Evidence map›Paper›PMID 36678879›Full record

ArticlePharmaceutics2023

Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-β-Lactamase and Serine-β-Lactamase Co-Producing

Jiayuan Zhang, Mengyuan Wu, Shuo Diao, Shixing Zhu, Chu Song, Jiali Yue, Frederico S Martins, Peijuan Zhu, Zhihua Lv, Yuanqi Zhu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 25% 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, 12 citations in OpenAlex.

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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

12 authors at 6 institutions in 3 countries.

Jiayuan ZhangSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Mengyuan WuSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Shuo DiaoSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Shixing ZhuSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Chu SongSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Jiali YueSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Frederico S MartinsFaculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil.
Peijuan ZhuDepartment of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zhihua LvSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Yuanqi ZhuDepartment of Laboratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Mingming YuSchool of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.ORCID 0000-0001-9504-891X
Sherwin K B SyDepartment of Statistics, State University of Maringá, Maringá 87020-900, Paraná, Brazil.ORCID 0000-0001-6405-9130
Ocean University of China · CNQingdao National Laboratory for Marine Science and Technology · CNQingdao University · CNUniversidade de São Paulo · BRUniversidade Estadual de Maringá · BRUniversity of Pennsylvania · US

Funding

Shandong Provincial Natural Science Foundation ZR2019BC025
6 · The paper itself

Abstract

This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-β-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories. This combination reduced the MIC of aztreonam and amoxicillin/clavulanate to values below their clinical breakpoint in 7/9 K. pneumoniae and 8/9 E. coli, depending on the β-lactamase genes detected in the isolate. In the majority of the tested isolates, the combination resulted in fT>MPC > 90% and fTMSW < 10% for both aztreonam and amoxicillin/clavulanate. Clinical dosing regimens of aztreonam and amoxicillin/clavulanate were sufficient to provide mutant restriction coverage for MPC and MIC ≤ 4 mg/L. This combination has limited coverage against NDM- and extended-spectrum β-lactamase co-producing E. coli and K. pneumoniae and is not effective against isolates carrying plasmid-mediated AmpC and KPC-2. This study offers a potential scope and limitations as to where the aztreonam/amoxicillin/clavulanate combination may succeed or fail.

Indexed as

Escherichia coliKlebsiella pneumoniaeMPCNDMpharmacodynamics

Identifiers

PMID36678879
PMCPMC9865866
OpenAlexW4315574228

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.