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Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model
Mohamed S Fayez1, Toka A Hakim2, Mona M Agwa3
1Center for Microbiology and Phage Therapy, Zewail City of Science and Technology, Giza 12578, Egypt.
Abstract:
(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic alternative for treating bacterial infections. This research aims at isolating and characterizing a specific phage and evaluate its topical activity against MDR-KP isolated from infected wounds. (Methods): A lytic phage ZCKP8 was isolated by using a clinical isolate KP/15 as a host strain then characterized. Additionally, phage was assessed for its in vitro host range, temperature, ultraviolet (UV), and pH sensitivity. The therapeutic efficiency of phage suspension and a phage-impeded gel vehicle were assessed in vivo against a K. pneumoniae infected wound on a rat model. (Result): The phage produced a clear plaque and was classified as Siphoviridae. The phage inhibited KP/15 growth in vitro in a dose-dependent pattern and it was found to resist high temperature (˂70 °C) and was primarily active at pH 5; moreover, it showed UV stability for 45 min. Phage-treated K. pneumoniae inoculated wounds showed the highest healing efficiency by lowering the infection. The quality of the regenerated skin was evidenced via histological examination compared to the untreated control group. (Conclusions): This research represents the evidence of effective phage therapy against MDR-KP.
Insights
Bacteriophage therapy shows promise for treating multi-drug-resistant Klebsiella pneumoniae (MDR-KP) wound infections. A specific phage, ZCKP8, effectively reduced bacterial load and promoted wound healing in a rat model.
Area of Science:
- Microbiology
- Infectious Diseases
- Biotechnology
Background:
- Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant threat to public health, particularly in wound infections.
- Antibiotic resistance limits treatment options for MDR-KP, necessitating alternative therapeutic strategies.
- Bacteriophages (phages) are viruses that infect bacteria and are being explored as potential alternatives to antibiotics.
Purpose of the Study:
- To isolate and characterize a lytic bacteriophage effective against MDR-KP.
- To evaluate the in vitro and in vivo efficacy of the isolated phage for treating MDR-KP wound infections.
Main Methods:
- Isolation and characterization of a lytic phage (ZCKP8) using a clinical MDR-KP isolate.
- Assessment of phage stability (temperature, UV, pH) and host range.
- In vivo evaluation of phage suspension and phage-gel formulation in a rat wound infection model.
Main Results:
- A lytic phage, ZCKP8 (family Siphoviridae), was isolated and characterized.
- Phage ZCKP8 demonstrated dose-dependent inhibition of MDR-KP in vitro and stability at temperatures up to 70°C, pH 5, and UV exposure for 45 minutes.
- Topical phage treatment significantly reduced infection and improved wound healing, confirmed by histological analysis.
Conclusions:
- Phage therapy presents a viable and effective treatment strategy against MDR-KP wound infections.
- The characterized phage ZCKP8 shows potential for topical application in wound care.
- This study provides evidence supporting the use of bacteriophages as an alternative to antibiotics for MDR-KP infections.
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