Short-course chemotherapy for pulmonary tuberculosis under routine programme conditions: a comparison of regimens of 28 and 36 weeks duration in Algeria

doi:10.1016/0041-3879(91)90034-P

Tubercle

Volume 72, Issue 2, June 1991, Pages 88-100

Tubercle

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Abstract

Two chemotherapy regimens of 28 weeks (6M) and 36 weeks (8M) duration were compared in patients with previously untreated pulmonary tuberculosis in 30 health districts of Algeria. In the 6M regimen, patients received isoniazid plus rifampicin daily throughout with streptomycin and pyrazinamide in addition for the first 8 weeks. In the 8M regimen patients received isoniazid daily throughout plus rifampicin for the first 16 weeks and streptomycin and pyrazinamide as well for the first 8 weeks. The districts were allocated to apply either the 6M or the 8M regimen to all eligible patients. However, 22% of eligible patients were not admitted, the most common reason being oversight on the part of the personnel in the local health centres.

A total of 2218 (977 6M,1241 8M) patients was admitted and the results were assessed 2 years after the due date of completion of chemotherapy, irrespective of whether or not management had deviated from the study protocol. An appreciable proportion of patients (25% of 6M, 29% of 8M) could not be assessed because they failed to attend for follow-up or the collection of specimens was overlooked or because of difficulties in the transport of specimens to the reference laboratory in Algiers, and a further 5% and 4% of patients died. Of those who were assessable 7 (1 %) of 731 6M and 15 (2%) of 875 8M were classified as having an unfavourable response during or after chemotherapy because they had one or more positive cultures. In addition 16 (2%) 6M and 18 (2%) 8M patients had received additional chemotherapy for failure, relapse or the development of non-pulmonary lesions but had achieved a favourable status.

Of 1018 (488 6M, 530 8M) patients assessed who had fully sensitive strains pretreatment and completed treatment as planned, 97% in both series had a favourable status 2 years after their chemotherapy was due to be completed. In patients with initial strains resistant to isoniazid the results were less good in the 8M than the 6M series: none of the 19 6M compared with 5 of 26 in the 8M series having an unfavourable outcome suggesting that the duration of rifampicin may have been important in patients with initial isoniazid resistance.

A slightly higher proportion of patients on the 8M regimen defaulted during chemotherapy (9.3% compared with 6.7% in the 6M regimen) but there was no difference between the regimens in other measures of compliance.

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Cited by (15)

Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis
2017, The Lancet Infectious Diseases
Citation Excerpt :
We added these newly identified articles to the 32 trials and ten cohorts identified for the previous review. The characteristics of the 33 trials7,12–43 and 19 cohort studies44–62 are summarised in the appendix. In seven of the cohort studies and 28 of the trials, data for patients with active drug-susceptible tuberculosis were also reported.
The results of some reports have suggested that treatment of isoniazid-resistant tuberculosis with the recommended regimens of first-line drugs might be suboptimal. We updated a previous systematic review of treatment outcomes associated with use of first-line drugs in patients with tuberculosis resistant to isoniazid but not rifampicin.
In this systematic review, we updated the results of a previous review to include randomised trials and cohort studies published in English, French, or Spanish to March 31, 2015, containing results of standardised treatment of patients with bacteriologically confirmed isoniazid-resistant tuberculosis (but not multidrug-resistant tuberculosis—ie, not resistant to rifampicin) in whom failure and relapse were bacteriologically confirmed. Results in patients with drug-sensitive tuberculosis included in the same studies were also analysed. We pooled treatment outcomes with random-effects meta-analysis.
We identified 19 cohort studies and 33 trials with 3744 patients with isoniazid-resistant tuberculosis and 19 012 patients with drug-sensitive disease. The pooled rates of failure or relapse, or both, and acquired drug resistance with all drug regimens were 15% (95% CI 12–18) and 3·6% (2–5), respectively, in patients with isoniazid-resistant tuberculosis and 4% (3–5) and 0·6% (0·3–0·9) in those with drug-sensitive tuberculosis. Of patients with initial isoniazid-resistant tuberculosis with acquired drug resistance, 96% (93–99) had acquired multidrug-resistant disease. Treatment of isoniazid-resistant tuberculosis with the WHO standard regimen for new patients resulted in treatment failure, relapse, and acquired multidrug resistance in 11% (6–17), 10% (5–15) and 8% (3–13), respectively; treatment with the standard WHO regimen for previously treated patients resulted in treatment failure in 6% (2–10), relapse in 5% (2–8), and acquisition of multidrug resistance in 3% (0–6). For patients with drug-sensitive disease treated with the standard retreatment regimen the rates were 1% (0–2), 5% (4–7), and 0·3% (0–0·6).
Treatment of isoniazid-resistant tuberculosis with first-line drugs resulted in suboptimal outcomes, supporting the need for better regimens. Standardised empirical treatment of new cases could be contributing substantially to the multidrug-resistant epidemic, particularly in settings where the prevalence of isoniazid resistance is high.
Canadian Institutes of Health Research.
Surveillance of drug resistance for tuberculosis control: Why and how?
1995, Tubercle and Lung Disease
The resistance of Mycobacterium tuberculosis to antibiotics, which reflects the quality of the chemotherapy applied in the community, is one of the elements of epidemiological surveillance used in national tuberculosis programmes. Measurement of drug resistance poses problems for biologists in standardization of laboratory methods and quality control. The definition of rates of acquired and primary drug resistance also necessitates standardization in the methods used to collect information transmitted by clinicians. Finally, the significance of the rates calculated depends on the choice of the patient sample on which sensitivity tests have been performed. National surveys of drug resistance therefore require multidisciplinary participation in order to select the only useful indicators: rates of primary resistance and of acquired resistance. These indicators, gathered in representative groups of patients over a long period, are a measurement of the impact of modern chemotherapy regimens on bacterial ecology.
La résistance de Mycobacterium tuberculosis aux antibiotiques, reflet de la qualité de la chimiothérapie antituberculeuse appliquée dans la collectivité, est l'un des éléments de surveillance épidémiologique des programmes nationaux antituberculeux. La mesure de la résistance bactérienne pose des problèmes de standardisation des méthodes de laboratoire et de contrôle de qualité aux bactériologistes. La définition des taux de resistance bactérienne acquise et primaire nécessite aussi une standardisation des méthodes de recueil des informations transmises par les cliniciens. Enfin, la signification des taux calculés dépend du choix de l'échantillon de malades pour lesquels des tests de sensibilité ont été faits. Les enquêtes nationales sur la résistance bactérienne impliquent donc une collaboration pluridisciplinaire pour choisir les seuls indicateurs utiles: le taux de la résistance primaire, et le taux de résistance acquise. Ces indicateurs, recueillies sur des échantillons représentatifs de malades et sur une longue période, permettent de mesurer l'impact sur l'écologie bactérienne des régimes de chimiothérapie moderne appliqués dans un pays.
La resistencia de Mycobacterium tuberculosis a los antibióticos, reflejo de la calidad de la quimioterapia antituberculosa aplicada en la colectividad, es uno de los elementos de la vigilancia epidemiológica de los programas nacionales de control de la tuberculosis. La determinación de la resistencia bacteriana plantea a los bacteriólogos ciertos problemas de estandarización de los métodos de laboratorio y de control de calidad. La definición de las tasas de resistencia bacteriana adquirida y primaria necesita también una estandarización de los métodos de recolección de las informaciones transmitidas por los clinicos. Finalmente, el significado de las tasas calculadas depende de la elección de la muestra de enfermos que han sido sometidos a tests de sensibilidad. Así, las encuestas nacionales sobre la resistencia bacterianas implican una colaboración pluridisciplinaria para elegir sólo los indicadores útiles : la tasa de resistencia primaria y la tasa de resistencia adquirida. Estos datos, recolectados en muestras representativas de enfermos y durante un largo período, permiten medir el impacto sobre la ecología bacteriana, de los esquemas modernos de quimioterapia aplicados en un país.
DNA fingerprints of Mycobacterium tuberculosis do not change during the development of rifampicin resistance
1993, Tubercle and Lung Disease
Drug-resistant tuberculosis has become a major public health problem. Resistance to rifampicin probably arises through mutations in the mycobacterial RNA polymerase. Patients may acquire rifampicin resistant tuberculosis by three mechanisms: (1) infection with a resistant organism, (2) selection of a sub-population of resistant organisms that remain contained whilst the more virulent wild type is present, (3) mutations within the population of bacilli causing the original infection. Sequential isolates of Mycobacterium tuberculosis were collected from 2 patients who developed rifampicin resistance whilst on treatment. One patient was immunosuppressed with HIV-infection; in the other patient the original isolate was also resistant to isoniazid. DNA fingerprinting techniques were used to type the isolates. No differences were found between the fingerprints of isolates from before and after the development of resistance. These data suggest that the third of the mechanisms listed above was responsible for the acquisition of rifampicin resistance in these 2 patients.
La tuberculose résistant aux drogues est devenue un problème majeur de santé publique. La résistance à la rifampicine est probablement due aux mutations de la ARN-polymérase mycobactérienne. Des patients peuvent acquérir une tuberculose résistant à la rifampicine par trois mécanismes: (1) infection par un organisme résistant, (2) sélection d'une sous-population d'organismes résistants qui demeurent conservés tant que le phénotype sauvage le plus virulent est présent, (3) mutations à l'intérieur de la population de bacilles responsables de l'infection d'origine. Des isolats séquentiels de Mycobacterium tuberculosis ont été recueillis à partir de deux patients qui avaient développé une résistance à la rifampicine au cours de leur traitement. L'un des patients était en état d'immunosuppression avec une infection VIH; chez l'autre patient l'isolat d'origine était résistant aussi à l'isoniazide. Des techniques d'empreinte génomique ont été utilisées pour typer les isolats. Aucune différence n'a été trouvée entre les empreintes des isolats effectués avant et après l'évolution de la résistance. Ces données suggèrent que le troisième des mécanismes cités ci-dessus a été responsable de l'acquisition d'une résistance à la rifampicine chez ces deux patients.
La tuberculosis resistente a los medicamentos ha llegado a ser un importante problema de salud pública. La resistencia a la rifampicina probablemente se produce a través de mutaciones en la ARN-polimerasa de las micobacterias. Los pacientes pueden adquirir una tuberculosis resistente a la rifampicina por tres mecanismos: (1) infección con un microrrganismo resistente; (2) selección de una subpoblación de microorganismos resisstentes que permanece inactiva mientras se encuentran presentes los tipos salvajes que son mas virulentos; (3) mutaciones dentro de la población de bacilos causantes de la infección original. Se recolectaron aislados de Mycobacterium tuberculosis en forma secuencial de dos pacientes que desarollaron una resistencia a la rifampicina durante el tratamiento. Uno de los pacientes presentaba una inmunodepresión con infection VIH; en el ontro paciente el aislado original también era resistente a la isoniacida. Para tipificar los aislados se usó la técnica de huellas (‘fingerprinting’) del ADN. No se encontró diferencia entre las huellas de los aislados recolectados antes y después del desarrollo de la resistencia. Estos resultados sugieren que el tercer mecanismo de la lista mencionada más ariba fue el responsable de la adquisición de la resistencia a la rifampicina en estos dos pacientes.
Drug combinations and the bioavailability of rifampicin
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Efficacy and safety of short-term chemotherapy for patients with spinal tuberculosis undergoing surgery in Chinese population: a meta-analysis
2021, Journal of Orthopaedic Surgery and Research
Twenty years of rifampicin resistance surveillance in Bangladesh: Periodic vs. continuous monitoring
2018, International Journal of Tuberculosis and Lung Disease

