Abstract:

Objective To evaluate individualized treatment of retreatment smear-positive pulmonary tuberculosis (PTB) patients based on molecular drug susceptibility testing (DST) and its short-term effectiveness. Methods A prospective, randomized and controlled study was conducted, and 400 retreatment PTB patients diagnosed and treated in Shanghai Pulmonary Hospital from March 2016 to January 2020 were enrolled. Sputum or bronchoalveolar lavage fluid of each patient was collected and cultured for mycobacterium. Then strains which were isolated from positive culture and identified as Mycobacterium tuberculosis were tested for phenotypic DST using Micropore-plate method (MicroDST). Meanwhile, 200 patients were randomly selected according to visiting time sequence and random number table, specimen of those patients were tested for molecular DST using PCR-reverse dot blot (RDB) hybridization, thus drug resistance related genes of isoniazid (H) and rifampicin(R) were detected. Before the results of MicroDST were reported, patients with H and (or) R resistance detected by PCR-RDB were treated with H- and (or) R-resistant chemotherapy regimen, while other patients were treated with H- and R-susceptible retreatment chemotherapy regimen; after the results of MicroDST were reported, the chemotherapy regimens of all patients were adjusted according to the results of MicroDST. The sputum smear negative conversion rates and bacterial load of smear-positive specimen at the time of MicroDST results being reported, and the sputum smear negative conversion rates at the end of 3, 6, 9 and 12 months after drug-resistant chemotherapy started, were compared between patients with PCR-RDB and patients without PCR-RDB among rifampicin-resistant patients diagnosed by MicroDST. Results For patients with PCR-RDB and patients without PCR-RDB among rifampicin-resistant patients diagnosed by MicroDST, the sputum smear negative conversion rates at the time of MicroDST results being reported were 18.9% (10/53) and 5.9% (3/51) respectively, the difference was statistically significant (χ²=4.007, P=0.045); the graded counts ”+, ++, +++, ++++” of acid-fast bacilli in smear-positive specimens of patients with PCR-RDB were 48.8% (21/43), 25.6% (11/43), 16.3% (7/43) and 9.3% (4/43), while for patients without PCR-RDB were 16.7% (8/48), 35.4% (17/48), 33.3% (16/48) and 14.6% (7/48) at the time of MicroDST results being reported, the difference of smear positive grading was significant statistically (χ²=11.212, P=0.011), and sputum bacterial load of smear-positive specimen of the former was lower. Sputum negative conversion rates of patients with PCR-RDB at the end of 3, 6, 9 and 12 months after treatment with rifampicin-resistant chemotherapy regimen were 64.0% (32/50),84.8% (39/46), 82.9% (34/41),84.2% (32/38), higher than those of patients without PCR-RDB (58.8% (30/51), 81.0% (34/42), 81.6% (31/38), 81.6% (31/38)), all differences were not statistically significant (χ²=0.285,P=0.593;χ²=0.593,P=0.218;χ²=0.025,P=0.874;χ²=0.093,P=0.761). Conclusion Patients treated with rifampicin-resistant chemotherapy regimen based on PCR-RDB could have sputum smear negative conversion rate increasing and sputum bacteria load decreasing earlier among retreatment smear-positive PTB patients diagnosed by MicroDST.

Key words: Tuberculosis, pulmonary, Retreatment, Microbial sensitivity tests, Drug therapy, Comparative effectiveness research