Evidence map›Paper›PMID 28587904›Full record

ArticleClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2018

Evaluation of a novel line probe assay to detect resistance to pyrazinamide, a key drug used for tuberculosis treatment.

M Driesen, Y Kondo, B C de Jong, G Torrea, S Asnong, C Desmaretz, K S M Mostofa, S Tahseen, M G Whitfield, D M Cirillo and 3 more

Abstract readEvaluation Study
In one paragraph

Article in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Heteroresistance inFrontiers in cellular and infection microbiology · 2026
    Review
  3. Article
  4. Review
  5. Prediction of pyrazinamide resistance inJAC-antimicrobial resistance · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Revisiting the methods for detectingAccess microbiology · 2021
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Detection ofAntimicrobial agents and chemotherapy · 2018
    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.

M DriesenMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium. Electronic address: mdriesen@itg.be.
Y KondoR&D Laboratory, NIPRO Corporation, Shiga, Japan.
B C de JongMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium; New York University, New York, USA; Medical Research Council Unit, Fajara, Gambia.
G TorreaMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
S AsnongMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
C DesmaretzMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
K S M MostofaNational TB Reference Laboratory, Dhaka, Bangladesh.
S TahseenNational TB Reference Laboratory, Islamabad, Pakistan.
M G WhitfieldSA MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa.
D M CirilloEmerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
P MiottoEmerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
A M CabibbeEmerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
L RigoutsMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium; Biomedical Sciences Department, Antwerp University, Antwerp, Belgium.

Funding

European Research Council 311725
6 · The paper itself

Abstract

objectivesThe development of rapid molecular diagnostic assays for pyrazinamide (PZA) resistance is considered technically challenging as mutations are highly diverse, scattered along the full length of the pncA gene and not all are associated with PZA resistance. We evaluated the performance of the novel Genoscholar PZA-TB II line probe assay (PZA-LPA2; NIPRO Corporation, Japan).

methodsTo evaluate the applicability of the PZA-LPA2 in clinical settings, we compared the performance of the PZA-LPA2 to a composite reference standard pncA Sanger and Illumina sequencing plus phenotypic susceptibility testing on a panel of 87 Mycobacterium tuberculosis isolates from World Health Organization (WHO) drug resistance surveys, harbouring mutations previously classified as associated or not associated with resistance according to data from peer-reviewed literature. In addition, the PZA-LPA2 was challenged against a selection of isolates with lineage-specific and non-resistance-associated mutations, for which the frequency among clinical isolates is unknown, and tested directly on 59 sputum extracts.

resultsFor the survey isolates, the PZA-LPA2 reached an overall agreement with the composite reference of 97.6% (80/82) or 94.3% (82/87) excluding or including heteroresistance, respectively. The PZA-LPA2 failed on 8.5% (5/59) of clinical samples; among valid results, 100% (14/14) sensitivity and 100% (7/7) specificity was reached relative to pncA Sanger sequencing.

conclusionsThe PZA-LPA2 represents a valid and rapid alternative for indirect PZA susceptibility testing. Preliminary findings on clinical samples show promise for direct testing. Further studies are needed to assess the clinical risk of missing heteroresistance and falsely detecting lineage-specific, silent and nonassociated mutations.

Indexed as

AmidohydrolasesAntitubercular AgentsDrug Resistance, BacterialHumansMicrobial Sensitivity TestsMutationMycobacterium tuberculosisPyrazinamideTuberculosis, PulmonaryAmidohydrolasesAntitubercular AgentsPncA protein, Mycobacterium tuberculosisPyrazinamideLine probe assayMycobacterium tuberculosispncAPyrazinamideResistance

Identifiers

PMID28587904
PMCPMC5756542

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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.