Trends in Microbiology
Volume 9, Issue 9, 1 September 2001, Pages 438-444
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Review
The rise and fall of antimicrobial resistance

https://doi.org/10.1016/S0966-842X(01)02130-8Get rights and content

Abstract

Antimicrobial resistance is a growing problem in nearly every infectious disease, but the extent and rate of increase of the problem varies widely with different pathogen–drug combinations. The rate of increase of resistance depends primarily on the availability of resistant variants and the intensity of selection imposed by antimicrobial treatment (appropriately measured). Declines in resistance following antimicrobial control measures are typically faster in hospital-acquired infections than in community-acquired ones, probably owing to the dependence in the latter case on the fitness cost of resistance. Open questions and approaches for testing the hypotheses proposed here are outlined.

Section snippets

The rise of resistance

The appearance and growth of antimicrobial resistance as a clinical problem requires several distinct steps. Any one of these steps can be ‘rate-limiting’; the span of time between the first use of a particular drug and the appearance of resistance to that drug as a clinical problem for a given pathogen depends on the rates at which these steps are accomplished.

First, resistance must be genetically and physiologically possible for the infectious agent. In some infections, such as TB, creation

The fall of resistance

Several efforts have been made to control and ultimately reduce antimicrobial resistance. The success of these efforts has varied considerably. Thanks to the considerable logistical difficulties in implementation and evaluation, there have been only a few studies of the effectiveness of measures to control resistance in community-acquired pathogens. Perhaps the best known of these studies is the reduction in the use of macrolides (such as erythromycin) in Finland in the 1990s, which was cited

Testing these hypotheses

The foregoing is an attempt to account for what we know about the population dynamics of antimicrobial resistance in populations using a few general principles. Although largely consistent with existing data, many of these principles (hypotheses) have not been subjected to prospective testing. With respect to the rise of resistance, ethical and logistical considerations limit the range of population-level experimental studies that can be done, and we must rely on adequate surveillance and

Questions for future research

  • What role does multiple resistance play in frustrating efforts to reduce resistance to individual drugs?

  • How do patterns of antibiotic use contribute to (or help to slow) the appearance of such strains?

  • How useful will vaccines be in combating resistance, and for how long?

  • To what degree are resistant organisms actually circulating in human populations suffering from a fitness cost of resistance, compared with their susceptible counterparts?

  • What role does infection control play in the prevention

Note added in press

A recent study in Finland showed a strong geographical correlation between macrolide resistance and the use of various antimicrobial agents 43. This confirms a series of studies showing such correlations, although interestingly, such studies in several cases find stronger correlations between the use of one class of antibiotics and resistance to another class, than between use of and resistance to the same class, indicating the importance of multiple resistance for selective dynamics 44.

Acknowledgements

I thank R. Antia, F. Baquero, C. Bergstrom, R. Dagan, B. Levin and M. Samore for valuable discussions that aided in the formulation of the ideas developed here, and A. McCormick for comments on the manuscript. The author is supported by NIH grant A148935.

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