Evidence map›Paper›PMID 25806811›Full record

ArticlePloS one2015

Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline.

Jie Feng, Paul G Auwaerter, Ying Zhang

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
11.0field-weighted citation impact, top 1% 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

73 citing papers in PubMed, 132 citations in OpenAlex.

  1. Comparative evaluation of viability assays and functional analysis ofApplied and environmental microbiology · 2026
    Article
  2. Daptomycin OvercomesInfection and drug resistance · 2026
    Article
  3. Probable European-profileFrontiers in medicine · 2026
    Article
  4. A rational approach to discovering new persister control agents.Antimicrobial agents and chemotherapy · 2025
    Article
  5. Genomic characterization and antibiotic susceptibility of biofilm-formingFrontiers in cellular and infection microbiology · 2025
    Article
  6. Eradication ofACS infectious diseases · 2024
    Article
  7. Review
  8. Review
  9. Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024
    Review
  10. Current and emerging approaches for eliminatingFrontiers in microbiology · 2024
    Review
  11. Amino acid substitutions in the region between RpoB clusters II and III on rifampin susceptibility in Haemophilus influenzae.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023
    Article
  12. Concurrent Infection of the Human Brain with MultipleInternational journal of molecular sciences · 2023
    Article
  13. The In Vitro Antimicrobial Susceptibility ofPathogens (Basel, Switzerland) · 2023
    Review
  14. Review
  15. Review
  16. Electrochemical Detection ofACS measurement science au · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. Eradication ofAntibiotics (Basel, Switzerland) · 2022
    Article

13 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

3 authors at 1 institution in 1 country.

Jie FengDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Paul G AuwaerterFisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Ying ZhangDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Johns Hopkins University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although most Lyme disease patients can be cured with antibiotics doxycycline or amoxicillin using 2-4 week treatment durations, some patients suffer from persistent arthritis or post-treatment Lyme disease syndrome. Why these phenomena occur is unclear, but possibilities include host responses, antigenic debris, or B. burgdorferi organisms remaining despite antibiotic therapy. In vitro, B. burgdorferi developed increasing antibiotic tolerance as morphology changed from typical spirochetal form in log phase growth to variant round body and microcolony forms in stationary phase. B. burgdorferi appeared to have higher persister frequencies than E. coli as a control as measured by SYBR Green I/propidium iodide (PI) viability stain and microscope counting. To more effectively eradicate the different persister forms tolerant to doxycycline or amoxicillin, drug combinations were studied using previously identified drugs from an FDA-approved drug library with high activity against such persisters. Using a SYBR Green/PI viability assay, daptomycin-containing drug combinations were the most effective. Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefoperazone or carbenicillin) or an energy inhibitor (clofazimine). Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations. These findings may have implications for improved treatment of Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human infection.

Indexed as

Anti-Bacterial AgentsBorrelia burgdorferiCefoperazoneDaptomycinDoxycyclineDrug Therapy, CombinationHumansLyme DiseaseAnti-Bacterial AgentsCefoperazoneDaptomycinDoxycycline

Identifiers

PMID25806811
PMCPMC4373819
OpenAlexW2087254697

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.