Limits...
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 from the two regimes: (a) with the lysis term and (b) without it.In each set, the top row shows the parameters under which resistance decreases with increasing dosage, and the bottom row shows those for which resistance increases with increasing dosage. The relationships between the two outcomes (treatment increasing or decreasing resistance) are unaffected by whether the lysis term is included. Removing the term is akin to including lysis in the equation for the resource usage, but with an e coefficient of 0; a more general model could include this with a coefficient el < e which would model the fact that resource consumption and release could happen with different efficiencies. Though we do not know what an appropriate choice for el would be, the results with el = 0 (bottom set of histograms) are the same as those with el = e (original model; top set of histograms).DOI:http://dx.doi.org/10.7554/eLife.10559.017
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4641510&req=5

fig14: Parameters from the two regimes: (a) with the lysis term and (b) without it.In each set, the top row shows the parameters under which resistance decreases with increasing dosage, and the bottom row shows those for which resistance increases with increasing dosage. The relationships between the two outcomes (treatment increasing or decreasing resistance) are unaffected by whether the lysis term is included. Removing the term is akin to including lysis in the equation for the resource usage, but with an e coefficient of 0; a more general model could include this with a coefficient el < e which would model the fact that resource consumption and release could happen with different efficiencies. Though we do not know what an appropriate choice for el would be, the results with el = 0 (bottom set of histograms) are the same as those with el = e (original model; top set of histograms).DOI:http://dx.doi.org/10.7554/eLife.10559.017

Mentions: We have shown only the parameters whose distributions are different in the two modes (compare to Appendix figure 7).


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

Colijn C, Cohen T - Elife (2015)

Parameters from the two regimes: (a) with the lysis term and (b) without it.In each set, the top row shows the parameters under which resistance decreases with increasing dosage, and the bottom row shows those for which resistance increases with increasing dosage. The relationships between the two outcomes (treatment increasing or decreasing resistance) are unaffected by whether the lysis term is included. Removing the term is akin to including lysis in the equation for the resource usage, but with an e coefficient of 0; a more general model could include this with a coefficient el < e which would model the fact that resource consumption and release could happen with different efficiencies. Though we do not know what an appropriate choice for el would be, the results with el = 0 (bottom set of histograms) are the same as those with el = e (original model; top set of histograms).DOI:http://dx.doi.org/10.7554/eLife.10559.017
© Copyright Policy
Related In: Results  -  Collection

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

fig14: Parameters from the two regimes: (a) with the lysis term and (b) without it.In each set, the top row shows the parameters under which resistance decreases with increasing dosage, and the bottom row shows those for which resistance increases with increasing dosage. The relationships between the two outcomes (treatment increasing or decreasing resistance) are unaffected by whether the lysis term is included. Removing the term is akin to including lysis in the equation for the resource usage, but with an e coefficient of 0; a more general model could include this with a coefficient el < e which would model the fact that resource consumption and release could happen with different efficiencies. Though we do not know what an appropriate choice for el would be, the results with el = 0 (bottom set of histograms) are the same as those with el = e (original model; top set of histograms).DOI:http://dx.doi.org/10.7554/eLife.10559.017
Mentions: We have shown only the parameters whose distributions are different in the two modes (compare to Appendix figure 7).

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