Authors : Siddharth Singh

Volume/Issue : Volume 11 - 2026, Issue 6 - June

Google Scholar : https://tinyurl.com/yfyf66ee

Scribd : https://tinyurl.com/3kz9nsb7

DOI : https://doi.org/10.38124/ijisrt/26jun1484

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (collectively the ESKAPE pathogens) cause the majority of healthcare-associated infections worldwide and are the cause of most multidrug-resistant (MDR) bacterial deaths. Phage-antibiotic combination therapy takes advantage of phage-antibiotic synergy (PAS), a mechanistically interesting concept, to overcome drug resistance in such organisms. Methods and objectives: Here we describe the molecular mechanisms that constitute PAS, which include exploitation of efflux pumps, cell filamentation using the SOS response, alteration of the bacterial outer membrane to improve permeability, dissolution of biofilms, and selection of bacteriophage-resistant mutants which are paradoxically again sensitive to antibiotics due to associated fitness cost trade-offs. Data for PAS with ESKAPE pathogens, as determined in checkerboard assays, time kill experiments or in vivo model studies, will be presented and discussed in view of standard laboratory approaches and the few clinical case series reported. PAS represents a convergent therapeutic principle in which the actions of phages and antibiotics are synergistic by acting in an interdependent way on bacteria. However, the lack of a harmonized methodology to determine the PAS effect, immature regulations and an insufficient database on the clinical application of phage-antibiotic combinations, particularly with respect to rational and optimal sequencing and dosing in practice, still hamper its clinical development. The European Pharmacopoeia's agreement on standard quality methods for bacteriophages for medicinal use in the coming year, and the EMA Guideline on Phage therapy (expected 2025), show considerable progress in reducing regulatory barriers, but key data are still needed to establish PAS as a reliable and robust therapy.

Keywords : Phage-Antibiotic Synergy, ESKAPE Pathogens, Bacteriophage Therapy, Antimicrobial Resistance, Efflux Pump, Biofilm, SOS Response, Clinical Translation, Regulatory Framework.

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