Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis. In the case of bedaquiline, the primary target is the key respiratory chain enzyme F/F-ATPase, whereas clofazimine is less selective, apparently inhibiting several targets, which may underpin the extremely low level of resistance to this agent. This review is focused on similarities and differences between clofazimine and bedaquiline, specifically in respect of molecular mechanisms of antimycobacterial action, targeting of quiescent and metabolically active organisms, therapeutic efficacy in the clinical setting of DR-TB, resistance mechanisms, pharmacodynamics, pharmacokinetics and adverse events.

Naphthoquinones and triterpenes isolated from the roots of Euclea natalensis. A.DC (Ebenaceae) were evaluated for their inhibitory activity against Mycobacterium tuberculosis.. Crude extract, diospyrin and 7-methyljuglone isolated from the plant, exhibited minimum inhibitory concentrations of 8.0, 8.0, and 0.5 µg ml, respectively, against M. tuberculosis. H37 Rv (ATCC 27294), a drug-sensitive strain. Minimum inhibitory concentrations (MICs) of 7- methyljuglone against a panel of clinical pan-sensitive and drug-resistant strains of M. tuberculosis. ranged from 0.32 to 1.25 µg/ml. The concentration of 7-methyljuglone that effected a 90% reduction of growth of M. tuberculosis. Erdman within J774.1 macrophages was 0.57 µg/ml. The superior intracellular and extracellular inhibition of M. tuberculosis. by 7-methyljuglone relative to that of the antituberculosis drugs streptomycin and ethambutol suggests that this compound be considered as a lead for further investigations.

Lippia javanica and Hoslundia opposita are aromatic herbs that occur all over Mozambique and are well known for their medicinal properties. A Phytochemical investigation of L. javanica led to the isolation of eight compounds, 4-ethyl-nonacosane (1), (E)-2(3)-tagetenone epoxide (2), myrcenone (3), piperitenone (4), apigenin (5), cirsimaritin (6), 6-methoxyluteolin 4'-methyl ether (7), 6-methoxyluteolin and 3',4',7-trimethyl ether (8). Three known compounds, 5,7-dimethoxy-6-methylflavone (9), hoslunddiol (10) and euscaphic acid (11) were isolated from H. opposita. This is the first report of compounds 1, 2, 5-8 from L. javanica and of compound (9) from H. opposita. The compounds were tested against Mycobacterium tuberculosis and HIV-1 reverse transcriptase for bioactivity. It was found that compounds 2, 4 and 9 inhibited the HIV-1 reverse transcriptase enzyme by 91, 53 and 52%, respectively, at 100 microg mL(-1). Of all the compounds tested against a drug-sensitive strain of M. tuberculosis, euscaphic acid (11) was found to exhibit a minimum inhibitory concentration of 50 microg mL(-1) against this strain.

Gravendeel JMT, Asapa AS, Becx-Bleumink M, Vrakking HA. Preliminary results of an operational field study to compare side-effects, complaints and treatment results of a single-drug short-course regimen with a four-drug fixed-dose combination (4FDC) regimen in

Microbial culture is the gold standard for determining the effectiveness of tuberculosis treatment. End-of-treatment (EOT) 18 F-FDG PET/CT findings are variable among patients with negative microbial culture results after completing a standard regimen of antituberculous treatment (ATT), with some patients having a complete metabolic response to treatment whereas others have residual metabolic activity (RMA). We herein determine the impact of findings on EOT 18 F-FDG PET/CT on tuberculosis relapse in patients treated with a standard regimen of ATT for drug-sensitive pulmonary tuberculosis (DS-PTB). Methods: Patients who completed a standard regimen of ATT for DS-PTB and were declared cured based on a negative clinical and bacteriologic examination were prospectively recruited to undergo EOT 18 F-FDG PET/CT. Images were assessed for the presence of RMA. Patients were subsequently followed up for 6 mo looking for symptoms of tuberculosis relapse. When new symptoms developed, relapse was confirmed with bacteriologic testing. Repeat 18 F-FDG PET/CT was done in patients who relapsed. Results: Fifty-three patients were included (mean age, 37.81 ± 11.29 y), with 62% being male and 75% HIV-infected. RMA was demonstrated in 33 patients (RMA group), whereas 20 patients had a complete metabolic response to ATT (non-RMA group). There was a higher prevalence of lung cavitation in the RMA group (P 5 0.035). The groups did not significantly differ in age, sex, presence of HIV infection, body mass index, or hemoglobin level (P . 0.05). On follow-up, no patients in the non-RMA group developed tuberculosis relapse. Three patients in the RMA group developed relapse. All patients who developed tuberculosis relapse had bilateral disease with lung cavitation. Conclusion: A negative EOT 18 F-FDG PET/CT result is protective against tuberculosis relapse. Nine percent of patients with RMA after ATT may experience tuberculosis relapse within 6 mo of completing ATT. Bilateral disease with lung cavitation is prevalent among patients with tuberculosis relapse.