Evidence map›Paper›PMID 17485505›Full record

Trial reportAntimicrobial agents and chemotherapy2007

Systematic comparison of the population pharmacokinetics and pharmacodynamics of piperacillin in cystic fibrosis patients and healthy volunteers.

J B Bulitta, S B Duffull, M Kinzig-Schippers, U Holzgrabe, U Stephan, G L Drusano, F Sörgel

Open access · greenAbstract readClinical TrialComparative Study
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 6 pooled it
4.1field-weighted citation impact, top 7% 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

70 citing papers in PubMed, 6 syntheses or guidelines pooled it, 118 citations in OpenAlex.

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  8. Clinical outcomes of extended versus intermittent administration of piperacillin/tazobactam for the treatment of hospital-acquired pneumonia: a randomized controlled trial.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017
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10 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 at 5 institutions in 3 countries.

J B BulittaInstitute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
S B Duffull
M Kinzig-Schippers
U Holzgrabe
U Stephan
G L Drusano
F Sörgel
Institute for Biomedical and Pharmaceutical Research · DEAlbany Research Institute · USUniversity of Duisburg-Essen · DEUniversity of Otago · NZUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Respiratory tract infections cause 90% of premature mortality in patients with cystic fibrosis (CF). Treatment of Pseudomonas aeruginosa infection is often very problematic. Piperacillin-tazobactam has good activity against P. aeruginosa, but its pharmacokinetics (PK) in CF patients has not been compared to the PK in healthy volunteers in a controlled clinical study. Therefore, we compared the population PK and pharmacodynamics (PD) of piperacillin between CF patients and healthy volunteers. We studied 8 adult (median age, 20 years) CF patients (average total body weight [WT], 43.1 +/- 7.8 kg) and 26 healthy volunteers (WT, 71.1 +/- 11.8 kg) who each received 4 g piperacillin as a 5-min intravenous infusion. We determined piperacillin levels by high-performance liquid chromatography, and we used NONMEM for population PK and Monte Carlo simulation. We used a target time of nonprotein-bound concentration above the MIC of 50%, which represents near-maximal bacterial killing. Unscaled total clearance was 25% lower, and the volume of distribution was 31% lower in CF patients. Allometric scaling by lean body mass reduced the unexplained (random) between-subject variability in clearance by 26% compared to the variability of linear scaling by WT. A standard dosage regimen of 3 g/70 kg body WT every 4 h as a 30-min infusion (daily dose, 18 g) achieved a robust (> or =90%) probability-of-target attainment (PTA) for MICs of < or =12 mg/liter in CF patients and < or =16 mg/liter in healthy volunteers. Alternative modes of administration allowed a marked dose reduction to 9 g daily. Prolonged (4-h) infusions of 3 g/70 kg WT every 8 h and continuous infusion (daily dose, 9 g), achieved a robust PTA for MICs of < or =16 mg/liter in both groups. Piperacillin achieved PTA expectation values of 64% and 89% against P. aeruginosa infection in CF patients, based on susceptibility data from two German CF clinics.

Indexed as

AdultAnti-Bacterial AgentsCase-Control StudiesComputer SimulationCystic FibrosisFemaleHalf-LifeHumansInfusions, IntravenousMaleMetabolic Clearance RateMicrobial Sensitivity TestsMonte Carlo MethodPiperacillinPopulationPseudomonas aeruginosaAnti-Bacterial AgentsPiperacillin

Identifiers

PMID17485505
PMCPMC1913222
OpenAlexW2085958466

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.