Objectives

To investigate possible mechanistic factors to explain cefiderocol (CFDC) non-susceptibility, we characterized 38 clinical isolates with cefiderocol MIC of >4 μg/mL from a multi-national surveillance study.

Methods

The minimum inhibitory concentration (MIC) measurement in the presence of β-lactamase inhibitors and whole genome sequencing were performed.

Results

The MIC decrease of CFDC by β-lactamase inhibitors were observed against all of the test isolates. Among 38 isolates, NDM or PER genes were observed in 5 and 25 isolates, respectively. No other β-lactamases responsible for high MIC were identified in other 8 isolates. MIC of CDFC against Escherichia coli isogenic strains introduced with NDM and PER β-lactamase increased by ≥16-fold, suggesting the contribution of NDM and PER to the non-susceptibility to CFDC. Against NDM producers, ≥8-fold MIC increase was observed only when both serine- and metallo-type beta-lactamase inhibitors were added. In addition, many of PER- or NDM-producers remained susceptible to CFDC. These results suggested that the presence of only NDM or PER would not lead to non-susceptibility to CFDC and that multiple factors would be related with CFDC resistance.

Conclusions

Multiple factors including NDM and PER could be related to reduced susceptibility to CFDC.

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