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Efficacies of ABT-773, a new ketolide, against experimental bacterial infections

M J Mitten1, J Meulbroek, M Nukkala

  • 1Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064-3537, USA. michael.j.mitten@abbott.com

Antimicrobial Agents and Chemotherapy
|August 15, 2001
PubMed

Insights

ABT-773, a novel ketolide, shows effectiveness against drug-resistant respiratory pathogens. This new antibacterial agent demonstrates promising efficacy in preclinical models for treating resistant bacterial infections.

Area of Science:

  • Pharmacology and Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Antibiotic resistance in respiratory tract pathogens poses a significant global health threat.
  • Novel therapeutic agents are urgently needed to combat infections caused by resistant bacteria.
  • Ketolides represent a class of antibiotics with potential against resistant strains.

Purpose of the Study:

  • To evaluate the pharmacokinetic profile of ABT-773 in rats.
  • To assess the in vivo efficacy of ABT-773 against various bacterial pathogens, including resistant strains.
  • To compare the efficacy of ABT-773 with existing macrolide antibiotics in preclinical infection models.

Main Methods:

  • Pharmacokinetic studies in rats to determine plasma and tissue concentrations (AUC, peak concentration, tissue-to-plasma ratio).
  • In vivo efficacy studies in mice against acute systemic infections caused by susceptible and resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Listeria monocytogenes.
  • Efficacy evaluation in a rat lung infection model against Streptococcus pneumoniae (including resistant strains) and Haemophilus influenzae.

Main Results:

  • ABT-773 exhibited favorable pharmacokinetic properties in rats, concentrating in lung tissue.
  • The compound demonstrated efficacy against macrolide-susceptible strains and resistant strains of S. pneumoniae, S. aureus, S. pyogenes, and L. monocytogenes in systemic infections.
  • In a rat lung infection model, ABT-773 showed superior efficacy compared to comparator macrolides against various S. pneumoniae strains and was effective against H. influenzae.

Conclusions:

  • ABT-773 possesses promising pharmacokinetic and pharmacodynamic properties for treating respiratory tract infections.
  • The novel ketolide is effective against both susceptible and resistant bacterial pathogens commonly implicated in respiratory infections.
  • ABT-773 represents a potential new therapeutic option for combating challenging bacterial respiratory infections.

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