International journal of antimicrobial agents · 2026
Efficacy and pharmacokinetics of a stepwise isolated phage cocktail against carbapenem-resistant Klebsiella pneumoniae in a murine pneumonia model.
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Yin Xin, Luo Huan, Feng Yu, Fang Qingqing, Zong Zhiyong
Аннотация
OBJECTIVES: Phage therapy is a potential alternative to conventional antibiotic therapy to combat carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Studies based on pharmacokinetic of phage therapy are scarce, representing a major barrier to clinical translation of phage therapy.
METHODS: We constructed CRKP pneumonia in mice to assess the efficacy and safety of phage cocktail. The mice were divided into four groups: CRKP infection group (bacteria), phage therapy group (bacteria and phage cocktail), the negative group (phage cocktail), and the blank group (no bacteria and no phage). Samples were collected at 4, 24, 48, and 72 hours after phage cocktail administration. Bacterial and phage counts, inflammatory factors, and histopathological examination were performed.
RESULTS: After 4-hour phage therapy, bacterial load in murine lung tissues in the phage therapy group started to decrease. After 72-hour phage therapy, bacterial counts of the lung tissue in the phage therapy group lowered by 7.45 log compared to those in the CRKP infection group. Treatment of phage cocktail reduced the level of inflammatory factors (IL-6 and TNF-α) and ameliorated congestion and inflammation in murine lung tissues. The half-lives of phages in the phage therapy were longer than those of the negative group. The phage titers in the phage therapy group were stable within 48 hours. No obvious toxic effect was observed in the negative group.
CONCLUSIONS: In conclusion, our study supports that phage cocktail could be considered as a potential therapeutic regimen for managing pneumonia due to CRKP.
METHODS: We constructed CRKP pneumonia in mice to assess the efficacy and safety of phage cocktail. The mice were divided into four groups: CRKP infection group (bacteria), phage therapy group (bacteria and phage cocktail), the negative group (phage cocktail), and the blank group (no bacteria and no phage). Samples were collected at 4, 24, 48, and 72 hours after phage cocktail administration. Bacterial and phage counts, inflammatory factors, and histopathological examination were performed.
RESULTS: After 4-hour phage therapy, bacterial load in murine lung tissues in the phage therapy group started to decrease. After 72-hour phage therapy, bacterial counts of the lung tissue in the phage therapy group lowered by 7.45 log compared to those in the CRKP infection group. Treatment of phage cocktail reduced the level of inflammatory factors (IL-6 and TNF-α) and ameliorated congestion and inflammation in murine lung tissues. The half-lives of phages in the phage therapy were longer than those of the negative group. The phage titers in the phage therapy group were stable within 48 hours. No obvious toxic effect was observed in the negative group.
CONCLUSIONS: In conclusion, our study supports that phage cocktail could be considered as a potential therapeutic regimen for managing pneumonia due to CRKP.