ethionamide and AIDS-Related-Opportunistic-Infections

An Argentinean reference hospital specialising in infectious diseases.. To assess the outcomes of all human immunodeficiency virus (HIV) negative multidrug-resistant tuberculosis (MDR-TB) patients referred to or diagnosed at Hospital Muñiz.. Clinical study for the period 1996-1999, with follow-up until June 2002.. One hundred and forty-one adult patients (52.5% female) with resistance to two to seven drugs were studied. Fifty patients (35.5%) had not been treated previously. The most frequently used second-line drugs were 5-F-quinolones, cycloserine and ethionamide in susceptibility based individually tailored three- to five-drug regimens. Hospital admission was associated with treatment success. Forty-five episodes of severe toxicity occurred. Treatment was successful in 51.8% of cases, but follow-up of 73 patients yielded 11.9% relapse. The mortality rate was 19.1% and default was 19.9%. Logistic regression analysis was statistically significant for treatment success in relation to patient admission, residence and resistance pattern.. The burden of MDR-TB in this setting--prolonged infection, treatment cost and difficulties, low rates of cure and treatment adherence and high rates of fatality and relapse--can be improved by strengthening TB control programme activities and fighting against poverty and HIV/AIDS.

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Argentina; Cycloserine; Drug Combinations; Ethionamide; Female; Follow-Up Studies; HIV Seronegativity; Hospitalization; Hospitals, Special; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Prognosis; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

We report a case of an HIV-infected child with a second episode of tuberculosis 22 months after completing antituberculosis treatment. DNA fingerprinting of organisms from both episodes showed an identical strain of Mycobacterium tuberculosis. We believe this to be the first case of confirmed relapsed tuberculosis in an HIV-infected child, and suggest that a longer course of antituberculosis treatment be given to such children. ¿ 2000 The British Infection Society.

Topics: AIDS-Related Opportunistic Infections; Amoxicillin-Potassium Clavulanate Combination; Antibiotics, Antitubercular; Antitubercular Agents; Child, Preschool; DNA, Bacterial; Drug Therapy, Combination; Ethionamide; HIV; HIV Infections; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length; Pyrazinamide; Radiography, Thoracic; Rifampin; Secondary Prevention; South Africa; Tomography, X-Ray Computed; Tuberculin Test; Tuberculosis; Tuberculosis, Meningeal

Tuberculosis-control programmes are compromised by the increased frequency of multidrug-resistant strains of Mycobacterium tuberculosis. We used the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis techniques to establish the molecular basis of resistance in 37 drug-resistant isolates of M tuberculosis, and correlated these findings with clinical and antibiotic-sensitivity data. Resistance to isoniazid was found in 36 strains, 16 of which were also resistant to ethionamide. Of the 36 isoniazid-resistant strains, 23 had mutations in the katG gene, and 5 of these also had mutations in the inhA gene. A further 5 strains had alterations in the inhA locus without the katG gene being mutated. Rifampicin resistance was less frequent (13 strains) and usually associated with isoniazid resistance (11 of 13 strains). Mutations in the rpoB gene were detected for all these rifampicin-resistant isolates. Mutations in the rpsL and rrs genes, associated with streptomycin resistance, were found in 13 of 25 and 2 of 25 streptomycin-resistant strains, respectively. The same chromosomal mutations, or combinations of mutations, were found in strains displaying single or multidrug resistance, from cases of both primary and secondary resistance, and from patients infected with human immunodeficiency virus. Thus, multidrug resistance is not due to a novel mechanism and tuberculosis chemotherapy is not subject to a new threat.

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Resistance, Microbial; Ethionamide; Female; Genes, Bacterial; Humans; Isoniazid; Male; Mutation; Mycobacterium tuberculosis; Polymerase Chain Reaction; Retrospective Studies; Rifampin; Streptomycin; Tuberculosis, Multidrug-Resistant