Bacterial temporal dynamics enable optimal design of antibiotic treatment.
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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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
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
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