1686. Antimicrobial Activity of Aztreonam-avibactam, Ceftazidime-Avibactam, and Comparator Agents against Pseudomonas aeruginosa from Cystic Fibrosis Patients

Abstract

Background. Aztreonam-avibactam (ATM-AVI) is under clinical development for the treatment of serious infections caused by Gram-negative bacteria, including MBL producers. Four other β-lactamase inhibitor combinations (BL/BLI) have been recently approved by the US FDA: ceftazidime-avibactam (CAZ-AVI), ceftolozane-tazobactam (C-T), meropenem-vaborbactam (MEM-VAB), and imipenem-relebactam (IMI-REL). We evaluated the in vitro activity of these 5 BL/ BLIs and comparators against P. aeruginosa (PSA) causing cystic fibrosis (CF) pulmonary exacerbation. Methods. 383 PSA isolates (1/patient) were recovered from 35 medical centers in the US (n=187) and 12 European countries (EU; n=196) in 2018-2021 and susceptibility tested by CLSI broth microdilution method. Results. ATM-AVI inhibited 83.4%/85.2% of isolates from US/EU at ≤8 mg/L. CAZ-AVI (MIC50/90, 2/8 mg/L; 96.3%/95.4% susceptible [S] in US/EU) was the most active agent, followed by IMI-REL (94.7%/92.5%S in US/EU) and C-T (89.8%/91.3%S in US/EU). MEM-VAB (not approved for PSA in the US) and MEM showed similar activity. Tobramycin (TOB)-S rates were 73.3%/85.7% in US/ EU (Table 1). Among TOB-non-S (NS) isolates, 84.6% were CAZ-AVI-S and 73.1% were inhibited at ATM-AVI MIC of ≤8 mg/L. CAZ-AVI retained good activity against C-T-NS (61.1%S), IMI-REL-NS (62.1%S), piperacillin-tazobactam (PIP-TAZ)-NS (86.7%S), meropenem (MEM)-NS (86.6%S), and ciprofloxacin (CIP)-NS (92.1%S) isolates (Table 2). Multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes were observed among 40.1%/30.1% and 24.6%/ 16.8% of isolates from US/EU, respectively. Among MDR isolates, 90.7%/84.7% were CAZ-AVI-S, 65.3%/66.1% were inhibited at ≤8 mg/L of ATM-AVI, and 78.7%/76.3% were TOB-S in US/EU. CAZ-AVI and TOB retained activity against 87.0%/75.8% and 39.1%/63.6% of XDR isolates in US/EU, respectively. Conclusion. ATM-AVI and CAZ-AVI exhibited potent activity against PSA isolated from CF patients in US and EU and retained good activity against isolates resistant to other antimicrobials, including MDR and XDR organisms; both compounds showed greater activity than TOB. ATM-AVI and CAZ-AVI may represent a valuable option to treat CF patients with pulmonary exacerbations due to PSA infection.