ArticleBMC infectious diseases2019
Underestimated pyrazinamide resistance may compromise outcomes of pyrazinamide containing regimens for treatment of drug susceptible and multi-drug-resistant tuberculosis in Tanzania.
Article in BMC infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Global prevalence of drug-resistant tuberculosis: a systematic review and meta-analysis.Infectious diseases of poverty · 2023Pooled it
- Animals as overlooked victims and vectors of tuberculosis: review ofOne health advances · 2026Review
- The epidemiology and gene mutation characteristics of pyrazinamide-resistantEmerging microbes & infections · 2025Article
- Optimizing Pyrazinamide Use: A Low-Hanging Fruit in Improving Outcomes with Tuberculous Meningitis? Narrative Review.Infectious diseases and therapy · 2025Review
- Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Whole genome sequencing of drug resistanceLife science alliance · 2023Article
- Ability of the MeltPro MTB/PZA Assay to Detect Susceptibility to Pyrazinamide in Rifampin-Resistant Tuberculosis Patients.Microbiology spectrum · 2023Article
- Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi'an China, a Retrospective Cohort Study.Infection and drug resistance · 2022Article
- Drug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China.PLoS neglected tropical diseases · 2021Article
- Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis.BMC infectious diseases · 2020Article
- Structure guided prediction of Pyrazinamide resistance mutations in pncA.Scientific reports · 2020Article
- Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.Journal of bacteriology · 2020Article
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10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTuberculosis (TB) is the leading cause of death from an infectious disease and the roll-out of rapid molecular diagnostics for rifampin resistance has resulted in a steady rise in the number of patients with multidrug-resistant (MDR)-TB referred for treatment. Pyrazinamide is used in susceptible TB treatment for 6 months when used in combination with rifampin, isoniazid and ethambutol and is an important companion drug in novel MDR-TB trials. This study was undertaken to determine the prevalence of pyrazinamide resistance by either phenotypic or pncA testing among patients admitted to a referral hospital in Tanzania for drug-susceptible and MDR-TB treatment.
methodsSurveillance sputa were sent among subjects beginning TB therapy at the national MDR-TB referral hospital during a 6 month period in 2013-2014. Mycobacterial cultures of pretreatment sputa were performed at the Kilimanjaro Clinical Research Institute (KCRI) in the BACTEC mycobacterial growth indicator tubes (MGIT) 960 system. Speciation of M. tuberculosis complex was confirmed by MTBc assay. Isolates were sub-cultured on to Lowenstein-Jensen (LJ) slants. Phenotypic resistance to pyrazinamide was performed in the MGIT system while a real-time PCR with High Resolution Melt (HRM) technique was used to determine mutation in the pncA gene from the same pure subculture. Sputa were then collected monthly to determine the time to culture negativity. Final treatment outcome was determined.
resultsNinety-one M. tuberculosis isolates from individual patients were available for analysis of which 30 (32.9%) had MDR-TB, the mean (±SD) age was 33 ± 10 years, and the majority 23 (76.7%) were males. Of the 30 MDR-TB patients, 15(50%) had isolates with pyrazinamide resistance by conventional MGIT testing. This proportion expectedly exceeded the number with pyrazinamide resistance in the 61 patients without MDR-TB, 13 (21.3%) (p = 0.008). Six (20%) of MDR-TB patients had a poor outcome including treatment failure. Among patients with treatment failure, 5 (83%) had pyrazinamide resistance compared to only 10 (41.6%) with treatment success (p = 0.08). Two patients died, and both had isolates with pyrazinamide resistance. No other pretreatment characteristic was associated with treatment outcome.
conclusionPyrazinamide susceptibility appears to be important in clinical outcomes for MDR-TB patients, and susceptibility testing appears to be a critical adjunct to TB care. The high proportion of PZA resistance in non-MDR TB cases calls for further local investigation.
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