How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis.
OBJECTIVE
To explore mechanisms by which drug resistance might arise as a result of poor compliance during short course chemotherapy.


METHODS
Four theoretical mechanisms are first described.


RESULTS
Examples of the way the mechanisms probably operate are taken from: 1) a study of once-weekly chemotherapy with streptomycin and isoniazid, and 2) the pattern of drug susceptibility in cultures from patients who relapsed after the end of treatment.


CONCLUSIONS
Good compliance is vitally important. The value of a fourth drug in the initial phase of chemotherapy in preventing resistance is questioned. An explanation for mono-resistance to rifampicin in patients with the acquired immune deficiency syndrome (AIDS) is suggested.
Mitchison
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Department of Medical Microbiology, St. George's Hospital Medical School, London, UK. dmitchis@sghms.ac.uk
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D004977:Ethambutol / Q000008:administration & dosage / Q000627:therapeutic use; D006679:HIV Seropositivity; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D010349:Patient Compliance; D011718:Pyrazinamide / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012293:Rifampin / Q000627:therapeutic use; D013307:Streptomycin / Q000008:administration & dosage / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000209:etiology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000209:etiology
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin