In Vitro Activity of Cefiderocol and Comparators against Multi-Drug Resistant Acinetobacter baumannii Isolates ^†

1. Introduction

Acinetobacter baumannii is an aerobic Gram-negative bacterium which causes facultative hospital infections and, in settings such as Greece, exhibits high resistance rates against most antimicrobial agents [1]. Cefiderocol is a siderophore cephalosporin intended to treat infections due to multi-drug resistant (MDR) Gram-negative aerobic bacteria [2]. The aim of our study was to assess the in vitro activity of cefiderocol and comparators against multidrug-resistant Acinetobacter baumannii isolates.

2. Methods

A total of 29 MDR Acinetobacter baumannii strains recovered from clinical samples (23 blood, 2 central line catheters, 2 bronchial aspirates, 1 pus and 1 urine) from January to April 2022 were included in the study. Species identification and antimicrobial susceptibility testing for most comparators were performed with the Vitek^® 2 automated system (bioMérieux, Lyon, France) except for colistin tested by the broth microdilution method using the ComASP™ Colistin 0.25–16 μg/mL panel (Liofilchem^®, Roseto degli Abruzzi, Italy) and tigecyclin tested by Liofilchem^® MIC Test Strips. Cefiderocol MICs were determined via the Liofilchem^® MIC Test Strips on Mueller Hinton II Agar (BD™, Heidelberg, Germany). MIC₅₀ and MIC₉₀ were calculated for all antimicrobials and EUCAST 2022 clinical breakpoints [3] were applied wherever applicable. Susceptibility to tigecyclin was interpreted according to the FDA breakpoints, and to cefiderocol according to the EUCAST PK/PD breakpoints. Pseudomonas aeruginosa ATCC25853 and Klebsiella pneumoniae ATCC700603 were used as quality control.

3. Results

Cefiderocol MICs ranged from 0.064 to >256 mg/L, with the majority of the isolates being susceptible. The comparators had very-low-to-zero susceptibility rates against the tested isolates. MIC₅₀, MIC₉₀, MIC range and susceptibility rates are displayed analytically on

Table 1. Antimicrobial activity of cefiderocol and comparators.

Antimicrobial Agent	MIC50 (mg/L)	MIC90 (mg/L)	MIC Range (mg/L)	Susceptibility (%) EUCAST/FDA
Cefiderocol	2	>256	0.064–>256	69.0
Meropenem	≥16	≥16	≥16–≥16	0.0
Imipenem	≥16	≥16	≥16–≥16	0.0
Colistin	8	>16	0.25–>16	34.5
Tigecyclin	4	≥8	0.5–32	18.5
Ciprofloxacin	≥4	≥4	≥4–≥4	0.0
Levofloxacin	≥8	≥8	4–≥8	3.4
Amikacin	≥64	≥64	16–≥64	0.0
Trimethoprim/sulfamethoxazole	≥320	≥320	≥320–≥320	0.0

.

4. Discussion

Cefiderocol exhibited potent in vitro activity against MDR Acinetobacter baumannii isolates. It seems to be a valuable option where limited or no therapeutic alternatives are available.