ABSTRACT
The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistance to all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.
La correlación entre resultados de pruebas de sensibilidad a drogas antituberculosas de segunda línea y evolución de los pacientes en tratamiento, aún es discutida. Se reanalizan aquí tres estudios realizados en la década del 60, sobre la relación entre resultados de pruebas de sensibilidad y tratamiento con estas drogas, en pacientes crónicos, internados en el hospital Muñiz, Buenos Aires, que habían sido tratados con el entonces régimen estándar, integrado por isoniacida, estreptomicina y PAS; se habían hecho resistentes al menos a dos de estas drogas y continuaban con cultivo positivo. La prueba de sensibilidad a etionamida, cicloserina y kanamicina se efectuó por el método de las proporciones en medio Löwenstein Jensen. Entre 4 y 13% de los pacientes previamente no tratados con estas drogas presentó cierto nivel de resistencia, fenómeno atribuido a la administración previa de drogas de primera línea con moléculas análogas. Se halló asociación significativa entre resistencia a etionamida y cicloserina, y tratamiento previo con estas drogas. La resistencia a las tres drogas fue detectada en los primeros tres meses de tratamiento, siendo la resistencia a etionamida la más frecuente, y la primera en emerger, seguida por cicloserina y kanamicina, cuya baja frecuencia en alcanzar resistencia estaría relacionada con las bajas dosis administradas. La resistencia simultánea a las tres drogas, pero no a una o dos, resultó marcadora de fracaso terapéutico. Se observó en cerca del 6% de los pacientes aparente reversión de la resistencia, en pruebas hechas en aislamientos sucesivos, interpretada como falla en la reproducibilidad de resultados.
Subject(s)
Humans , Anti-Bacterial Agents/therapeutic use , Antitubercular Agents/therapeutic use , Evidence-Based Medicine , Microbial Sensitivity Tests/standards , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/drug therapy , Argentina , Antibiotics, Antitubercular/therapeutic use , Antitubercular Agents/pharmacology , Clinical Trials as Topic , Cycloserine/therapeutic use , Drug Resistance, Microbial , Drug Therapy, Combination , Ethionamide/therapeutic use , Follow-Up Studies , Isoniazid/therapeutic use , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary/microbiologyABSTRACT
BACKGROUND: We carried out this study to determine the efficacy and safety of a regimen containing kanamycin, ethionamide, isoniazid, para-aminosalicylic acid (PAS) and cycloserine in the treatment of multidrug-resistant tuberculosis (MDR-TB). METHODS: A prospective, uncontrolled study of 39 pulmonary tuberculosis patients, who had received adequate first-line antituberculosis treatment including supervised category II retreatment regimen, and were still sputum smear positive for acid-fast bacilli (AFB) in whom sputum culture revealed isolates of M. tuberculosis resistant to rifampicin and isoniazid with and without resistance to other antituberculosis drugs. They received kanamycin (initial 4-6 months), ethionamide, isoniazid, PAS and cycloserine for a minimum period of two years. RESULTS: Out of 39 patients, 29 (74.3%) achieved sputum conversion within six months and remained so at the end of two years. Two (5.1%) patients died, six (20.6%) patients were lost to follow up, and two (5.1%) patients remained sputum smear-positive for AFB through out the period of study. Twenty-nine patients, declared cured, were followed for an average period of 16 months (3-48 months), during which two (6.9%) patients relapsed, four (13.8%) patients were lost to follow-up and remaining 23 remained sputum smear-negative. Eight (21.1%) patients developed major side effects which required stoppage/change of drugs. CONCLUSION: In MDR-TB patients, regimen consisting of ethionamide, isoniazid, PAS and cycloserine and kanamycin appears to be effective and safe.
