Evidence map›Paper›PMID 30496459›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018

Gatifloxacin Pharmacokinetics/Pharmacodynamics-based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis.

Devyani Deshpande, Jotam G Pasipanodya, Shashikant Srivastava, Paula Bendet, Thearith Koeuth, Sujata M Bhavnani, Paul G Ambrose, Wynand Smythe, Helen McIlleron, Guy Thwaites and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 7% 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.

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

16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018
    Pooled it
  3. 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
    Trial
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Article
  10. Article
  11. Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018
    Article
  12. Article
  13. Article
  14. Article
  15. The Role of Novel Approaches and New Findings in the Pharmacology of Tuberculosis Medicines in Improving Treatment Outcomes.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018
    Article
  16. Article
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 at 6 institutions in 6 countries.

Devyani DeshpandeCenter for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Jotam G PasipanodyaCenter for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Shashikant SrivastavaCenter for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Paula BendetCenter for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Thearith KoeuthCenter for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Sujata M BhavnaniInstitute for Clinical Pharmacodynamics, Schenectady, New York.
Paul G AmbroseInstitute for Clinical Pharmacodynamics, Schenectady, New York.
Wynand SmytheDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, South Africa.
Helen McIlleronDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, South Africa.
Guy ThwaitesNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Churchill Hospital, Oxford, United Kingdom.
Mourad GumusbogaInstitute of Tropical Medicine, Antwerp, Belgium.
Armand Van DeunInstitute of Tropical Medicine, Antwerp, Belgium.
Tawanda GumboCenter for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Baylor University Medical Center · USInstitute for Clinical Pharmacodynamics (United States) · USUniversity of Cape Town · ZAChurchill Hospital · GBInstituut voor Tropische Geneeskunde · BEInternational Union Against Tuberculosis and Lung Disease · FR

Funding

Wellcome Trust
6 · The paper itself

Abstract

Background: Gatifloxacin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The optimal dose is unknown. Methods: We performed a 28-day gatifloxacin hollow-fiber system model of tuberculosis (HFS-TB) study in order to identify the target exposures associated with optimal kill rates and resistance suppression. Monte Carlo experiments (MCE) were used to identify the dose that would achieve the target exposure in 10000 adult patients with meningeal or pulmonary MDR-TB. The optimal doses identified were validated using probit analyses of clinical data from 2 prospective clinical trials of patients with pulmonary and meningeal tuberculosis. Classification and regression-tree (CART) analyses were used to identify the gatifloxacin minimum inhibitory concentration (MIC) below which patients failed or relapsed on combination therapy. Results: The target exposure associated with optimal microbial kill rates and resistance suppression in the HFS-TB was a 0-24 hour area under the concentration-time curve-to-MIC of 184. MCE identified an optimal gatifloxacin dose of 800 mg/day for pulmonary and 1200 mg/day for meningeal MDR-TB, and a clinical susceptibility breakpoint of MIC ≤ 0.5 mg/L. In clinical trials, CART identified that 79% patients failed therapy if MIC was >2 mg/L, but 98% were cured if MIC was ≤0.5 mg/L. Probit analysis of clinical data demonstrated a >90% probability of a cure in patients if treated with 800 mg/day for pulmonary tuberculosis and 1200 mg/day for meningeal tuberculosis. Doses ≤400 mg/day were suboptimal. Conclusions: Gatifloxacin doses of 800 mg/day and 1200 mg/day are recommended for pulmonary and meningeal MDR-TB treatment, respectively. Gatifloxacin has a susceptible dose-dependent zone at MICs 0.5-2 mg/L.

Indexed as

Antitubercular AgentsGatifloxacinHumansLungMicrobial Sensitivity TestsMonte Carlo MethodMycobacterium tuberculosisProspective StudiesTuberculosis, MeningealTuberculosis, Multidrug-ResistantTuberculosis, PulmonaryAntitubercular AgentsGatifloxacin

Identifiers

PMID30496459
PMCPMC6904296
OpenAlexW2904447774

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.