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Bacterial temporal dynamics enable optimal design of antibiotic treatment.

Publication ,  Journal Article
Meredith, HR; Lopatkin, AJ; Anderson, DJ; You, L
Published in: PLoS Comput Biol
April 2015

There is a critical need to better use existing antibiotics due to the urgent threat of antibiotic resistant bacteria coupled with the reduced effort in developing new antibiotics. β-lactam antibiotics represent one of the most commonly used classes of antibiotics to treat a broad spectrum of Gram-positive and -negative bacterial pathogens. However, the rise of extended spectrum β-lactamase (ESBL) producing bacteria has limited the use of β-lactams. Due to the concern of complex drug responses, many β-lactams are typically ruled out if ESBL-producing pathogens are detected, even if these pathogens test as susceptible to some β-lactams. Using quantitative modeling, we show that β-lactams could still effectively treat pathogens producing low or moderate levels of ESBLs when administered properly. We further develop a metric to guide the design of a dosing protocol to optimize treatment efficiency for any antibiotic-pathogen combination. Ultimately, optimized dosing protocols could allow reintroduction of a repertoire of first-line antibiotics with improved treatment outcomes and preserve last-resort antibiotics.

Duke Scholars

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Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

April 2015

Volume

11

Issue

4

Start / End Page

e1004201

Location

United States

Related Subject Headings

  • beta-Lactams
  • beta-Lactamases
  • beta-Lactam Resistance
  • Time Factors
  • Models, Biological
  • Drug Therapy, Computer-Assisted
  • Drug Administration Schedule
  • Dose-Response Relationship, Drug
  • Computer Simulation
  • Cell Survival
 

Citation

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Meredith, H. R., Lopatkin, A. J., Anderson, D. J., & You, L. (2015). Bacterial temporal dynamics enable optimal design of antibiotic treatment. PLoS Comput Biol, 11(4), e1004201. https://doi.org/10.1371/journal.pcbi.1004201
Meredith, Hannah R., Allison J. Lopatkin, Deverick J. Anderson, and Lingchong You. “Bacterial temporal dynamics enable optimal design of antibiotic treatment.PLoS Comput Biol 11, no. 4 (April 2015): e1004201. https://doi.org/10.1371/journal.pcbi.1004201.
Meredith HR, Lopatkin AJ, Anderson DJ, You L. Bacterial temporal dynamics enable optimal design of antibiotic treatment. PLoS Comput Biol. 2015 Apr;11(4):e1004201.
Meredith, Hannah R., et al. “Bacterial temporal dynamics enable optimal design of antibiotic treatment.PLoS Comput Biol, vol. 11, no. 4, Apr. 2015, p. e1004201. Pubmed, doi:10.1371/journal.pcbi.1004201.
Meredith HR, Lopatkin AJ, Anderson DJ, You L. Bacterial temporal dynamics enable optimal design of antibiotic treatment. PLoS Comput Biol. 2015 Apr;11(4):e1004201.

Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

April 2015

Volume

11

Issue

4

Start / End Page

e1004201

Location

United States

Related Subject Headings

  • beta-Lactams
  • beta-Lactamases
  • beta-Lactam Resistance
  • Time Factors
  • Models, Biological
  • Drug Therapy, Computer-Assisted
  • Drug Administration Schedule
  • Dose-Response Relationship, Drug
  • Computer Simulation
  • Cell Survival