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New TB Drug May Shorten Treatment Times
NEW YORK (Reuters Health) Dec 09 /04-
A new antibiotic specific to mycobacteria is expected to “dramatically improve TB control programs,” according to a report published online December 9th in Science.
Dr. Koen Andries, of Johnson & Johnson Pharmaceutical Research and Development in Beerse, Belgium, and his multinational research team developed a series of compounds, diarylquinolines, which possess potent in vitro activity against several mycobacterial species.
The most active compound of the class, R207910, appears to have a novel target, inhibiting the proton pump of mycobacterial ATP synthase.
There is no concern about an interaction with human ATP synthase, Dr. Andries told Reuters Health during a teleconference, because “when we compare the gene sequence of mycobacterial ATP synthase with the ATP synthase of the human genome, they are quite different.” And indeed, phase I trials in humans revealed no adverse effects during 2 weeks of treatment, he added.
Further studies showed that R207910 lacks cross-resistance with other currently used anti-TB agents. In fact, the authors note, 30 different isolates of multiple drug-resistant (MDR) TB strains and 10 fully susceptible strains were susceptible to 0.100 g/mL of R207910, concentrations readily achieved when administered to mice and humans.
The agent appears to be effective against all mycobacteria, including the human pathogens M. tuberculosis, M. kansasii, M. fortuitum, M. abscessus, and Mycobacterium avium complex (MAC).
“In the mouse model, our drug as a monotherapy is as active as the current standard of care, triple therapy with rifampin, isoniazid and pyrazinamide,” Dr. Andries said. “Of course, our drug is not to be used as a monotherapy because that would inevitably lead to emergence of resistance, but it does demonstrate the high potency of the compound.”
Perhaps even more importantly, “when we compared the results of R207910 combined with isoniazid and pyrazinamide with the standard of care, our combo achieved the same result after 1 month as that obtained after 2 months of standard of care combination therapy.”
“We are optimistic that we will be able shorten treatment duration by about 50% based on these data,” he added.
He also pointed out that the R207910 combination is compatible with HIV treatment combinations, whereas treatment that includes rifampin is associated with drug-drug interactions that increase the metabolism some HIV agents.
Science 2004.
www.sciencexpress.org/9 December 2004/Page 1/10.1126/science.1106753
Note: This article was published as indicated above December 2004
A 2013 FDA Approval article Next
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Articles in the Section ‘Antibiotic Research’ have been collected at various times
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I include them here as part of all around information without any recommendations.
Some of them may have been updated at later stages.
Atypical TB - MAC 