Efficacy evaluation of a lytic bacteriophage cocktail against carbapenem–resistant pseudomonas aeruginosa - infected wounds in mice
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Date
2021-11
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Kampala International University
Abstract
Background: Pseudomonas aeruginosa is an opportunistic infectious agent associated with burns/surgical infections. With the global emergence of resistance to carbapenems and last-resort drugs such as colistin, carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been placed in the critical category of microorganisms for which alternatives to antibiotics are urgently needed. With bacteriophage application being one of the most promising alternatives to conventional antibiotics being pursued, the purpose of this study was to assess the efficacy of a locally formulated lytic bacteriophage cocktail against CRPA clinical isolates in a wound-infection mouse model.
Materials and methods: The study involved isolation of phages from hospital effluent followed by evaluation of the lytic effects and in vitro activity of a phage cocktail against CRPA. The phage enrichment and isolation of bacteriophages were conducted according to the method described by Clokie et al., (2018), with modifications. The purification of the phage isolates was done according to the modified procedure of Bhensdadia et al., (2014) while the spot assay technique by Clokie et al., (2018) was employed for the quantification of the bacteriophages. In vivo efficacy of the bacteriophage cocktail on the healing of wounds infected with CPRPA was then evaluated using a mouse model.
Results: Four phages were isolated from the hospital effluents and the cocktail, coded C12, from three of the isolates in a 2:1:1 ratio had the highest efficacy after 48 hours. The mean wound diameters at the end of the experiment showed that the phage cocktail-treated wounds registered satisfactory closures of at least 67.7% and the results were statistically significant from those of the meropenem-treated wounds (p < 0.0001).
Conclusion:The locally formulated and optimized three-phage cocktail demonstrated satisfactory efficacy (p < 0.0001) in the treatment of wounds infected with carbapenem – resistant Pseudomonas aeruginosa clinical isolate when topically administered in sufficient doses and at optimal frequencies.
Description
A dissertation submitted in partial fulfillment of the requirements for the award of the degree of Master of Science in pharmacology of Kampala International University