Counting pyrazinamide in regimens for multidrug-resistant tuberculosis.

Area of Science:

• Infectious Diseases
• Tuberculosis Research
• Pharmacology

Background:

• World Health Organization (WHO) guidelines recommend four effective drugs plus pyrazinamide (PZA) for multidrug-resistant tuberculosis (MDR-TB).
• The effectiveness of PZA varies among individual patients, raising questions about the optimal regimen when PZA is unlikely to be effective.
• This study addresses the need to optimize MDR-TB treatment regimens for improved patient outcomes.

Purpose of the Study:

• To compare mortality rates between patients receiving four versus five likely effective drugs during MDR-TB intensive phase treatment.
• To evaluate the impact of pyrazinamide (PZA) effectiveness on the WHO-recommended MDR-TB regimen.
• To determine if supplementing the WHO regimen is necessary when PZA is unlikely to be effective.

Main Methods:

• A comparative study involving 668 patients undergoing MDR-TB treatment.
• Analysis of mortality risk based on the number of likely effective drugs in the regimen.
• Comparison of regimens including pyrazinamide (PZA) versus those without, considering PZA effectiveness.

Main Results:

• Regimens with four likely effective drugs were associated with significantly higher mortality (aHR, 2.87) compared to five drugs.
• The WHO-recommended regimen used in patients with unlikely PZA effectiveness also showed higher mortality (aHR, 2.76).
• Using five likely effective drugs with PZA showed similar mortality to five drugs without PZA, suggesting PZA's effectiveness is key.

Conclusions:

• Including five likely effective drugs, particularly an injectable, during intensive MDR-TB treatment may reduce mortality.
• If pyrazinamide (PZA) is unlikely to be effective for an individual patient, adding another likely effective drug is suggested.
• Optimizing MDR-TB treatment by tailoring drug selection based on individual PZA effectiveness can improve survival.