Subject(s)
Adolescent , Adult , Antitubercular Agents/therapeutic use , Cycloserine/therapeutic use , Drug Therapy, Combination , Ethionamide/therapeutic use , Female , Humans , Kanamycin/therapeutic use , Male , Middle Aged , Prospective Studies , Sputum/microbiology , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Aminosalicylic Acid/therapeutic useABSTRACT
Säo apresentados 4 pacientes com resistência a mais de uma das drogas que fazem parte dos esquemas terapêuticos preconizados pela OMS contra a hanseníase. Os autores discutem o modo de aparecimento dessa múltipla resistência e consideram a possibilidade de ocorrer esse fenômeno de maneira inicial, isto é, paciente que se infectam com bacilos já resistentes a mais de uma droga. Lembram o que está acontecendo nos Estados Unidos com a tuberculose, onde aumentou consideravalmente o número de casos com resistência inicial a múltiplos fármacos e admitem a possibilidade da AIDS que é responsável pela maior parte dessa situaçäo, vir a ter papel semelhante na hanseníase. Alertam também para o fato de drogas ainda em fase experimental e que já se acham disponíveis no comércio, começarem a ser utilizadas indevidamente, comprometendo o seu uso no futuro
Subject(s)
Middle Aged , Mice , Humans , Animals , Male , Dapsone/therapeutic use , Ethionamide/therapeutic use , Leprosy/drug therapy , Rifampin/therapeutic use , Drug Therapy, Combination , Drug Resistance, MicrobialSubject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Antitubercular Agents/adverse effects , Chemical and Drug Induced Liver Injury/therapy , Ethambutol/therapeutic use , Ethionamide/therapeutic use , Isoniazid/therapeutic use , Length of Stay , Pyrazinamide/therapeutic use , Retrospective Studies , Streptomycin/therapeutic use , Tuberculosis/drug therapySubject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Antitubercular Agents/adverse effects , Chemical and Drug Induced Liver Injury/therapy , Ethambutol/therapeutic use , Ethionamide/therapeutic use , Isoniazid/therapeutic use , Length of Stay , Pyrazinamide/therapeutic use , Retrospective Studies , Streptomycin/therapeutic use , Tuberculosis/drug therapyABSTRACT
Os autores estudam a aplicabilidade da etionamida da hanseníase nas susas diversas formas clínicas, em regime de multidrogaterapia
Subject(s)
Child , Adolescent , Adult , Male , Female , Middle Aged , Ethionamide/therapeutic use , Leprosy/drug therapy , Drug Therapy, CombinationABSTRACT
Se estudia la efectividad clínica de la asociación de pirazinamida, ethambutol, ethionamida y estreptomicina en el retratamiento de la tuberculosis pulmonar en 15 pacientes tuberculosos (5 hombres y 10 mujeres) con edades comprendidas entre 28 y 82 años. Fueron sometidos a retratamiento de tuberculosis pulmonar en el Servicio de Neumonología del Hospital "Dr. Luis Gómez López", ya que representaban casos crónicos y recidivas, administrándoseles la combinación de fármacos a base de estreptomicina, ethambutol, ethionamida y pirazinamida diariamente por un tiempo de tres meses. La evolución se considera satisfactoria, observándose negativización de la baciloscopia a la séptima semana de terapia. Igualmente, podemos afirmar esta aseveración en cuanto al aspecto radiológico, mejorando las lesiones pulmonares desde avanzadas a moderadas y leves. Desde el punto de vista clínico, radiológico y baciloscópico, la mejoría estuvo representada para un 80 por ciento de resultado BUENO y un 20 por ciento resultado MALO
Subject(s)
Adult , Middle Aged , Humans , Male , Female , Ethambutol/therapeutic use , Ethionamide/therapeutic use , Pyrazinamide/therapeutic use , Streptomycin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Drug Therapy, CombinationSubject(s)
Animals , Clofazimine/therapeutic use , Dapsone/therapeutic use , Drug Resistance, Microbial , Drug Therapy, Combination , Ethionamide/therapeutic use , Foot/microbiology , Humans , Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Mice , Mycobacterium leprae/drug effects , Prothionamide/therapeutic use , Pyrazinamide/therapeutic use , Rats , Rifampin/adverse effects , Thioacetazone/therapeutic useABSTRACT
The latest time bound WHO regimens for the treatment of paucibacillary (I, TT, BT) and multibacillary leprosy is discussed. The rationale, indications of above regimens and cautions necessary are highlighted.
Subject(s)
Clofazimine/therapeutic use , Dapsone/therapeutic use , Drug Administration Schedule , Ethionamide/therapeutic use , Humans , Leprosy/drug therapy , Prothionamide/therapeutic use , Rifampin/therapeutic useABSTRACT
The steady increase in the prevalence of dapsone-resistant strains of leprosy threatens to undermine all the advances thus made for the control of this disease. Adoption of multidrug therapy, which can reverse this trend, is urgent.
Subject(s)
Clofazimine/therapeutic use , Dapsone/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Ethionamide/therapeutic use , Humans , Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Microbial Sensitivity Tests , Prothionamide/therapeutic use , Rifampin/therapeutic useABSTRACT
Se presentan los resultados de las pruebas de resistencia hechas a 22 pacientes nuevos, sin tratamientos previos, descubiertos en el Hospital de la Maria en Noviembre de 1982. A pesar de que la muestra no es representativa, la alta proporcion de germenes resistentes (32%) y especificamente a la INH, hace necesario y urgente mas investigacion al respecto o un cambio en la politica de tratamiento.
Subject(s)
Humans , Cycloserine/therapeutic use , Ethambutol/therapeutic use , Ethionamide/therapeutic use , Isoniazid/therapeutic use , Drug Resistance, Microbial , Rifampin/therapeutic use , Streptomycin/therapeutic use , Thiosemicarbazones/therapeutic use , Tuberculosis/drug therapyABSTRACT
Já es reconocida la necesidad de una terapéutica para la lepra basada en la administración simultánea de dos o más drogas. Son detallados esquemas terapéuticos, recomendados por la OMS, en casos multibacilares y paucibacilares