Efeito pÃs-antibiÃticos de um novo derivado 1,2,4-oxadiazol-hidrazida e suas associaÃÃes frente ao Mycobacterium fortuitum e Mycobacterium smegmatis

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

The frequent resistance of atypical micobacteria for antituberculous drugs, the absence of efficient therapeutical scheme and the studies about applications of new molecules against micobactÃrias induced us to determinate the postantibiotic effect (PAE) in vitro of a new derivative 1,2,4-oxadiazole-hidrazide (HHBA) and its associations with ofloxacin (OFLO) and m-fluoro-phenylalanine (m-FFen), an cell wall biosynthesis inhibitor. The PAE was evaluated after 2 and 4 hours time exposure against Mycobacterium fortuitum and Mycobacterium smegmatis. This drugs was tested at their minimal inhibitory concentration (MIC). PAE is a pharmacodimamic parameter and perform its major importance at the antimicrobial agent choice, at therapeutical doses regime and theirs administration interval. The PAE can be induced through to microrganism exposure to a drug for a determinate time, followed an rapid removal of this drug, and follow the microrganism regrowth. For quantitation of the PAE the following equation was developed: PAE=T-C, where T is the time required for the count of UFC in the test culture to increase 1 log10, above the count observed immediately after drug removal and C is the time required for the count of UFC in an untreated control to increase by 1 log10, above the count observed immediately after completion of the same procedure on the test culture for drug removal. About the M. fortuitum PAE after 2 hours exposure the OFLO showed the longest PAE, 8,60Â1,50 hours. All associations were antagonistic, except HHBA-m-FFen who induced an indifferent PAE of 1,20 Â 1,20 hours. After 4 hours exposure, the OFLO continued showing the highest PAE of 11,50 Â 2,00 hours, and its association with m-FFen showed an indifferent PAE of 11,00 Â 2,70 hours. All others associations were antagonistic. The PAE of HHBA against M. smegmatis after 2 hours exposure was 2,40 Â 2,80 hours and its association with OFLO was the best association with a PAE of 3,30Â 2,80 hours. After 4 hours of contact the HHBA PAEâs did not change, remaining in 3,30 Â 2,60 hours. The increase of contact time induced an increase of PAE values at the tested drugs and theirs associations, except the m-FFen, and the associations OFLO-HHBA and OFLO-HHBA-m-FFen against the M. smegmatis, and the HHBA and its association with m-FFen, against M. fortuitum. The ofloxacin was the drug that induced the best PAEs against the Mycobacterium fortuitum, and the HHBA was the drug that induced the best PAEs against the Mycobacterium smegmatis. The increase of exposure time, from 2 to 4 hours, provided an increase in the PAEs induced for all studied drugs. All associations tested were antagonistic, except the association OFLO-m-FFen, after 4 hours exposure, against M. smegmatis. The exposure times and the MIC used in all assay was not sufficient to induce synergic PAEs. As the mechanisms of the PAEs for the different drugs are still unclear, it would be difficult to speculate about the processes underlying the variations in PAEs when drugs are tested in different combinations

ASSUNTO(S)

metabolismo e bioenergetica efeito pÃs-antibÃticos - 1,2,4-oxadiazol-hidrazida 1,2,4-oxadiazol-hidrazida - associaÃÃes

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