Sequential treatment effects on phage-antibiotic synergistic application against multi-drug-resistant Acinetobacter...

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Phage therapy offers a promising alternative for treating multidrug-resistant (MDR) bacterial infections.
• However, limitations such as narrow host spectrum and rapid resistance development hinder clinical application.
• Phage-antibiotic combinations, known as phage-antibiotic synergy (PAS), enhance bacterial killing but require optimization.

Purpose of the Study:

• To investigate the impact of treatment order on phage-antibiotic synergy (PAS) in vitro.
• To evaluate the efficacy of different administration timings for phage and antibiotic combinations against Acinetobacter baumannii.
• To assess the development of bacterial resistance under varying treatment orders.

Main Methods:

• Utilized Acinetobacter baumannii phage vB_AbaM-IME-AB2 and colistin as a model PAS combination.
• Assessed in vitro antibacterial and antibiofilm activities across different treatment sequences (phage-first, antibiotic-first, simultaneous).
• Monitored the emergence of phage resistance following various treatment orders.

Main Results:

• Applying phage 8 hours before colistin yielded the highest antibacterial synergy but did not prevent phage resistance.
• Simultaneous application and antibiotic-first application effectively suppressed or delayed resistance development.
• Simultaneous administration demonstrated superior antibacterial and antibiofilm activities compared to other sequences.

Conclusions:

• Treatment order significantly impacts the efficacy and resistance profile of phage-antibiotic combinations.
• Simultaneous phage and antibiotic application is a promising strategy for enhancing synergistic killing and preventing resistance.
• Further in vivo studies are warranted to validate these in vitro findings for clinical translation.