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How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance.

Colijn C, Cohen T - Elife (2015)

Bottom Line: In this study, we demonstrate how one can understand and resolve these apparently contradictory conclusions.We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host.We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, Imperial College London, London, United Kingdom.

ABSTRACT
Understanding how our use of antimicrobial drugs shapes future levels of drug resistance is crucial. Recently, there has been debate over whether an aggressive (i.e., high dose) or more moderate (i.e., lower dose) treatment of individuals will most limit the emergence and spread of resistant bacteria. In this study, we demonstrate how one can understand and resolve these apparently contradictory conclusions. We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host. We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence. From this perspective as well, we find that the magnitude of effective competition between resistant and sensitive strains determines whether an aggressive approach or moderate approach minimizes the burden of resistance in the population.

No MeSH data available.


Related in: MedlinePlus

Parameters where the two contrasting policies work best in the population level model.Top row: treatment decreases resistance. Bottom row: treatment increases resistance.DOI:http://dx.doi.org/10.7554/eLife.10559.019
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fig16: Parameters where the two contrasting policies work best in the population level model.Top row: treatment decreases resistance. Bottom row: treatment increases resistance.DOI:http://dx.doi.org/10.7554/eLife.10559.019

Mentions: Appendix figure 9, Figures 6, 7 illustrate how the best policy depends on the fitness of the DR strain and the other parameters. Treatment decreases resistance when the R0 values of both strains are relatively low, the rate of acquisition of resistance is high and the similarity coefficient is low. We find that the parameter groups where aggressive therapy minimizes resistance are well separated by those where moderate therapy is best, by a single DAPC function (Appendix figure 6). Here, the strongest driver of a moderate policy being best is a high similarity coefficient (c, coefficient 0.93). High R02 and R01 (coefficients 1.01, 0.65) contribute, as does a low acquisition rate (coefficient −0.56). Somewhat surprisingly, the rate of competitive release does not contribute to the DAPC weighting (−0.02).


How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance.

Colijn C, Cohen T - Elife (2015)

Parameters where the two contrasting policies work best in the population level model.Top row: treatment decreases resistance. Bottom row: treatment increases resistance.DOI:http://dx.doi.org/10.7554/eLife.10559.019
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4641510&req=5

fig16: Parameters where the two contrasting policies work best in the population level model.Top row: treatment decreases resistance. Bottom row: treatment increases resistance.DOI:http://dx.doi.org/10.7554/eLife.10559.019
Mentions: Appendix figure 9, Figures 6, 7 illustrate how the best policy depends on the fitness of the DR strain and the other parameters. Treatment decreases resistance when the R0 values of both strains are relatively low, the rate of acquisition of resistance is high and the similarity coefficient is low. We find that the parameter groups where aggressive therapy minimizes resistance are well separated by those where moderate therapy is best, by a single DAPC function (Appendix figure 6). Here, the strongest driver of a moderate policy being best is a high similarity coefficient (c, coefficient 0.93). High R02 and R01 (coefficients 1.01, 0.65) contribute, as does a low acquisition rate (coefficient −0.56). Somewhat surprisingly, the rate of competitive release does not contribute to the DAPC weighting (−0.02).

Bottom Line: In this study, we demonstrate how one can understand and resolve these apparently contradictory conclusions.We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host.We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, Imperial College London, London, United Kingdom.

ABSTRACT
Understanding how our use of antimicrobial drugs shapes future levels of drug resistance is crucial. Recently, there has been debate over whether an aggressive (i.e., high dose) or more moderate (i.e., lower dose) treatment of individuals will most limit the emergence and spread of resistant bacteria. In this study, we demonstrate how one can understand and resolve these apparently contradictory conclusions. We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host. We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence. From this perspective as well, we find that the magnitude of effective competition between resistant and sensitive strains determines whether an aggressive approach or moderate approach minimizes the burden of resistance in the population.

No MeSH data available.


Related in: MedlinePlus