Trends in Microbiology
ReviewThe rise and fall of antimicrobial resistance
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
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What role does multiple resistance play in frustrating efforts to reduce resistance to individual drugs?
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How do patterns of antibiotic use contribute to (or help to slow) the appearance of such strains?
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How useful will vaccines be in combating resistance, and for how long?
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To what degree are resistant organisms actually circulating in human populations suffering from a fitness cost of resistance, compared with their susceptible counterparts?
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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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