In the Journals

Antibiotic combos using four to five drugs effective against E. coli

Despite the consensus that using more than two antibiotics to treat bacterial infections may produce more harm than benefit, research published in npj Systems Biology and Applications demonstrates that nearly 8,000 combinations using four or five antimicrobial drugs are effective in treating infection with Escherichia coli.

“There is a tradition of using just one drug, maybe two,” Pamela Yeh, PhD, assistant professor of ecology and evolutionary biology at the University of California, Los Angeles, said in a press release. “We are offering an alternative that looks very promising. We should not limit ourselves to just single drugs or two-drug combinations in our medical toolbox. We expect several of these combinations, or more, will work much better than existing antibiotics.”

Yeh and colleagues evaluated the efficacy of 18,278 four- and five-drug combinations that could be made using ampicillin, cefoxitin sodium salt, trimethoprim, ciprofloxacin hydrochloride, streptomycin, doxycycline hyclate, erythromycin, and fusidic acid sodium salt.

In their analysis, over 1,500 four-drug combinations stopped bacterial growth better than the researchers expected, and 6,443 five-drug combinations performed better than expected.

Pamela Yeh with Elif Tekin
UCLA researchers Pamela Yeh (left) and Elif Tekin are studying the efficacy of thousands of combinations of antibiotics.
Source: Reed Hutchinson/UCLA.

“I was blown away by how many effective combinations there are as we increased the number of drugs,” Van Savage, PhD, professor of ecology, evolutionary biology and biomathematics at UCLA, said in the release. “People may think they know how drug combinations will interact, but they really do not.”

However, numerous combinations were less effective than expected (2,331 four-drug combinations; 5,199 five-drug combinations).

The researchers suggested that the efficacy of certain combinations might have been influenced by each antibiotic’s mechanism for treating E. coli infection.

“Some drugs attack the cell walls, others attack the DNA inside,” Savage said. “It is like attacking a castle or fortress. Combining different methods of attacking may be more effective than just a single approach.”

Although treatment using a combination of four and five antibiotics looks promising, Yeh said that using four- and five-drug combinations has not been tested in humans. She suspects that it will be years before these combinations are tested in humans.

“With the specter of antibiotic resistance threatening to turn back health care to the pre-antibiotic era, the ability to more judiciously use combinations of existing antibiotics that singly are losing potency is welcome,” Michael Kurilla, MD, PhD, director of the division of clinical innovation at the NIH’s National Center for Advancing Translational Sciences, said in the release. “This work will accelerate the testing in humans of promising antibiotic combinations for bacterial infections that we are ill-equipped to deal with today.” – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

Despite the consensus that using more than two antibiotics to treat bacterial infections may produce more harm than benefit, research published in npj Systems Biology and Applications demonstrates that nearly 8,000 combinations using four or five antimicrobial drugs are effective in treating infection with Escherichia coli.

“There is a tradition of using just one drug, maybe two,” Pamela Yeh, PhD, assistant professor of ecology and evolutionary biology at the University of California, Los Angeles, said in a press release. “We are offering an alternative that looks very promising. We should not limit ourselves to just single drugs or two-drug combinations in our medical toolbox. We expect several of these combinations, or more, will work much better than existing antibiotics.”

Yeh and colleagues evaluated the efficacy of 18,278 four- and five-drug combinations that could be made using ampicillin, cefoxitin sodium salt, trimethoprim, ciprofloxacin hydrochloride, streptomycin, doxycycline hyclate, erythromycin, and fusidic acid sodium salt.

In their analysis, over 1,500 four-drug combinations stopped bacterial growth better than the researchers expected, and 6,443 five-drug combinations performed better than expected.

Pamela Yeh with Elif Tekin
UCLA researchers Pamela Yeh (left) and Elif Tekin are studying the efficacy of thousands of combinations of antibiotics.
Source: Reed Hutchinson/UCLA.

“I was blown away by how many effective combinations there are as we increased the number of drugs,” Van Savage, PhD, professor of ecology, evolutionary biology and biomathematics at UCLA, said in the release. “People may think they know how drug combinations will interact, but they really do not.”

However, numerous combinations were less effective than expected (2,331 four-drug combinations; 5,199 five-drug combinations).

The researchers suggested that the efficacy of certain combinations might have been influenced by each antibiotic’s mechanism for treating E. coli infection.

“Some drugs attack the cell walls, others attack the DNA inside,” Savage said. “It is like attacking a castle or fortress. Combining different methods of attacking may be more effective than just a single approach.”

Although treatment using a combination of four and five antibiotics looks promising, Yeh said that using four- and five-drug combinations has not been tested in humans. She suspects that it will be years before these combinations are tested in humans.

“With the specter of antibiotic resistance threatening to turn back health care to the pre-antibiotic era, the ability to more judiciously use combinations of existing antibiotics that singly are losing potency is welcome,” Michael Kurilla, MD, PhD, director of the division of clinical innovation at the NIH’s National Center for Advancing Translational Sciences, said in the release. “This work will accelerate the testing in humans of promising antibiotic combinations for bacterial infections that we are ill-equipped to deal with today.” – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.