Effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis: A multicenter study in China

Background and objective Retreatment pulmonary tuberculosis (PTB) still accounts for a large proportion of tuberculosis, and the treatment outcome is unfavorable. The recurrence of retreatment PTB based on long-term follow-up has not been well demonstrated. This study aimed to evaluate effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis. Methods This multicenter cohort study was conducted in 29 hospitals from 23 regions of China from July 1, 2009, to December 31, 2020. Patients were divided into two treatment regimen groups including experimental group [modified regimen (4H-Rt2-E-Z-S(Lfx)/4H-Rt2-E)]and control group [standard regimen (2H-R-E-Z-S/6H-R-E or 3H-R-E-Z/6H-R-E)]. The patients enrolled were followed up of 56 months after successful treatment. We compared the treatment success rate, treatment failure rate, adverse reaction rate, and recurrence rate between two regimens. Multivariate Cox regression model was used to identify the potential risk factors for recurrence after successful treatment with proportional hazards assumptions tested for all variables. Results A total of 381 patients with retreatment PTB were enrolled, including 244 (64.0%) in the experimental group and 137 (36.0%) in the control group. Overall, the treatment success rate was significant higher in the experimental group than control group (84.0 vs. 74.5%, P = 0.024); no difference was observed in adverse reactions between the two groups (25.8 vs. 21.2%, P > 0.05). A total of 307 patients completed the 56 months of follow-up, including 205 with the modified regimen and 102 with the standard regimen. Among these, 10 cases (3.3%) relapsed, including 3 in the experimental group and 7 in the control group (1.5% vs 6.9%, P = 0.035). Reduced risks of recurrence were observed in patients treated with the modified regimen compared with the standard regimen, and the adjusted hazard ratio was 0.19 (0.04–0.77). Conclusion The modified retreatment regimen had more favorable treatment effects, including higher treatment success rate and lower recurrence rate in patients with retreated drug-sensitive PTB.

[1]  Jing-Yu Zhou,et al.  Recurrent pulmonary tuberculosis after treatment success: a population-based retrospective study in China. , 2021, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[2]  R. Warren,et al.  Deciphering Within-Host Microevolution of Mycobacterium tuberculosis through Whole-Genome Sequencing: the Phenotypic Impact and Way Forward , 2019, Microbiology and Molecular Biology Reviews.

[3]  K. Naidoo,et al.  A moxifloxacin-based regimen for the treatment of recurrent drug-sensitive pulmonary tuberculosis: An open-label randomised controlled trial. , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  B. Ledergerber,et al.  Delayed Sputum Culture Conversion in Tuberculosis–Human Immunodeficiency Virus–Coinfected Patients With Low Isoniazid and Rifampicin Concentrations , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  W. Shu,et al.  [Relationship between the weight of hospitalized patients with pulmonary tuberculosis and the oral dose of isoniazid]. , 2018, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[6]  Y. Pang,et al.  Factors Associated with Missed Detection of Mycobacterium tuberculosis by Automated BACTEC MGIT 960 System , 2016, BioMed research international.

[7]  Zongde Zhang,et al.  Drug resistance to Mycobacterium tuberculosis: From the traditional Chinese view to modern systems biology , 2015, Critical reviews in microbiology.

[8]  A. Efron,et al.  Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis. , 2015, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[9]  John L. Johnson,et al.  Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial. , 2015, American journal of respiratory and critical care medicine.

[10]  M. Zignol,et al.  Guidelines for surveillance of drug resistance in tuberculosis , 2015 .

[11]  L. Gabbasova,et al.  Global tuberculosis report (2014) , 2014 .

[12]  J. Pasipanodya,et al.  Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  Yu Wang,et al.  National survey of drug-resistant tuberculosis in China. , 2012, The New England journal of medicine.

[14]  K. Dooley,et al.  Safety and Pharmacokinetics of Escalating Daily Doses of the Antituberculosis Drug Rifapentine in Healthy Volunteers , 2012, Clinical pharmacology and therapeutics.

[15]  E. Chitsaz,et al.  Revised Category II Regimen as an Alternative Strategy for Retreatment of Category I Regimen Failure and Irregular Treatment Cases , 2011, American journal of therapeutics.

[16]  P. D. Picon,et al.  Retreatment of tuberculosis patients in the city of Porto Alegre, Brazil: outcomes. , 2011, Jornal Brasileiro de Pneumologia.

[17]  M. Akindele,et al.  Five year review of treatment outcome of directly observed therapy (DOT) for re-treatment pulmonary tuberculosis patients in UCH, Ibadan, Nigeria. , 2011, African journal of medicine and medical sciences.

[18]  Ruth McNerney,et al.  Effectiveness of the Standard WHO Recommended Retreatment Regimen (Category II) for Tuberculosis in Kampala, Uganda: A Prospective Cohort Study , 2011, PLoS medicine.

[19]  T. Yoshiyama,et al.  Risk of relapse and failure after retreatment with the Category II regimen in Nepal. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[20]  Philip Supply,et al.  Impact of HIV infection on the recurrence of tuberculosis in South India. , 2010, The Journal of infectious diseases.

[21]  V. Preedy,et al.  Prospective Cohort Study , 2010 .

[22]  N. Chaouki,et al.  Results of cohort analysis by category of tuberculosis retreatment cases in Morocco from 1996 to 2003. , 2006, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[23]  R. Harrington Part II , 2004, Bitter Freedom.

[24]  M. Eller,et al.  Single and multiple dose pharmacokinetics of rifapentine in man: part II. , 1999, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.