XDR/PDR P. aeruginosa may carry some rare MBLs (e.g.: IND-6, SLB-1, THIN-B). isolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/L. All isolates producing IND-6 plus other serine β-lactamases were high-level resistant to CZA/AZA (MICs >64 mg/L). All simulated dosing regimens of CZA/AZA against BSIs-causing XDR/PDR achieved 100% PTA when the MIC was ≤32 mg/L. AZA has been considered as an option for the treatment of infections caused by XDR/PDR producing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposure may be an optimal treatment option for XDR/PDR with a high-level MIC of CZA/AZA.