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Tuberculosis in Romania

Present and future in the use of anti-tuberculosis drugs

Cristian Didilescu
Present and future in the use of anti-tuberculosis drugs


After several decades without any notable progress, there are encouraging results in research and development of anti-TB drugs, the result of a large number of projects now in competition. Along with developing new drugs to treat tuberculosis (TMC207, SQ109, LL3858) are being reassessed others to optimize their effectiveness in order to shorten and simplify therapy (rifampin and rifapentine) and three other drugs, currently used for other indications, were forwarded towards TB (gatifloxacin and moxifloxacin, linezolid). Time to approval as a antiTB drug is 10-15 years, consisting of phases of preclinical and clinical research. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis resulted in a small but statistically nonsignificant increase in 8th- week culture negativity. TMC207, a diarylquinoline with a unique way to address Mycobacterial ATP synthetase, shows high activity in vitro against Mycobacterial strains sensitive or resistant to all drugs in the first and second line, including fluoroquinolones, demonstrating exceptional qualities in vivo against several species of mycobacteria, in various animal models. TMC207 was added to a basic standard regimen in a study of MDR-TB patients. After two months and satisfactory tolerability, sputum conversion rate in culture was 48% (vs 9% in the placebo group). Two nitroimidazole (PA-824 and OPC-67683) are currently in clinical development. PA-824 demonstrated good safety and tolerability in adult patients with pulmonary TB in South Africa, when given once daily for 7 days. Associating isoniazid, would prevent the selection of mutants resistant to Isoniazid. Linezolid 600 mg is currently being tested in a Phase II for treatment of XDR-TB in the Republic of Korea. PNU-100480, analogous to the previous one, has the potential to significantly shorten the treatment in cases where there is sensitivity and in those with resistance to drugs. 300 mg dose is under investigation in a phase II pilot study in MDR-TB in South Africa. With this interest and commitment, it appears that there is a chance of having a new drug available soon.

Keywords: treatment of tuberculosis, new antituberculosis drugs, MDR-TB