Applying Optimization Algorithms to Tuberculosis Antibiotic Treatment Regimens

Article

Abstract

Introduction

Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively. Here we propose a method that combines an agent-based multi-scale model capturing TB granuloma formation with algorithms for mathematical optimization to identify optimal TB treatment regimens.

Methods

We define two different single-antibiotic treatments to compare the efficiency and accuracy in predicting optimal treatment regimens of two optimization algorithms: genetic algorithms (GA) and surrogate-assisted optimization through radial basis function (RBF) networks. We also illustrate the use of RBF networks to optimize double-antibiotic treatments.

Results

We found that while GAs can locate optimal treatment regimens more accurately, RBF networks provide a more practical strategy to TB treatment optimization with fewer simulations, and successfully estimated optimal double-antibiotic treatment regimens.

Conclusions

Our results indicate surrogate-assisted optimization can locate optimal TB treatment regimens from a larger set of antibiotics, doses and schedules, and could be applied to solve optimization problems in other areas of research using systems biology approaches. Our findings have important implications for the treatment of diseases like TB that have lengthy protocols or for any disease that requires multiple drugs.

Keywords

Tuberculosis Antibiotics Agent-based modeling Genetic algorithm Surrogate-assisted optimization 

Abbreviation

TB

Tuberculosis

INH

Isoniazid

RIF

Rifampin

GA

Genetic algorithm

RBF

Radial basis function

PK/PD

Pharmacokinetics/pharmacodynamics

ODE

Ordinary differential equation

PDE

Partial differential equation

LHS

Latin hypercube sampling

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Copyright information

© Biomedical Engineering Society 2017

Authors and Affiliations

  1. 1.Department of Chemical EngineeringUniversity of MichiganAnn ArborUSA
  2. 2.Department of Microbiology and ImmunologyUniversity of Michigan Medical SchoolAnn ArborUSA

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