In vitro activity of cefiderocol against carbapenem-resistant Acinetobacter baumannii carrying various β-lactamase encoding genes

Abstract

Abstract Objectives This study aimed to determine the in vitro efficacy of cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates and evaluate the disk-diffusion (DD) method as an alternative method to broth-microdilution (BMD). Methods Totally 89 CRAB isolates were included. Cluster analysis was determined by Pulsed-Field Gel Electrophoresis (PFGE). Resistance genes; blaOXA−51, blaOXA−23, blaOXA−24, blaOXA−58,blaPER−1, blaNDM, blaIMP and mcr-1 were screened. Cefiderocol susceptibility testing was performed by both DD and BMD. Interpretation was made according to EUCAST and CLSI. Categorical agreement (CA), minor errors (mEs), major errors (MEs), and very major errors (VMEs) were determined. Results PFGE revealed 5 distinct pulsotypes; 86 of the isolates were extensively drug-resistant (XDR). All the isolates were negative for blaNDM, blaIMP, mcr-1, while positive for blaOXA−58 and blaOXA51. blaPER−1 was positive for 33.7%; blaOXA−23 for 74.2%; blaOXA−24 for 12.3%. According to CLSI, the MEs rate was 1.85%, mEs was 7.86% and there were no VMEs. According to EUCAST, MEs rate was 3.70%, there were no mEs and VMEs. CA was 91% for CLSI and 97.8% for EUCAST. MICs of cefiderocol against A. baumannii isolates ranged from 0.06 to > 128 mg/L, with MIC50 and MIC90 values of 0.5 and > 128 mg/L, respectively. Conclusions Cefiderocol susceptibility was 60.7% in CRAB isolates. MIC50, MIC90 of blaPER−1 positive and blaPER−1 negative groups were > 128/>128 and 0.25/>128 mg/L. A correlation between the presence of blaPER−1 and cefiderocol resistance was observed (p < 0.0001). Among colistin-resistant isolates, the presence of blaPER−1 was 47.1% and 75% of them were resistant to cefiderocol respectively.