Abstract

The global rise of multidrug resistant (MDR) bacteria has outpaced the development of new
antibiotics, creating an urgent need for alternative therapeutic strategies. Bacteriophage
(phage) therapy, the use of viruses that specifically kill bacteria, represents a re-emerging
approach with century-old roots but recent advances in manufacturing, regulatory pathways, and clinical evidence. This comprehensive review synthesizes evidence from 150 studies
(2010–2025) examining the potential of phage therapy as a public health tool against MDR
bacteria, including carbapenem-resistant Enterobacteriaceae (CRE), methicillinresistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extensively drug-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii. We
analyze phage biology (host specificity, lytic vs. lysogenic cycles), clinical applications
(compassionate use, personalized therapy, fixed cocktail preparations), safety data, and
challenges (phage resistance, pharmacokinetics, regulatory hurdles). Evidence from
compassionate use case series (n > 500 patients) shows clinical improvement in 70–90% of
patients with otherwise untreatable MDR infections, with minimal adverse events. Recent
randomized controlled trials for chronic wound infections and prosthetic joint infections
confirm safety and suggest efficacy. We recommend establishing phage therapy as a regulated
adjunct to antibiotics, investing in phage library infrastructure, developing standardized
susceptibility testing, integrating phage therapy into AMR action plans, and funding high- quality RCTs. Phage therapy is not a replacement for antibiotics but a critically needed
complement.