Background Drug resistant pulmonary TB has poor outcomes despite prolonged treatment. Surgery is ... more Background Drug resistant pulmonary TB has poor outcomes despite prolonged treatment. Surgery is an option in DR-PTB patients with localized cavitary disease having adequate pulmonary reserve.1 Methods This is a retrospective analysis of patients with pulmonary DR-TB who underwent lung resection surgery between 2007 and 2018 at a single private tertiary care hospital in Mumbai. All patients received chemotherapy preoperatively and postoperatively. The indications for surgery included failure of medical treatment or persistent cavity with high probability of relapse. Patient demographic data, clinical characteristics, surgical procedures and surgical outcomes were studied. Results A total of 39 patients were enrolled from a single private hospital in Mumbai. Of these, there were 26 female and 13 males, with a mean age of 31 years and a mean BMI of 17 kg/m2. DR-TB was diagnosed on culture and drug susceptible test, showing 13 had XDR-TB, 19 had MDR-TB + fluoroquinolone resistance and 7 had MDR-TB. The lung involvement was evaluated on Chest CT scan, using the Timika Score. 61% of patients presented a left lung involvement, 35% right involvement and 69% had cavities. The type of surgery performed is given in the table 1. For outcome evaluation, culture status post-surgery and at the end of treatment were considered. A positive outcome was shown in 58% of patients, in particular 46% among XDR- TB cases, 68% in pre-XDR group and 71% in MDR-TB. Postoperative complications were observed in 4 patients only; 2 showed surgical wound infection and 1 patient had the left vocal cord palsy. One patient had a bronchopleural fistula post left pneumonectomy for which he required thoracoplasty. Conclusions As the numbers of drugs need to treat DR-TB are limited, surgery has an important adjunctive role. Pulmonary resection in combination with appropriate chemotherapy in carefully selected patients appears to be an effective measure with improved outcomes. Reference Russell R Kempker, Sergo Vashakidze, Nelly Solomonia, Nino Dzidzikashvili, Henry M Blumberg, Surgical treatment of drug-resistant tuberculosis, Lancet Infect Dis 2012; 12:157–66Abstract S113 Table 1 Type of Pulmonary Resection Type of lung surgery MDR TB 7 (17%) Pre-XDR TB 19 (49%) XDR TB No 13 (34%) Right upper lobectomy 1 (14%) 3 (15%) 3 (23%) Right lower lobectomy 2 (10%) 1 (7%) Right pneumonectomy 2 (10%) 1 (7%) Left upper lobectomy 1 (14%) 6 (31%) 1 (7%) Left lower lobectomy 1 (5%) 1 (7%) Left pneumonectomy 3 (42%) 5 (26%) 5 (38%) Right upper and medium lobectomy 1 (7%) Left Pneumonectomy and Thoracoplasty 1 (14%) Left Upper lobectomy and Thoracoplasty 1(14%) MDR TB: multidrug-resistant tuberculosis; pre-XDR TB: MDR-TB associated with resistance to FQ or a second-line injectable; XDR TB: extensive drug-resistant tuberculosis.
Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) ... more Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) are lacking. The aim of this study is to evaluate effectiveness and safety of BQ in a large retrospective, observational study conducted in 25 centres in 15 countries on 5 continents. Methods: Bacteriological conversion rates, treatment outcomes (WHO definitions) and adverse events observed in confirmed MDR-TB BQ-treated patients were analysed. Results: 428 MDR-TB cases (representing 10-100% of all national cases treated from January 2007 to March 2015) were enrolled: median age (IQR): 35 years (27-44); 61.3% males; 22.1% HIV-positive; 45.6% XDR-TB. The median (IQR) number of hospital admission days was 179 (92-280) and exposure to BQ 168 days (86-180). 5 cases received both BQ and delamanid. Treatment regimens included linezolid (82.0% of cases), moxifloxacin (53.7%) and carbapenems (15.7%). Sputum smear (SS) and culture (C) conversion rates were at 30 days 63.6 and 30.1%; at 60 days 81.1 and 56.7%; at 90 days 85.5 and 80.5% and the end of treatment 90.0 and 91.8%, respectively. The time to SS and C conversion was 34 (30-60) and 60 (33-90) days. Out of 246 cases completing treatment, 71.1% achieved success (62.2% cured; 8.9% treatment completed), 13.4% died, 8.1% failed and 7.3% were lost to follow-up. 51/428 (11.2%) cases interrupted BQ for any reason, 23/428 permanently (5.4%; 16/428 -1.4% - because of cardiologic disorders). Conclusions: The results of this study, the largest ever done, indicate that BQ-containing regimens used at the programmatic level achieve satisfactory outcomes and bacteriological conversion rates even with a significant proportion of XDR-TB cases.
