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, 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.@ERSpublications Six antimicrobial drugs are not listed in WHO guidelines on MDR-TB treatment but could offer potential for TB treatment

Mefloquine as a potential drug against multidrug-resistant tuberculosis

“…In the article by ALSAAD et al [1] in a recent issue of the European Respiratory Journal the authors reviewed six drugs with antimicrobial activity against Mycobacterium tuberculosis ( phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) which are not listed in the World Health Organization guidelines on multidrug-resistant tuberculosis (MDR-TB) treatment, but could be potential candidates for this use. Despite of the release of new drugs (delamanid, bedaquiline), treatment alternatives are still warranted, last but not least because of treatment costs.…”

Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner

“…Efficacy studies and the establishment of comprehensive safety profiles may take up to 6 years per drug, with time estimates for a new four-drug cocktail approaching 25 years (10). Repurposing of already approved drugs for new medical uses is therefore a faster and more economical approach as safety profiles in humans have already been established, and there are multiple promising candidates (11).…”

Pulmonary Tuberculosis Management: 2015 Update

“…Other drugs, including sulfamides and mefloquine, have been used in difficult-to-treat cases, although the evidence is anecdotal [63][64][65] . OBR: optimized background regimen; C: culture; HR: hazard ratio; CI: confidence interval; CFU: colony-forming unit; SS: sputum smear; AE: adverse events; BCI: Bayesian credibility interval; BID: twice daily; QT: measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; ECG: electrocardiogram; EBA: early bactericidal activity; DS: drug-susceptible; DR: drug-resistant; MDR-TB: multidrug-resistant tuberculosis; PTB: pulmonary tuberculosis; DR-TB: drug-resistant-tuberculosis; TB: tuberculosis; WBA: whole blood bactericidal activity; OB: once daily; MIC: minimum inhibitory concentration; H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; Bql: bedaquiline; Pto: pretomanid; Del: delamanid; Cfz: cloafazimine.…”