[In vitro antimycobacterial activity of clarithromycin and its therapeutic efficacy against Mycobacterium intracellulare infection induced in mice].
A new macrolide, clarithromycin (CAM), with increased acid-stability and thus having a markedly improved absorption efficiency from gastrointestinal tract, was evaluated for its in vitro antimicrobial activity against various mycobacterial species. CAM had nearly the same level of anti-mycobacterial activity as that of sparfloxacin (SPFX) and slightly higher activity than rifampicin (RFP), except that its anti-M. tuberculosis activity was much lower than those of SPFX and RFP. Anti-M. avium complex activity of CAM (MIC90 values against M. avium and M. intracellulare were 12.5 and 6.25 micrograms/ml, respectively) was in similar level as SPFX and RFP. However, MIC distribution pattern revealed that anti-M. avium activity was in the order of SPFX > CAM > RFP, while anti-M. intracellulare activities of them were almost the same with each other. Moreover, CAM showed bactericidal action against M. intracellulare growing in 7H9 medium. Furthermore, we investigated the therapeutic efficacy of CAM against M. intracellulare infection induced in mice and also determined its combined effect with other antimicrobials including KRM-1648, SPFX and ethambutol (EB). When CAM suspended in 5% gum arabic-saline was given s.c. to mice infected i.v. with M. intracellulare (8 x 10(6) CFU) at 0.2 to 2 mg/mouse/day, once daily six times per week from day 1 for 8 weeks, CAM exhibited a potent therapeutic efficacy, in terms of reduction in the incidence of gross lung lesions and reduction of bacterial loads in the visceral organs (reduction of bacterial CFU by 0.9-3.4 log units in the lung and by 0.4-4.6 log units in the spleen during week 4 to 8, depending on its administration dose).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Microbiology and Immunology, Shimane Medical University, Japan.
H
H
Tomioka
K
K
Sato
H
H
Saito
D000818:Animals; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D009162:Mycobacterium avium / Q000187:drug effects*; D015269:Mycobacterium avium Complex / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009170:Nontuberculous Mycobacteria / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy*
D017291:Clarithromycin