Experimental Protection of Diabetic Mice against LethalP. aeruginosaInfection by Bacteriophage

Abstract

The emergence of antibiotic-resistant bacterial strains has become a global crisis and is vulnerable for the exploration of alternative antibacterial therapies. The present study emphasizes the use of bacteriophage for the treatment of multidrug resistant P. aeruginosa. P. aeruginosa was used to induce septicemia in streptozotocin (STZ) induced diabetic and nondiabetic mice by intraperitoneal (i.p.) injection of 3 × 108 CFU, resulting in a fatal bacteremia within 48 hrs. A single i.p. injection of 3 × 109 PFU phage GNCP showed efficient protection in both diabetic (90%) and nondiabetic (100%) bacteremic mice. It was further noted that the protection rate was reduced in diabetic mice when phage GNCP was administered after 4 h and 6 h of lethal bacterial challenge. In contrast, nondiabetic bacteremic mice were rescued even when treatment was delayed up to 20 h after lethal bacterial challenge. Evaluation of results confirmed that a single intraperitoneal injection of the phage dose (3 × 109 PFU/mL) was more effective than the multiple doses of imipenem. These results uphold the efficacy of phage therapy against pernicious P. aeruginosa infections, especially in cases of immunocompromised host.

Efficacy of &phi;km18p phage therapy in a murine model of extensively drug-resistant <em>Acinetobacter baumannii</em> infection

“…The results showed that protection was reduced when the phage treatment was delayed for 4 and 6 hours after a lethal bacterial challenge. 37 Nevertheless, the phage could rescue nondiabetic bacteremic mice even when the treatment was delayed to 20 hours after a lethal bacterial challenge.…”

Bacteriophage Therapy of Bacterial Infections: The Rediscovered Frontier

“…Phage GNCP treatment of multi-drug-resistant P. aeruginosa infection in diabetic and non-diabetic mice, which caused fatal bacteremia within 2 d, at a 10:1 ratio of phage:bacteria resulted in protection of 90% of diabetic animals and 100% of non-diabetic animals [91]. Bacteriophages were also effective in reducing inflammation in a murine acute infection model of P. aeruginosa [92].…”

Towards Inhaled Phage Therapy in Western Europe

“…injection of MDR P. aeruginosa , a single i.p. injection of phages 20 min after bacterial injection increased survival [19]. The authors reported a survival rate of 90% in diabetic and 100% in nondiabetic mice even when treatment started 4 h after bacterial challenge.…”

“…Treatment started 6 h after infection resulted in lower survival rates among diabetic mice. Further delay of treatment (12 h) also reduced the effectiveness of phage therapy in nondiabetic mice [19]. This suggests, phage therapy is effective in both immunocompetent and -incompetent mice.…”