Investigation Of The Use Of Phage In Treatment Of Infection Caused By Antibiotic-resistant Pseudomonas Aeruginosa

Objective: Isolate and screen out phages of imipenem-resistant Pseudomonas aeruginosa(IMPR-Pa)with broad host range, and further explore their latent of anti-infection and distribution in vivo,analyse it's likely mechanism.Method: Isolate phages of imipenem-resistant Pseudomonas aeruginosa from sewage and investigate the related biology and morphologic characteristics. phages that were screened out in vitro experiments are used to rescue BALB/c mice from systematic infection caused by clinical isolates of Imipenem-resistance Pseudomonas aeruginosa.Result: 29 strains of phage were isolated from our hospital sewage, and phage ?A392 was representatively used for all testing because it has lytic activity against a wide range of clinical isolates of IMPR-Pa. We found that intraperitoneal (i.p.) injections of one IMPR-Pa strain (3×107 CFU) caused bacteremia and all mice death within 24 h. A single i.p. inoculation of the phage strain (MOI≥0.01) at up to 60 min after the bacterial challenge was sufficient to rescue 100% of the animals. This lifesaving effect coincided with the rapid appearance of ?A392 in the circulation (within 2 h after i.p. injection), which remained at substantially higher levels for up to 48 h until the bacteria were eradicated. However, the survival rates of the mice were dropped to approximately 50% and 20% when the same dose of this purified phage preparation was administered at 180 min and 360 min, respectively, after IMPR-Pa infections. In addition, we demonstrated that the ability of this phage to rescue bacteremic animals was due to the functional capabilities of the phage and not to a nonspecific immune effect. The protection of mice death occurred only in animals inoculated with bacteria-specific virulent phage strains. When the heat-inactivated phages were used, the survival rate of the infected mice was dramatically reduced to 20% or lower. Moreover, the levels of the antibody against the phage were not significantly changed at the time when the bacteremic animals were protected by the active phages. Finally, our observations revealed that the inoculation of the mice with high-doses of ?A392 alone produced no adverse effects attributable to the phage.Conclusion: The phage screened out had a broad host range and a relatively high adsorption rate and a relatively short latent period. Phages are effective method to control bacteria infections and have no adverse effect on the normal tissue. It will be a alternative method to control clinical Pseudomonas aeruginosa Infections.