Objective: To determine primary and acquired resistance to pyrazinamide in Mycobacterium tuberculosis strains isolated in sputum samples from patients with pulmonary tuberculosis.

Methods: This was a prospective, descriptive study conducted between April and November of 2011 at a referral hospital for tuberculosis in the city of Recife, Brazil. Cultures, drug sensitivity tests, and tests of pyrazinamidase activity were conducted in a private laboratory in Recife.

Results: Of the 71 patients included in the study, 37 were treatment-naïve and 34 represented cases of retreatment. Pyrazinamide-resistant strains were isolated in 14 (41.2%) of the 34 patients who had previously been treated for tuberculosis and in none of the 37 treatment-naïve patients. Of the 14 isolates, 10 (90.9%) tested negative for pyrazinamidase activity. A total of 60 isolates tested positive for pyrazinamidase activity. Of those, 56 (93.3%) were found to be sensitive to pyrazinamide.

Conclusions: The high frequency of pyrazinamide-resistant strains (41.2%) in patients previously treated for tuberculosis highlights the need for drug susceptibility testing prior to the adoption of a new treatment regimen.

Download full-text PDF

Source
http://dx.doi.org/10.1590/s1806-37132012000600009DOI Listing

Publication Analysis

Top Keywords

pyrazinamidase activity
12
primary acquired
8
patients pulmonary
8
referral hospital
8
city recife
8
recife brazil
8
strains isolated
8
pyrazinamide-resistant strains
8
412% patients
8
patients treated
8

Similar Publications

Quantitative MODS-Wayne assay for rapid detection of pyrazinamide resistance in from sputum samples.

Microbiol Spectr

November 2024

Laboratorio de Bioinformática, Biología Molecular y Desarrollos Tecnológicos. Laboratorios de Investigación y Desarrollo. Facultad de Ciencias e Ingeniería. Universidad Peruana Cayetano Heredia, Lima, Peru.

Unlabelled: Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains, such as those resistant to pyrazinamide (PZA). The current scarcity of affordable and precise quantitative diagnostic tests for PZA resistance underscores the urgent need for more accessible diagnostic tools. We evaluated PZA susceptibility in 264 TB-positive samples by quantifying pyrazinoic acid (POA) production, using both the MODS-Wayne qualitative assay and our newly developed quantitative approach (MODS-WQ).

View Article and Find Full Text PDF

The rise of pyrazinamide (PZA)-resistant strains of Mycobacterium tuberculosis (MTB) poses a major challenge to conventional tuberculosis (TB) treatments. PZA, a cornerstone of TB therapy, must be activated by the mycobacterial enzyme pyrazinamidase (PZase) to convert its active form, pyrazinoic acid, which targets the ribosomal protein S1. Resistance, often associated with mutations in the RpsA protein, complicates treatment and highlights a critical gap in the understanding of structural dynamics and mechanisms of resistance, particularly in the context of the G97D mutation.

View Article and Find Full Text PDF

Due to its emerging resistance to first-line anti-TB medications, tuberculosis (TB) is one of the most contagious illness in the world. According to reports, the effectiveness of treating TB is severely impacted by drug resistance, notably resistance caused by mutations in the pncA gene-encoded pyrazinamidase (PZase) to the front-line drug pyrazinamide (PZA). The present study focused on investigating the resistance mechanism caused by the mutations D12N, T47A, and H137R to better understand the structural and molecular events responsible for the resistance acquired by the pncA gene of Mycobacterium tuberculosis (MTB) at the structural level.

View Article and Find Full Text PDF
Article Synopsis
  • The pncA gene mutations in Mycobacterium tuberculosis are linked to resistance against the antibiotic pyrazinamide (PZA), with notable differences between sensitive and resistant strains.
  • The study identified three specific mutations in the resistant strain (pncAR1) that altered key amino acids, resulting in decreased enzyme activity for activating PZA.
  • The findings suggest a need for further structural studies on the mutated PZase protein to better understand how these mutations contribute to drug resistance and to aid in the design of more effective tuberculosis treatments.
View Article and Find Full Text PDF
Article Synopsis
  • The study focused on the high prevalence of pyrazinamide (PZA) resistance in multidrug-resistant TB (MDR-TB) in Hunan province, China, discovering a PZA resistance rate of 60.4% among tested MDR-TB isolates.
  • It utilized drug susceptibility testing and genetic analysis methods on 298 MDR isolates, identifying 98 mutation patterns in PZA-resistant strains, with a significant number being new mutations that could provide insights into drug resistance mechanisms.
  • The findings suggest that both DNA sequencing and PZase activity testing are promising tools for predicting PZA resistance in TB strains, highlighting the importance of understanding genetic diversity in effective treatment strategies.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!