Evidence map›Paper›PMID 24189253›Full record

Trial reportAntimicrobial agents and chemotherapy2014

Moxifloxacin population pharmacokinetics and model-based comparison of efficacy between moxifloxacin and ofloxacin in African patients.

Simbarashe P Zvada, Paolo Denti, Frederick A Sirgel, Emmanuel Chigutsa, Mark Hatherill, Salome Charalambous, Stanley Mungofa, Lubbe Wiesner, Ulrika S H Simonsson, Amina Jindani and 2 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2014. 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 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 13% of its field
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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

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  10. Moxifloxacin Pharmacokinetics, Cardiac Safety, and Dosing for the Treatment of Rifampicin-Resistant Tuberculosis in Children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
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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

12 authors at 7 institutions in 4 countries.

Simbarashe P ZvadaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Paolo Denti
Frederick A Sirgel
Emmanuel Chigutsa
Mark Hatherill
Salome Charalambous
Stanley Mungofa
Lubbe Wiesner
Ulrika S H Simonsson
Amina Jindani
Thomas Harrison
Helen M McIlleron
University of Cape Town · ZASt George's, University of London · GBAurum Institute · ZAMinistry of Health and Child Welfare · ZWSouth African Tuberculosis Vaccine Initiative · ZAStellenbosch University · ZAUppsala University · SE

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701Wellcome TrustWellcome Trust 41216Wellcome Trust 5374Wellcome Trust WT081199/Z/06/Z
6 · The paper itself

Abstract

Pharmacokinetic exposure and the MIC of fluoroquinolones are important determinants of their efficacy against Mycobacterium tuberculosis. Population modeling was used to describe the steady-state plasma pharmacokinetics of moxifloxacin in 241 tuberculosis (TB) patients in southern Africa. Monte Carlo simulations were applied to obtain the area under the unbound concentration-time curve from 0 to 24 h (fAUC0-24) after daily doses of 400 mg or 800 mg moxifloxacin and 800 mg ofloxacin. The MIC distributions of ofloxacin and moxifloxacin were determined for 197 drug-resistant clinical isolates of Mycobacterium tuberculosis. For a specific MIC, the probability of target attainment (PTA) was determined for target fAUC0-24/MIC ratios of ≥53 and ≥100. The PTAs were combined with the MIC distributions to calculate the cumulative fraction of response (CFR) for multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Even with the less stringent target ratio of ≥53, moxifloxacin at 400 mg and ofloxacin at 800 mg achieved CFRs of only 84% and 58% for multidrug-resistant isolates with resistance to an injectable drug, while the 800-mg moxifloxacin dose achieved a CFR of 98%. Using a target ratio of ≥100 for multidrug-resistant strains (without resistance to injectable agents or fluoroquinolones), the CFR was 88% for moxifloxacin and only 43% for ofloxacin, and the higher dose of 800 mg moxifloxacin was needed to achieve a CFR target of >90%. Our results indicate that moxifloxacin is more efficacious than ofloxacin in the treatment of MDR-TB. Further studies should determine the optimal pharmacodynamic target for moxifloxacin in a multidrug regimen and clarify safety issues when it is administered at higher doses.

Indexed as

AdultAntitubercular AgentsFemaleFluoroquinolonesHumansMaleMicrobial Sensitivity TestsMiddle AgedMonte Carlo MethodMoxifloxacinOfloxacinTuberculosis, Multidrug-ResistantYoung AdultAntitubercular AgentsFluoroquinolonesMoxifloxacinOfloxacin

Identifiers

PMID24189253
PMCPMC3910772
OpenAlexW2014274983

What OpenQuestion holds

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Read underepoch 390

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.