Evidence map›Paper›PMID 23901086›Full record

ArticleThe Journal of infectious diseases2013

Serum drug concentrations predictive of pulmonary tuberculosis outcomes.

Jotam G Pasipanodya, Helen McIlleron, André Burger, Peter A Wash, Peter Smith, Tawanda Gumbo

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 272 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
272citing papers in PubMed, 15 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.

NCT03827811 unknown statusnot on this mapstarted 2020, after this paper: background citation

Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis

TypeobservationalSponsorUniversity of Cape TownRan2020 to 2023Enrolled625ConditionsMulti-drug Resistant Tuberculosis
NCT06585358 recruitingnot on this mapstarted 2025, after this paper: background citation

DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis

TypeobservationalSponsorKarolinska InstitutetRan2025 to 2027Enrolled30ConditionsTuberculosis, PulmonaryArmsMIPD
3 · Its place in the literature

Who cites it

272 citing papers in PubMed, 15 syntheses or guidelines pooled it.

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  8. Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
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  12. A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020
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  16. Effect of HIV on bedaquiline and delamanid pharmacokinetics in patients with multidrug-resistant TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2025
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  18. Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
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  19. Optimising pyrazinamide for the treatment of tuberculosis.The European respiratory journal · 2021
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212 more citing papers are in PubMed but not listed here.

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

6 authors.

Jotam G PasipanodyaOffice of Global Health, University of Texas Southwestern Medical Center, Dallas, Texas.
Helen McIlleron
André Burger
Peter A Wash
Peter Smith
Tawanda Gumbo

Funding

Efflux pump inhibitors to reduce duration of antituberculosis therapyDP2OD001886 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI GUMBO, TAWANDA · 2007 to 2007
$2.4M
PK-PD of combination antituberculosis therapy for suppression of drug-resistanceR01AI079497 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GUMBO, TAWANDA · 2008 to 2011
$2.3M
NIAID NIH HHS R01 AI079497NIAID NIH HHS R01AI079497NIH HHS DP2 OD001886
6 · The paper itself

Abstract

backgroundBased on a hollow-fiber system model of tuberculosis, we hypothesize that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic variability.

methodsClinical and pharmacokinetic data were prospectively collected from 142 tuberculosis patients in Western Cape, South Africa. Compartmental pharmacokinetic parameters of isoniazid, rifampin, and pyrazinamide were identified for each patient. Patients were then followed for up to 2 years. Classification and regression tree analysis was used to identify and rank clinical predictors of poor long-term outcome such as microbiologic failure or death, or relapse.

resultsDrug concentrations and pharmacokinetics varied widely between patients. Poor long-term outcomes were encountered in 35 (25%) patients. The 3 top predictors of poor long-term outcome, by rank of importance, were a pyrazinamide 24-hour area under the concentration-time curve (AUC) ≤ 363 mg·h/L, rifampin AUC ≤ 13 mg·h/L, and isoniazid AUC ≤ 52 mg·h/L. Poor outcomes were encountered in 32/78 patients with the AUC of at least 1 drug below the identified threshold vs 3/64 without (odds ratio = 14.14; 95% confidence interval, 4.08-49.08). Low rifampin and isoniazid peak and AUC concentrations preceded all cases of acquired drug resistance.

conclusionsLow drug AUCs are predictive of clinical outcomes in tuberculosis patients.

Indexed as

AdolescentAdultAgedAntitubercular AgentsArea Under CurveFemaleHumansIsoniazidMaleMicrobial Sensitivity TestsMiddle AgedMycobacterium tuberculosisProspective StudiesPyrazinamideRifampinTreatment OutcomeAntitubercular AgentsIsoniazidPyrazinamideRifampinclassification and regression tree analysisdrug concentrationshollow-fiber systemnonlinear systemsoutcomespharmacokinetic variabilitytuberculosis

Identifiers

PMID23901086
PMCPMC3789573

What OpenQuestion holds

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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.