Evidence map›Paper›PMID 40802129›Full record

Observational studyInfection2025

Predictors of therapeutic exposure and pharmacokinetic variability of second-line anti-TB drugs in MDR-TB patients: a retrospective study.

Chilie Quncuo, Wei Dan Ye, Jing Yang, Jian-Qing He

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Infection, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Observational
  3. 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.

Chilie QuncuoDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Wei Dan YeDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Jing YangDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Jian-Qing HeDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China. jianqing_he@scu.edu.cn.

Funding

West China Hospital, Sichuan University 22HXFH006
6 · The paper itself

Abstract

backgroundTherapeutic drug monitoring (TDM) is increasingly recommended for managing multidrug-resistant tuberculosis (MDR-TB) due to significant interindividual pharmacokinetic variability. However, data on plasma concentration variability and associated patient factors for second-line anti-TB drugs remain limited.

methodsWe conducted a retrospective observational study including 74 patients with MDR-TB at West China Hospital, Sichuan University, from January 2022 to December 2024. Plasma concentrations of second-line drugs (levofloxacin, cycloserine, clofazimine, bedaquiline, and linezolid) were measured at steady-state. We analyzed therapeutic target attainment rates, evaluated correlations between drug concentrations and patient baseline characteristics, and explored predictors of drug exposure using multivariable linear regression.

resultsSignificant interindividual variability in drug exposure was observed across the studied second-line anti-TB drugs. Clofazimine demonstrated the highest therapeutic target attainment (72.7%), while bedaquiline had the lowest (21.1%). For levofloxacin, 29.8% of patients achieved therapeutic concentrations, whereas cycloserine reached target levels in 43.2% of cases. Age was positively correlated with cycloserine concentrations (ρ = 0.328, p = 0.030). Multivariable regression identified age and liver enzymes (ALT and AST) as independent predictors of levofloxacin exposure. Specifically, elevated ALT was associated with lower levofloxacin levels (B = -0.191, 95% CI: -0.337 to -0.045), while elevated AST was linked to higher levels (B = 0.292, 95% CI: 0.080 to 0.503). Linezolid trough concentrations showed a negative correlation with RBC count, and peak concentrations were positively associated with ESR. Additionally, bedaquiline concentrations correlated positively with CRP levels.

conclusionOur findings highlight substantial pharmacokinetic variability among second-line anti-TB drugs, influenced by patient age, liver function, and systemic inflammation. These results underscore the potential importance of individualized dosing and routine TDM in optimizing drug exposure and minimizing toxicity in patients with MDR-TB.

Indexed as

Antitubercular AgentsTuberculosis, Multidrug-ResistantAdultAgedChinaClofazimineCycloserineDiarylquinolinesDrug MonitoringFemaleHumansLevofloxacinLinezolidMaleMiddle AgedRetrospective StudiesAntitubercular AgentsbedaquilineClofazimineCycloserineDiarylquinolinesLevofloxacinLinezolidBedaquilineClofazimineCycloserineLevofloxacinLinezolidMultidrug-resistant tuberculosisPharmacokineticsSecond-line drugsTherapeutic drug monitoring

Identifiers

PMID40802129

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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.