Girl's life saved by novel two-drug therapy for extensively drug-resistant tuberculosis

10 May 2011 - Brussels - Belgian doctors report they have cured a young patient with extensively drug-resistant tuberculosis (XDR-TB) using a novel two-drug combination developed by researchers at the Albert Einstein College of Medicine of Yeshiva University in New York City. The report, published in the Pediatric Infectious Disease Journal, marks the first known clinical use of this treatment for XDR-TB.

In 2010, doctors at Hôpital Universitaire Saint-Pierre in Brussels, Belgium, oversaw the care of a 14-year-old girl from Chechnya with XDR-TB. The acutely ill and malnourished patient failed to respond to standard first- and second-line TB medications. Tests showed that her TB strain was extensively drug resistant.

As a last resort, the Belgian doctors decided to try clavulanate and meropenem, a combination therapy they had read about in a paper in the journal Science authored by Dr. John Blanchard from the New York research institution. "We had nothing to lose," wrote Dr. Marie-Christine Payen, leader of the Belgian team, in an e-mail to Einstein officials.

The girl showed clinical improvement after four weeks of therapy, the Belgian team reported in the Pediatric Infectious Disease Journal. After 11 weeks, her sputum tests were negative for TB.

"It was extremely rewarding to see that our studies would contribute to a successful clinical outcome for this seriously ill girl. I applaud the courage of the Belgian physicians," said Dr. Blanchard.

Dr. Blanchard and his colleagues reported in the February 27, 2009 issue of Science that a combination of clavulanate and meropenem inhibited the growth of drug-susceptible laboratory strains of TB as well as XDR-TB strains isolated from TB patients. The drugs work in tandem: clavulanate inhibits a bacterial enzyme (beta-lactamase) that normally shields TB bacteria from meropenem, an antibiotic.

The U.S. Food and Drug Administration has approved Meropenem for adult and pediatric use, and clavulanate is used in combination with amoxicillin as an FDA-approved antibiotic. Clavulanate-meropenem therapy for XDR-TB has not yet been evaluated in clinical trials.

"This is early and limited evidence that the therapy will be efficacious, but it's very encouraging," said Brian Currie, assistant dean at Einstein. "We look forward to beginning clinical trials with our colleagues in South Africa, where drug-resistant TB is a significant and growing problem."

Dr. Payen's paper, "Meropenem/clavulanate and linezolid treatment for extensively drug-resistant Tuberculosis," was published March 3, 2011, in the online edition of the Pediatric Infectious Disease Journal.