Evidence map›Paper›PMID 21537013›Full record

ReviewAntimicrobial agents and chemotherapy2011

Protein binding: do we ever learn?

Markus A Zeitlinger, Hartmut Derendorf, Johan W Mouton, Otto Cars, William A Craig, David Andes, Ursula Theuretzbacher

Registry-linked trialAbstract readReview
In one paragraph

Review in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03634904 (Prospective Observational Study of Serum Ceftazidime Concentrations in Hemodialysis Patients at the University Hospital of Charleroi, Belgium), which is not on this map. Cited by 126 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 4 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.

NCT03634904 naunknown statusnot on this mapstarted 2018, after this paper: background citation

Prospective Observational Study of Serum Ceftazidime Concentrations in Hemodialysis Patients at the University Hospital of Charleroi, Belgium

TypeinterventionalSponsorCentre Hospitalier Universitaire de CharleroiRan2018 to 2021Enrolled20ConditionsBacterial Infections, Ceftazidime, Renal Failure Chronic Requiring HemodialysisArmsDrug bood sampling
3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
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  16. Host Biomarkers and Antibiotic Tissue Penetration in Sepsis: Insights from Moxifloxacin.European journal of drug metabolism and pharmacokinetics · 2025
    Article
  17. Review
  18. Article
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66 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

7 authors.

Markus A ZeitlingerDepartment of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Hartmut Derendorf
Johan W Mouton
Otto Cars
William A Craig
David Andes
Ursula Theuretzbacher

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agents in vitro. This might explain the somewhat contradictory results obtained from different studies. Simple in vitro models which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Within in vitro test systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibiotics in vitro become even more urgent. In addition, the quantitative relationship between the effects of protein binding in vitro and in vivo needs to be established, since the physiological conditions differ. General recommendations for testing the impact of protein binding in vitro are suggested.

Indexed as

AnimalsAnti-Bacterial AgentsHumansHydrogen-Ion ConcentrationMicrobial Sensitivity TestsProtein BindingProteinsTemperatureAnti-Bacterial AgentsProteins

Identifiers

PMID21537013
PMCPMC3122431

What OpenQuestion holds

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Registered trials

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.