Enhancement of antibiotic activity against poly-drug resistant Mycobacterium tuberculosis by phenothiazines.
Phenothiazines have been shown to inhibit the in vitro growth of multi-drug resistant (resistant to rifampicin and isoniazid) Mycobacterium tuberculosis (MDRTB). They have been considered as potential adjuvants to regimens employing four or more antibiotics for the management of freshly diagnosed infections of M. tuberculosis in patients from areas known to have a high prevalence of MDRTB. Chlorpromazine has been shown to enhance the activity of antibiotics (except ethambutol) to which M. tuberculosis is susceptible. This might result in a reduction in the dose of some or all of the antibiotics employed without sacrificing the integrity of treatment. Chlorpromazine, thioridazine and promethazine were shown to enhance the activity of rifampicin and streptomycin when used in combinations at concentrations that are minimally effective when employed separately against clinical strains of M. tuberculosis resistant to two or more antibiotics (poly-drug resistant MTB). The phenothiazines had no effect on the activity of isoniazid against poly-drug resistant MTB.
Mycobacteriology Unit, The Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349-008, Lisbon, Portugal.
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Viveiros
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Amaral
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D010640:Phenothiazines / Q000494:pharmacology*; D011398:Promethazine / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D013881:Thioridazine / Q000494:pharmacology
D000904:Antibiotics, Antitubercular; D007155:Immunologic Factors; D010640:Phenothiazines; D011398:Promethazine; D013881:Thioridazine; D002746:Chlorpromazine; D012293:Rifampin; D013307:Streptomycin