ArticleAntimicrobial agents and chemotherapy2004
Pharmacodynamic functions: a multiparameter approach to the design of antibiotic treatment regimens.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
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179 citing papers in PubMed, 365 citations in OpenAlex.
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- Synergistic Antimicrobial Activity of BrSPR20-P1 Peptide and Silver Nanoparticles Against Pathogenic Bacteria.International journal of molecular sciences · 2025Article
- Lineage-dependent variations in single-cell antibiotic susceptibility reveal the selective inheritance of phenotypic resistance in bacteria.Nature communications · 2025Article
- Epistasis-mediated compensatory evolution in a fitness landscape with adaptational tradeoffs.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adaptive evolutionary trajectories in complexity: Transitions between unicellularity and facultative differentiated multicellularity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
119 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
There is a complex quantitative relationship between the concentrations of antibiotics and the growth and death rates of bacteria. Despite this complexity, in most cases only a single pharmacodynamic parameter, the MIC of the drug, is employed for the rational development of antibiotic treatment regimens. In this report, we use a mathematical model based on a Hill function-which we call the pharmacodynamic function and which is related to previously published E(max) models-to describe the relationship between the bacterial net growth rates and the concentrations of antibiotics of five different classes: ampicillin, ciprofloxacin, tetracycline, streptomycin, and rifampin. Using Escherichia coli O18:K1:H7, we illustrate how precise estimates of the four parameters of the pharmacodynamic function can be obtained from in vitro time-kill data. We show that, in addition to their respective MICs, these antibiotics differ in the values of the other pharmacodynamic parameters. Using a computer simulation of antibiotic treatment in vivo, we demonstrate that, as a consequence of differences in pharmacodynamic parameters, such as the steepness of the Hill function and the minimum bacterial net growth rate attained at high antibiotic concentrations, there can be profound differences in the microbiological efficacy of antibiotics with identical MICs. We discuss the clinical implications and limitations of these results.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.