A two-drug combination is one of the most promising advances in decades
for the treatment of tuberculosis (TB) -- a disease that kills 2 million
people annually -- a scientist reported March 26 at the 243rd National
Meeting & Exposition of the American Chemical Society (ACS). The
treatment, which combines two medications already approved by the U.S.
Food and Drug Administration (FDA), delivers a knockout punch to forms
of TB that shrug off other antibiotics.
John Blanchard, Ph.D., pointed out that TB is fostering a global
public health crisis. Up to one-third of the world's population is
infected with Mycobacterium tuberculosis (Mtb), the bacterium
that causes TB. Mtb can be especially serious among the elderly,
individuals infected with the AIDS virus and others with weakened immune
systems. Of special concern is the emergence of drug-resistant forms of
the TB microbe, including the so-called XDR and MDR strains that shrug
off the most powerful antibiotics.
But treatment with the antibiotic meropenem plus another drug, clavulanate, offers new hope for dealing with the disease.
"We've tested this combination against laboratory strains of Mtb, XDR
and MDR strains from patients," explained Blanchard, who is Professor
of Biochemistry at the Albert Einstein School of Medicine of Yeshiva
University in New York City. "In all cases, the combination doesn't just
slow down growth -- it kills the bacterium in laboratory tests."
The standard TB treatment consists of a so-called "short-course" of
four drugs that was developed in the 1960s and 1970s. Patients take
isoniazid, rifampin, pyrazinamide and ethambutol for two months, and
then isoniazid and rifampicin alone for an additional four months.
"As you can well imagine, after 40 or 45 years of people being
treated with the same drugs, what's happening is that the bacterium is
developing resistance to those drugs," said Blanchard. "Some forms, or
strains, are resistant to many drugs (MDR, or multidrug-resistant), and
some are resistant to almost all known antibiotics (XDR, or extensively
drug-resistant). A physician I know in India just reported a strain of
TB that is totally drug-resistant. There's nothing currently available
that he can use to treat these patients."
But now, there's hope. Blanchard and colleagues at Einstein and the
National Institutes of Health found the potent two-drug combination that
knocks out regular, MDR and XDR strains of Mtb. Discovery of the drug
combo's effectiveness emerged from a study by Blanchard's team. Mtb
microbes have an enzyme, beta-lactamase, that destroys many types of
antibiotics, even meropenem and others in its medicinal family, which is
called the "beta-lactams" or "carbapenems." These antibiotics were
specifically developed with a molecular architecture to withstand the
effects of the beta-lactamase enzyme. The increase in antibiotic
resistance, however, reduced the effectiveness of these medications, and
drug companies began marketing combinations of antibiotics and
clavulanate. Those medications now are the last resort for treating
certain drug-resistant infections.
Blanchard and colleagues found that clavulanate could stop this
enzyme in TB microbes from destroying antibiotics. In doing so, it
clears the way for antibiotics to do their job. The best combination in
their research was clavulanate and meropenem, an ultra-broad spectrum
antibiotic given by injection.
The two-drug combination also cuts in half the number of drugs that a
patient would have to take compared with the current standard treatment
regime, which would make it easier for a patient to stick with the
treatment. Meropenem is expensive, but its cost is expected to decline
later this year when it goes off-patent, and generic drug companies can
begin producing low-cost versions of it.
Clinical trials testing safety and effectiveness of the two-drug
treatment in people have not yet been done. However, a physician in
Brussels, Dr. Marie-Christine Payen, has reported using the drugs to
treat a young patient with severe TB. "Clinical validation of our
biochemical studies has come with the recent publication of this case
study in which a 14 year-old girl was cured after eight months of
treatment," said Blanchard.
Einstein has filed a patent application on the two-drug combination
to encourage drug companies to get involved with clinical trial
development and improvements to the treatment, he noted.
The scientists acknowledged funding from the National Institutes of
Health (NIH; AI33696 to J.S.B.) and in part by the Intramural Research
Program of the NIH, National Institute of Allergy and Infectious
Diseases.
Story Source:
The above story is reprinted from materials provided by American Chemical Society (ACS), via Newswise.
Courtesy: ScienceDaily
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