A team of tuberculosis experts at Johns Hopkins and in
Brazil have evidence that substituting
the antibiotic moxifloxacin in the regimen of drugs used to
treat the highly contagious form of lung
disease could dramatically shorten the time needed to cure
the illness from six months to four.
Adding moxifloxacin to a standard combination of other
antibiotics increased by 17 percent the
number of patients who cleared active infections from their
lungs — raising cure rates from 68 percent
to 85 percent — after just two months of therapy and
when compared to patients taking the standard
combination with another, older antibiotic, ethambutol.
"This is the most compelling evidence in nearly 25
years that a novel antibiotic drug combination
works better than the current gold standard at curing
active TB infection," said study senior author
Richard E. Chaisson, a professor of medicine at the Johns
Hopkins School of Medicine and founding
director of its Center
for Tuberculosis Research. Chaisson, who holds a joint
appointment in Public
Health, presented his team's findings Sept. 18 in Chicago
at the 47th Interscience Conference on
Antimicrobial Agents and Chemotherapy.
"Beyond the obvious value of healing patients more
quickly, a shorter treatment time could also
cut down on transmission of the disease to others and make
it easier for health care workers
worldwide, who are overwhelmed by large numbers of
patients, to treat more people and to treat them
faster," said Chaisson, who started the study in 2003.
He notes that worldwide, nearly 9 million new cases of
TB are diagnosed each year, and more
than 1.5 million people die from the disease, caused by
TB also remains the leading cause of death worldwide
among those with HIV and AIDS and is
epidemic in developing countries with the highest HIV
The new study of more than 170 men and women with
active TB in Rio de Janeiro, Brazil, showed
that combination drug therapy with moxifloxacin was more
potent than combination therapy with an
older, more traditional anti-TB drug, ethambutol. Symptoms
of active TB include fever, cough, night
sweats and weight loss.
After two months of combination therapy, cultured
sputum samples from patients taking
moxifloxacin were significantly less likely to grow TB
bacteria than samples from those on traditional
ethambutol therapy. The time to clear the infectious
organism from sputum was also significantly
shorter in the moxifloxacin group.
Conventional TB therapy prescribes a mix of
antibiotics, typically four, given in view of a
caregiver and taken together for six months. Commonly
known by its acronym DOTS, for Directly
Observed Therapy Short-Course, the treatment cures on
average 95 percent of patients who finish
taking their medications as originally prescribed.
But experts say the lengthy treatment period has
proven a problem for patients, who
sometimes miss taking their drugs on time, minimizing the
therapy's effectiveness and increasing the
risk that drug-resistant strains will develop.
History, Chaisson said, demonstrates that shorter
regimens boost drug compliance and cure
rates, often by as much as 50 percent. In the 1950s, TB
treatment lasted from 18 to 24 months, and
nearly a quarter of patients failed to complete therapy. It
was not until new drugs appeared in the
1970s and 1980s, when treatment times were shortened to an
average of six months, that cure rates
In the latest study, all participants were given a
standard combination of three antibiotic pills —
isoniazid, rifampin and pyrazinamide — and were
randomly assigned to receive a fourth pill, either
moxifloxacin or ethambutol. Moxifloxacin, approved for use
in the United States since 1999 as a
treatment for pneumonia, is not currently approved as a
treatment for TB. However, ethambutol has
been approved to treat TB since 1962.
The three combination drugs, which must be taken
several times daily for six to eight months,
have all been widely used to treat TB disease for decades:
isoniazid, since 1952; rifampin, 1968; and
"It was remarkable to see just how potent moxifloxacin
was," Chaisson said. After just two
weeks of therapy with moxifloxacin, 21 percent of the
sputum samples were negative and cleared of
visible disease, while in the ethambutol study group, it
was just 3 percent. After four weeks, the gap
widened to 51 percent and 29 percent, respectively.
Chaisson says that substituting moxifloxacin for one
of the key ingredients in DOTS could also
make treatment far less costly overall, allowing TB
programs to expand their coverage. The medication
currently costs $10 per day for short-term use, but the
researcher says that the drug's
manufacturer, Bayer Healthcare AG, has promised to make the
drug available at affordable prices in
poor countries should it gain approval for use in TB.
Chaisson and his team next plan to investigate a
potentially even more potent drug combination
that includes traditional DOTS drugs with yet another
substitution, rifapentine in place of rifampin.
Rifapentine became available in the United States in 1998,
and scientists say it is more effective
against drug-resistant strains of TB.
Chaisson and colleagues conducted their research with
funding from the Food and Drug
Administration's Office of Orphan Product Development. The
study was part of a series of studies on
moxifloxacin being coordinated by the nonprofit Global
Alliance for TB Drug Development in
collaboration with Bayer.
The Global Alliance for TB Drug Development estimates
that by the year 2020, 1 billion people
worldwide will be infected with tuberculosis, of whom 200
million will fall ill and 35 million will die.
As part of the research program, Bayer donated
supplies of moxifloxacin.
In addition to the moxifloxacin study, Chaisson
directs the Johns Hopkins-based Consortium to
Respond Effectively to the AIDS/TB Epidemic, called CREATE,
an international effort to control the
spread of tuberculosis and treat the disease in countries
hit most hard by the dual epidemics.
CREATE is sponsored by the Bill and Melinda Gates
In addition to Chaisson, researchers from Johns
Hopkins involved in this study were Anne
Efron, Malathi Ram, Mohammed Chaudhary and William Bishai.
Researchers from Federal University of
Rio de Janeiro in Brazil were M. Conde, C. Loredo, G. de
Souza, N. GraŤa, M. Cezar and A. Kritski.
For more on the Center for Tuberculosis Research, go