Novel antibiotic protocol selects against drug resistance

Tailoring antibiograms aids in antibiotic prescribing
Tailoring antibiograms aids in antibiotic prescribing

HealthDay News -- A new approach to drug cycling may help healthcare providers select against the development of antimicrobial resistance, findings from a proof of concept study suggest.

Dubbed collateral sensitivity cycling, this method of antibiotic stewardship consisting of tailoring cycles of three-to-four carefully-selected drugs that are switched out based on the ability of one drug to induce sensitivity to another. This differs from current drug cycling methods that rely on restricting certain drugs on an ad hoc basis to reduce resistance.

"Here, we propose a fundamentally different approach to drug cycling that builds on the finding that the development of resistance to one drug can perturb drug susceptibility profiles in the bacterial cell," Lejla Imamovic, PhD, and Morten O.A. Sommer, PhD, from the Technical University of Denmark in Lyngby reported in Science Translational Medicine.

Imamovic and Sommer evolved parallel lineages of Escherichia coli that were resistant to 23 clinically relevant antibiotics from 11 chemical classes and mechanisms of action. The researchers found that E. coli strains that were resistant to one antibiotic became sensitive to another antibiotic in a phenomenon they call "collateral sensitivity."

Antibiotics with compatible "collateral sensitivity" profiles were used to sequentially and cyclically to treat E. coli infection and to select against the development of drug resistance.

"For example, when a strain develops resistance to gentamicin, several drugs can be chosen to which gentamicin-resistant strains will be collaterally sensitive (for example, colistin, nalidixic acid, or cefuroxime)," the researchers explained. "Again, when resistance evolves to the next drug (for example, colistin), the treatment can be switched to the next possible option to which the colistin-resistant strain will be collaterally sensitive and so on."

In all, Imamovic and Sommer identified 207 possible two-to-four drug cycles within the E. coli collateral sensitivity network. They then validated their findings in related bacterial pathogens.

"These results provide proof of principle for collateral sensitivity cycling as a sustainable treatment paradigm that may be generally applicable to infectious diseases and cancer," the researchers concluded.

They called for more research to explore the effectiveness of collateral sensitivity cycling, particularly for Gram-negative bacterial infections and chronic infections in which multiple pathogens are involved, and clinical studies to confirm whether the concept holds up in hospital settings.


References

  1. Imamovic L, Sommer MOA. Sci Trans Med. 2013; doi:10.1126/scitranslmed.3006609.

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