Follow-up of patients with multidrug resistant tuberculosis four years after standardized first-line drug treatment.

BACKGROUND: In 2004, an anti-tuberculosis (TB) drug resistance survey in Heilongjiang province, China, enrolled 1574 (79%) new and 421 (21%) retreatment patients. Multi-drug resistant (MDR) TB was detected in 7.2% of new and 30.4% of retreatment patients. All received treatment with standardized first-line drug (FLD) regimens. METHODOLOGY/PRINCIPAL FINDINGS: We report treatment outcomes of the 2004 cohort, and long-term outcomes as assessed in the second half of 2008. The reported cure rate for MDR-TB patients was 83% (94/113) among new and 66% (85/128) among retreatment patients (P<0.001). Ten of the 241 MDR-TB patients died during treatment. Of the remaining 231, 129 (56%) could be traced in 2008. The overall recurrence rates among new and retreatment cases were 46% and 66%, respectively (P = 0.03). The overall death rates among new and retreatment cases were 25% and 46%, respectively (P = 0.02). Forty percent of the traced new cases and 24% of the retreatment cases were alive and without recurrent TB (P = 0.01). Of the 16 patients who failed or defaulted from treatment in 2004, only two patients were not re-diagnosed with TB by 2008. Of the 111 (86%) patients with an initial successful treatment outcome 63 (57%) had developed recurrent TB, 40 (36%) had died, 27 (24%) of them died of TB. The follow-up period of four years precluded follow-up of all patients. In a highly conservative sensitivity analysis in which we assumed that all non-included patients were alive and did not have recurrent TB, the recurrence and death rate were 33% and 21%. CONCLUSIONS/SIGNIFICANCE: Documentation of cure based on conventional smear microscopy was a poor predictor of long term outcomes. MDR-TB patients in Heilongjiang province in China had high recurrence and death rates four years after treatment with standardized FLD regimens, reinforcing the need for early diagnosis and treatment of MDR-TB, including assessment of treatment outcomes with more sensitive laboratory methods.

[Study on the efficacy and safety of short-term treatment including fluoroquinolones anti-tuberculosis drugs for rifampicin resistant pulmonary tuberculosis].

OBJECTIVE: To evaluate the efficacy and safety of short-term treatment including fluoroquinolones anti-tuberculosis drugs for rifampicin resistant pulmonary tuberculosis (TB) in those areas carrying out the 'TB control project'. METHODS: TB cases involved in this study were from TB drug resistance surveillance in Heilongjiang province, Zhejiang province and Shenzhen city from 2004 to 2006. TB cases with rifampicin resistant were randomly divided into the treatment group (including fluoroquinolones anti-tuberculosis drugs group) and the control group (re-treatment regimen group). The treatment group was treated with 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH while the control group was treated with 3 H3R3Z3E3S3/5 H3R3E3. Efficacy of short-term treatment was analyzed by per-protocol analysis (PP analysis) and intention-to-treat analysis (ITT analysis) while drug adverse reactions was also observed. RESULTS: (1) 154 patients with rifampicin resistant pulmonary tuberculosis were recruited among them, 25 (16.2%) were only resistant to rifampicin, 114 (74.0%) to MDR-TB and 15 (9.8%) to others (resistant R+S, resistant R+E and resistant R+E+S). 114 TB cases completed the full course of treatment,with 71 in the treatment group and 43 in the control group. (2) Sputum negative conversion rate of the treatment group and the control group were 78.9% and 65.1% (chi2CMH = 4.558, P = 0.011) respectively, by per-protocol analysis. Sputum negative conversion rate of the treatment group and the control group were 65.9% and 40.6% (chi2CMH = 0.272, P = 0.001) respectively, by intention-to-treat analysis. The sputum negative conversion rate of the treatment group was higher than in the control group when treating rifampicin resistant pulmonary tuberculosis and MDR-TB patients. (3) Three patients withdrew in each of the two groups because of adverse effects to the drugs. Rates of adverse reaction to drugs appeared to be 23.9% (17/71) and 18.6% (8/43) in the treatment and in the control groups, with no statistically significant difference between the two groups. CONCLUSION: The efficacy of treatment including fluoroquinolones anti-tuberculosis drugs group seemed better than the re-treatment regimen group in treating patients with rifampicin resistant pulmonary tuberculosis and those MDR-TB patients.

[Effects of two treatment regimens for drug-resistant tuberculosis in tuberculosis control project areas: a comparative study].

OBJECTIVES: To search for an ideal therapeutic regimen for multidrug resistant tuberculosis conforming to the situation of China. METHODS: One hundred and fifty-four patients with rifampin-resistant tuberculosis, 114 multi-drug resistant (MDR-TB) and 40 resistant to other drugs, in Heilongjiang, Zhejiang, and Shenzhen, 107 males and 47 females, aged 39 (19-77), were randomly divided into 2 groups: 85 patients in the group of drug-resistant regimen, 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH regimen, including rifapentine (RFT), amikacin (Am), ofloxacin (Ofx), protionamide (Pto), para-aminosalicylic acid-isoniazid (PAS-INH) for 3 months and then RFT, Ofx, Pto, and PAS-INH for 5 months, and 69 in the retreatment regimen group undergoing 3 H3R3Z3E3S3/5 H3R3E3, including isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) for 3 months and then H, R, and E for 5 months. Sputum smear was checked and the sputum smear conversion rate was calculated as an effective treatment indicator 3, 6, and 8 months later. RESULTS: One hundred and fourteen of the 154 patients were treated for a good 8 months. The sputum smear conversion rate 8 months after treatment of the drug-resistant regimen group was 65.9% (56/85), significantly higher than that of the retreatment regimen group [40.6% (28/69), chi2 = 9.834, P = 0.002]. Eighty-five of the 114 MDR-TB patients had been treated for a good 8 months with a sputum smear conversion rate of 61.8% (42/68), significantly higher than that of the retreatment regimen group [39.1% (18/46), chi2 = 5.638, P = 0.018]. Sputum smear conversion at the end of the 8th month was related to age, course of disease, therapeutic regimen, and the type of drug-resistance (all P < 0.05). The side-effect rate of the drug-resistant regimen group was 23.9% (17/71), higher than that of the retreatment regimen group [18.6% (8/43)], but not significantly (chi2 = 0.446, P = 0.504). CONCLUSION: The drug-resistant regimen recommended above is more effective than the retreatment regimen and should be considered in the areas where the WHO guideline fails to be followed or drug sensitivity test (DST) cannot be conducted and adjusted according to the results of DST and treatment.