Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosisAlsaad, N., Wilffert, B., van Altena, R., de Lange, W. C. M., van der Werf, T. S., Kosterink, J. G. W. & Alffenaar, J-W. C., 1-Mar-2014, In : European Respiratory Journal. 43, p. 884-897 14 p.
Research output: Contribution to journal › Review article › Academic › peer-review
- Pharmacotherapy and Pharmaceutical Care
- Methods in Medicines evaluation & Outcomes research (M2O)
- Reproductive Origins of Adult Health and Disease (ROAHD)
- Microbes in Health and Disease (MHD)
- Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Targeted Gynaecologic Oncology (TARGON)
Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of already available drugs. Six drugs with antimicrobial activity (phenothiazine, metronidazole, doxycydine, disulfiram, tigecydine and co-trimoxazole) are not listed in the World Health Organization guidelines on MDR-TB treatment but could be potential candidates for evaluation against Mycobacterium tuberculosis.
A systematic review was conducted to evaluate antituberculous activity of these drugs against M. tuberculosis. We searched PubMed, Google Scholar and Embase for English articles published up to December 31, 2012.
We reviewed in vitro, in vivo and clinical antituberculous activity of these drugs in addition to pharmacokinetics and side-effects. Of the drugs effective against actively replicating M. tuberculosis, cotrimoxazole seems to be the most promising, because of its consistent pharmacokinetic profile, easy penetration into tissue and safety profile. For the dormant state of TB, thioridazine may play a potential role as an adjuvant for treatment of MDR-TB. A strategy consisting of pharmacokinetic/pharmacodynamic studies, dose finding and phase III studies is needed to explore the role of these drugs in MDR-TB treatment.
|Number of pages||14|
|Journal||European Respiratory Journal|
|Publication status||Published - 1-Mar-2014|
- IN-VITRO ACTIVITY, MYCOBACTERIUM-TUBERCULOSIS, TRIMETHOPRIM-SULFAMETHOXAZOLE, DRUG-RESISTANCE, ANTIMYCOBACTERIAL ACTIVITY, DIHYDROFOLATE-REDUCTASE, REDUCES MORTALITY, THIORIDAZINE, METRONIDAZOLE, PHARMACOKINETICS