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A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
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Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Rat Pneumonia Model

Ziad Tarazi1, Mojgan Sabet1, Michael N Dudley1

  • 1The Medicines Company, San Diego, California, USA.

Antimicrobial Agents and Chemotherapy
|November 7, 2018
PubMed

Insights

Minocycline effectively treats Acinetobacter baumannii pneumonia in rats. Achieving specific minocycline exposures, measured by the AUC/MIC ratio, correlates with both bacteriostatic and bactericidal effects against this pathogen.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Microbiology

Background:

  • Minocycline is FDA-approved for treating infections caused by susceptible Acinetobacter species.
  • Acinetobacter baumannii is a significant cause of hospital-acquired infections, often exhibiting antibiotic resistance.

Purpose of the Study:

  • To determine the pharmacokinetic/pharmacodynamic (PK/PD) exposures of minocycline linked to antibacterial activity against Acinetobacter baumannii.
  • To evaluate minocycline efficacy in a preclinical rat pneumonia model.

Main Methods:

  • A rat pneumonia model was utilized, infecting rats with six clinical isolates of Acinetobacter baumannii.
  • Rats were administered minocycline via 30-minute intravenous infusions.
  • The relationship between minocycline exposure (free 24-h AUC/MIC ratio) and antibacterial effect (bacteriostatic and bactericidal) was assessed.

Main Results:

  • Minocycline demonstrated a bacteriostatic effect at a free 24-h AUC/MIC ratio of 10 to 16.
  • A free 24-h AUC/MIC ratio of 13 to 24 resulted in approximately 1 log of bacterial killing.
  • These effective exposures are achievable with current intravenous minocycline dosing regimens approved by the FDA.

Conclusions:

  • The study establishes PK/PD targets for minocycline against Acinetobacter baumannii in a relevant animal model.
  • Current FDA-approved intravenous minocycline dosages can likely achieve exposures sufficient for treating Acinetobacter baumannii infections.
Keywords:
Acinetobacter baumanniiminocyclinepneumonia

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