Preclinical Research on Bacteriophage Therapy for Carbapenem-Resistant Klebsiella Pneumoniae: A Systematic Review

Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a substantial threat to global health. As the effectiveness of first-line antibiotics like tigecycline and polymyxins wanes, bacteriophage therapy, including phage cocktails and integrated approaches, has emerged as a feasible alternative. This systematic review evaluated the bactericidal efficacy of bacteriophages against carbapenem-resistant K. pneumoniae in preclinical studies.

A comprehensive search of PubMed, Web of Science, and Embase databases was conducted for records published between January 2010 and December 2024. Risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE tool). Primary endpoints were animal mortality and tissue bacterial burden, reported as pooled Risk Ratios (RRs) and mean differences using random-effects models. The study was registered with PROSPERO (CRD420251018670).

Of 191 screened references, 18 studies met the selection criteria and were assessed as having low to moderate risk of bias. In animal infection models, subgroup analyses demonstrated a statistically significant association between bacteriophage therapy and reduced mortality in both murine (RR 0.30 (95% CI 0.22, 0.41), I2= 0.0%) and Galleria mellonella larva models (RR 0.36 (95% CI 0.16,0.81), I2= 23.7%), with no significant difference between subgroups (p= 0.689). The overall pooled analysis confirmed a significant reduction in mortality (RR 0.32 (95% CI 0.24,0.42), I2= 0.0%), indicating substantial improvement in infection outcomes. Bacteriophage therapy remained non-inferior to conventional antibiotic therapy for CRKP.

The findings substantiate the potent bactericidal activity of bacteriophage therapy against CRKP in preclinical settings, highlighting its feasibility and safety profile. The consistency of results across different animal models strengthens the evidence base. However, the translation of these promising results into clinical practice requires further validation. Limitations of this review include the relatively small number of available studies and occasional missing experimental details.

Bacteriophage therapy exhibits significant potential as an effective intervention against CRKP infections in preclinical models. Future research should focus on expanding the sample size and rigor of preclinical studies to corroborate these findings and provide a robust foundation for clinical application.