Evidence map›Paper›PMID 40048098›Full record

ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2025

Beta-lactam combination treatment overcomes rifampicin resistance in Mycobacterium tuberculosis.

Diana H Quan, Trixie Wang, Elena Martinez, Hanna Y Kim, Vitali Sintchenko, Warwick J Britton, James A Triccas, Jan-Willem Alffenaar

Abstract read
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In one paragraph

Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 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.

Diana H QuanTuberculosis Research Program, Centenary Institute, The University of Sydney, Sydney, NSW, 2006, Australia. diana.quan@sydney.edu.au.
Trixie WangTuberculosis Research Program, Centenary Institute, The University of Sydney, Sydney, NSW, 2006, Australia.
Elena MartinezCentre for Infectious Diseases and Microbiology, The Westmead Institute, Westmead, NSW, Australia.
Hanna Y KimSchool of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
Vitali SintchenkoCentre for Infectious Diseases and Microbiology, The Westmead Institute, Westmead, NSW, Australia.
Warwick J BrittonTuberculosis Research Program, Centenary Institute, The University of Sydney, Sydney, NSW, 2006, Australia.
James A TriccasSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia.
Jan-Willem AlffenaarSchool of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The significant global impact of tuberculosis (TB) on human health is exacerbated by the increasing prevalence of multi-drug resistant tuberculosis (MDR-TB) and the challenges of novel drug discovery for the treatment of drug-susceptible and drug-resistant strains of M. tuberculosis. Rifampicin is a key first-line TB drug and rifampicin resistance is a major obstacle to treating MDR-TB. Utilising existing antimicrobial drugs to supplement combination therapy and overcome rifampicin resistance is a promising solution due to their widespread availability and proven clinical safety profile. Therefore, this study aimed to explore the feasibility of using beta-lactam/beta-lactamase inhibitor combinations with rifampicin to inhibit the growth of multidrug-resistant M. tuberculosis. Based on inhibitory concentration (IC), oral bioavailability, pricing, commercial availability, five beta-lactams and the beta-lactamase inhibitor, clavulanate, were selected for testing. These were combined with rifampicin for in vitro testing against Mycobacterium tuberculosis H37Rv. Resazurin assays and colony forming unit (CFU) enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose reduction index (DRI). The combination of tebipenem-clavulanate/rifampicin and cephradine-clavulanate/rifampicin were found to be synergistic and highly effective against clinical isolates of MDR-TB, overcoming rifampicin resistance in vitro. Beta-lactam synergy may provide viable combination therapies with rifampicin to address the issue of drug resistance in TB.

Indexed as

Antitubercular Agentsbeta-LactamsMycobacterium tuberculosisRifampinTuberculosis, Multidrug-Resistantbeta-Lactamase InhibitorsClavulanic AcidDrug Resistance, Multiple, BacterialDrug SynergismDrug Therapy, CombinationHumansMicrobial Sensitivity TestsAntitubercular Agentsbeta-Lactamase Inhibitorsbeta-LactamsClavulanic AcidRifampinBeta-lactamBeta-lactamase inhibitorDrug resistanceTuberculosis

Identifiers

PMID40048098
PMCPMC12062089

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Registered trials

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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.