Effectiveness of bacteriophage Pm3 and ciprofloxacin in treating experimental proteus infections in mice

In recent years, bacteriophages have been widely used to prevent and to treat various bacterial infections in humans. Lytic phages are often the only effective tool to combat multi-antibiotic resistant microorganisms. The high specificity of the bacteriophages allows avoiding negative effects on the human microbiome, making them more therapeutically attractive compared to broad-spectrum antibacterials. In our work, we evaluated therapeutic and prophylactic effects of bacteriophage Pm3 by using two models of Proteus-associated infection in mice, lethal sepsis and skin burn wound infection. Our results showed that a single preventive intraperitoneal administration of the phage at 108 PFU saved 90% of animals infected with a lethal dose of Proteus mirabilis M32. The course treatment of generalized Proteus infection initiated 1.5 hours after infection protected 80% of mice from death and was comparable to antibiotic therapy (90% therapeutic effect). Parenteral and external use of bacteriophage Pm3 for treating Proteus infection of burns showed a weak therapeutic effect manifested as decreased contamination of the wound surface with P. mirabilis M32 cells and prevention of infection invasion in some animals. Ciprofloxacin applied as a wound irrigation solution or subcutaneously gave a pronounced therapeutic effect: the wound surface and deep skin layers were sanitized in 100% of cases, and Proteus culture in the spleen and kidneys of the animals was absent. Thus, in vivo antibacterial activity of bacteriophage Pm3 was close to that of ciprofloxacin, but in preventing and treating Proteus-associated sepsis only. The phage is low effective in treating burn Proteus infection. Ciprofloxacin is highly effective in treating both Proteus-associated sepsis and skin thermal wound infections caused by P. mirabilis M32 in mice. Keywords: Proteus mirabilis, Proteus infection, sepsis, burn infection, mouse model, bacteriophage, phage therapy, ciprofloxacin