Evidence map›Paper›PMID 26763957›Full record

ArticleJournal of clinical microbiology2016

Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis.

Maha R Farhat, Karen R Jacobson, Molly F Franke, Devinder Kaur, Alex Sloutsky, Carole D Mitnick, Megan Murray

Open access · bronzeAbstract read
In one paragraph

Article in Journal of clinical microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 77 citations in OpenAlex.

  1. Molecular Mechanisms Underlying Antimicrobial Resistance in Mycobacteria.International journal of molecular sciences · 2026
    Review
  2. Review
  3. Article
  4. Identification and quantification ofJournal of clinical microbiology · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Molecular Analysis of Anti-Tuberculosis Drug Resistance ofAntibiotics (Basel, Switzerland) · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Exploratory development of PCR-fluorescent probes in rapid detection of mutations associated with extensively drug-resistant tuberculosis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021
    Article
  14. Article
  15. Article
  16. Article
  17. Infection and drug resistance · 2021
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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

7 authors at 5 institutions in 2 countries.

Maha R FarhatDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA mrfarhat@partners.org.
Karen R JacobsonSection of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, USA DST/NRF Centre of Excellence for Biomedical TB Research/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Molly F FrankeDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Devinder KaurUniversity of Massachusetts Medical School, Massachusetts Supranational TB Reference Laboratory, Boston, Massachusetts, USA.
Alex SloutskyUniversity of Massachusetts Medical School, Massachusetts Supranational TB Reference Laboratory, Boston, Massachusetts, USA.
Carole D MitnickDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA Department of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Megan MurrayDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Harvard University · USUniversity of Massachusetts Boston · USBrigham and Women's Hospital · USMassachusetts General Hospital · USStellenbosch University · ZA

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Sequencing CoreU19AI109755 · NIAID · HARVARD MEDICAL SCHOOL · PI CHANDLER, DARRELL P, CULHANE, AEDIN C · 2014 to 2018
$29.1M
New Tools for the interpretation of Pathogen Genomic Data with a focus on Mycobacterium tuberculosisK01ES026835 · NIEHS · MASSACHUSETTS GENERAL HOSPITAL · PI FARHAT, MAHA · 2015 to 2019
$1.1M
Geospatial clustering and molecular and social epidemiology of drug resistant TBK01TW009213 · FIC · MASSACHUSETTS GENERAL HOSPITAL · PI JACOBSON, KAREN R · 2011 to 2015
$715k
FIC NIH HHS K01 TW009213NIAID NIH HHS P30 AI060354NIAID NIH HHS U19 AI109755NIAID NIH HHS U19-AI109755NIEHS NIH HHS K01 ES026835
6 · The paper itself

Abstract

Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment.

Indexed as

Drug Resistance, BacterialMutationAnti-Bacterial AgentsAntitubercular AgentsDNA GyraseFluoroquinolonesHumansMicrobial Sensitivity TestsMutation RateMycobacterium tuberculosisPhylogenySequence Analysis, DNATuberculosis, Multidrug-ResistantAnti-Bacterial AgentsAntitubercular AgentsDNA GyraseFluoroquinolones

Identifiers

PMID26763957
PMCPMC4767988
OpenAlexW2238396700

What OpenQuestion holds

Textmetadata
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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.