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Antibiotic resistance--what's dosing got to do with it?
Jason A Roberts1, Peter Kruger, David L Paterson
1Burns Trauma and Critical Care Research Centre, University of Queensland, Herston, Australia. j.roberts2@uq.edu.au
Critical Care Medicine
|July 4, 2008
Summary
Optimizing antibiotic dosing is crucial to combat rising antibiotic resistance. Higher doses, guided by pharmacodynamics, can suppress resistant bacterial subpopulations and prevent further infections.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Antibiotic resistance is a growing global health crisis, particularly in intensive care settings.
- Inadequate antibiotic dosing may accelerate the development of resistance.
- Emerging data link antibiotic exposure to resistance patterns.
Purpose of the Study:
- To review research on antibiotic dosing and resistance development across various antibiotic classes.
- To apply pharmacodynamic principles to guide clinical practice in suppressing resistance.
- To discuss concepts like mutant selection window and mutant prevention concentration.
Main Methods:
- Systematic review of original research articles.
- Searches conducted in PubMed, EMBASE, and Cochrane Controlled Trial Register.
- Inclusion of studies correlating antibiotic dose/exposure with resistance formation.
Main Results:
- Evidence suggests low antibiotic doses contribute to increased resistance rates.
- Fluoroquinolone research is extensive; other classes are increasingly studied.
- Pharmacodynamically guided dosing regimens are essential to mitigate resistance.
Conclusions:
- Antibiotic dosing should target both the primary infection and resistant subpopulations.
- Maximizing antibiotic exposure, potentially through higher doses, is key.
- This strategy aims to prevent the selection pressure that drives resistance.
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