Two FDA-approved drugs show promise in treating extensively drug-resistant tuberculosis (XDR-TB), according to laboratory tests made at the Albert Einstein College of Medicine and the National Institute of Allergy and Infectious Diseases.
Researchers at both institutes found that a combination of drugs clavulanate and meropenem inhibited the growth of 13 XDR-TBstrains. This combination was also effective against normal TB.
Clavulanate is sold by GlaxoSmithKline, while meropenem, also called MERREMI.V. is sold by AstraZeneca. The fist one is not commercially available, except in combination with beta-lactam antibiotics, such as amoxicillin. The combination has been used against other types of bacteria to inhibit beta-lactamase activity and make beta-lactams more effective.
Extensively drug-resistant tuberculosis is a relatively rare type of multidrug-resistant tuberculosis (MDR-TB). Because XDR TB is resistant to the most powerful first-line and second-line drugs, patients are left with treatment options that are much less effective and often have worse treatment outcomes. XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system. These persons are more likely to develop TB disease once they are infected, and also have a higher risk of death once they develop TB disease.
According to the World Health Organization, cases of XDR TB are being seen around the world at the highest rates ever. There are 9 million TB cases annually, 490,000 of them being MDR-TB, while about 40,000 are XDR-TB, according to 2006 data.
“There are increasing numbers of cases of TB that are drug resistant, either multi-drug resistant (MDR) or extensively drug resistant (XDR), which are extremely difficult and costly to treat, if possible at all,” John Blanchard of Albert Einstein College of Medicine of Yeshiva University in New York, study senior author, said.
Health care experts see the combination of clavulanate and meropenem as very promising. “If proven in human subjects, the ability to simplify treatment to just two drugs that work against drug-susceptible [TB], multi-drug-resistant [TB] and XDR-TB could help patients better adhere to therapy,” Blanchard said.
The researchers plan to launch a phase two clinical study of clavulanate potassium-meropenem drug combination in South Korea by the end of 2009. It will involve approximately 100TB patients. Additionally, a separate trial is slated for 2009 in South Africa as part of a joint collaboration between Montefiore Medical Center, The University Hospital and Academic Medical Center for Albert Einstein College of Medicine, and the Nelson Mandela School of Medicine in Durban, South Africa.
If these two clinical trials prove successful, a trial involving a larger number of XDR-TB patients will be conducted.
“We see tremendous potential for treating not only XDR-TB cases, but also routine TB cases," said Brian Currie, M.D., M.P.H., assistant dean for clinical research, and professor of medicine and of clinical epidemiology and population health at Einstein.
The finding appears in this week’s issue of the journal Science.
