Evidence map›Paper›PMID 40022145›Full record

ArticleAnnals of clinical microbiology and antimicrobials2025

In vitro activity of rifampicin, rifapentine and rifabutin in combination with their 25-deacetyl-metabolites against various Mycobacterium tuberculosis lineages.

Charlotte Genestet, Chloé Bourg, Elisabeth Hodille, Olivier Bahuaud, Florence Ader, Sylvain Goutelle, Oana Dumitrescu, Lyon TB study group

Abstract read
In one paragraph

Article in Annals of clinical microbiology and antimicrobials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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.

Charlotte GenestetCIRI - Centre International de Recherche en Infectiologie, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon-1, Inserm U1111, CNRS UMR5308, Lyon, France. charlotte.genestet@gmail.com.
Chloé BourgCIRI - Centre International de Recherche en Infectiologie, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon-1, Inserm U1111, CNRS UMR5308, Lyon, France.
Elisabeth HodilleCIRI - Centre International de Recherche en Infectiologie, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon-1, Inserm U1111, CNRS UMR5308, Lyon, France.
Olivier BahuaudCIRI - Centre International de Recherche en Infectiologie, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon-1, Inserm U1111, CNRS UMR5308, Lyon, France.
Florence AderCIRI - Centre International de Recherche en Infectiologie, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon-1, Inserm U1111, CNRS UMR5308, Lyon, France.
Sylvain GoutelleBiometrics and Evolutionary Biology Laboratory, CNRS UMR 5558, Université Lyon 1, Villeurbanne, France.
Oana DumitrescuCIRI - Centre International de Recherche en Infectiologie, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon-1, Inserm U1111, CNRS UMR5308, Lyon, France.
Lyon TB study group

Funding

Agence Nationale de la Recherche ANR-18-CE17-0020
6 · The paper itself

Abstract

objectivesRifamycin agents (rifampicin (RIF), rifapentine (RFP), rifabutin (RFB)) are the cornerstone of tuberculosis (TB) therapy. Rifamycins are metabolized into 25-deacetyl-metabolites, which have been described has active and may contribute to in vivo drug effect. However, little is known about the combined effect of rifamycins and their metabolites across different Mycobacterium tuberculosis complex (MTBC) lineages.

methodsThis study included 14 MTBC strains representing the main lineages. Minimum inhibitory concentrations (MICs) were determined using microdilution assays for the three rifamycins and their metabolites. A checkerboard assay was used to assess drug interactions, with the fractional inhibitory concentration (FIC) index calculated for synergy or antagonism.

resultsMICs varied across rifamycins, RIF and its metabolite showed the highest MICs, followed by RFP and RFB and their respective metabolites. FIC indices for rifamycin-metabolite combinations indicated additive effects (FIC between 0.5 and 1.25), with no antagonism observed, even at clinically relevant metabolite-to-parent drug ratios, and without impact of MTBC lineage.

conclusionsRifamycin metabolites exhibit additive effects with parent drugs, potentially enhancing bactericidal activity. This highlights that rifamycin susceptibility testing should account for both parent drugs and their metabolites, as these metabolites also exhibit antimicrobial activity. Additionally, these findings support further pharmacokinetic/pharmacodynamic studies to optimize TB treatment regimens, particularly in relation to metabolite-to-parent drug ratios in patients.

Indexed as

Antitubercular AgentsMycobacterium tuberculosisRifabutinRifampinAntibiotics, AntitubercularDrug InteractionsDrug SynergismHumansMicrobial Sensitivity TestsTuberculosisAntibiotics, AntitubercularAntitubercular AgentsRifabutinRifampinrifapentine25-deacetyl-metaboliteCheckerboard assayFractional inhibitory concentrationMycobacterium tuberculosisRifabutinRifampicinRifamycinRifapentine

Identifiers

PMID40022145
PMCPMC11871726

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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.