Phenotypic Characterization of Pyrazinamide-Resistant Mycobacterium tuberculosis Isolated in Poland

Introduction: Pyrazinamide (PZA) is an important first-line anti-tuberculous drug, which is applied together with INH, RMP, EMB, and SM. This drug plays a unique role in the first phase of TB therapy because it is active within macrophages and kills tubercle bacilli. Testing the resistibility of Mycobacterium tuberculosis to PZA is technically difficult because PZA is active only at acid pHs. Therefore, routine drug resistibility testing of M. tuberculosis for PZA is not performed in many laboratories. The objective of our study was to estimate the resistibility for PZA among M. tuberculosis isolates from polish patients in the years 2000–2008. Material and methods: We analyzed M. tuberculosis strains with different resistibility to first-line anti-tuberculous drugs. The strains were isolated from 1909 patients with tuberculosis. The strains were examined for PZA resistibility by the radiometric Bactec 460-TB method. The PZA-resistant strains were examined for the following MIC PZA for drug concentrations: 100, 300, 600, 900 μg/mL. Results: PZA resistance among M. tuberculosis strains was found in 6.7% of untreated patients and in 22.2% of previously treated patients (p < 0.001). In both groups, resistance to PZA correlated with drug resistance for INH+RMP+SM+EMB—in 32.7% of untreated patients and in 34.5% previously treated patients (p < 0.8). PZA-monoresistant strains were observed in 20.8% of untreated patient groups. Among the resistant strains: in 3.4% MIC for PZA was > 100 μg/mL, in 11.6% ≥ 300 μg/mL, in 8.9% ≥ 600 μg/mL, and in 76% ≥ 900 μg /mL. Conclusions: Among M. tuberculosis strains, PZA resistance was found in 6.7% of untreated patients and in 22.2% of previously treated patients. Among the PZA-resistant strains, very high MIC values for PZA (≥900 μg/mL) were revealed for 76% M. tuberculosis strains.