PHAGE THERAPY VS. ANTIBIOTICS: A COMPARATIVE STUDY IN MULTIDRUG-RESISTANT KLEBSIELLA PNEUMONIA

Abstract

The rapid emergence of multidrug-resistant (MDR) Klebsiella pneumoniae has rendered conventional antibiotic treatments increasingly ineffective, prompting the exploration of alternative therapeutic strategies. This study provides a comparative evaluation of phage therapy and antibiotic treatment against MDR K. pneumoniae using in vitro assays and an in vivo murine infection model. Clinical isolates exhibited high resistance levels to key antibiotics, particularly meropenem (95%) and colistin (80%). Three lytic bacteriophages (KP1, KP2, KP3) were isolated and demonstrated broad host range (80–90%), high burst sizes, and genetic stability, confirming their potential as therapeutic agents. Time-kill assays revealed that phage-antibiotic combinations achieved significantly greater bacterial clearance than either agent alone. Checkerboard assays confirmed synergy across all isolates, with fractional inhibitory concentration index (FICI) values below 0.5. In vivo studies mirrored in vitro findings, with the combination therapy group showing the lowest bacterial load (1.9 log10 CFU/g) in thigh muscle tissue. Furthermore, phage therapy preserved host microbiota diversity (Shannon Index = 3.4), in contrast to the microbiome-disrupting effects of antibiotics alone (Index = 2.0). Figures and tables comprehensively illustrate the superior efficacy and safety profile of phage therapy. Collectively, these results highlight the promise of phage therapy, particularly in combination with antibiotics, as a targeted, effective, and microbiota-sparing strategy against MDR K. pneumoniae infections. This study supports the urgent need for further clinical development and regulatory consideration of phage-based therapeutics in addressing the global antimicrobial resistance crisis.