Evidence map›Paper›PMID 36567467›Full record

ArticlePharmacotherapy2023

In silico evaluation of a beta-lactam dosing guideline among adults with serious infections.

Paul Williams, Menino Osbert Cotta, Mohd H Abdul-Aziz, Kathryn Wilks, Andras Farkas, Jason A Roberts

Open access · bronzeAbstract read
In one paragraph

Article in Pharmacotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 29% 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

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Article
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

6 authors at 2 institutions in 3 countries.

Paul WilliamsUniversity of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-4867-4456
Menino Osbert CottaUniversity of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-2058-2314
Mohd H Abdul-AzizUniversity of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-8889-5579
Kathryn WilksInfectious Diseases Department, Sunshine Coast University Hospital, Birtinya, Queensland, Australia.
Andras FarkasDepartment of Pharmacy, Mount Sinai West, New York, New York, USA.
Jason A RobertsUniversity of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0001-6218-435X
The University of Queensland · AUMount Sinai Hospital · US

Funding

Advancing Queensland Clinical FellowshipNational Health and Medical Research Council APP2007007National Health and Medical Research Council APP2009736
6 · The paper itself

Abstract

STUDY

objectiveThe aim of this study was to compare the achievement of therapeutic pharmacokinetic-pharmacodynamic (PK-PD) exposure targets for beta-lactam antibiotics using product information dosing or guideline-based dosing for the treatment of serious infections.

designIn silico study. DATA SOURCE: ID-ODS PATIENTS AND

interventionNone. MEASUREMENTS AND MAIN

resultsIn silico product information and guideline-based dosing simulations for cefepime, ceftazidime, flucloxacillin, meropenem, and piperacillin/tazobactam were performed using pharmacokinetic models from seriously ill patient populations. The median simulated concentration at 48 and 96 h was used to measure the probability of target attainment (PTA) to achieve predefined therapeutic and toxicity PK-PD targets. A multiple linear regression model was constructed to identify the effect of guideline-based dosing covariates on achieving pre-defined therapeutic targets. In total, 480 dosing simulations were performed. The PTA percentage with guideline-based dosing at 48 and 96 h was 80% and 68%, respectively, yielding significantly higher results when compared to product information dosing (48.45% and 49%, respectively), p < 0.001 at both time points. At 48 h, predefined toxicity thresholds were exceeded in 4.7% and 0% of simulations for guideline-based and product information-based dosing, respectively (p = 0.002). eGFR was significantly associated with the % PTA by guideline-based dosing, with eGFR values of 20 and 50 ml/min both statistically significant in leading to an increase in PTA.

conclusionsOur study demonstrated that achievement of PK-PD exposures associated with an increased likelihood of effectiveness was more likely to occur with guideline-based dosing; especially at 48 h.

Indexed as

Anti-Bacterial AgentsLactamsAdultCefepimeCeftazidimeCritical IllnessHumansMeropenemMicrobial Sensitivity TestsAnti-Bacterial AgentsCefepimeCeftazidimeLactamsMeropenembeta-lactamcritically illguidelinenomogram

Identifiers

PMID36567467
PMCPMC10946580
OpenAlexW4312194656

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.