Effect of Two Isoniazid Derivatives and Pas Hydrazide on Isoniazid Susceptible and Resistant Tubercle Bacilli.

Publisher Website
Google Scholar
Abstract
Two isoniazid derivatives, N-isonicotinoyl-N[image]-(salicylidene) hydrazine (INSH) and N-isonicotinoyl-N[image]-(2,2-dimethyl-3-hydroxypropylidene) hydrazine (IHPH), have an in vitro tuberculostatic effect similar to that of INH but both exhibit cross resistance with the parent compound. H37Rv Tubercle bacilli were easily made resistant to INSH by serial passage in drug-containing liquid medium, after which the strain was found to have lost its former virulence for guinea pigs. Resistance was much slower to appear, however, in medium containing a combination of INH plus INSH. p-Aminosalicylic acid hydrazide (PASH) showed about the same in vitro effect as, and cross resistance with, PAS, but there was no cross resistance with INH. Tubercle bacilli could easily be made resistant to PASH by serial passage in drug-containing medium. This compound had very little beneficial effect in mice infected intravenously with the H37Rv strain. INSH pro- duced therapeutic results similar to those seen with INH in experimental tuberculosis of rabbits infected intravenously with a virulent bovine strain. Guinea pigs were infected sub-cutaneously with 4 INH-resistant strains of tubercle bacilli; 3 were human strains and the 4th, a bovine strain isolated from a rabbit. Treatment with INH, INSH, or IHPH produced good results in the animals infected with the 2 strains showing least in vitro resistance, but very little beneficial effect in those infected with the 2 strains containing at least 1.0% of individual organisms resistant to 5 [mu]g/ml. There was no significant difference in the results obtained in any of the 4 groups with INH or either of its 2 derivatives. In none of the groups was treatment with PASH beneficial. INSH and IHPH are similar in effect to INH in experimental tuberculosis produced by INH-sensitive and -resistant tubercle bacilli.