RESUMO
The main objective of this study was to compare in vitro activities of a novel fluoroquinolone (FQ), UB-8902, with ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MOX) against Mycobacterium tuberculosis isolates. Eleven OFX-resistant and 11 drug-susceptible clinical isolates were studied. Individual minimum inhibitory concentrations of OFX, LFX, MOX, and UB-8902 were determined using Middlebrook 7H11 agar. The concentrations studied ranged from 0.125 to 128 µg/mL in twofold dilutions. UB-8902 was more active than LFX and similar to MOX for OFX-resistant M. tuberculosis isolates. In addition, UB-8902 and MOX showed equal activity against drug-susceptible isolates, both being more active than OFX and LFX. In conclusion, the new FQ, UB-8902, showed good activity against OFX-resistant isolates. Moreover, it showed better activity than OFX and LFX and was equivalent to MOX against FQ-susceptible clinical isolates. UB-8902 can be considered as a drug with potential antituberculous activity, similar to MOX.
Assuntos
Antituberculosos/farmacologia , Ciprofloxacina/análogos & derivados , Farmacorresistência Bacteriana/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Ofloxacino/farmacologia , Ciprofloxacina/farmacologia , DNA Girase/genética , DNA Girase/metabolismo , Farmacorresistência Bacteriana/genética , Expressão Gênica , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Moxifloxacina/farmacologia , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/microbiologiaRESUMO
Chronic otitis externa in dogs is often associated with Pseudomonas aeruginosa infection. Fluoroquinolones are often used for treating such infections. Fluoroquinolone resistance mechanisms were characterized in 10 strains of P. aeruginosa isolated from chronic canine otitis externa. Nine out of ten strains harbored a mutation in the gyrA gene and presented an overexpression of efflux pump(s). There was a good correlation between the lipophilicity of the fluoroquinolone being tested and the effect of the efflux pump inhibitor in the final MIC. Therefore, both mechanisms, mutation in the gyrA gene and increased efflux pump(s), seem to play an important role in the acquisition of fluoroquinolone resistance in veterinary clinical isolates of P. aeruginosa. Levels of resistance to fluoroquinolones suggest that they could not be a good choice for systemic therapy of Pseudomonas otitis.
