Evidence map›Paper›PMID 22021624›Full record

ArticleThe Journal of infectious diseases2011

Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability.

Shashikant Srivastava, Jotam G Pasipanodya, Claudia Meek, Richard Leff, Tawanda Gumbo

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03827811 (Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis), which is not on this map. Cited by 155 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 6 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
3 · Its place in the literature

Who cites it

155 citing papers in PubMed, 6 syntheses or guidelines pooled it.

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  5. A meta-analysis of self-administered vs directly observed therapy effect on microbiologic failure, relapse, and acquired drug resistance in tuberculosis patients.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2013
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  6. Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2012
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  9. Artificial intelligence-derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018
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95 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Shashikant SrivastavaDepartment of Medicine, University of Texas Southwestern Medical Center at Dallas, TX, USA.
Jotam G Pasipanodya
Claudia Meek
Richard Leff
Tawanda Gumbo

Funding

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 R01AI079497
6 · The paper itself

Abstract

backgroundIt is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level of nonadherence associated with emergence of MDR-tuberculosis is unknown. Performance of a randomized controlled trial in which some patients are randomized to nonadherence would be unethical; therefore, other study designs should be utilized.

methodsWe performed hollow fiber studies for both bactericidal and sterilizing effect, with inoculum spiked with 0.5% rifampin- and isoniazid-resistant isogenic strains in some experiments. Standard therapy was administered daily for 28-56 days, with extents of nonadherence varying between 0% and 100%. Sizes of drug-resistant populations were compared using analysis of variance. We also explored the effect of pharmacokinetic variability on MDR-tuberculosis emergence using computer-aided clinical trial simulations of 10 000 Cape Town, South Africa, tuberculosis patients.

resultsTherapy failure was only encountered at extents of nonadherence ≥60%. Surprisingly, isoniazid- and rifampin-resistant populations did not achieve ≥1% proportion in any experiment and did not achieve a higher proportion with nonadherence. However, clinical trial simulations demonstrated that approximately 1% of tuberculosis patients with perfect adherence would still develop MDR-tuberculosis due to pharmacokinetic variability alone.

conclusionsThese data, based on a preclinical model, demonstrate that nonadherence alone is not a sufficient condition for MDR-tuberculosis emergence.

Indexed as

Computer SimulationMedication AdherenceAntitubercular AgentsDrug Resistance, Multiple, BacterialHumansIsoniazidModels, BiologicalMonte Carlo MethodMycobacterium tuberculosisPyrazinamideRifampinTuberculosis, Multidrug-ResistantAntitubercular AgentsIsoniazidPyrazinamideRifampin

Identifiers

PMID22021624
PMCPMC3209814

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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.