**4.4 Metronidazole (Nitroimidazole)**

Metronidazole is a broad-spectrum antibiotic used in the treatment of gastrointestinal infections. Some parasitic infections including amebiasis, giardiasis and trichomoniasis are also treated by this drug [42]. The exact mechanism of this drug has not been fully elucidated, but it has been hypothesised that the drug renders its action through the blocking of nucleic acid synthesis via an intermediate of metronidazole and through the production of a toxic metabolite in anaerobic bacteria through the reduction of the nitro group by the redox potential of the electron transport chain [43]. It has been shown that metronidazole was able to inhibit the growth of mycobacterial bacilli under anaerobic non-replicating conditions but showed no activity under aerobic conditions [44]. *In vivo* studies in macaques (a non-human primate model), showed similar efficacy of inhibiting reactivation of latent TB, as compared to a combination of isoniazid and rifampicin [45]. In a phase 2 clinical trial investigating the effect of metronidazole vs. placebo on pulmonary MDR-TB, some efficacy was observed in sputum smears after 1 month of treatment, but the benefit was not sustained past 2 months of treatment. The study was ultimately halted due to the occurrence of peripheral neuropathies within the test subject group [46]. Although metronidazole is associated with several adverse effects, other and newer nitroimidazoles are extremely important within the clinical pipeline against TB. These include pretomanid and delamanid which are both part of multiple phase 2 and 3 clinical trials.
