The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy

Andrew F. Read, Troy Day, Silvie Huijben

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet "radical pathogen cure" maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.

Original languageEnglish (US)
Pages (from-to)10871-10877
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue numberSUPPL. 2
DOIs
StatePublished - Jun 28 2011

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Keywords

  • Antibiotic resistance
  • Evolutionary medicine
  • Long-course chemotherapy
  • Patient treatment regimens
  • Plasmodium

ASJC Scopus subject areas

  • General

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