P-1221. In Vitro Activity of Cefiderocol Against Clinical Strains Collected from China in 2023

TL;DR

This study evaluates the effectiveness of cefiderocol, a new antibiotic, against a wide range of drug-resistant bacteria collected from China in 2023.

Contribution

The study provides new data on cefiderocol's in vitro activity against meropenem-resistant Gram-negative bacteria in a large, diverse clinical sample from China.

Findings

Cefiderocol showed high susceptibility rates (93.5% to 100%) against most Gram-negative bacteria, including meropenem-resistant strains.

Cefiderocol outperformed carbapenems and β-lactam/β-lactamase inhibitor combinations against many tested bacteria.

Against meropenem-resistant E. coli and K. pneumoniae, cefiderocol had MIC90 values of 8 mg/L and 4 mg/L, with 86.4% and 91.0% susceptibility, respectively.

Abstract

Cefiderocol, a siderophore cephalosporin, combats Gram-negative pathogens by hijacking iron transport to accumulate in the periplasm and inhibit PBP3-mediated cell wall synthesis. Here we evaluated the in vitro activity of cefiderocol against Gram-negative bacilli isolated from clinical settings in China in 2023, with a focus on meropenem-resistant isolates.

A total of 2,049 clinical strains, were collected from 63 hospitals across China, including Enterobacterales (n=993), Pseudomonas aeruginosa (n=377), Acinetobacter baumannii (n=368), Stenotrophomonas maltophilia (n=188), and Burkholderia cepacia (n=123). Antimicrobial susceptibility testing was performed using the broth microdilution according to CLSI M100 (2024) standards, with iron-depleted cation-adjusted Mueller-Hinton broth for cefiderocol. Minimum inhibitory concentrations (MICs) were interpreted according to CLSI breakpoints.

About 50.8% (1040/2049), 15.8% (323/2049) and 9.3% (190/2049) of the isolates were obtained from respiratory tract, urinary tract and blood, respectively. The MIC50 values of cefiderocol against Enterobacterales ranged from ≤ 0.03 mg/L to 0.25 mg/L, MIC90 values ranged from 0.25 mg/L to 4 mg/L, and susceptibilities ranged from 93.5% to 100% (Table 1; data shown for Enterobacterales, E. coli and K. pneumoniae). For meropenem-resistant E. coli and K. pneumoniae, the MIC50 values were both 2 mg/L, and MIC90 values were 8 mg/L and 4 mg/L, with susceptibilities of 86.4% and 91.0%, respectively. Susceptibility for P. aeruginosa, A. baumannii, including meropenem-resistant isolates, and S. maltophilia ranged from 98.4% to 99.7% (Table 1). For B. cepacia, MIC50 and MIC90 values were 0.06 mg/L and 0.25 mg/L, respectively. Cefiderocol showed similar antibacterial activity with polymyxin E and tigecycline against most bacteria, outperforming carbapenems and β-lactam/β-lactamase inhibitor combinations. In particular against meropenem-resistant strains, cefiderocol was one of the most active agents, except for tigecyline or polymyxin E.

Cefiderocol exhibits significant potential as a critical therapeutic option for Gram-negative bacterial infections in China.

Xin Zhao, n/a, Shionogi China Co., Ltd.: Grant/Research Support

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