Evidence map›Paper›PMID 33442721›Full record

ArticleThe Journal of antimicrobial chemotherapy2021

Effective antimicrobial combination in vivo treatment predicted with microcalorimetry screening.

Kasper Nørskov Kragh, Desiree Gijón, Ainhize Maruri, Alberto Antonelli, Marco Coppi, Mette Kolpen, Stephanie Crone, Chaitanya Tellapragada, Badrul Hasan, Stine Radmer and 7 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
5.7field-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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. d-[5-ACS infectious diseases · 2025
    Article
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  4. Review
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  6. Antibiotics againstPharmaceutics · 2024
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  9. Adaptation ofMicrobiology (Reading, England) · 2023
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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

17 authors at 7 institutions in 5 countries.

Kasper Nørskov KraghDepartment of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark.
Desiree GijónServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Ainhize MaruriServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Alberto AntonelliDepartment of Experimental and Clinical Medicine, University of Florence, 50121 Firenze, Italy.
Marco CoppiDepartment of Experimental and Clinical Medicine, University of Florence, 50121 Firenze, Italy.
Mette KolpenDepartment of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark.
Stephanie CroneDepartment of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark.
Chaitanya TellapragadaDepartment of Laboratory Medicine, Karolinska Institutet, 14183 Stockholm, Sweden.
Badrul HasanDepartment of Laboratory Medicine, Karolinska Institutet, 14183 Stockholm, Sweden.
Stine RadmerDepartment of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark.
Corné de VogelDepartment of Medical Microbiology and Infectious Diseases, Erasmus University, Erasmus MC, 3000CA Rotterdam, The Netherlands.
Willem van WamelDepartment of Medical Microbiology and Infectious Diseases, Erasmus University, Erasmus MC, 3000CA Rotterdam, The Netherlands.
Annelies VerbonDepartment of Medical Microbiology and Infectious Diseases, Erasmus University, Erasmus MC, 3000CA Rotterdam, The Netherlands.
Christian G GiskeDepartment of Laboratory Medicine, Karolinska Institutet, 14183 Stockholm, Sweden.
Gian Maria RossoliniDepartment of Experimental and Clinical Medicine, University of Florence, 50121 Firenze, Italy.
Rafael CantónServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Niels Frimodt-MøllerDepartment of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark.
Rigshospitalet · DKErasmus MC · NLInstituto Ramón y Cajal de Investigación Sanitaria · ESUniversity of Florence · ITKarolinska Institutet · SEKarolinska University Hospital · SEUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe worldwide emergence of antibiotic resistance calls for effective exploitation of existing antibiotics. Antibiotic combinations with different modes of action can synergize for successful treatment. In the present study, we used microcalorimetry screening to identify synergistic combination treatments against clinical MDR isolates. The synergistic effects were validated in a murine infection model.

methodsThe synergy of meropenem combined with colistin, rifampicin or amikacin was tested on 12 isolates (1 Escherichia coli, 5 Klebsiella pneumoniae, 3 Pseudomonas aeruginosa and 3 Acinetobacter baumannii) in an isothermal microcalorimeter measuring metabolic activity. One A. baumannii strain was tested with two individual pairings of antibiotic combinations. The microcalorimetric data were used to predict in vivo efficacy in a murine peritonitis/sepsis model. NMRI mice were inoculated intraperitoneally and after 1 h treated with saline, drug X, drug Y or X+Y. Bacterial load was determined by cfu in peritoneal fluid and blood after 4 h.

resultsIn vitro, of the 13 combinations tested on the 12 strains, 3 of them exhibited a synergistic reduction in MIC (23% n = 3/13), 5 showed an additive effect (38.5% n = 5/13) and 5 had indifferent or antagonistic effects (38.5% n = 5/13). There was a significant correlation (P = 0.024) between microcalorimetry-screening FIC index values and the log reduction in peritoneal fluid from mice that underwent combination treatment compared with the most effective mono treatment. No such correlation could be found between chequerboard and in vivo results (P = 0.16).

conclusionsThese data support microcalorimetic metabolic readout to predict additive or synergistic effects of combination treatment of MDR infections within hours.

Indexed as

Acinetobacter baumanniiDrug Resistance, Multiple, BacterialAnimalsAnti-Bacterial AgentsColistinDrug SynergismMiceMicrobial Sensitivity TestsAnti-Bacterial AgentsColistin

Identifiers

PMID33442721
PMCPMC7953322
OpenAlexW3120681903

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.