In Vitro and In Vivo Activities of Novel Fluoroquinolones Alone and in Combination with Clarithromycin against Clinically Isolated Mycobacterium avium Complex Strains in Japan

Abstract

Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required.

Activities of Moxifloxacin in Combination with Macrolides against Clinical Isolates of Mycobacterium abscessus and Mycobacterium massiliense

“…Thus, our results indicate that it may be difficult to predict the in vivo therapeutic effects of MXF based on its in vitro MIC test result. These results are in agreement with those of a similar study conducted on the Mycobacterium avium complex (32). Factors that could account for this may be differences in the ability of the strain to grow in the medium versus in vivo or differences in the penetrating power of the antibiotics.…”

“…Tomioka et al showed that CLR decreases the activities of gatifloxacin and levofloxacin against M. avium complex strains in vitro (44). Kohno et al also reported that the activity of CLR against M. avium complex strains was attenuated when combined with fluoroquinolones, including MXF, using both in vitro and in vivo models (32). Another study by Bermudez et al revealed that the MXF-AZM combination was significantly less active than AZM alone for the treatment of mice infected with M. avium (4).…”

“…To determine the effect of antibiotic interactions in macrophages and in mice, the antibiotic activity of the combination treatment was defined as the log 10 CFU reduction as previously reported with slight modifications (32,40). Briefly, the antimycobacterial activity was assessed by counting the CFU from the macrophage lysates or the homogenates of inoculated organs on 7H10 agar supplemented with 10% OADC and determining the log 10 CFU per ml after 5 days.…”

“…At 4 days postinfection, treatment was initiated with the antimicrobial agents (100 mg/kg of body weight/day of each drug alone or in combination with 100 mg/kg/day of MXF). The dose of each antibiotic was selected based on the results of previous studies that determined the effective dose of each drug in murine infection models of other mycobacteria (5,6,32). Antimicrobial agents were administered daily by oral gavage for 12 days.…”

Treatment of Refractory Mycobacterium avium Complex Lung Disease with a Moxifloxacin-Containing Regimen

“…A recent experimental study revealed that mild antagonism occurred between MXF and CLR when they were given in combination, and this seemed to be MAC strain dependent (26). In addition, using a fluoroquinolones as the only companion drugs for CLR in MAC treatment regimens was associated with the development of CLR-resistant MAC strains (17).…”