Journal Article

The resistance ratchet: theoretical implications of cyclic selection pressure

J. T. Magee

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 2, pages 427-430
Published in print August 2005 | ISSN: 0305-7453
Published online June 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki229
The resistance ratchet: theoretical implications of cyclic selection pressure

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Objectives: To investigate the effects of cyclic antibiotic selection pressure on resistance in a simple mathematical model.

Methods: The model assumed that resistance in microbial ecologies changes slowly with changing selection pressure, at a rate proportional to the difference between the current resistance level and the resistance level that would be in equilibrium with current selection pressure. The maximum rate of increase in resistance during periods of increasing selection was assumed to be greater than the maximum rate of decrease during decreased selection.

Results: Under a simulated annual cyclic selection pressure variation of 40%, with maximum resistance rise and fall rates of 10 and 0.5%, respectively, resistance rose above the level expected from the mean selection pressure by small ratchet-like increments. Over 50 simulated years, resistance increased to 62%, rather than the 50% expected from the mean level of selection. Welsh community prescribing for a selection of antibiotics showed a seasonal cyclic variation of 13–45%.

Conclusions: The intuitive assumption that cyclic selective pressure would produce resistance levels commensurate with the mean selection pressure was contradicted; rather resistance drifted towards a level commensurate with maximum selection pressure. If the ratchet effect exists in reality, it may produce unexpected excess resistance, particularly in the community for antibiotics used in respiratory infection, where cycling is pronounced, or in ITU antibiotic rotation. It should be most pronounced for resistance systems with strong asymmetry between rates of adaptation under rising and falling selection pressure. Non-linear dynamic systems in physics and ecology are notorious for producing counter-intuitive effects; resistance epidemiology may be similar.

Keywords: cyclic selection pressure; seasonal antibiotic prescribing; antibiotic resistance; ratchet effect

Journal Article.  2269 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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