Efficacy of mefloquine and its enantiomers in a murine model of Mycobacterium avium infection

The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-...

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Vydané v:	PloS one Ročník 19; číslo 9; s. e0311167
Hlavní autori:	Froment, Antoine, Delomez, Julia, Da Nascimento, Sophie, Dassonville-Klimpt, Alexandra, Andréjak, Claire, Peltier, François, Joseph, Cédric, Sonnet, Pascal, Lanoix, Jean-Philippe
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 30.09.2024
Predmet:	Aerosols Animal experimentation Animal models Animal welfare Animals Antibiotics Antitubercular Agents - chemistry Antitubercular Agents - pharmacology Biology and Life Sciences Care and treatment Clarithromycin Clarithromycin - pharmacology Complications and side effects Diagnosis Disease Models, Animal Drug development Drug efficacy Drug interactions Drug Therapy, Combination Effectiveness Enantiomers Ethambutol Ethambutol - pharmacology Ethanol Evaluation Female Human health and pathology In vivo methods and tests Infections Infectious diseases Life Sciences Lung - drug effects Lung - microbiology Lung - pathology Lungs Medicine and Health Sciences Mefloquine Mefloquine - pharmacology Mice Mice, Inbred BALB C Mycobacterial infections Mycobacterium avium Mycobacterium avium - drug effects Patient outcomes Physical Sciences Research and Analysis Methods Rifampin Rifampin - pharmacology Stereoisomerism Sterilization Tuberculosis - drug therapy Tuberculosis - microbiology France
ISSN:	1932-6203, 1932-6203
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Shrnutí:	The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-mefloquine ((-)-EMQ)) have shown efficacy in both in vitro and in vivo , in a mouse model of M . avium intraveinous infection. However, no study reports aerosol model of infection or combination with gold standard treatment. That was the aim of our study. In an aerosol model of M . avium infection in BALB/c mice, we used five treatment groups as followed: Clarithromycin-Ethambutol-Rifampicin (CLR-EMB-RIF, standard of care, n = 15), CLR-EMB-MFQ (n = 15), CLR-EMB-(+)-EMQ (n = 15), CLR-EMB-(-)-EMQ (n = 15) and an untreated group (n = 25). To evaluate drug efficacy, we sacrificed each month over 3 months, 5 mice from each group. Lung homogenates were diluted and plated for colony forming unit count (CFU) expressed in Log10. At each time point, we found a significant difference between the untreated group and each of the treatment groups (p<0.005). The (+)-EMQ-CLR-EMB group was the group with the lowest CFU count at each time point but never reached statistical significance. The results of each group 3 months after treatment are: (+)-EMQ-CLR-EMB (4.43 ± 0.26), RIF-CLR-EMB (4.83 ± 0.37), (-)-EMQ-CLR-EMB (4.82 ± 0.18), MFQ-CLR-EMB (4.70 ± 0.21). In conclusion, MFQ and its enantiomers appear to be as effective as rifampicin in combination therapy. Further studies are needed to evaluate the ability of these drugs to prevent selection of clarithromycin resistant strains and potential for lung sterilization.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0311167