Therapeutic Use of Bacteriophage and Antibiotic Formulations for the Treatment of Antibiotic Resistant Acinetobacter Baumannii

Abstract

Widespread use of antibiotics has enriched global bacteria populations for strains possessing antibiotic resistance (AR) genes. Proliferation of AR genes and mechanisms have resulted in numerous multidrug resistant (MDR) infections for which there are no effective treatments. Acinetobacter baumannii is a major cause of hospital acquired (nosocomial) infections and is associated with outbreaks of MDR infections. Virulent bacteriophages (phages) present a way to remedy bacterial infections, while also having built-in mechanisms to circumvent resistance. This proposed study aims to develop a phage therapeutic targeting antibiotic resistant A. baumannii. The phages chosen for the final formulation exhibited high bactericidal activity and were able to infect several strains of A. baumannii from a provided library. Additionally, the phage-antibiotic synergy (PAS) effect was investigated in formulations with sub-lethal doses of ampicillin and chloramphenicol. The effectiveness of the phage therapeutic at different multiplicity of infections (MOI) and antibiotic concentrations were assessed relative to standard antibiotic doses. Well-plate studies suggest that higher MOI and antibiotic concentrations resulted in the greatest initial bactericidal effects, longest time to develop resistance, and lowest overall bacteria concentration. In future formulation studies, we would like to expand and optimize the current phage-antibiotic formulation and explore cocktail effects, whereby the formulation consists of a mixture of different phages that increases selective pressure.