Abstract
Objective:
To explore mechanisms by which drug resistance might arise as a result of poor compliance during short course chemotherapy.
Design:
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.
Conclusion:
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.
MeSH terms
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AIDS-Related Opportunistic Infections / drug therapy
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Antibiotics, Antitubercular / administration & dosage
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Antibiotics, Antitubercular / therapeutic use
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Antitubercular Agents / administration & dosage
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Antitubercular Agents / therapeutic use*
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Drug Administration Schedule
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Drug Resistance, Microbial
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Ethambutol / administration & dosage
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Ethambutol / therapeutic use
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HIV Seropositivity
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Humans
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Isoniazid / administration & dosage
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Isoniazid / therapeutic use
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Mutation / genetics
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / growth & development
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Patient Compliance*
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Pyrazinamide / administration & dosage
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Pyrazinamide / therapeutic use
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Recurrence
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Rifampin / therapeutic use
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Streptomycin / administration & dosage
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Streptomycin / therapeutic use
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Tuberculosis, Multidrug-Resistant / etiology*
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Tuberculosis, Pulmonary / drug therapy*
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Tuberculosis, Pulmonary / etiology
Substances
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Antibiotics, Antitubercular
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Antitubercular Agents
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Pyrazinamide
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Ethambutol
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Isoniazid
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Rifampin
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Streptomycin