Evidence map›Paper›PMID 22203587›Full record

ArticleAntimicrobial agents and chemotherapy2012

Reevaluation of the critical concentration for drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide using wild-type MIC distributions and pncA gene sequencing.

J Werngren, E Sturegård, P Juréen, K Ängeby, S Hoffner, T Schön

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing 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

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

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Enhancing diagnostic efficiency of pyrazinamide resistance inCurrent research in microbial sciences · 2025
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  14. Structural and Dynamic Insights into the W68L, L85P, and T87A Mutations ofInternational journal of environmental research and public health · 2022
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  15. Frontiers in pharmacology · 2022
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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

J WerngrenDepartment of Preparedness, Unit of Highly Pathogenic Microorganisms, Swedish Institute for Communicable Disease Control, SMI, Solna, Sweden. jim.werngren@smi.se.
E Sturegård
P Juréen
K Ängeby
S Hoffner
T Schön

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pyrazinamide (PZA) is a potent first-line agent for the treatment of tuberculosis (TB) with activity also against a significant part of drug-resistant Mycobacterium tuberculosis strains. Since PZA is active only at acid pH, testing for susceptibility to PZA is difficult and insufficiently reproducible. The recommended critical concentration for PZA susceptibility (MIC, 100 mg/liter) used in the Bactec systems (460 and MGIT 960) has not been critically evaluated against wild-type MIC distributions in clinical isolates of Mycobacterium tuberculosis. Using the Bactec MGIT 960 system, we determined the PZA MICs for 46 clinical M. tuberculosis isolates and compared the results to pncA sequencing and previously obtained Bactec 460 data. For consecutive clinical isolates (n = 15), the epidemiological wild-type cutoff (ECOFF) for PZA was 64 mg/liter (MIC distribution range, ≤ 8 to 64 mg/liter), and no pncA gene mutations were detected. In strains resistant in both Bactec systems (n = 18), the PZA MICs ranged from 256 to ≥ 1,024 mg/liter. The discordances between pncA sequencing, susceptibility results in Bactec 460, and MIC determinations in Bactec MGIT 960 were mainly observed in strains with MICs close to or at the ECOFF. We conclude that in general, wild-type and resistant strains were clearly separated and correlated to pncA mutations, although some isolates with MICs close to the ECOFF cause reproducibility problems within and between methods. To solve this issue, we suggest that isolates with MICs of ≤ 64 mg/liter be classified susceptible, that an intermediary category be introduced at 128 mg/liter, and that strains with MICs of >128 mg/liter be classified resistant.

Indexed as

Drug Resistance, BacterialAmidohydrolasesAntitubercular AgentsGenotypeHumansHydrogen-Ion ConcentrationMicrobial Sensitivity TestsMutationMycobacterium tuberculosisPyrazinamideReproducibility of ResultsSequence Analysis, DNATuberculosis, Multidrug-ResistantAmidohydrolasesAntitubercular AgentsPncA protein, Mycobacterium tuberculosisPyrazinamide

Identifiers

PMID22203587
PMCPMC3294906

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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.