A model of optimal dosing of antibiotic treatment in biofilm

Biofilms are heterogeneous matrix enclosed micro-colonies ofbacteria mostly found on moist surfaces. Biofilm formation is theprimary cause of several persistent infections found in humans. Wederive a mathematical model of biofilm and surrounding fluiddynamics to investigate the effect of a periodic...

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Main Authors: Mudassar Imran, Hal L. Smith
Format: Article
Language:English
Published: AIMS Press 2013-12-01
Series:Mathematical Biosciences and Engineering
Subjects:
Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2014.11.547
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author Mudassar Imran
Hal L. Smith
author_facet Mudassar Imran
Hal L. Smith
author_sort Mudassar Imran
collection DOAJ
description Biofilms are heterogeneous matrix enclosed micro-colonies ofbacteria mostly found on moist surfaces. Biofilm formation is theprimary cause of several persistent infections found in humans. Wederive a mathematical model of biofilm and surrounding fluiddynamics to investigate the effect of a periodic dose of antibioticon elimination of microbial population from biofilm. The growth rateof bacteria in biofilm is taken as Monod type for the limitingnutrient. The pharmacodynamics function is taken to be dependentboth on limiting nutrient and antibiotic concentration. Assumingthat flow rate of fluid compartment is large enough, we reduce thesix dimensional model to a three dimensional model. Mathematicallyrigorous results are derived providing sufficient conditions fortreatment success. Persistence theory is used to derive conditionsunder which the periodic solution for treatment failure is obtained. We also discuss the phenomenon of bi-stability where both infection-free state and infection state are locally stable when antibiotic dosing is marginal. In addition, we derive the optimal antibiotic application protocols for different scenarios using control theory and show that such treatments ensure bacteria elimination for a wide variety of cases. The results show that bacteria are successfully eliminated if the discrete treatment is given at an early stage in the infection or if the optimal protocol is adopted. Finally, we examine factors which if changed can result in treatment success of the previously treatment failure cases for the non-optimal technique.
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spelling doaj-art-cc631cfac0a54b498a491adb905f3ce12025-01-24T02:28:12ZengAIMS PressMathematical Biosciences and Engineering1551-00182013-12-0111354757110.3934/mbe.2014.11.547A model of optimal dosing of antibiotic treatment in biofilmMudassar Imran0Hal L. Smith1Department of Mathematics, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, LahoreSchool of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ 85287-1804Biofilms are heterogeneous matrix enclosed micro-colonies ofbacteria mostly found on moist surfaces. Biofilm formation is theprimary cause of several persistent infections found in humans. Wederive a mathematical model of biofilm and surrounding fluiddynamics to investigate the effect of a periodic dose of antibioticon elimination of microbial population from biofilm. The growth rateof bacteria in biofilm is taken as Monod type for the limitingnutrient. The pharmacodynamics function is taken to be dependentboth on limiting nutrient and antibiotic concentration. Assumingthat flow rate of fluid compartment is large enough, we reduce thesix dimensional model to a three dimensional model. Mathematicallyrigorous results are derived providing sufficient conditions fortreatment success. Persistence theory is used to derive conditionsunder which the periodic solution for treatment failure is obtained. We also discuss the phenomenon of bi-stability where both infection-free state and infection state are locally stable when antibiotic dosing is marginal. In addition, we derive the optimal antibiotic application protocols for different scenarios using control theory and show that such treatments ensure bacteria elimination for a wide variety of cases. The results show that bacteria are successfully eliminated if the discrete treatment is given at an early stage in the infection or if the optimal protocol is adopted. Finally, we examine factors which if changed can result in treatment success of the previously treatment failure cases for the non-optimal technique.https://www.aimspress.com/article/doi/10.3934/mbe.2014.11.547perturbationantibiotic treatmentstability.biofilmbactericidalpersistence
spellingShingle Mudassar Imran
Hal L. Smith
A model of optimal dosing of antibiotic treatment in biofilm
Mathematical Biosciences and Engineering
perturbation
antibiotic treatment
stability.
biofilm
bactericidal
persistence
title A model of optimal dosing of antibiotic treatment in biofilm
title_full A model of optimal dosing of antibiotic treatment in biofilm
title_fullStr A model of optimal dosing of antibiotic treatment in biofilm
title_full_unstemmed A model of optimal dosing of antibiotic treatment in biofilm
title_short A model of optimal dosing of antibiotic treatment in biofilm
title_sort model of optimal dosing of antibiotic treatment in biofilm
topic perturbation
antibiotic treatment
stability.
biofilm
bactericidal
persistence
url https://www.aimspress.com/article/doi/10.3934/mbe.2014.11.547
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