Emprego da associação sulfametoxazol + trimetoprim no tratamento da paracoccidioidose (blastomicose Sul-Americana)

Abstract

Acentuando a necessidade da continuação das pesquisas terapêuticas em INTRODUÇÃODesde 1940, quando Ribeiro (17) intro duziu os derivados sulfamídicos na tera pêutica da paracoccidioidose, nenhum ou tro avanço comparável foi até o momento obtido. Apesar da descoberta e emprego clí nico de diversas outras drogas, entre as quais se destaca a anfotericina B, os deri vados sulfamídicos permanecem como pri meira escolha em seu tratam ento. Através de constantes aperfeiçoamentos que os tor naram cada vez menos tóxicos e de mais fácil administração, consolidou-se o seu va lor, passados mais de 30 anos (2,8,11,12,13,16). Entretanto, são conhecidos casos de sulfa-resistência, sejam primários ou ta r dios, estes últimos conseqüentes quer a tra tam ento insuficiente em dose ou tempo, quer a seleção de cepas resistentes'. Macha do Filho e M iranda (14) referem 17 casos de sulfa-resistência em 394 tratados, e Lo pes e Armond (10) 12 casos em 122 tra ta dos com diversos derivados sulfamídicos, entre outros autores (1,3,4,6,19,20), res saltando o problema terapêutico destes ca sos. Até recentemente a única opção para estes pacientes era o emprego da anfoteri cina B. Numerosos autores que a emprega ram

In vitro susceptibility testing of Paracoccidioides brasiliensis to sulfonamides

“…Mackinnon, using adequate culture medium but prolonged 300C incubation, recorded only partial inhibition of his 6 isolates with 150 ,ug of sulfadiazine per ml (8). It is tempting to postulate a correlation between the in vitro findings and the recorded proportion of patients refractory to sulfonamide treatment from the start of therapy (7,8,14,16,18).…”

“…This may explain therapy failures in patients who had initially responded but became refractory shortly afterwards or when control of a relapse in a previously treated patient proved unsuccessful (7,14).…”

“…A modification of the Mueller-Hinton medium was devised which gave good growth of the yeast form. The minimum inhibitory concentrations for only 51.6% of the isolates were in the range of the recommended blood serum concentration (50 ,ug/ml (7,14).…”

“…A modification of the Mueller-Hinton medium was devised which gave good growth of the yeast form. The minimum inhibitory concentrations for only 51.6% of the isolates were in the range of the recommended blood serum concentration (50 ,ug/ml (7,14).In spite of these observations, there has been no survey of the in vitro susceptibility of the causative agent, Paracoccidioides brasiliensis, to sulfonamides. Earlier studies either employed complex culture media, which could have antagonized the effect of the drug, or made use of the fungus mycelial phase, which is different from the phase found in tissues, that is, the yeast phase of this dimorphic fungus (5,8,15 This report describes the procedure developed for sulfonamide susceptibility testing and presents data on the susceptibility pattern of 60 different isolates of P. brasiliensis to sulfadiazine and sulfadimethoxyne.…”

“…Clinical observations have also revealed that relapses occur in approximately 10% of the cases, presumably because of fungal resistance acquired during the course of inadequate treatment. Some patients, however, appear refractory to sulfonamides from the beginning of sulfonamide therapy, suggesting infection with a sulfonamide-resistant strain (7,14).…”