Evidence map›Paper›PMID 21807983›Full record

ArticleAntimicrobial agents and chemotherapy2011

Pharmacokinetic/pharmacodynamic (PK/PD) indices of antibiotics predicted by a semimechanistic PKPD model: a step toward model-based dose optimization.

Elisabet I Nielsen, Otto Cars, Lena E Friberg

Abstract read
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In one paragraph

Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  11. When and How to Use Subcutaneous Antibiotics.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Review
  12. Uncertainty undermines the validity of antimicrobial pharmacodynamics.Journal of pharmacokinetics and pharmacodynamics · 2026
    Article
  13. Review
  14. Article
  15. Article
  16. Spondylodiscitis relevant tissue concentrations of cefuroxime - a large animal microdialysis study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025
    Article
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57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Elisabet I NielsenDepartment of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden. elisabet.nielsen@farmbio.uu.se
Otto Cars
Lena E Friberg

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A pharmacokinetic-pharmacodynamic (PKPD) model that characterizes the full time course of in vitro time-kill curve experiments of antibacterial drugs was here evaluated in its capacity to predict the previously determined PK/PD indices. Six drugs (benzylpenicillin, cefuroxime, erythromycin, gentamicin, moxifloxacin, and vancomycin), representing a broad selection of mechanisms of action and PK and PD characteristics, were investigated. For each drug, a dose fractionation study was simulated, using a wide range of total daily doses given as intermittent doses (dosing intervals of 4, 8, 12, or 24 h) or as a constant drug exposure. The time course of the drug concentration (PK model) as well as the bacterial response to drug exposure (in vitro PKPD model) was predicted. Nonlinear least-squares regression analyses determined the PK/PD index (the maximal unbound drug concentration [fC(max)]/MIC, the area under the unbound drug concentration-time curve [fAUC]/MIC, or the percentage of a 24-h time period that the unbound drug concentration exceeds the MIC [fT(>MIC)]) that was most predictive of the effect. The in silico predictions based on the in vitro PKPD model identified the previously determined PK/PD indices, with fT(>MIC) being the best predictor of the effect for β-lactams and fAUC/MIC being the best predictor for the four remaining evaluated drugs. The selection and magnitude of the PK/PD index were, however, shown to be sensitive to differences in PK in subpopulations, uncertainty in MICs, and investigated dosing intervals. In comparison with the use of the PK/PD indices, a model-based approach, where the full time course of effect can be predicted, has a lower sensitivity to study design and allows for PK differences in subpopulations to be considered directly. This study supports the use of PKPD models built from in vitro time-kill curves in the development of optimal dosing regimens for antibacterial drugs.

Indexed as

Anti-Bacterial AgentsArea Under CurveAza CompoundsCefuroximeComputer SimulationErythromycinEscherichia coliFluoroquinolonesGentamicinsHumansMicrobial Sensitivity TestsMoxifloxacinPenicillin GQuinolinesStreptococcus pyogenesVancomycinAnti-Bacterial AgentsAza CompoundsCefuroximeErythromycinFluoroquinolonesGentamicinsMoxifloxacinPenicillin GQuinolinesVancomycin

Identifiers

PMID21807983
PMCPMC3186970

What OpenQuestion holds

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Registered trials

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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.