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ArticleBMC infectious diseases2025

Impact of rpoB gene mutations and Rifampicin-resistance levels on treatment outcomes in Rifampicin-resistant tuberculosis.

Maria Jose Vadakunnel, Vijayalakshmi Jawaharlal Nehru, Usharani Brammacharry, Venkateswari Ramachandra, Suganthi Palavesam, Anbazhagi Muthukumar, Balasundaram Revathi Mani, Sriramkumar S R, Gunavathy Pradhabane, Azger Dusthackeer Vn and 3 more

Abstract read
In one paragraph

Article in BMC infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

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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

13 authors.

Maria Jose VadakunnelInstitute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Vijayalakshmi Jawaharlal NehruInstitute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Usharani BrammacharryInstitute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Venkateswari RamachandraInstitute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Suganthi PalavesamInstitute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Anbazhagi MuthukumarDepartment of Environmental Science, Central University, Kasaragod, Kerala, India.
Balasundaram Revathi ManiDepartment of Biochemistry, Queen Mary's College, Madras, Tamil Nadu, India.
Sriramkumar S RCentre for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Nagar, Thandalam, Chennai, 602105, India.
Gunavathy PradhabaneDepartment of Biotechnology, Indira Gandhi College of Arts and Science, Indira Nagar, Puducherry, India.
Azger Dusthackeer VnDepartment of Bacteriology, National Institute of Research in Tuberculosis, Indian Council of Medical Research, Chennai, Tamil Nadu, India.
Sangeetha SubramaniDepartment of Microbiology, State TB Training and Demonstration Centre, Intermediate Reference Laboratory, Government Hospital for Chest Diseases, Puducherry, India.
Muthuraj MuthaiahDepartment of Microbiology, State TB Training and Demonstration Centre, Intermediate Reference Laboratory, Government Hospital for Chest Diseases, Puducherry, India. drmuthurajm@gmail.com.
Govindarajan SoundappanDepartment of Microbiology, State TB Training and Demonstration Centre, Intermediate Reference Laboratory, Government Hospital for Chest Diseases, Puducherry, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough many studies have examined the connection between mutations in the rpoB gene and drug resistance, the impact of common mutations on treatment outcomes for RR-TB is not yet fully understood.

objectivesThis study explores the relationship between rpoB gene mutations and drug-resistant phenotypes, assesses their role in predicting RR-TB prognosis, and investigates the impact of disputed rpoB mutations in M. tuberculosis on treatment outcomes.

methods192 rifampicin-resistant isolates were retested for drug susceptibility and gene sequencing. Minimum inhibitory concentrations (MICs) were determined for 98 isolates with disputed rpoB gene mutations. These mutations can cause low-level resistance to rifampicin, leading to inconsistencies in drug susceptibility testing and impacting medication therapy decisions.

resultsOf 192 cases, 116 (60.4%) achieved successful outcomes, while 76 (39.6%) were unsuccessful. Among the 98 isolates tested for phenotypic drug susceptibility testing (DST) based on minimum inhibitory concentration (MIC), 67 (68.4%) showed high-level resistance with a MIC of ≥ 1 µg/mL. In contrast, 31 (31.6%) drug-susceptible tuberculosis isolates exhibited low-level resistance with a MIC of < 1.0 µg/mL. Of the 31 isolates with low-level resistance, 14 (45.2%) had successful treatment outcomes, while 17 (54.8%) did not. Among the 67 isolates with high-level resistance, 41 (61.2%) achieved successful outcomes, whereas 26 (38.8%) did not. In analysing the 14 codons of the Rifampicin Resistance Determining Region (RRDR) of the rpoB gene, the Leu430Pro codon showed the highest odds ratio (OR) of 2.98 (95% CI: 0.96-9.27) with a p-value of 0.0591, indicating statistically not significant. However, this suggests a potential association with rifampicin resistance that requires further investigation, particularly in areas with high drug-resistant tuberculosis prevalence. Other reported variants had lower odds ratios: Asp435Val with 1.23 (95% CI: 0.32-4.75), Asp435Tyr with 1.86 (95% CI: 0.60-5.76), His445Tyr with 1.16 (95% CI: 0.47-2.91), and Ser450Leu with 1.44 (95% CI: 0.81-2.58).

conclusionsThis study indicates that low-level rifampicin mono-resistance in tuberculosis (TB) patients is associated with poor clinical outcomes. A mutation at the Leu430Pro codon showed the highest odds ratio of 2.98 (p-value 0.0591), suggesting a potential association with rifampicin resistance that warrants further research, especially in areas with high drug-resistant TB. It highlights the need for more aggressive treatment strategies for patients with low-level rifampicin resistance, even if they seem solely mono-resistant.

Indexed as

Antitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesDrug Resistance, BacterialMutationMycobacterium tuberculosisRifampinTuberculosis, Multidrug-ResistantAdultFemaleHumansMaleMicrobial Sensitivity TestsMiddle AgedTreatment OutcomeAntitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesRifampinrpoB protein, Mycobacterium tuberculosisDisputed rpoB mutationsHigh-level resistanceLow-level resistanceMinimal inhibitory concentrationMycobacterium tuberculosisTreatment outcomes

Identifiers

PMID40016696
PMCPMC11866845

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