# Development of a Rapid Phenotypic Pyrazinamide Susceptibility Testing for Mycobacterium tuberculosis Using Well-Standardized Protocol

> **NIH NIH R44** · PZA INNOVATION LLC · 2024 · $840,857

## Abstract

Abstract:
 Drug-resistant infectious diseases pose a significant threat to public health. To overcome this challenge, drug
susceptibility testing (DST) is essential for identifying the most effective drugs to treat and monitoring drug
resistance in these diseases. Pyrazinamide (PZA) is a critical component of current tuberculosis (TB) treatment,
shortening drug susceptible TB (DS-TB) treatment duration from 9-12 months to 6 months. PZA is also used in
multidrug resistant TB (MDR-TB) treatment. Unfortunately, PZA resistance is increasing, with a pooled
prevalence of PZA resistance among all TB cases estimated at 16.2%, leading to worse consequences, including
death. Unlike other TB drugs, current PZA susceptibility tests are unreliable, complicated, and expensive, leading
to underutilization, even in high TB burden areas. Misclassifying PZA-resistant infections as PZA-susceptible
infections results in significantly worse clinical outcomes for the patients and development of further drug
resistance. Conversely, considering PZA-susceptible infections as PZA-resistant infection leads to longer
treatment with more expensive and toxic medicines unnecessarily. The global burden of PZA-resistant TB is
estimated at 1.4 million new cases out of 10.6 million active TB cases per year, highlighting a significant
challenge for current TB control. According to the CDC, treatment costs for DR-TB are significantly higher than
for DS-TB, at times, costing $528,000 (2020 USD) more to treat a patient with DR-TB than to treat a patient with
DS-TB. Due to the importance of PZA in many TB regimens, the emergence of PZA resistance and systematic
problems in current PZA DST, reliable PZA susceptibility testing has been assigned a high priority in the target
product profile by the WHO. To address this challenge, it is urgent to develop a rapid, reliable and accurate PZA
DST that can be routinely performed in mycobacterial labs worldwide. This will ensure that TB patients receive
the most effective and adequate treatment, prevent the further development of TB drug resistance and limit its
spread. Our goal is to develop such a test, which is substantiated by our preliminary findings indicating that (1)
PZA is active in liquid and agar media at pH 6.8, which is optimal for the growth of M. tuberculosis, unlike the
current acidic conditions that are unstable when bacteria grow, leading to a high rate of false resistance and
technical difficulties; (2) The new testing can determine the critical proportion of PZA-resistant M. tuberculosis
highly correlated with treatment outcomes, with one of the important specifications of DST at 1%, compared with
10% for the current test; (3) The new PZA susceptibility testing can be conducted without the need for expensive
readout equipment, which is a significant improvement from current test such as the BACTEC MGIT 960 PZA
that relies completely on such equipment; (4) the turnaround time for the new test is much shorter, with results
being...

## Key facts

- **NIH application ID:** 10821311
- **Project number:** 1R44AI181252-01
- **Recipient organization:** PZA INNOVATION LLC
- **Principal Investigator:** Wanliang Shi
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $840,857
- **Award type:** 1
- **Project period:** 2024-01-02 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821311

## Citation

> US National Institutes of Health, RePORTER application 10821311, Development of a Rapid Phenotypic Pyrazinamide Susceptibility Testing for Mycobacterium tuberculosis Using Well-Standardized Protocol (1R44AI181252-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10821311. Licensed CC0.

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