Abstract:

Objective To analyze the predictive value of single-drug minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) to the outcome of treatment in pulmonary tuberculosis patients firstly retreated with ultra-short course treatment. Methods Forty-eight drug-resistant tuberculosis patients firstly retreated with the ultra-short course treatment for pulmonary (Mfx-Pa-Rft-E-Z; 6 months; Mfx: moxifloxacin; Pa: isoniazid para amino salicylic acid; Rft: rifapentine; E: ethambutol; Z: pyazinamide) from Shanghai Pulmonary Hospital Affiliated to Tongji University were selected. All the patients completed the treatment and were divided into successful group (n=38, sputum was negative after treatment) and failure group (n=10, sputum was not negative after treatment). In the successful group, 18 patients were extensive-drug resistance (XDR) and 20 patients were multidrug-drug resistance (MDR). Patients in failure groups were all XDR. Strains were isolated from sputum specimens preserved before treatment. In vitro drug sensitivity test was performed on Mfx, Pa, Rft and Mfx-Pa, Pa-Rft, Mfx-Pa-Rft by three-dimensional checkboard method. The correlation between MIC and FICI and prognosis was analyzed. Results MIC values (median (quartile)) of Mfx, Pa and Rft were 0.50 (0.06, 1.00), 8.0 (3.5, 16.0) and 32.0 (4.0, 64.0) mg/L, respectively, in the successful group, and 1.00 (0.50, 1.00), 16.0 (3.5, 28.0) and 48.0 (24.5, 64.0) mg/L, respectively, in the failure group. The MIC value of Mfx in the successful group was significantly lower than that in the failure group (Z=-2.251, P=0.026). The results of the combined drug sensitivity test of Mfx-Pa and Pa-Rft showed that the synergistic rates of the successful group were 2.6% (1/38) and 44.7% (17/38), and of the failure group were 1/10 and 6/10, respectively. No antagonism was found, and the difference between the two groups was not statistically significant (Fisher’s exact probability method, P values were 0.377 and 0.487, respectively). The results of Mfx-Pa-Rft combined drug sensitivity test showed that the synergistic rates were 26.3% (10/38) in the successful group and 1/10 in the failure group. The antagonism rates were 13.2% (5/38) in the successful group and 3/10 in the failure group. There was no significant difference between the two groups (χ²=2.221, P=0.136). The results of Mfx-Pa-Rft combined drug sensitivity test for XDR patients showed that in the successful group, the synergy rate was 38.9% (7/18), higher than that in the failed group (1/10); the antagonism rate was 5.6% (1/18), lower than that in the failure group (3/10), and the difference was statistically significant (χ²=4.480, P=0.034). The FICI values (median (quartile)) of Mfx-Pa combined drug sensitivity test were 1.50 (1.00, 2.00) in the successful group and 1.75 (1.05, 2.02) in the failure group. FICI values of Pa-Rft combined drug sensitivity test were 0.51 (0.47, 0.63) in the successful group and 0.44 (0.28, 0.65) in the failure group. FICI values of Mfx-Pa-Rft combined drug sensitivity test were 1.25 (0.75, 2.50) in the successful group and 2.31 (1.47, 4.25) in the failure group. There were no significant differences (Z values were -0.662, -1.134, -1.168, P values were 0.523, 0.263, 0.097, respectively). Conclusion The better the drug synergy of the core drugs in the treatment regimen of the first retreatment for tuberculosis patients, the greater the sputum negative conversion rate at the end of treatment; the combined drug sensitivity test of treatment regimen drugs should be performed before the application of different treatment combination regimens, and the treatment regimen should be optimized by judging the sensitivity of patients to drugs and the synergy of drugs, so as to improve the success rate of treatment.

Key words: Tuberculosis, pulmonary, Retreatment, Drug resistance, multiple, Microbial sensitivity tests, Outcome assessment (health care)