Evidence map›Paper›PMID 25963982›Full record

ArticleAntimicrobial agents and chemotherapy2015

In vitro activity of daptomycin in combination with β-lactams, gentamicin, rifampin, and tigecycline against daptomycin-nonsusceptible enterococci.

Janet A Hindler, Annie Wong-Beringer, Carmen L Charlton, Shelley A Miller, Theodoros Kelesidis, Marissa Carvalho, George Sakoulas, Poochit Nonejuie, Joseph Pogliano, Victor Nizet and 1 more

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

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

18 citing papers in PubMed, 42 citations in OpenAlex.

  1. Vancomycin-ResistantJournal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada · 2025
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  11. Observational
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  18. Mechanisms of drug resistance: daptomycin resistance.Annals of the New York Academy of Sciences · 2015
    Review
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

11 authors at 4 institutions in 2 countries.

Janet A HindlerPathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Annie Wong-BeringerSchool of Pharmacy, University of Southern California, Los Angeles, Los Angeles, California, USA.
Carmen L CharltonPathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA Laboratory Medicine and Pathology, University of Alberta, and the Provincial Laboratory for Public Health (ProvLab), Edmonton, AB, Canada.
Shelley A MillerPathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Theodoros KelesidisDivision of Infectious Diseases, University of California, Los Angeles, Los Angeles, California, USA.
Marissa CarvalhoPathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
George SakoulasDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Poochit NonejuieDepartment of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
Joseph PoglianoDepartment of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
Victor NizetDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
Romney HumphriesPathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA rhumphries@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of California, San Diego · USProvincial Laboratory of Public Health · CAUniversity of Southern California · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
TRAINING & OUTREACH COREU54HD071600 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRADLEY, JOHN S · 2011 to 2015
$3.6M
Identification of natural products targeting new pathways in bacteriaR01AI113295 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI POGLIANO, JOSEPH A, POGLIANO, KIT J · 2014 to 2018
$3.3M
Oxidized HDL in the intersection of HIV, immune activation and atherosclerosisK08AI108272 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KELESIDIS, THEODOROS · 2013 to 2017
$915k
NCATS NIH HHS UL1 TR000124NIAID NIH HHS K08 AI108272NIAID NIH HHS R01 AI113295NICHD NIH HHS U54 HD071600-01
6 · The paper itself

Abstract

Enterococci that are nonsusceptible (NS; MIC > 4 μg/ml) to daptomycin are an emerging clinical concern. The synergistic combination of daptomycin plus beta-lactams has been shown to be effective against vancomycin-resistant Enterococcus (VRE) species in vitro. This study systematically evaluated by in vitro time-kill studies the effect of daptomycin in combination with ampicillin, cefazolin, ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs and different resistance-conferring mutations. We found that ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the liaFSR system. Daptomycin binding was found to be enhanced by ampicillin in a representative isolate with such mutations but not for an isolate with mutation to the yycFGHIJ system. In contrast, ampicillin enhanced the killing of the LL-37 human antimicrobial peptide against daptomycin-NS E. faecium with either the liaFSR or yycFGHIJ mutation. Antagonism was noted only for rifampin and tigecycline and only for 2 or 3 isolates. These data add support to the growing body of evidence indicating that therapy combining daptomycin and ampicillin may be helpful in eradicating refractory VRE infections.

Indexed as

AmpicillinAnti-Bacterial AgentsAntimicrobial Cationic Peptidesbeta-LactamsCathelicidinsDaptomycinDNA, BacterialDNA Mutational AnalysisDrug CombinationsDrug InteractionsDrug Resistance, BacterialDrug SynergismEnterococcusEnterococcus faeciumErtapenemGentamicinsAmpicillinAnti-Bacterial AgentsAntimicrobial Cationic Peptidesbeta-LactamsCathelicidinsDaptomycinDNA, BacterialDrug CombinationsErtapenemGentamicinsRifampin

Identifiers

PMID25963982
PMCPMC4468720
OpenAlexW2151488009

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.