Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC). METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 x 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. RESULTS: Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%). At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated. Flu-like symptoms predominated in the IFN gamma group. No severe events were recorded. CONCLUSION: These data suggest that IFN gamma is useful and well tolerated as adjuvant therapy in patients with pulmonary atypical Mycobacteriosis, predominantly MAC. Further wider clinical trials are encouraged. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70900209.

Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: a randomized, double-blind, placebo-controlled study

Background High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC). MethodsA randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. Results Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75 percent men, 84 percent white; MAC infection prevailed (94 percent). At the end of treatment, 72 percent of patients treated with IFN gamma were evaluated as complete responders, but only 36 percent in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7 percent of the patients in the placebo group and only 11.1 percent in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN... (AU)

Adjuvant interferon gamma in patients with drug - resistant pulmonary tuberculosis: a pilot study.

BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments. METHODS: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 x 10(6) IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. RESULTS: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. CONCLUSIONS: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

Adjuvant interferon gamma in patients with drug resistant pulmonary tuberculosis: a pilot study

Background: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments. Methods: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 106 IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. Results: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. Conclusions: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged(AU)

Antecedentes: La tuberculosis (TB) es cada vez mayor en el mundo y resistente a fármacos (DR) atrae a nuevos tratamientos de enfermedades. Métodos: Para evaluar la acción del interferón (IFN) gamma immunoadjuvant como a la quimioterapia DR-pulmonar en los pacientes con tuberculosis, a título experimental, ensayo clínico abierto se llevó a cabo en el barrio cubano de referencia para la gestión de esta enfermedad. Los ocho temas existentes en el país en el momento recibidas, como en los pacientes, 1 × 106 UI de IFN gamma recombinante humana por vía intramuscular, diariamente durante un mes y luego tres veces por semana hasta 6 meses como adyuvante a la quimioterapia se indica, según a sus antibiogramas y directrices de la OMS. Recogida de muestras de esputo para la observación directa de Papanicolau y la cultura, así como la rutina clínica y radiografía de tórax se realizaron evaluaciones mensuales. Resultados: frotis de esputo y la cultura pasó a ser negativa para el ácido-rápido-bacilos antes de tres meses de tratamiento en todos los pacientes. El tamaño de las lesiones se redujo al final de 6 meses de tratamiento, las lesiones desaparecieron en un caso. La mejoría clínica fue evidente, el aumento de índice de masa corporal en general. Interferón gamma fue bien tolerada. Pocos efectos adversos fueron registrados, en su mayoría leves, fiebre y artralgias prevalecido. Conclusiones: Estos datos sugieren que el IFN gamma es útil y bien tolerado como tratamiento adyuvante en pacientes con TB-DR. Más ensayos clínicos controlados se anima