Evidence map›Paper›PMID 26525790›Full record

ArticleAntimicrobial agents and chemotherapy2016

Pharmacodynamics of Ceftazidime and Avibactam in Neutropenic Mice with Thigh or Lung Infection.

Johanna Berkhout, Maria J Melchers, Anita C van Mil, Seyedmojtaba Seyedmousavi, Claudia M Lagarde, Virna J Schuck, Wright W Nichols, Johan W Mouton

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 4% 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

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.

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2 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

8 authors at 3 institutions in 2 countries.

Johanna BerkhoutDepartment of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-4387-4464
Maria J MelchersDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Anita C van MilDepartment of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
Seyedmojtaba SeyedmousaviDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-6194-7447
Claudia M LagardeDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Virna J SchuckAstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA.
Wright W NicholsAstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA.
Johan W MoutonDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands jwmouton@gmail.com.ORCID http://orcid.org/0000-0001-6736-4149
Radboud University Nijmegen · NLAstraZeneca (United States) · USCanisius-Wilhelmina Ziekenhuis · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Avibactam is a new non-β-lactam β-lactamase inhibitor that shows promising restoration of ceftazidime activity against microorganisms producing Ambler class A extended-spectrum β-lactamases (ESBLs) and carbapenemases such as KPCs, class C β-lactamases (AmpC), and some class D enzymes. To determine optimal dosing combinations of ceftazidime-avibactam for treating infections with ceftazidime-resistant Pseudomonas aeruginosa, pharmacodynamic responses were explored in murine neutropenic thigh and lung infection models. Exposure-response relationships for ceftazidime monotherapy were determined first. Subsequently, the efficacy of adding avibactam every 2 h (q2h) or q8h to a fixed q2h dose of ceftazidime was determined in lung infection for two strains. Dosing avibactam q2h was significantly more efficacious, reducing the avibactam daily dose for static effect by factors of 2.7 and 10.1, whereas the mean percentage of the dosing interval that free drug concentrations remain above the threshold concentration of 1 mg/liter (%fT>C(T) 1 mg/liter) yielding bacteriostasis was similar for both regimens, with mean values of 21.6 (q2h) and 18.5 (q8h). Dose fractionation studies of avibactam in both the thigh and lung models indicated that the effect of avibactam correlated well with %fT>C(T) 1 mg/liter. This parameter of avibactam was further explored for four P. aeruginosa strains in the lung model and six in the thigh model. Parameter estimates of %fT>C(T) 1 mg/liter for avibactam ranged from 0 to 21.4% in the lung model and from 14.1 to 62.5% in the thigh model to achieve stasis. In conclusion, addition of avibactam enhanced the effect of ceftazidime, which was more pronounced at frequent dosing and well related with %fT>C(T) 1 mg/liter. The thigh model appeared more stringent, with higher values, ranging up to 62.5% fT>C(T) 1 mg/liter, required for a static effect.

Indexed as

AnimalsAnimals, Outbred StrainsAnti-Bacterial AgentsAzabicyclo CompoundsCeftazidimeColony Count, MicrobialDrug Administration ScheduleDrug CombinationsFemaleLungMiceMicrobial Sensitivity TestsNeutropeniaOrgan SpecificityPseudomonas aeruginosaPseudomonas InfectionsAnti-Bacterial Agentsavibactamavibactam, ceftazidime drug combinationAzabicyclo CompoundsCeftazidimeDrug Combinations

Identifiers

PMID26525790
PMCPMC4704241
OpenAlexW2262202809

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.