Two drug combo combats hard-to-treat TB

New research suggests that combining the antibiotic meropenem with clavulanate, a drug that stops bacteria from destroying drugs like meropenem, is effective in killing so-called extensively drug-resistant tuberculosis, which is resistant to first-, second-, and even third-line drugs.

Better yet, “both clavulanate and meropenem are FDA-approved drugs, and both clavulanate and meropenem are sufficiently free of side effects to be approved for pediatric use in children over 3 months old,” according to the report in the journal Science.

Because treatment options are so limited, extensively drug-resistant strains of tuberculosis can kill people within a matter of days to weeks, note Dr. John S. Blanchard, at Albert Einstein College of Medicine, New York and colleagues there and at the National Institute of Allergy and Infectious Diseases.

“Beta-lactam” type drugs, such as meropenem, are typically ineffective against tuberculosis because of an enzyme produced by the microbe that destroys them. However, Blanchard’s team determined that clavulanate permanently inhibits this enzyme. Moreover, as it turns out, the enzyme really was not that good at destroying meropenem in the first place.

When the two drugs were added to actively growing cultures of tuberculosis, the bacteria were totally wiped out within 12 days.

When tested against 13 extensively drug-resistant strains, the clavulanate-meropenem combination was as effective as with strains with no drug resistance, the easiest to treat.

“The synergism of the clavulanate-meropenem combination and the uniform activity against drug-susceptible, laboratory, and extensively drug-resistant strains suggest this combination could be useful in the treatment of tuberculosis,” Blanchard and his associates conclude, even for “patients with currently untreatable disease.”

SOURCE: Science, February 27, 2009.