Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?

The inappropriate treatment of drug-susceptible tuberculosis can lead to the selection and transmission of multidrug-resistant tuberculosis (MDR-TB), indicating resistance to at least isoniazid and rifampicin. In the treatment of MDR-TB, residual first-line drugs, such as ethambutol, pyrazinamide an...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2004-09, Vol.54 (3), p.593-602
Main Authors: Di Perri, Giovanni, Bonora, Stefano
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - therapeutic use
Biological and medical sciences
Drug Resistance, Multiple, Bacterial
Humans
M. tuberculosis
Medical sciences
multidrug-resistant tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Pharmacology. Drug treatments
second-line agents
therapy
Treatment Outcome
Tuberculosis - drug therapy
Tuberculosis - microbiology
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Summary:The inappropriate treatment of drug-susceptible tuberculosis can lead to the selection and transmission of multidrug-resistant tuberculosis (MDR-TB), indicating resistance to at least isoniazid and rifampicin. In the treatment of MDR-TB, residual first-line drugs, such as ethambutol, pyrazinamide and streptomycin must be appropriately combined with additional second-line drugs, guided by individual susceptibility patterns. The clinical pharmacology of these second-line antituberculous drugs is reviewed. Fluoroquinolones represent the only substantial therapeutic advance in the last 20 years. Many factors potentially affect the outcome of MDR-TB. Treatment adherence, prior exposure to antituberculous drugs, the number of drugs to which the infection is still susceptible and the time since the first diagnosis of tuberculosis are the most relevant. The management of MDR-TB requires considerable expertise. When initiating or revising therapy for MDR-TB, the process of selecting drugs should rely on prior treatment history, results of susceptibility testing and an evaluation of the patient's adherence. In making drug selection, we propose to follow a hierarchy based on the intrinsic activity against Mycobacterium tuberculosis and the clinical evidence of efficacy of the available active compounds.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkh377