(dailyRx)

A combination of two drugs already approved for fighting other bacterial infections shows potential for treating extensively drug resistant tuberculosis (XDR-TB), the most deadly form of the infection.

This finding is reported by scientists from Albert Einstein College of Medicine of Yeshiva University in the February 27 issue of Science.

TB is caused by the bacterium Mycobacterium tuberculosis (Mtb). An estimated one-third of the world’s population is infected with TB. Active disease develops in approximately 10 percent of infected people over a lifetime, particularly those with weak immune systems such as infants, the elderly, and people infected with HIV. Globally, cases of active TB have increased significantly since the 1980s due to the AIDS pandemic and the emergence of Mtb strains resistant to standard antibiotic treatment.

In the Science paper, Einstein researchers and collaborators at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, describe a two-drug combination that inhibited both the growth of susceptible laboratory strains and 13 XDR-TB strains isolated from TB patients in laboratory culture medium. The drugs truly work in tandem: One of them (clavulanate) inhibits a bacterial enzyme, ?-lactamase, which normally shields TB bacteria from the other antibiotic (meropenem, a member of the ?-lactam class of antibiotics).

The idea of inhibiting ?-lactamase to make ?-lactam antibiotics effective isn’t new, which is why ?-lactamase inhibitors, such as clavulanate, already exist. The strategy finally proved effective against XDR-TB because Einstein researchers conducted a detailed, methodical investigation of the ?-lactamase enzyme to find the ideal combination of ?-lactamase inhibitor and ?-lactam antibiotic. ?-lactam antibiotics include penicillin, the first antibiotic discovered and one of the safest.

Amoxicillin/clavulanic acid and meropenem have excellent safety profiles and are FDA-approved for adult and pediatric use.

“This is a great example of how, in a collaborative environment, basic, old-fashioned, hypothesis-driven science can lead to timely clinical applications,” said John S. Blanchard, Ph.D., senior author of the Science paper, whose research was funded by the National Institute of Allergy and Infectious Diseases.

In parts of Asia, 70 percent of new TB cases are multi-drug resistant, meaning they don’t respond to the two antibiotics most commonly used against TB. Recently, an even greater health threat has emerged: extensively drug-resistant (XDR) bacteria that resist at least four of the drugs used to treat TB and can prove deadly. The cure rate for patients infected with XDR-TB ranges from 12 percent to 60 percent.