Susceptibility of cefiderocol and other antibiotics against carbapenem-resistant, Gram-negative bacteria

BACKGROUND: Cefiderocol is a promising antimicrobial agent against carbapenem-resistant, Gram-negative bacteria, but susceptibility data from the Chinese mainland are lacking. The aim of the present study was to test the susceptibility of cefiderocol against carbapenem-resistant, Gram-negative bacteria collected from Beijing, China. METHODS: Carbapenem-resistant Klebsiella pneumoniae (CR-KP; n=105), carbapenem-resistant Acinetobacter baumannii (CR-AB; n=126), carbapenem-resistant Pseudomonas aeruginosa (CR-PA; n=74), and Stenotrophomonas maltophilia (SM; n=72) isolates were collected from inpatients at 4 tertiary hospitals in Beijing, China. Minimum inhibitory concentrations (MICs) for cefiderocol were determined using iron-depleted cation-adjusted Mueller Hinton broth (CAMHB), and for comparators using CAMHB, according to the recommended Clinical and Laboratory Standards Institute (CLSI) methodology. Carbapenemase and other β-lactamase gene profiles were determined using polymerase chain reaction (PCR). RESULTS: Cefiderocol inhibited 100% of CR-KP and CR-PA, and 98.6% of the SM isolates at the susceptibility breakpoint concentration of 4 mg/L. However, the susceptibility rate for cefiderocol against CR-AB was only 62.7%, with MIC(90) values as high as 128 mg/L. Nearly all the cefiderocol-susceptible CR-AB isolates were found to be positive for bla(OXA-23) and bla(TEM), whereas all the cefiderocol-resistant CR-AB isolates were found to be positive for the bla(PER) genes, in addition to bla(OXA-23) and bla(TEM). CONCLUSIONS: Cefiderocol showed potent in vitro activity against CR-KP, CR-PA, and SM isolates collected from Beijing, China. However, the resistance rate for cefiderocol against CR-AB was higher than that reported by other research centers, and the presence of bla(PER) might contribute to resistance in non-susceptible CR-AB isolates.