COLUMBUS, Ohio -- Chemical cousins of an often-used antimalarial drug may help treat serious antibiotic-resistant infections, new research shows.
If further testing shows these compounds to be safe and effective, the chemicals would represent a new class of antibiotics for the treatment of such problems as tuberculosis, and staphylococcal, streptococcal, and yeast infections.
These drugs, originally developed to treat malaria and other parasitic infections, are not usually thought of as antibiotic agents.
"Our results represent an important lead on a new class of antibiotics," said Calvin Kunin, Pomerene professor of internal medicine at Ohio State University. "If these drugs were to be developed by a pharmaceutical company, they have the potential to treat a wide variety of life-threatening and drug-resistant infections.
"Based on laboratory experiments, these compounds are as active as many currently used drugs. They have the same ability to kill bacteria -- even better in some instances -- than currently available drugs."
Kunin cautions that the drugs must be tested for safety and efficacy before they could be used in humans. The research was published in a recent issue of the journal Antimicrobial Agents and Chemotherapy.
Kunin stumbled onto the antimicrobial activity of one antimalarial drug about five years ago. "We discovered by accident that one of these drugs had some antibacterial activity of a very marginal nature," he said.
Out of curiosity, he tested the major antimalarial drug in use today, mefloquine, in the test tube against a standard assortment of disease-causing bacteria.
Mefloquine proved to be quite active against staphylococcus and streptococcus bacteria, both of which can produce life-threatening infections. It also showed activity against the pneumococcus organism that causes pneumonia. Other investigators have shown that it has great potential for the treatment of infections caused by bacteria related to tuberculosis. But the concentrations of drug needed were higher than those considered acceptable in the body.
"So I thought it would be a good idea to see if there were related drugs that could accomplish this," he said.
Kunin contacted the Walter Reed Army Institute of Research, which developed mefloquine, to learn if similar compounds existed that he could test.
That's how he met the co-author of the paper, William Ellis, who oversaw the Institute's assortment of antimalarial compounds and who was intimately familiar with their chemistry.
"Over a number of years, the Institute sent me 400 compounds, all of which were related to mefloquine," said Kunin.
Of these, more than 30 were active in the test tube against a panel of about 20 troublesome bacteria species that are commonly used to screen substances for antibacterial activity.
"They killed these bacteria extremely rapidly; they were extremely lethal," he said.
Kunin also tested the antimalarial drugs in combination with 8 or 10 older antibiotics. In many cases, he said, "the two acted together almost in a synergistic manner so that less of either drug is needed to do the same job."
The antibiotics from the gentamicin family proved to be the most potent, and for good reason, he said. The mefloquine-like compounds interfere with the surface membranes of the bacteria, making them more permeable to the gentamicin, which ordinarily don't penetrate the bacterial cell wall very well.
The mefloquine compounds enable the gentamicin to enter the bacterium and go to work," he said.
Contact:
Jeff Grabmeier, Research Communications, Ohio State
614-292-8457; Grabmeier.1@osu.edu
Written by Darrell E. Ward
Journal
Antimicrobial Agents and Chemotherapy