Systematic design of pulse dosing to eradicate persister bacteria: The case of fluoroquinolones

Area of Science:

• Microbiology
• Pharmacology
• Mathematical Biology

Background:

• Bacterial persisters are a small fraction of pathogens that survive antibiotic treatment.
• Pulse dosing is a potential strategy for eradicating persisters.
• Previous work developed optimal pulse dosing for beta-lactam antibiotics.

Purpose of the Study:

• To extend optimal pulse dosing methods for fluoroquinolone antibiotics.
• To investigate fluoroquinolone-induced bacterial dynamics, including persister formation and post-antibiotic effects.
• To compare the efficacy of designed pulse dosing with constant dosing for fluoroquinolones.

Main Methods:

• Mathematical modeling to design optimal pulse dosing regimens.
• Experimental validation of designed pulse dosing strategies.
• Model fitting and parameter estimation to analyze bacterial persister mechanisms.

Main Results:

• Pulse dosing designed by the proposed method achieved rapid bacterial population reduction compared to constant dosing.
• Fluoroquinolones induce distinct bacterial dynamics, including persister formation and post-antibiotic effects, compared to beta-lactams.
• Differences in persister mechanisms between fluoroquinolones and beta-lactams were identified.

Conclusions:

• Optimal pulse dosing strategies can be effectively designed for fluoroquinolones using simple formulas and experimental data.
• This approach offers a promising method for the efficient use of fluoroquinolone antibiotics.
• The study highlights the adaptability of pulse dosing strategies across different antibiotic classes.