Work

Additive effects of ceftiofur-neomycin combination against multidrug-resistant pathogenic Escherichia coli in a murine infection model

Year: 2026

Type: article

Abstract: This study aimed toevaluate the therapeutic efficacy ofaceftiofur-neomycin combination against apathogenic multidrug-resistant Escherichia coli strain, KECS-0513, isolated from pigs, using acombination ofgenomic, invitro, and invivo approaches. The minimum inhibitory concentration, minimum bactericidal concentration, and checkerboard assays were performed. Time–kill assays were used toassess bactericidal activity over time, and amurine intraperitoneal infection model was used toevaluate survival outcomes following treatment with monotherapies orcombination regimens. Whole genome sequencing indicated that KECS-0513 harboured multiple resistance genes, including blaTEM-1B, sul3, aadA12, aad(3)-IVa, aph(3’)-Ia, and aph(4)-Ia. The resistance genes were localised within amobile, element-rich plasmid. Invitro checkerboard assays revealed anadditive interaction between ceftiofur and neomycin (fractional inhibitory concentration index= 1.0), and time–kill experiments demonstrated enhanced andsustained bacterial clearance with combination therapy. Invivo infection studies inmice demonstrated that the dual treatment resulted inasubstantially higher survival rate (66.7%) compared totreatment with either agent alone (33.3% for each). These results support the practical application ofceftiofur-neomycin combination therapy for controlling swine-associated multidrug-resistant E.coli while minimising the risk of resistance emergence.

Source: Veterinární Medicína

DOI: 10.17221/38/2025-vetmed