Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model

Si-Yun Wang1, Xin Tan2, Zi-Qiang Liu2

  • 1Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing Key Laboratory of Pediatrics , Chongqing, China.

Microbiology Spectrum
|November 28, 2023
PubMed
Abstract

Insights

PA_LZ7 phage therapy shows promise against multi-drug-resistant Pseudomonas aeruginosa. Studies in mice indicate it is safe and effective, with rapid clearance from the body and no significant toxicity observed.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Antibiotic resistance is a growing global health threat.
  • Phage therapy offers a potential alternative to antibiotics for treating bacterial infections.
  • Multi-drug-resistant (MDR) Pseudomonas aeruginosa is a significant pathogen in healthcare settings.

Purpose of the Study:

  • To evaluate the pharmacokinetics and safety of PA_LZ7, a bacteriophage targeting MDR P. aeruginosa.
  • To determine the in vivo behavior and potential toxicity of PA_LZ7 in a mouse model.

Main Methods:

  • Intravenous administration of PA_LZ7 phage to mice.
  • Monitoring of phage plasma concentration over time.
  • Assessment of plasma cytokines and spleen weight as indicators of toxicity.

Main Results:

  • PA_LZ7 exhibited exponential decay in plasma, with concentrations significantly reduced within 24 hours across all tested doses.
  • Higher doses of PA_LZ7 led to temporary increases in specific plasma cytokines and spleen weight.
  • No significant overall toxicity was observed in the mouse model.

Conclusions:

  • PA_LZ7 demonstrates favorable pharmacokinetic properties and a good safety profile in mice.
  • PA_LZ7 is a potential candidate for further development as a therapeutic agent against MDR P. aeruginosa infections.
  • Phage therapy with PA_LZ7 warrants further investigation for clinical applications.