Activity of KRM 1648 or rifabutin alone or in combination with clarithromycin against Mycobacterium avium complex in human alveolar macrophages.
METHODS
The activity of KRM 1648 (KRM), a new benzoxazinorifamycin, and rifabutin (RBT), alone or in combination with clarithromycin (CLA), was evaluated against Mycobacterium avium complex (MAC) that multiplied in human alveolar macrophages (AM).


METHODS
AM were recovered by bronchoalveolar lavage, incubated in RPMI 1640 medium with 10% human AB serum, infected with four strains of MAC (of non-acquired immune deficiency syndrome [AIDS] origin), and then treated with each drug alone or in combination. After incubation for 7 days, colony forming units in each well were counted on 7H10 agar.


RESULTS
Although concentrations between 0.2 microgram/ml and 20 micrograms/ml of both rifamycins showed clear dose-dependent activities against all MAC strains tested, only 20 micrograms/ml of each drug had modest bactericidal effect. In combination with 2.0 micrograms/ml of CLA, however, 0.2 microgram/ml of both drugs caused a bactericidal response against two of the four MAC strains examined.


CONCLUSIONS
According to this human alveolar macrophage model of MAC infection, KRM and RBT in combination with CLA was found to be a promising candidate against human pulmonary MAC infection, and deserves clinical evaluation.
Suzuki
K
K
Department of Infection and Inflammation, Kyoto University, Japan. ksuzuki@chest.kyoto-u.ac.jp
Tsuyuguchi
K
K
Matsumoto
H
H
Yamamoto
T
T
Hashimoto
T
T
Tanaka
E
E
Amitani
R
R
Kuze
F
F
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development; D012016:Reference Values; D017828:Rifabutin / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*; D012907:Smoking
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C068980:KRM 1648; D017828:Rifabutin; D007770:L-Lactate Dehydrogenase; D017291:Clarithromycin