Evaluation of phage-antibiotic combinations in the treatment of extended-spectrum β-lactamase-producing enteritidis strain PT1.

Foodborne infections caused by spp. are among the most common foodborne diseases in the world. We isolated a lytic phage against extended-spectrum beta-lactam producing strain PT1 derived from chicken carcass. Results from electronmicrography indicated that phiPT1 belonged to the family, , in the order, . Phage phiPT1 was stable at temperatures from 4 °C to 60 °C and inactivated at 90 °C. phiPT1 retained a high titer from pH 4 to pH 10 for at least 1 h. Nevertheless, it displayed a significant decrease ( < 0.05) in titer at pH 11 and 12, with phage titers of 5.5 and 2.4 log PFU/mL, respectively. The latent time and burst size of phiPT1 were estimated to be 30 min and 252 PFU/infected cell, respectively. The virulence of phage phiPT1 was evaluated against Enteritidis strain PT1 at different MOIs. phiPT1 reduced proliferation relative to the negative control (MOI 0) at all MOIs ( < 0.05). However, there is no significant difference among the MOIs ( > 0.05). The phage-antibiotic combination analysis (PAS) indicated that synergism was not detected at higher phiPT1 titer (10 PFU/mL) with all tested antibiotics at all subinhibitory concentrations. However, synergistic activities were recorded at 0.25 × MIC of four tested antibiotics: cefixime, gentamicin, ciprofloxacin, and aztreonam in combination with phage at 10, 10 and 10 PFU/mL (ΣFIC ≤0.5). Synergism was detected for all antibiotics (0.1 × MIC) except meropenem and colistin in combination with phiPT1 at 10, 10 and 10 PFU/mL (ΣFIC ≤0.5). Synergism also displayed at the lowest concentrations of all antibiotics (0.01 MIC) in combination with phiPT1 at all titers except 10 PFU/mL. Such characteristic features make phiPT1 to be a potential candidate for therapeutic uses.