Evidence map›Paper›PMID 23114778›Full record

ArticleAntimicrobial agents and chemotherapy2013

Pharmacokinetics and pharmacodynamics of anidulafungin for experimental Candida endophthalmitis: insights into the utility of echinocandins for treatment of a potentially sight-threatening infection.

J L Livermore, T W Felton, J Abbott, A Sharp, J Goodwin, L Gregson, P A Warn, S J Howard, W W Hope

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 35% of its field
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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016
    Guideline
  2. Article
  3. Antimicrobial guide to posterior segment infections.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021
    Review
  4. Article
  5. Article
  6. Intermittent Dosing of Micafungin Is Effective for Treatment of Experimental Disseminated Candidiasis in Persistently Neutropenic Rabbits.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015
    Article
  7. Tissue penetration of antifungal agents.Clinical microbiology reviews · 2014
    Review
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

9 authors at 4 institutions in 2 countries.

J L LivermoreThe University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
T W Felton
J Abbott
A Sharp
J Goodwin
L Gregson
P A Warn
S J Howard
W W Hope
University of Manchester · GBManchester Academic Health Science Centre · GBChildren's of Alabama · USUniversity of Liverpool · GB

Funding

Department of Health CS/08/08/10Medical Research Council G1000417
6 · The paper itself

Abstract

Candida chorioretinitis and endophthalmitis are relatively common manifestations of disseminated candidiasis. Anidulafungin is increasingly used for the treatment of disseminated candidiasis, but its efficacy for Candida endophthalmitis is not known. A nonneutropenic model of hematogenous Candida endophthalmitis was used. Anidulafungin at 5, 10, and 20 mg/kg was initiated at 48 h postinoculation. The fungal densities in the kidney and vitreous humor were determined. Anidulafungin concentrations in the plasma and vitreous humor were measured using high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic model was used to link anidulafungin concentrations with the observed antifungal effect. The area under the concentration-time curve (AUC) associated with stasis was determined in the both the kidney and the vitreous humor. The results were bridged to humans to identify likely dosages that are associated with significant antifungal activity within the eye. Inoculation of Candida albicans resulted in logarithmic growth in both the vitreous humor and the kidney. The pharmacokinetics of anidulafungin were linear. There was dose-dependent penetration of the anidulafungin into the vitreous humor. The exposure-response relationships in the kidney and vitreous were completely discordant. AUCs of 270 and 100 were required for stasis in the eye and kidney, respectively. The currently licensed regimen results in an AUC for an average patient that is associated with stasis in the kidney but minimal antifungal activity in the eye. We conclude that anidulafungin penetrates the eye in a dose-dependent manner and that dosages higher than those currently licensed are required to achieve significant antifungal activity in the eye.

Indexed as

AnidulafunginAnimalsAntifungal AgentsArea Under CurveCandida albicansCandidiasisChromatography, High Pressure LiquidDisease Models, AnimalDose-Response Relationship, DrugDrug Administration ScheduleDrug Dosage CalculationsEchinocandinsEndophthalmitisKidneyMaleModels, BiologicalAnidulafunginAntifungal AgentsEchinocandins

Identifiers

PMID23114778
PMCPMC3535903
OpenAlexW2147399380

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.