In vitro evaluation of the novel antibiotic zosurabalpin against carbapenem-resistant Acinetobacter baumannii...

To evaluate the in vitro activity of zosurabalpin (ZAB), a novel tethered macrocyclic peptide antibiotic, developed by Roche, against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates.

A total of 100 clinical CRAB isolates were obtained from respiratory samples and blood cultures of patients who were hospitalized at the University Hospital Policlinico Umberto I in Rome. Carbapenem resistance was confirmed by meropenem susceptibility testing with the MicroScan WalkAway system (Beckman Coulter). These isolates were tested for their susceptibility to ZAB and cefiderocol (FDC). ZAB MICs were determined by broth microdilution according to Clinical and Laboratory Standards Institute guidelines, using homemade cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with 20% heat-inactivated horse serum. Instead, antimicrobial susceptibility to FDC was tested using the microdilution method with homemade iron-depleted CAMHB. The concentrations of both antibiotics ranged from 32 mg/L to ≤0.015 mg/L. Clinical break points for FDC and meropenem were defined according to the European Committee on Antimicrobial Susceptibility Testing 2025 guidelines.

ZAB demonstrated potent in vitro activity against all clinical CRAB isolates, with an MIC₉₀ value of 0.25 mg/L and MIC values ranging from ≤0.015 to 0.5 mg/L. Eleven of the 100 clinical isolates showed resistance to FDC, with MIC values between 4 and >32 mg/L. Interestingly, these strains were susceptible to ZAB, with MIC values between 0.06 and 0.5 mg/L.

These findings indicate that ZAB exhibits strong in vitro activity against CRAB, including strains resistant to last-line commercially available antibiotics such as FDC.