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

Abstract

ABT-773 is a novel ketolide effective against antibacterial-resistant respiratory tract pathogens. The pharmacokinetic profile of ABT-773 was studied in rats and consisted of a mean peak concentration in plasma of 1.07 microg/ml and an area under the concentration-time curve (AUC) of 12.03 microg. h/ml when the compound was delivered at a dose of 25 mg/kg of body weight. It concentrated in rat lung tissue, with a lung tissue-to-plasma ratio of 29 based on the AUC. In acute systemic infections in mice, ABT-773 showed efficacy against macrolide-susceptible strains of Staphylococcus aureus, Streptococcus pneumoniae, S. pyogenes, and Listeria monocytogenes. Additionally, ABT-773 improved the survival of mice infected with resistant S. pneumoniae containing either the ermB gene, the mefE gene, or altered penicillin binding protein genes. In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated against the following strains of S. pneumoniae: a macrolide-lincosamide-streptogramin B-susceptible strain, an ermB strain, and an mefE strain. ABT-773 was also effective against Haemophilus influenzae lung infections in rats. Thus, ABT-773 may prove to be a useful new antibacterial agent for the treatment of respiratory tract infections.

• Authors: M J Mitten, J Meulbroek, M Nukkala, L Paige, K Jarvis, A Oleksijew, A Tovcimak, L Hernandez, J D Alder, P Ewing, Y S Or, Z Ma, A M Nilius, K Mollison, R K Flamm
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 45 Issue 9 Pg. 2585-93 (Sep 2001) ISSN: 0066-4804 [Print] United States
• PMID: 11502533 (Publication Type: Journal Article)

Chemical References

• Ketolides
• Erythromycin
• cethromycin

Topics

• Animals
• Bacterial Infections (drug therapy, metabolism)
• Disease Models, Animal
• Drug Resistance, Microbial
• Erythromycin (analogs & derivatives, pharmacokinetics, therapeutic use)
• Female
• Haemophilus Infections (drug therapy, metabolism)
• Haemophilus influenzae (drug effects)
• Ketolides
• Listeriosis (drug therapy, metabolism)
• Lung Diseases (drug therapy, metabolism, microbiology)
• Male
• Mice
• Rats
• Rats, Sprague-Dawley
• Respiratory Tract Diseases (drug therapy, metabolism)
• Staphylococcal Infections (drug therapy, metabolism)
• Streptococcal Infections (drug therapy, metabolism)
• Streptococcus pneumoniae (drug effects)
• Treatment Outcome