Evidence map›Paper›PMID 38573915›Full record

ArticlePLoS neglected tropical diseases2024

Amoxicillin/clavulanate in combination with rifampicin/clarithromycin is bactericidal against Mycobacterium ulcerans.

Emma Sáez-López, Ana C Millán-Placer, Ainhoa Lucía, Santiago Ramón-García

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05169554 (Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.9field-weighted citation impact, top 14% 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.

NCT05169554 phase2unknown statusnot on this map

Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy: Comparison of 8 Weeks Standard Therapy (Rifampicin Plus Clarithromycin) vs. 4 Weeks Standard Plus Amoxicillin/Clavulanate Therapy [RC8 vs. RCA4]

TypeinterventionalSponsorFundacion Agencia Aragonesa para la Investigacion y Desarrollo (ARAID)Ran2021 to 2026Enrolled140ConditionsBuruli UlcerArmsStandard [RC8]: rifampicin plus clarithromycin (RC) therapy for 8 weeks., Investigational [RCA4]: standard (RC) plus amoxicillin/clavulanate (A) for 4 weeks.
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Drug combinations targeting antibiotic resistance.npj antimicrobials and resistance · 2024
    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

4 authors at 1 institution in 1 country.

Emma Sáez-LópezDepartment of Microbiology, Paediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.ORCID 0000-0001-8313-3017
Ana C Millán-PlacerDepartment of Microbiology, Paediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.
Ainhoa LucíaDepartment of Microbiology, Paediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.
Santiago Ramón-GarcíaDepartment of Microbiology, Paediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.
Universidad de Zaragoza · ES

Funding

Anesvad FoundationSpanish GovernmentTres Cantos Open Lab Foundation
6 · The paper itself

Abstract

backgroundBuruli ulcer (BU) is a skin neglected tropical disease (NTD) caused by Mycobacterium ulcerans. WHO-recommended treatment requires 8-weeks of daily rifampicin (RIF) and clarithromycin (CLA) with wound care. Treatment compliance may be challenging due to socioeconomic determinants. Previous minimum Inhibitory Concentration and checkerboard assays showed that amoxicillin/clavulanate (AMX/CLV) combined with RIF+CLA were synergistic against M. ulcerans. However, in vitro time kill assays (TKA) are a better approach to understand the antimicrobial activity of a drug over time. Colony forming units (CFU) enumeration is the in vitro reference method to measure bacterial load, although this is a time-consuming method due to the slow growth of M. ulcerans. The aim of this study was to assess the in vitro activity of RIF, CLA and AMX/CLV combinations against M. ulcerans clinical isolates by TKA, while comparing four methodologies: CFU enumeration, luminescence by relative light unit (RLU) and optical density (at 600 nm) measurements, and 16S rRNA/IS2404 genes quantification. METHODOLOGY/PRINCIPAL

findingsTKA of RIF, CLA and AMX/CLV alone and in combination were performed against different M. ulcerans clinical isolates. Bacterial loads were quantified with different methodologies after 1, 3, 7, 10, 14, 21 and 28 days of treatment. RIF+AMX/CLV and the triple RIF+CLA+AMX/CLV combinations were bactericidal and more effective in vitro than the currently used RIF+CLA combination to treat BU. All methodologies except IS2404 quantitative PCR provided similar results with a good correlation with CFU enumeration. Measuring luminescence (RLU) was the most cost-effective methodology to quantify M. ulcerans bacterial loads in in vitro TKA. CONCLUSIONS/SIGNIFICANCE: Our study suggests that alternative and faster TKA methodologies can be used in BU research instead of the cumbersome CFU quantification method. These results provide an in vitro microbiological support to of the BLMs4BU clinical trial (NCT05169554, PACTR202209521256638) to shorten BU treatment.

Indexed as

Buruli UlcerMycobacterium ulceransAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial AgentsClarithromycinHumansRifampinRNA, Ribosomal, 16SAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial AgentsClarithromycinRifampinRNA, Ribosomal, 16S

Identifiers

PMID38573915
PMCPMC10994486
OpenAlexW4393929837

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.