Treatment of experimental infections of mice with bacteriophages

This study evaluated bacteriophage therapy against three clinically problematic bacterial species in mice. Phages were tested against Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus in peritoneal infection models. The acinetobacter phage BS46 provided remarkable protection at extremely low doses (as few as 102 particles), protecting mice against 5 LD50 of virulent A. baumannii, with evidence of phage replication in vivo. The pseudomonas phage BS24 also protected effectively against 5 LD50 of P. aeruginosa, with a protective dose (PD50) of 1.2 × 107 particles. However, the staphylococcal phage 4-131 failed to protect mice infected with either S. aureus strain tested, likely due to its poor lytic activity in vitro. The study demonstrates that highly lytic bacteriophages can effectively treat experimental infections caused by susceptible bacteria, with in vivo phage replication amplifying the protective effect. These findings support investigating phage therapy as a treatment option for infections caused by antibiotic-resistant bacterial strains, particularly those commonly found in burn wound infections.

Key findings

• Acinetobacter baumannii phage BS46 protected mice against lethal infection at remarkably low doses (as few as 10² particles), with evidence of phage multiplication in vivo reaching 100,000-fold higher counts than injected doses
• Pseudomonas aeruginosa phage BS24 provided significant protection against 5 LD50 bacterial challenge with a calculated PD50 of 1.2 × 10⁷ phage particles
• Staphylococcus aureus phage 4-131 failed to protect mice despite clinical reports of efficacy, likely due to poor in vitro lytic activity requiring 10⁶ pfu for complete bacterial clearing
• In vivo phage replication demonstrated in surviving animals suggests bacteriophages could be valuable for treating infections in tissues with poor blood supply and orthopedic implant infections
• Results support development of mixed phage preparations targeting antibiotic-resistant bacteria as a therapeutic strategy