Evidence map›Paper›PMID 30962340›Full record

ArticleAntimicrobial agents and chemotherapy2019

Ceftolozane-Tazobactam Population Pharmacokinetics and Dose Selection for Further Clinical Evaluation in Pediatric Patients with Complicated Urinary Tract or Complicated Intra-abdominal Infections.

Kajal B Larson, Yogesh T Patel, Susan Willavize, John S Bradley, Elizabeth G Rhee, Luzelena Caro, Matthew L Rizk

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

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  19. New β-Lactam-β-Lactamase Inhibitor Combinations.Clinical microbiology reviews · 2020
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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 3 institutions in 1 country.

Kajal B LarsonMerck & Co, Inc., Kenilworth, New Jersey, USA.
Yogesh T PatelCognigen Corporation, Buffalo, New York, USA.
Susan WillavizeCognigen Corporation, Buffalo, New York, USA.
John S BradleyUniversity of California, San Diego, California, USA.
Elizabeth G RheeMerck & Co, Inc., Kenilworth, New Jersey, USA.
Luzelena CaroMerck & Co, Inc., Kenilworth, New Jersey, USA.ORCID 0000-0003-2275-8771
Matthew L RizkMerck & Co, Inc., Kenilworth, New Jersey, USA matthew_rizk@merck.com.
Merck & Co., Inc., Rahway, NJ, USA (United States) · USCognizant (United States) · USUniversity of California San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the well-established extended-spectrum β-lactamase inhibitor tazobactam, is approved for treating complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses likely to be safe and efficacious in phase 2 pediatric trials for the same indications, single-dose ceftolozane-tazobactam plasma pharmacokinetic data from a recently completed phase 1 trial in pediatric patients (birth to <18 years old) with proven/suspected Gram-negative bacterial infections, along with pharmacokinetic data from 12 adult studies, were integrated into a population pharmacokinetic (popPK) analysis. Two-compartment linear models with first-order elimination described the concentration-time profiles of ceftolozane and tazobactam in pediatric patients well. Renal function and body weight were identified to be significant predictors of ceftolozane-tazobactam pharmacokinetics. Renal function, as measured by the estimated glomerular filtration rate (eGFR), significantly affected the clearance of both ceftolozane and tazobactam. Body weight significantly affected clearance and the distribution volume, also of both ceftolozane and tazobactam. Patients with infections had a 32.3% lower tazobactam clearance than healthy volunteers. Using the final popPK models, simulations of various dosing regimens were conducted to assess each regimen's plasma exposure and the probability of pharmacokinetic/pharmacodynamic target attainment. Based on these simulations, the following doses are recommended for further clinical evaluation in phase 2 pediatric trials for cUTI and cIAI (in patients with an eGFR of ≥50 ml/min/1.73 m

Indexed as

AdolescentAdultAnti-Bacterial AgentsCephalosporinsChildChild, PreschoolFemaleHumansIntraabdominal InfectionsMaleMiddle AgedTazobactamUrinary Tract InfectionsYoung AdultAnti-Bacterial Agentsceftolozaneceftolozane, tazobactam drug combinationCephalosporinsTazobactamcephalosporinchildrenEnterobacteralesPseudomonastarget attainment

Identifiers

PMID30962340
PMCPMC6535558
OpenAlexW2936169514

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.