VinodKumar C.S

Abstract

Introduction: Multidrug-resistant strains of Acinetobacter baumannii, a significant hospital pathogen, have developed resistance to virtually all available antibiotics. Carbapenems antibiotics are among the most commonly used antibiotics against Acinetobacter infections, but they can be rendered ineffective by the metallo-beta-lactamase enzyme. In this study, bacteriophage isolated against blaSPM-1 producing Acinetobacter baumannii was evaluated for its therapeutic potential in the rabbit pneumonia model. Materials and Methods: Acinetobacter baumannii was isolated from the sputum and was speciated as per the standard microbiological techniques. Bacteriophage specific for blaSPM-1 producing Acinetobacter baumannii from the sewage water. Pneumonia was introduced in the rabbits as per Esposito Pennington method and efficacy of the bacteriophage in resolving pneumonia was evaluated. For in-vivo experiments, five groups of rabbits were used including infection-free, phage control, bacteria-infected control, and the other two groups infected with Acinetobacter baumannii and treated either with an antibiotic, colistin (2.5 mg/kg, twice a day intraperitoneally) or Acinetobacter phage (3×109 PFU/mL, given once through nebulizer). The experimental animals were monitored for 72 hours for mortality, and the surviving rabbits were killed for bacteriological and histopathological analysis. Results: In the infected group, pneumonia was developed within 48 hours, and 6/10 animals were dead after 72 hours. All the animals in the antibiotic group survived but showed signs of pneumonia, and there was up to 4 log CFU/g±0.24 reduction in the bacterial count. In phage treated group, all the animals survived at the end of 72 hours and all the animals were healthy with no signs of pneumonia. Conclusions: The experiment showed new insights into the application of bacteriophage through nebulization, a non-invasive method of phage delivery to rescue rabbits from pneumonia caused by blaSPM-1-producing Acinetobacter baumannii. Keywords: Rabbit models, bla SPM­1, Acinetobacter baumannii, Nebulization, Phage therapy, Pneumonia.

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Abstract

Introduction: Exploration for an alternative to antibiotics to treat bacterial diseases is becoming more important due to the emergence of antibiotic resistance. Bacteriophage or phage has been used for the treatment of superficial infections. Materials and Methods: In this study, phage isolated from the environment was used as a therapeutic agent against NDM-producing causing respiratory disease in an experimental mouse model. The isolated phage was found to belong to the family based on morphology. For experiments, five groups of mice were used including infection-free, phage-only, bacteria-infected, and the other two groups infected with and treated either with an antibiotic, levofloxacin (50 mg/kg, twice a day intraperitoneally) or phage (3×10 PFU/mL). All the animals were observed for 72 hours for mortality, and the surviving mice were killed for analysis. Results: In the infected group, pneumonia was developed after 48 hours, and 8/10 animals were dead after 72 hours. When pneumonia infected mice were treated with an antibiotic, levofloxacin all the animals survived but showed the signs of pneumonia, and there was up to 6 log CFU/g±0.82 reduction in the bacterial count. In phage treated group, all the animals survived at the end of 72 hours and all the animals were healthy with no signs of pneumonia. Conclusions: The experiment showed new insights into the biology of the broad host range of phage, demonstrating that phage has prospects for the treatment of pneumonia caused by the NDM-producing .   Keywords: Phage therapy, Pneumonia, Phage efficacy, Mice models, NDM­4

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