Evidence map›Paper›PMID 24034230›Full record

ArticleBMC infectious diseases2013

Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania.

Stellah G Mpagama, Eric R Houpt, Suzanne Stroup, Happiness Kumburu, Jean Gratz, Gibson S Kibiki, Scott K Heysell

Abstract readEvaluation Study
In one paragraph

Article in BMC infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 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

19 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  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. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Drug Resistance Characteristics ofFrontiers in cellular and infection microbiology · 2019
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Understanding pharmacokinetics to improve tuberculosis treatment outcome.Expert opinion on drug metabolism & toxicology · 2014
    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

7 authors.

Stellah G MpagamaDivision of Infectious Diseases and International Health, University of Virginia, PO Box 801340, Charlottesville, Virginia 22908, USA. skh8r@virginia.edu.
Eric R Houpt
Suzanne Stroup
Happiness Kumburu
Jean Gratz
Gibson S Kibiki
Scott K Heysell

Funding

INFECTIOUS DISEASES TRAINING PROGRAMT32AI007046 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Alison K Criss, William A Petri · 1985 to 2026
$15.3M
Tuberculosis Second Line Drug Susceptibility ChipR01AI093358 · NIAID · UNIVERSITY OF VIRGINIA · PI HOUPT, ERIC R · 2011 to 2015
$4.0M
Molecular Diagnostic Tools for Patient Oriented Field Studies in Infectious DiseasesK24AI102972 · NIAID · UNIVERSITY OF VIRGINIA · PI HOUPT, ERIC R · 2013 to 2022
$1.5M
Global Infectious Disease Research Training Program AwardD43TW008270 · FIC · UNIVERSITY OF VIRGINIA · PI HOUPT, ERIC R · 2010 to 2014
$735k
Clinical Impact of Anti-TB Drug Levels and M. Tuberculosis SusceptibilityK23AI099019 · NIAID · UNIVERSITY OF VIRGINIA · PI HEYSELL, SCOTT K · 2012 to 2016
$649k
FIC NIH HHS D43 TW008270NIAID NIH HHS K23 AI099019NIAID NIH HHS K23AI099019NIAID NIH HHS K24 AI102972NIAID NIH HHS R01 AI093358NIAID NIH HHS R01AI093358NIAID NIH HHS T32 AI007046
6 · The paper itself

Abstract

backgroundLack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may limit treatment success.

methodsMycobacterium tuberculosis isolates from patients referred to Kibong'oto National TB Hospital in Tanzania for second-line TB treatment underwent confirmatory speciation and susceptibility testing. Minimum inhibitory concentration (MIC) testing on MYCOTB Sensititre plates was performed for all drugs available in the second-line formulary. We chose to categorize isolates as borderline susceptible if the MIC was at or one dilution lower than the resistance breakpoint. M. tuberculosis DNA was sequenced for resistance mutations in rpoB (rifampin), inhA (isoniazid, ethionamide), katG (isoniazid), embB (ethambutol), gyrA (fluoroquinolones), rrs (amikacin, kanamycin, capreomycin), eis (kanamycin) and pncA (pyrazinamide).

resultsOf 22 isolates from patients referred for second-line TB treatment, 13 (59%) were MDR-TB and the remainder had other resistance patterns. MIC testing identified 3 (14%) isolates resistant to ethionamide and another 8 (36%) with borderline susceptibility. No isolate had ofloxacin resistance, but 10 (45%) were borderline susceptible. Amikacin was fully susceptible in 15 (68%) compared to only 11 (50%) for kanamycin. Resistance mutations were absent in gyrA, rrs or eis for all 13 isolates available for sequencing, but pncA mutation resultant in amino acid change or stop codon was present in 6 (46%). Ten (77%) of MDR-TB patients had at least one medication that could have logically been modified based on these results (median 2; maximum 4). The most common modifications were a change from ethioniamide to para-aminosalicylic acid, and the use of higher dose levofloxacin.

conclusionsIn Tanzania, quantitative second-line susceptibility testing could inform and alter MDR-TB management independent of drug-resistance mutations. Further operational studies are warranted.

Indexed as

AdultAntitubercular AgentsBacterial ProteinsFemaleHumansMaleMicrobial Sensitivity TestsMiddle AgedMycobacterium tuberculosisTanzaniaTuberculosis, Multidrug-ResistantYoung AdultAntitubercular AgentsBacterial Proteins

Identifiers

PMID24034230
PMCPMC3848720

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Registered trials

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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.