EDP-420, a Bicyclolide (Bridged Bicyclic Macrolide), Is Active against Mycobacterium avium
| Autor: | Guoqiang Wang, Ly Tam Phan, Clark B. Inderlied, Peter Kolonoski, Lowell S. Young, Gyulnar Baimukanova, Priscilla Aralar, Christopher B. Chee, Nima Motamedi, Luiz E. Bermudez |
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| Rok vydání: | 2007 |
| Předmět: |
Bridged-Ring Compounds
medicine.medical_treatment Spleen Microbial Sensitivity Tests Microbiology Mice In vivo Clarithromycin Drug Resistance Bacterial medicine Animals Humans Experimental Therapeutics Pharmacology (medical) Antibacterial agent Pharmacology Protein synthesis inhibitor Dose-Response Relationship Drug biology Immunosuppression biology.organism_classification In vitro Anti-Bacterial Agents Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Female Macrolides Mycobacterium avium Mycobacterium medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 51:1666-1670 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01303-06 |
| Popis: | Infection caused by Mycobacterium avium complex (MAC) is common in patients with immunosuppression, such as AIDS, and deficiencies of gamma interferon and interleukin-12, as well as patients with chronic lung diseases. Treatment of MAC disease is limited since few drugs show in vivo activity. We tested a new bridged bicyclic macrolide, EDP-420, against MAC in vitro and in beige mice. EDP-420 was inhibitory in vitro at a concentration ranging from 2 to 8 μg/ml (MIC 50 of 4 μg/ml and MIC 90 of 8 μg/ml). In macrophages, EDP-420 was inhibitory at 0.5 μg/ml, suggesting that the drug concentrates intracellularly. Mice infected with macrolide-susceptible MAC strain 101 were given 100 mg of EDP-420/kg of body weight daily for 4 weeks and showed a significant reduction in the number of bacteria in both liver and spleen which was greater than the reduction observed with clarithromycin treatment at the same dose ( P < 0.05). However, macrolide-resistant MAC 101 did not respond to EDP-420 treatment. A combination of EDP-420 with mefloquine was shown to be indifferent; mefloquine alone was active against macrolide-resistant MAC. The frequency of resistance to EDP-420 in MAC 101 was 10 −9 , which is significantly less than the emergence of resistance to clarithromycin, ∼10 −7 ( P < 0.05). Further evaluation of EDP-420 in the treatment of MAC disease is warranted. |
| Databáze: | OpenAIRE |
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