In vitro activity of cefiderocol and comparator antibiotics against multidrug-resistant non-fermenting Gram-negative bacilli

Yu-Shan Huang; Yu-Chung Chuang; Pao-Yu Chen; Pei-Chun Chou; Jann-Tay Wang

doi:10.1093/jacamr/dlae006

In vitro activity of cefiderocol and comparator antibiotics against multidrug-resistant non-fermenting Gram-negative bacilli

JAC Antimicrob Resist. 2024 Feb 1;6(1):dlae006. doi: 10.1093/jacamr/dlae006. eCollection 2024 Feb.

Authors

Yu-Shan Huang^{1

2}, Yu-Chung Chuang¹, Pao-Yu Chen^{1

2}, Pei-Chun Chou³, Jann-Tay Wang¹

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
² Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
³ Laboratory of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Abstract

Background: This study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli.

Methods: Bacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam.

Results: The MIC_50/90s of ceﬁderocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32 mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4 mg/L, and 97.9% (46/47) of S. maltophilia at ≤1 mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8 mg/L. Aztreonam/avibactam had MIC_50/90s of 16/>32, 8/16 and 4/8 mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8 mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC₅₀s and MIC₉₀s > 32 mg/L.

Conclusion: Cefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.