1691. Bacteriophage and Protein Synthesis Pathway Inhibitor Combinations: Antibiotic mechanism of action drives antagonistic interactions

Abstract Background Bacteriophage (phage) to augment antibiotic efficacy is a possible therapeutic option in the era of antimicrobial resistance. Studies date have assessed phage-antibiotic synergy (PAS), however, its may be dependent upon mechanism action. Here, we report our in-vitro evaluation antagonism (PAA) among phage and protein synthesis inhibitor combinations multidrug-resistant clinical strains P. aeruginosa, S. aureus, E. faecium. Methods The following bacteria regimens were evaluated: 10266 (EM) R9010 (14207) (P. aeruginosa) against gentamicin (GEN), azithromycin (AZM), ciprofloxacin (CIP); N315 494 (Intesti) (S. aureus), R497 HOU503 (NV-497) (E. faecium) linezolid (LNZ), minocycline (MIN), daptomycin (DAP). Modified checkerboard (CB) MIC assays used for preliminary screening followed by 24h time kill analyses (TKA). For CB, synergy, additive activity, defined as an FIC index ≤0.5, 1–4, >4, respectively. In TKA, additivity ≥2 ≥1 log10 CFU/mL reduction from baseline, while was with higher than most effective single treatment at 24h. Data compared one-way ANOVA Tukey (HSD) test (P< 0.05). Results CB TKA aureus faecium isolates, phage-LZD phage-MIN antagonistic (FIC >4) phage-DAP synergistic 0.5) (ANOVA range mean differences 0.52 2.59 CFU/mL; P< 0.001). phage-AZM phage-GEN (FIC=1), respectively 1.04 1.95 Conclusion Our results suggest that antibiotics act on pathway lead PAA, PAA interactions highly bacterial inhibition (i.e., location ribosomal inhibition, bactericidal vs. bacteriostatic) inhibit. assessing wider array are warranted. Disclosures Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Support|Merck: Support.