In vitro activity of sitafloxacin (DU-6859a) alone, or in combination with rifampicin, against Mycobacterium ulcerans

Abstract

The antimicrobial effect of sitafloxacin (DU-6859a), used either singly or in combination with rifampicin, was evaluated in vitro against Mycobacterium ulcerans. Growth of M. ulcerans was measured by plate counts and the BACTEC radiometric method. The MICs and MBCs of sitafloxacin for M. ulcerans were in the range 0.125-0.5 mg/L. The values for other fluoroquinolones were two- to four-fold higher than for sitafloxacin. Combination of sitafloxacin and rifampicin exhibited synergy with five of the eight strains, whereas the combination of ofloxacin and rifampicin resulted in additive effects only. These results suggest that the combination of sitafloxacin and rifampicin has potential in the treatment of M. ulcerans infection.

Mycobacterium ulcerans infection: control, diagnosis, and treatment

“…49 Sitafl oxacin, a new fl uoroquinolone, has been demonstrated to be superior to other fl uoroquinolones both in vitro and in vivo, especially when combined with rifampicin. 53,54 The combination of rifampicin, clarithromycin, and sparfl oxacin has been tested in mice but it is not as eff ective as rifampicin with an aminoglycoside. 49,55,56 Rifalazil (benzoxazinorifamycin or KRM-1648), derived from rifampicin, seems to have a better inhibitory activity than rifampicin in mice.…”

Antimicrobial Treatment of Mycobacterium ulcerans Infection

“…The MIC of ofloxacin in tested strains of M. ulcerans was 1.26 μg/ml [40]; in another study, ofloxacin was least active of all fluoroquinolones tested with an MIC of 2 μg/ml [21]. Moxifloxacin (MIC 0.14 μg/ml), sitafloxacin (MIC 0.125-0.5 μg/ml) and prulifloxacin (MIC 1-3 μM) are also effective [49,57,58]. Of note, fluoroquinolones have increasingly been used in Ghana, one of the countries highly burdened with Buruli ulcer; an alarming rate of fluoroquinolone-resistant E. coli was noticed [59].…”

“…Yet some of the compounds that are active against the first, failed to prove efficacy in the latter. SQ641, PA-824 a promising nitroimidazopyran for tuberculosis, semisynthetic ketolides (HMR 3647 and HMR 3004), bisbenzaldehydes, as well as quinolinyl pyrimidines and phenothiazines showed only moderate or no antimicrobial effect against M. ulcerans (Table 1) [21,39,49,51,52,57,58,67,70].…”

Bacterial Infections in the Elderly Patient: Focus on Sitafloxacin

“…116 The MIC values of sitafloxacin for M. ulcerans were in the range of 0.125-0.5 µg/mL, much lower than that of other quinolones. 117 Sitafloxacin showed favourable antimycobacterial activity in vitro and in vivo, as compared with moxifloxacin against Mycobacterium avium infection in mice. Although moxifloxacin exhibited the strongest activity against intramacrophage M. avium , when each test quinolone was administered alone to infected mice, sitafloxacin and gatifloxacin exhibited greater therapeutic efficacy than moxifloxacin based on intrapulmonary bacterial elimination.…”

“…In vitro activity (MIC 90 values) of sitafloxacin in comparison to ofloxacin against Mycobacteria (MIC 90 = minimal inhibitory concentration of 90% of the isolates). [115][116][117]119 Bacterial greater activity in killing bacteria in the spleen. Sitafloxacin and moxifloxacin exhibited combined effects on intrapulmonary bacterial elimination when administered to mice in combination with clarithromycin plus ethambutol.…”