HWN Suggests

The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD

In 2018, tuberculosis (TB) claimed more lives than any other infectious disease. This is primarily because TB is rampant precisely in the areas where it is most challenging to treat due to the poverty of those areas and the lengthy treatment course. Adding to the difficulty in effective treatment is widespread drug resistance. Of the four front-line anti-TB drugs (isoniazid, rifampin, pyrazinamide (PZA), and ethambutol), PZA has been an irreplaceable component in clinical TB regimens due to its unique activity against persisters in chronic Mtb infections and ability to shorten treatment times. It is for these reasons that PZA is recommended by the WHO as an integral component in the treatment…

read full article

Articles of Interest

A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis

Even though PZA is a crucial component of TB treatment, little is known about the prevalence of PZA resistance, particularly on a global scale.

Counting Pyrazinamide in Regimens for Multidrug-Resistant Tuberculosis

For treatment of multidrug-resistant tuberculosis, World Health Organization (WHO) guidelines recommend four likely effective drugs plus pyrazinamide (PZA), irrespective of the likely effectiveness of PZA in an individual patient. Whether this regimen should be supplemented in the absence of likely PZA effectiveness is an open question.

Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid

Pyrazinamide is an important sterilizing drug that shortens tuberculosis (TB) therapy. However, the mechanism of action of pyrazinamide is poorly understood because of its unusual properties.

Optimising pyrazinamide for the treatment of tuberculosis

Pyrazinamide is a potent sterilising agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimises efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further. Pyrazinamide commonly causes arthralgias, but its most dreaded toxicity is liver injury.

Optimizing pyrazinamide for the treatment of tuberculosis

Pyrazinamide is a potent sterilizing agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimizes efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further.

Pyrazinamide Inhibits Trans-Translation in Mycobacterium tuberculosis

Pyrazinamide (PZA) is a first-line tuberculosis drug that plays a unique role in shortening the duration of tuberculosis chemotherapy. PZA is hydrolyzed intracellularly to pyrazinoic acid (POA) by pyrazinamidase (PZase, encoded by pncA), an enzyme frequently lost in PZA-resistant strains, but the target of POA in Mycobacterium tuberculosis has remained elusive.

Pyrazinamide Is a Two-Edged Sword: Do WHO Guidelines Matter?

Two recent studies have suggested that pyrazinamide is a two-edged sword in the treatment of multidrug-resistant tuberculosis (MDR-TB).

The Bewildering Antitubercular Action of Pyrazinamide

Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB.

The high incidence of severe adverse events due to pyrazinamide in elderly patients with tuberculosis

Pyrazinamide (PZA) is a common drug that causes serious adverse events (SAEs). The aim of this study was to determine the incidence of and risk factors for SAEs due to PZA during first-line anti-tuberculosis treatment.

Resources

TB Alliance

Pyrazinamide (PZA) is one of the drugs used in standard, first-line TB therapy for drug-sensitive patients. It was discovered in 1954, though it wasn’t until approximately 30 years later that it became part of the standard TB treatment. Adding it to TB treatment enabled the shortening of treatment from 9 to 6 months.