Using machine learning to optimize antibiotic combinations: dosing strategies for meropenem and polymyxin B against carbapenem-resistant Acinetobacter baumannii.

Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
PMID: 32061797

Abstract

OBJECTIVES: Increased rates of carbapenem-resistant strains of Acinetobacter baumannii have forced clinicians to rely upon last-line agents, such as the polymyxins, or empirical, unoptimized combination therapy. Therefore, the objectives of this study were: (a) to evaluate the in vitro pharmacodynamics of meropenem and polymyxin B (PMB) combinations against A. baumannii; (b) to utilize a mechanism-based mathematical model to quantify bacterial killing; and (c) to develop a genetic algorithm (GA) to define optimal dosing strategies for meropenem and PMB.

Authors

  • N M Smith
    Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USA; New York State Center of Excellence in Life Sciences and Bioinformatics, Buffalo, NY, USA.
  • J R Lenhard
    California Northstate University, College of Pharmacy, Elk Grove, CA, USA.
  • K R Boissonneault
    Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USA; New York State Center of Excellence in Life Sciences and Bioinformatics, Buffalo, NY, USA.
  • C B Landersdorfer
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
  • J B Bulitta
    Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
  • P N Holden
    Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USA; New York State Center of Excellence in Life Sciences and Bioinformatics, Buffalo, NY, USA.
  • A Forrest
    School of Pharmacy, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA.
  • R L Nation
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
  • J Li
    Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
  • B T Tsuji
    Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USA; New York State Center of Excellence in Life Sciences and Bioinformatics, Buffalo, NY, USA. Electronic address: btsuji@buffalo.edu.

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