Alternating Antibiotics Can Combat Drug-Resistance

While exposing bacteria to sublethal doses of antibiotics is normally thought to promote drug-resistance, new research has found that alternating 2 separate antibiotics at these lower doses can effectively kill drug-resistant bacteria unaffected by other combo drugs.

“So-called ‘cocktail’ treatments are often proposed as a way of enhancing the potency of antibiotics, based on the idea that multiple drugs can synergise when used together as part of a single combined therapy,” according to a team of international researchers.

“We investigated whether any other multidrug deployment strategies are as effective as—or perhaps even better than—synergistic antibiotic combinations at reducing bacterial densities.”
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They explained that “collateral sensitivities,” when the effort of a type of bacteria to combat a particular antibiotic makes it more sensitive to the subsequent use of another, are often observed.

In order to explore the potential of exploiting this effect, researchers exposed semi-drug-resistant E. coli bacteria to erythromycin and doxycycline in 3 different forms: singularly, in combination, and subsequently.

Overall, researchers observed that sequential treatment with the antibiotics at low doses effectively cleared the infection, even when higher doses of the antibiotics—alone or in combination—had no effect.

“[O]urs is a very simple treatment model inspired by bacterial infections, and we do not wish to overstate its predictive power in relation to the treatment of humans…It is not our intention to advocate for the indiscriminate clinical use of low-dose regimens,” they concluded.

“Rather, we are claiming that sequential dosing strategies exist for administering antibiotics that are sufficiently potent, and which prevent adaptation enough, to clear a bacterium when the equivalent dose combination treatment fails to do so.”

The full study is published in PLOS Biology.

—Michael Potts

Reference:

1. Fuentes-Hernandez A, Plucain J, Gori, F, Beardmore R, et al. Using a sequential regimen to eliminate bacteria at sublethal antibiotic dosages. PLOS Biology. 2015 April 8 [epub ahead of print] DOI: 10.1371/journal.pbio.1002104