Influence of ESBL PER-7 on cefiderocol susceptibility in OXA-23 or OXA-72 carbapenemase producing A. baumannii.

Question

In 2022, an OXA-23 or OXA-72 carbapenemase was detected in approximately 90 % of the A. baumannii isolates sent to the NRC for Multidrug-resistant Gram-negative bacteria. About 3 % of the isolates carried bla_NDM-1. While the majority of A. baumannii producing OXA-23 or OXA-72 show an inhibition zone diameter of ≥ 17 mm for cefiderocol, this is often significantly smaller for A. baumannii producing metallo-β-lactamases. But nevertheless, some OXA-23/OXA-72 producing isolates show an inhibition zone diameter of < 17 mm. In four out of five of these isolates, whole genome sequencing revealed the additional presence of the extended spectrum β-lactamase (ESBL) PER-7. The focus of this study is to identify the influence of PER-7 on cefiderocol susceptibility in OXA-23 or OXA-72 carbapenemase producing A. baumannii.

Methods

42 OXA-23 or OXA-72 carbapenemase producing A. baumannii isolates with cefiderocol inhibition zone diameters < 17 mm were selected from the NRC strain collection and screened for the presence of PER-7 by PCR and sequencing. To test whether the increased resistance to cefiderocol was due to the presence of PER-7, the per-7 gene was inserted into an expression plasmid. This was transformed into OXA-23 or OXA-72 producing A. baumannii with cefiderocol inhibition zone diameters ≥ 17 mm to allow heterologous expression. The clinical isolates and transformed complementants were screened for altered cefiderocol susceptibility using phenotypic tests such as microdilution and agar diffusion assays.

Results

PCR and sequencing results showed that 25 out of 42 A. baumannii isolates with cefiderocol inhibition zone diameters < 17 mm carried the per-7 gene. In addition, the heterologous expression of the per-7 gene in OXA-23 or OXA-72 producing, cefiderocol susceptible A. baumannii increased cefiderocol resistance.

Conclusion

The majority of clinical A. baumannii isolates with bla_OXA-23 or bla_OXA-72 and a cefiderocol inhibition zone < 17 mm produced a PER-7 ESBL. Heterologous expression of per-7 in OXA-23 or OXA-72 producing A. baumannii isolates led to a significantly lower susceptibility to cefiderocol than in the absence of this ESBL.