title: Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis.
abstract: 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, doxycycline, disulfiram, tigecycline 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, co-trimoxazole 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.
authors.affiliation: University Medical Center Groningen, Dept of Hospital and Clinical Pharmacy, Groningen.
authors.forename: Noor
authors.initials: N
authors.lastname: Alsaad
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.forename: Richard
authors.initials: R
authors.lastname: van Altena
authors.forename: Wiel C M
authors.initials: WC
authors.lastname: de Lange
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical / Q000639:trends; D002986:Clinical Trials as Topic; D004221:Disulfiram / Q000627:therapeutic use; D004318:Doxycycline / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D008795:Metronidazole / Q000627:therapeutic use; D008911:Minocycline / Q000031:analogs & derivatives / Q000627:therapeutic use; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010640:Phenothiazines / Q000627:therapeutic use; D000078304:Tigecycline; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D010640:Phenothiazines; D008795:Metronidazole; D000078304:Tigecycline; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D008911:Minocycline; C031637:phenothiazine; D004318:Doxycycline; D004221:Disulfiram