Evidence map›Paper›PMID 27397590›Full record

ArticleThe Lancet. Infectious diseases2016

Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project.

Matteo Zignol, Anna S Dean, Natavan Alikhanova, Sönke Andres, Andrea Maurizio Cabibbe, Daniela Maria Cirillo, Andrei Dadu, Andries Dreyer, Michèle Driesen, Christopher Gilpin and 24 more

Open access · hybridAbstract read
In one paragraph

Article in The Lancet. Infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 3 pooled it
18.7field-weighted citation impact, top 1% 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

93 citing papers in PubMed, 3 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019
    Guideline
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  12. Pyrazinamide killsbioRxiv : the preprint server for biology · 2025
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  18. A simplified pyrazinamidase test forJournal of clinical microbiology · 2024
    Article
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  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 17 institutions in 11 countries.

Matteo ZignolGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland. Electronic address: zignolm@who.int.
Anna S DeanGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
Natavan AlikhanovaScientific Research Institute of Lung Diseases, Baku, Azerbaijan.
Sönke AndresNational and Supranational Reference Laboratory for Mycobacterium, Borstel, Germany.
Andrea Maurizio CabibbeIRCCS San Raffaele Scientific Institute, Milan, Italy.
Daniela Maria CirilloIRCCS San Raffaele Scientific Institute, Milan, Italy.
Andrei DaduRegional Office for Europe, World Health Organization, Copenhagen, Denmark.
Andries DreyerNational Institute for Communicable Diseases, Sandringham, South Africa.
Michèle DriesenMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
Christopher GilpinGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
Rumina HasanDepartment of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Zahra HasanDepartment of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Sven HoffnerDepartment of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
Ashaque HusainNational Tuberculosis Control Programme, Dhaka, Bangladesh.
Alamdar HussainNational Tuberculosis Reference Laboratory, National Tuberculosis Control Programme, Islamabad, Pakistan.
Nazir IsmailNational Institute for Communicable Diseases, Sandringham, South Africa; University of Pretoria, Pretoria, South Africa.
Mostofa KamalNational Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh.
Mikael MansjöDepartment of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
Lindiwe MvusiTuberculosis Control and Management, National Department of Health, Pretoria, South Africa.
Stefan NiemannNational and Supranational Reference Laboratory for Mycobacterium, Borstel, Germany.
Shaheed V OmarNational Institute for Communicable Diseases, Sandringham, South Africa.
Ejaz QadeerNational Tuberculosis Control Programme, Ministry of National Health Services, Regulation and Coordination, Islamabad, Pakistan.
Leen RigoutsMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium; Biomedical Sciences, Antwerp University, Antwerp, Belgium.
Sabine Ruesch-GerdesNational and Supranational Reference Laboratory for Mycobacterium, Borstel, Germany.
Marco SchitoCritical Path Institute, Tucson, AZ, USA.
Mehriban SeyfaddinovaScientific Research Institute of Lung Diseases, Baku, Azerbaijan.
Alena SkrahinaRepublican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
Sabira TahseenNational Tuberculosis Reference Laboratory, National Tuberculosis Control Programme, Islamabad, Pakistan.
William A WellsBureau for Global Health, US Agency for International Development, Washington, DC, USA.
Ya Diul MukadiBureau for Global Health, US Agency for International Development, Washington, DC, USA.
Michael KimerlingKNCV Tuberculosis Foundation, The Hague, Netherlands.
Katherine FloydGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
Karin WeyerGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
Mario C RaviglioneGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
World Health Organization · CHAga Khan University · PKInstituut voor Tropische Geneeskunde · BENational Institute for Communicable DiseasesUnited States Agency for International Development · USCritical Path Institute · USDepartment of Health · ZAIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleKarolinska Institutet · SEMinistry of National Health Services Regulation and Coordination · PKNational Institute of Cardiovascular Diseases · BDPublic Health Agency of Sweden · SERepublican Scientific and Practical Centre of Pulmonology and Tuberculosis · BYRespiratory and Meningeal Pathogens Research Unit · ZATuBerculosis Vaccine Initiative · NLVita-Salute San Raffaele University · ITWorld Health Organization Regional Office for Europe · DK

Funding

World Health Organization 001
6 · The paper itself

Abstract

backgroundPyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available.

methodsIn a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system.

findingsPyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3·0-42·1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1·0-16·6% for ofloxacin, to 0·5-12·4% for levofloxacin, and 0·9-14·6% for moxifloxacin when tested at 0·5 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/mL was low in all countries.

interpretationAlthough pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19-63% of patients with rifampicin-resistant tuberculosis. Even though the high level of resistance to ofloxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fluoroquinolones documented in all survey sites is an encouraging finding. Rational use of this class of antibiotics should therefore be ensured to preserve its effectiveness.

fundingBill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.

Indexed as

Population SurveillanceAnti-Infective AgentsAntitubercular AgentsAsiaFluoroquinolonesHumansMicrobial Sensitivity TestsMycobacterium tuberculosisPyrazinamideRetrospective StudiesRifampinSouth AfricaTuberculosis, Multidrug-ResistantTuberculosis, PulmonaryAnti-Infective AgentsAntitubercular AgentsFluoroquinolonesPyrazinamideRifampin

Identifiers

PMID27397590
PMCPMC5030278
OpenAlexW2461516359

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.