Journal of Association of Physicians of India, 2016
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which ai... more Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment f...
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which ai... more Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment f...
The Journal of the Association of Physicians of India, Aug 1, 2016
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which ai... more Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment f...
Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) ... more Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) are lacking. The aim of this study is to evaluate effectiveness and safety of BQ in a large retrospective, observational study conducted in 25 centres in 15 countries on 5 continents. Methods: Bacteriological conversion rates, treatment outcomes (WHO definitions) and adverse events observed in confirmed MDR-TB BQ-treated patients were analysed. Results: 428 MDR-TB cases (representing 10-100% of all national cases treated from January 2007 to March 2015) were enrolled: median age (IQR): 35 years (27-44); 61.3% males; 22.1% HIV-positive; 45.6% XDR-TB. The median (IQR) number of hospital admission days was 179 (92-280) and exposure to BQ 168 days (86-180). 5 cases received both BQ and delamanid. Treatment regimens included linezolid (82.0% of cases), moxifloxacin (53.7%) and carbapenems (15.7%). Sputum smear (SS) and culture (C) conversion rates were at 30 days 63.6 and 30.1%; at 60 days 81.1 and 56.7%; at 90 days 85.5 and 80.5% and the end of treatment 90.0 and 91.8%, respectively. The time to SS and C conversion was 34 (30-60) and 60 (33-90) days. Out of 246 cases completing treatment, 71.1% achieved success (62.2% cured; 8.9% treatment completed), 13.4% died, 8.1% failed and 7.3% were lost to follow-up. 51/428 (11.2%) cases interrupted BQ for any reason, 23/428 permanently (5.4%; 16/428 -1.4% - because of cardiologic disorders). Conclusions: The results of this study, the largest ever done, indicate that BQ-containing regimens used at the programmatic level achieve satisfactory outcomes and bacteriological conversion rates even with a significant proportion of XDR-TB cases.
No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This s... more No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resist... more Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) t...
Background Drug resistant pulmonary TB has poor outcomes despite prolonged treatment. Surgery is ... more Background Drug resistant pulmonary TB has poor outcomes despite prolonged treatment. Surgery is an option in DR-PTB patients with localized cavitary disease having adequate pulmonary reserve.1 Methods This is a retrospective analysis of patients with pulmonary DR-TB who underwent lung resection surgery between 2007 and 2018 at a single private tertiary care hospital in Mumbai. All patients received chemotherapy preoperatively and postoperatively. The indications for surgery included failure of medical treatment or persistent cavity with high probability of relapse. Patient demographic data, clinical characteristics, surgical procedures and surgical outcomes were studied. Results A total of 39 patients were enrolled from a single private hospital in Mumbai. Of these, there were 26 female and 13 males, with a mean age of 31 years and a mean BMI of 17 kg/m2. DR-TB was diagnosed on culture and drug susceptible test, showing 13 had XDR-TB, 19 had MDR-TB + fluoroquinolone resistance and 7 had MDR-TB. The lung involvement was evaluated on Chest CT scan, using the Timika Score. 61% of patients presented a left lung involvement, 35% right involvement and 69% had cavities. The type of surgery performed is given in the table 1. For outcome evaluation, culture status post-surgery and at the end of treatment were considered. A positive outcome was shown in 58% of patients, in particular 46% among XDR- TB cases, 68% in pre-XDR group and 71% in MDR-TB. Postoperative complications were observed in 4 patients only; 2 showed surgical wound infection and 1 patient had the left vocal cord palsy. One patient had a bronchopleural fistula post left pneumonectomy for which he required thoracoplasty. Conclusions As the numbers of drugs need to treat DR-TB are limited, surgery has an important adjunctive role. Pulmonary resection in combination with appropriate chemotherapy in carefully selected patients appears to be an effective measure with improved outcomes. Reference Russell R Kempker, Sergo Vashakidze, Nelly Solomonia, Nino Dzidzikashvili, Henry M Blumberg, Surgical treatment of drug-resistant tuberculosis, Lancet Infect Dis 2012; 12:157–66Abstract S113 Table 1 Type of Pulmonary Resection Type of lung surgery MDR TB 7 (17%) Pre-XDR TB 19 (49%) XDR TB No 13 (34%) Right upper lobectomy 1 (14%) 3 (15%) 3 (23%) Right lower lobectomy 2 (10%) 1 (7%) Right pneumonectomy 2 (10%) 1 (7%) Left upper lobectomy 1 (14%) 6 (31%) 1 (7%) Left lower lobectomy 1 (5%) 1 (7%) Left pneumonectomy 3 (42%) 5 (26%) 5 (38%) Right upper and medium lobectomy 1 (7%) Left Pneumonectomy and Thoracoplasty 1 (14%) Left Upper lobectomy and Thoracoplasty 1(14%) MDR TB: multidrug-resistant tuberculosis; pre-XDR TB: MDR-TB associated with resistance to FQ or a second-line injectable; XDR TB: extensive drug-resistant tuberculosis.
Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) ... more Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) are lacking. The aim of this study is to evaluate effectiveness and safety of BQ in a large retrospective, observational study conducted in 25 centres in 15 countries on 5 continents. Methods: Bacteriological conversion rates, treatment outcomes (WHO definitions) and adverse events observed in confirmed MDR-TB BQ-treated patients were analysed. Results: 428 MDR-TB cases (representing 10-100% of all national cases treated from January 2007 to March 2015) were enrolled: median age (IQR): 35 years (27-44); 61.3% males; 22.1% HIV-positive; 45.6% XDR-TB. The median (IQR) number of hospital admission days was 179 (92-280) and exposure to BQ 168 days (86-180). 5 cases received both BQ and delamanid. Treatment regimens included linezolid (82.0% of cases), moxifloxacin (53.7%) and carbapenems (15.7%). Sputum smear (SS) and culture (C) conversion rates were at 30 days 63.6 and 30.1%; at 60 days 81.1 and 56.7%; at 90 days 85.5 and 80.5% and the end of treatment 90.0 and 91.8%, respectively. The time to SS and C conversion was 34 (30-60) and 60 (33-90) days. Out of 246 cases completing treatment, 71.1% achieved success (62.2% cured; 8.9% treatment completed), 13.4% died, 8.1% failed and 7.3% were lost to follow-up. 51/428 (11.2%) cases interrupted BQ for any reason, 23/428 permanently (5.4%; 16/428 -1.4% - because of cardiologic disorders). Conclusions: The results of this study, the largest ever done, indicate that BQ-containing regimens used at the programmatic level achieve satisfactory outcomes and bacteriological conversion rates even with a significant proportion of XDR-TB cases.
Journal of Association of Physicians of India, 2016
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which ai... more Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment f...
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which ai... more Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment f...
The Journal of the Association of Physicians of India, Aug 1, 2016
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which ai... more Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment f...
Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) ... more Introduction: Well designed studies on BQ used programmatically to treat M/XDR tuberculosis (TB) are lacking. The aim of this study is to evaluate effectiveness and safety of BQ in a large retrospective, observational study conducted in 25 centres in 15 countries on 5 continents. Methods: Bacteriological conversion rates, treatment outcomes (WHO definitions) and adverse events observed in confirmed MDR-TB BQ-treated patients were analysed. Results: 428 MDR-TB cases (representing 10-100% of all national cases treated from January 2007 to March 2015) were enrolled: median age (IQR): 35 years (27-44); 61.3% males; 22.1% HIV-positive; 45.6% XDR-TB. The median (IQR) number of hospital admission days was 179 (92-280) and exposure to BQ 168 days (86-180). 5 cases received both BQ and delamanid. Treatment regimens included linezolid (82.0% of cases), moxifloxacin (53.7%) and carbapenems (15.7%). Sputum smear (SS) and culture (C) conversion rates were at 30 days 63.6 and 30.1%; at 60 days 81.1 and 56.7%; at 90 days 85.5 and 80.5% and the end of treatment 90.0 and 91.8%, respectively. The time to SS and C conversion was 34 (30-60) and 60 (33-90) days. Out of 246 cases completing treatment, 71.1% achieved success (62.2% cured; 8.9% treatment completed), 13.4% died, 8.1% failed and 7.3% were lost to follow-up. 51/428 (11.2%) cases interrupted BQ for any reason, 23/428 permanently (5.4%; 16/428 -1.4% - because of cardiologic disorders). Conclusions: The results of this study, the largest ever done, indicate that BQ-containing regimens used at the programmatic level achieve satisfactory outcomes and bacteriological conversion rates even with a significant proportion of XDR-TB cases.
No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This s... more No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resist... more Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) t...
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Papers by Rohit Amale