Synergistic Activity of Clofazimine and Clarithromycin in an Aerosol Mouse Model of Mycobacterium avium Infection

Infections with nontuberculous mycobacteria (NTM) have a poor prognosis in patients with underlying respiratory diseases. Clofazimine (CFZ) showed both experimental and clinical promising results against clinically relevant NTM. However, there are no data on CFZ in combination with the current recom...

Full description

Saved in:
Bibliographic Details
Published in:Antimicrobial agents and chemotherapy Vol. 64; no. 5
Main Authors: Lanoix, Jean-Philippe, Joseph, Cédric, Peltier, François, Castelain, Sandrine, Andréjak, Claire
Format: Journal Article
Language:English
Published: United States 21.04.2020
Subjects:
Aerosols
Animals
Antitubercular Agents - administration & dosage
Antitubercular Agents - therapeutic use
Clarithromycin - administration & dosage
Clarithromycin - therapeutic use
Clofazimine - pharmacology
Clofazimine - therapeutic use
Colony Count, Microbial
Drug Synergism
Ethambutol - therapeutic use
Female
Lung - microbiology
Mice
Mice, Inbred BALB C
Microbial Sensitivity Tests
Mycobacterium avium - drug effects
Mycobacterium avium-intracellulare Infection - drug therapy
Mycobacterium avium-intracellulare Infection - microbiology
Rifampin - therapeutic use
Treatment Outcome
Mycobacterium avium
treatment
clofazimine
mouse model
ISSN:1098-6596, 1098-6596
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Infections with nontuberculous mycobacteria (NTM) have a poor prognosis in patients with underlying respiratory diseases. Clofazimine (CFZ) showed both experimental and clinical promising results against clinically relevant NTM. However, there are no data on CFZ in combination with the current recommended treatment; therefore, we aimed to study its activity in an aerosol mouse model of In an aerosol infection BALB/c mouse model using strain Chester, we treated 58 mice with four combinations of rifampin (RIF) at 10 mg/kg, CFZ at 25 mg/kg, and clarithromycin (CLR) and ethambutol (EMB) at 100 mg/kg. Treatment efficacy was assessed on the basis of lung CFU counts after 2 (M2) and 4 (M4) months of treatment. At M2, CLR-RIF-EMB was slightly but significantly more efficient than CFZ-RIF-EMB (3.02 ± 0.12 versus 3.55 ± 0.28, respectively, < 0.01), whereas CLR-CFZ-EMB and CLR-CFZ-RIF-EMB dramatically decreased lung CFU counts by 4.32 and 4.47 log , respectively, compared to untreated group. At M4, CLR-RIF-EMB was significantly more efficient than CFZ-RIF-EMB (2 ± 0.53 versus 2.66 ± 0.22, respectively, = 0.01). The addition of CLZ to CLR dramatically decreased the lung CFU count, with CFU counts 5.41 and 5.79 log lower in the CLR-CFZ-EMB and CLR-CFZ-RIF-EMB groups, respectively, than in the untreated group. The addition of CFZ to CLR seems to improve the efficacy of CLR as early as M2 and was confirmed at M4. CFZ, in addition to RIF and EMB, on the other hand, is less effective than CLR-RIF-EMB. These results need to be confirmed by similar studies along with CFZ potential for shortening treatment.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1098-6596
1098-6596
DOI:10.1128/AAC.02349-19