Evidence map›Paper›PMID 23917322›Full record

SynthesisAntimicrobial agents and chemotherapy2013

Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems.

Oren Zusman, Tomer Avni, Leonard Leibovici, Amos Adler, Lena Friberg, Theodouli Stergiopoulou, Yehuda Carmeli, Mical Paul

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 7 pooled it
7.1field-weighted citation impact, top 2% 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

109 citing papers in PubMed, 7 syntheses or guidelines pooled it, 230 citations in OpenAlex.

  1. Pooled it
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  5. Guideline
  6. Combination antibiotic treatment versus monotherapy for multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter infections: a systematic review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2014
    Pooled it
  7. Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
    Pooled it
  8. Trial
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  14. Antimicrobial potential of compounds from the MMV pandemic response box and COVID box against carbapenem-resistant Acinetobacter baumannii.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025
    Article
  15. Review
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49 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 5 institutions in 3 countries.

Oren ZusmanDepartment of Medicine E, Rabin Medical Center, Petah-Tiqva, Israel.
Tomer Avni
Leonard Leibovici
Amos Adler
Lena Friberg
Theodouli Stergiopoulou
Yehuda Carmeli
Mical Paul
Rabin Medical Center · ILTel Aviv Sourasky Medical Center · ILCentre Hospitalier Universitaire de Liège · BERambam Health Care Campus · ILUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.

Indexed as

Anti-Bacterial AgentsCarbapenemsDrug SynergismMicrobial Sensitivity TestsPolymyxinsAnti-Bacterial AgentsCarbapenemsPolymyxins

Identifiers

PMID23917322
PMCPMC3811454
OpenAlexW1964226118

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.