Phage-Antibiotic Combinations for Pseudomonas: Successes in the Clinic and In Vitro Tenuously Connected

Abstract

Antimicrobial resistance challenges researchers to innovate strategies to enhance the effectiveness of our existing antibiotics. Bacteriophage (phage, bacterial virus)-antibiotic combinations present a promising synergistic approach, particularly for drug-resistant infections such as those caused by Pseudomonas aeruginosa. This approach offers many advantages: enhanced bacterial killing (both planktonic and biofilm), eliminating persister cells, re-sensitization to drugs, and inhibiting resistance spread by targeting plasmids encoding resistant genes. Interestingly, even phages traditionally excluded from therapy – those capable of entering dormancy in the bacterial host – exhibit unique, potent synergy with antibiotics. Despite these clear in vitro benefits and the comparatively strong performance of phage antibiotic combinations in the clinic, translating in vitro efficacy to patient outcomes remain challenging. The lack of standardized metrics for measuring phage-antibiotic interaction complicates cross-study comparisons. In many instances, it is also difficult to translate these in vitro findings to clinically relevant metrics – for example, increased progeny size in vitro is unlikely to contribute meaningfully to treatment success. Addressing these gaps will allow us to fully harness the potential of phage-antibiotic combinations and bridge the disconnect between in vitro results and clinical success.