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Original articlesShort-course chemotherapy for pulmonary tuberculosis under routine programme conditions: a comparison of regimens of 28 and 36 weeks duration in Algeria

Abstract

Br J Dis Chest

Short-course chemotherapy for pulmonary tuberculosis and some problems of its programme application with particular reference to India

Bull IUAT

La chimiothérapie de la tuberculose en 1983

Bull IUAT

Comparaison de trois régimes de six mois dans la tuberculose pulmonaire en pratique de routine á Alger. Résultats au 19 mois

Rev Fr Mal Resp

Enquête contrôlée comparant trois regimes de chimiothérapie quotidiens de six mois dans la tuberculose pulmonaire en pratique de routine a Alger

Rev Fr Mal Resp

Controlled clinical trial comparing a 6-month and l2-month regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara

Am Rev Respir Dis

Comparison of a 6-month chemotherapy regimen to a 12-month chemotherapy regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara

Bull IUAT

Résultats d'un essai thérapeutique comparant un régime de 6 mois á un régime de 12 mois dans la tuberculose pulmonaire au Sahara algérian

Rev Fr Mal Resp

Etude comparée de la coloration du bacille tuberculeux par la méthode en fluorescence dans I'examen des piéces d'exérèse pulmonaire

Arch Inst Pasteur D'Algérie

Techniques et indications des examens bactériologiques en tuberculose.

Original articles
Short-course chemotherapy for pulmonary tuberculosis under routine programme conditions: a comparison of regimens of 28 and 36 weeks duration in Algeria