Abstract

This study aimed to explore the influence of pyrazinamide (PZA) monoresistance on the treatment outcome of otherwise drug susceptible tuberculosis (TB). A cohort of 194 TB patients that were infected with strains susceptible to isoniazid (INH), rifampin (RIF) and ethambutol (EMB) were included in a retrospective study at the Guangzhou Chest Hospital. We reported 148 (76.3%) PZA- susceptible TB cases and 46 (23.7%) PZA-monoresistance TB cases identified by the BACTEC MGIT 960 system. All patients were treated with the standard 6 months WHO recommended regimen, which included 2 months of INH + RIF + EMB + PZA in the intensive-phase, and the subsequent 4 months of INH + RIF during continuation-phase. Bacterial burden in the lungs was estimated using sputum smear acid-fast bacillary count while the lung lesions and cavitations were examined by X-ray at the end of first 2 months of chemotherapy. After intensive-phase treatment, there were 164 (84.5%) cases of smear-negative conversion and 151 (77.9%) cases of total or partial lesion elimination. The rates of smear-negative conversion (78.3%) and lesion elimination (39.1%) of the PZA-monoresistant patients were similar with the PZA-sensitive group (P > 0.05). However, lung cavitation was more likely to be resolved in PZA-sensitive patients than in the PZA-patients (X2 = 9.623, P = 0.002). The smear-negative conversion rates were 95.9% for the PZA-sensitive patients and 87.0% for the PZA-monoresistant patients after 6 months of treatment (X2 = 3.461, P = 0.063). Together, our data suggest that PZA-monoresistance contributes to the delay of resolution of the lung cavitations in the Southern China population without affecting the sputum conversion and lesion elimination rates.

Highlights

  • Pyrazinamide (PZA) is a unique first-line anti-TB drug that acts against the tubercle bacilli at the acidic environment of caseous lesions caused by inflammation [1]

  • In this study we explored the effect of PZA-monoresistance on TB treatment outcome in otherwise drug susceptible TB patients

  • It is of interest to note that 75.4% (95 of 126 cases) PZA-sensitive patients had lung cavitations resolution after 2-month intensive treatment

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Summary

Introduction

Pyrazinamide (PZA) is a unique first-line anti-TB drug that acts against the tubercle bacilli at the acidic environment (pH < 5.5) of caseous lesions caused by inflammation [1]. Several studies reported bactericidal effect of PZA in the first two months of treatment, which may be related to the acid environment created by active inflammatory lesions [2] [4]. The standardized regimen for initial TB treatment uses combination of isoniazid (INH), rifampin (RIF), PZA and ethambutol (EMB) in the intensive phase for 2 - 4 months, followed by a 4-month continuation phase treatment with INH and RIF. In this study we explored the effect of PZA-monoresistance on TB treatment outcome in otherwise drug susceptible TB patients

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