Delafloxacin Resistance and MIC-Distribution in Ciprofloxacin-Resistant Enterobacterales: A Retrospective Evaluation of Minimum Inhibitory Concentrations.

Objectives: The fourth-generation fluoroquinolone delafloxacin (DFX) is propagated as a novel (oral) treatment option for infections with multidrug-resistant Gram-negatives. To date, efficacy data for Enterobacterales is only available for wild-type isolates but not for those with pre-existing resistance against third-generation fluoroquinolones. Methods: One hundred twenty-nine non-duplicate clinical isolates of Enterobacterales that demonstrated ciprofloxacin resistance in VITEK 2 testing were collected and analyzed for CIP and DFX minimum inhibitory concentrations (MICs) via broth microdilution. Results: DFX MICs ranged from 0.5 to ≥ 16 mg L-1 (median: 4 mg L-1). All Escherichia coli isolates (n = 56; 43% of all isolates), the only species with EUCAST breakpoints, were classified as DFX resistant. All other isolates belonging to species for which EUCAST epidemiological cut-offs (ECOFFs) are available (n = 64; 50% of all isolates) demonstrated MICs above the ECOFF. With a minimum and median MIC of 2 and 8 mg L-1, respectively, the remaining isolates (6%) achieved similar results. A moderate correlation between the MIC values of the two fluoroquinolones was found. For the majority of isolates (64%), other oral options for antibiotic therapy, such as amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, were still available. Conclusions: Our data suggests that, compared to CIP, DFX does not demonstrate increased in vitro efficacy against fluoroquinolone-resistant Enterobacterales. Subsequent DFX testing seems to be of limited additional value.