Journal Article > ResearchFull Text
PLOS One. 16 June 2020 (Issue 6); DOI:10.1371/journal.pone.0234651.
Chavan VV, Dalal A, Nagaraja SB, Thekkur P, Mansoor H, et al.
PLOS One. 16 June 2020 (Issue 6); DOI:10.1371/journal.pone.0234651.
Background
Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.
Objective
We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.
Methods
A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.
Results
Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients’ home for optimal care.
Conclusion
Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.
Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.
Objective
We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.
Methods
A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.
Results
Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients’ home for optimal care.
Conclusion
Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.
Journal Article > ResearchFull Text
Trop Med Infect Dis. 26 May 2020; Volume 5 (Issue 2); 83.; DOI:10.3390/tropicalmed5020083
Paryani R, Gupta V, Singh P, Verma M, Sheikh S, et al.
Trop Med Infect Dis. 26 May 2020; Volume 5 (Issue 2); 83.; DOI:10.3390/tropicalmed5020083
While risk of tuberculosis (TB) is high among household contacts (HHCs) of pre-extensively drug resistant (pre-XDR) TB and XDR-TB, data on yield of systematic longitudinal screening are lacking. We aim to describe the yield of systematic longitudinal TB contact tracing among HHCs of patients with pre-XDR-TB and XDR-TB. At the Médecins Sans Frontières (MSF) clinic, Mumbai, India a cohort comprising 518 HHCs of 109 pre-XDR and XDR index cases was enrolled between January 2016 and June 2018. Regular HHC follow-ups were done till one year post treatment of index cases. Of 518 HHCs, 23 had TB (21 on TB treatment and two newly diagnosed) at the time of first visit. Of the rest, 19% HHCs had no follow-ups. Fourteen (3.5%) TB cases were identified among 400 HHCs; incidence rate: 2072/100,000 person-years (95% CI: 1227-3499). The overall yield of household contact tracing was 3% (16/518). Of 14 who were diagnosed with TB during follow-up, six had drug susceptible TB (DSTB); six had pre-XDR-TB and one had XDR-TB. Five of fourteen cases had resistance patterns concordant with their index case. In view of the high incidence of TB among HHCs of pre-XDR and XDR-TB cases, follow-up of HHCs for at least the duration of index cases' treatment should be considered.
Journal Article > ResearchFull Text
Clin Infect Dis. 2 November 2021; Volume 73 (Issue 9); e3496-e3504.; DOI:10.1093/cid/ciaa1577
Das M, Dalal A, Laxmeshwar C, Ravi S, Mamnoon F, et al.
Clin Infect Dis. 2 November 2021; Volume 73 (Issue 9); e3496-e3504.; DOI:10.1093/cid/ciaa1577
BACKGROUND
The Médecins Sans Frontières clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
METHODS
This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included.
RESULTS
Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients.
CONCLUSIONS
The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.
The Médecins Sans Frontières clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
METHODS
This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included.
RESULTS
Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients.
CONCLUSIONS
The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.
Journal Article > ResearchFull Text
PLOS One. 1 July 2013; Volume 8 (Issue 7); DOI:10.1371/journal.pone.0068869
Isaakidis P, Paryani R, Khan S, Mansoor H, Manglani M, et al.
PLOS One. 1 July 2013; Volume 8 (Issue 7); DOI:10.1371/journal.pone.0068869
Poor Outcomes in a Cohort of HIV-Infected Adolescents
Undergoing Treatment for Multidrug-Resistant
Tuberculosis in Mumbai, India
Petros Isaakidis1*, Roma Paryani1, Samsuddin Khan1, Homa Mansoor1, Mamta Manglani2,
Asmaa Valiyakath1, Peter Saranchuk3, Jennifer Furin4
1Me ́decins Sans Frontie`res, Mumbai, India, 2Pediatric Centre of Excellence for HIV Care, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai,
India, 3Southern Africa Medical Unit, Me ́decins Sans Frontie`res, Cape Town, South Africa, 4Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
United States of America
BACKGROUND
Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected
adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10–19 years
receiving second-line anti-TB treatment in a Me ́decins Sans Frontie`res (MSF) project in Mumbai, India.
METHOD
A retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was
undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under
direct observation.
RESULTS
The median age was 16 (IQR 14–18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB),
two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was
162.7 cells/ml (IQR: 84.8–250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results
were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven
patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never
started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon
after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation
of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire
second-line TB or antiretroviral regimens.
CONCLUSIONS
Early mortality and mortality after default were the most common reasons for poor outcomes in this study.
Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from
active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous,
intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected
adolescents will be especially important in designing effective interventions for this vulnerable group.
Undergoing Treatment for Multidrug-Resistant
Tuberculosis in Mumbai, India
Petros Isaakidis1*, Roma Paryani1, Samsuddin Khan1, Homa Mansoor1, Mamta Manglani2,
Asmaa Valiyakath1, Peter Saranchuk3, Jennifer Furin4
1Me ́decins Sans Frontie`res, Mumbai, India, 2Pediatric Centre of Excellence for HIV Care, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai,
India, 3Southern Africa Medical Unit, Me ́decins Sans Frontie`res, Cape Town, South Africa, 4Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
United States of America
BACKGROUND
Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected
adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10–19 years
receiving second-line anti-TB treatment in a Me ́decins Sans Frontie`res (MSF) project in Mumbai, India.
METHOD
A retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was
undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under
direct observation.
RESULTS
The median age was 16 (IQR 14–18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB),
two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was
162.7 cells/ml (IQR: 84.8–250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results
were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven
patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never
started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon
after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation
of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire
second-line TB or antiretroviral regimens.
CONCLUSIONS
Early mortality and mortality after default were the most common reasons for poor outcomes in this study.
Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from
active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous,
intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected
adolescents will be especially important in designing effective interventions for this vulnerable group.
Journal Article > ResearchFull Text
Clin Infect Dis. 20 October 2020; DOI:10.1093/cid/ciaa1577
Das M, Dalal A, Laxmeshwar C, Ravi S, Mamnoon F, et al.
Clin Infect Dis. 20 October 2020; DOI:10.1093/cid/ciaa1577
Background
Médecins Sans Frontières clinic in Mumbai, India has been providing concomitant Bedaquiline (BDQ) and Delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
Methods
This was a retrospective cohort study based on routinely collected programme data. In clinic, treatment regimens are designed based on culture-drug sensitivity test patterns, previous drug-exposures and are provided for 20-22 months. The BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February2016-February2018 were included.
Result
Of the 70 patients included, the median (IQR) age was 25(22-32) years and 56% were females. All except one were fluoroquinolone resistant. The median(IQR) duration of exposure to BDQ and DLM was 77(43-96) weeks. Thirty-nine episodes of serious-adverse-events(SAEs) were reported among 30(43%) patients, including five instances of QTc prolongation-assessed as possibly related to BDQ and/or DLM. Majority(69%) had culture conversion before 24 weeks of treatment. In 61(87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49(70%) patients.
Conclusion
The successful treatment outcomes of this cohort show that regimens including concomitant bedaquiline and delamanid for longer than 24 weeks are effective and can be safely administered on ambulatory basis. National TB programmes globally should scale up access to life saving DR-TB regimens with new drugs.
Médecins Sans Frontières clinic in Mumbai, India has been providing concomitant Bedaquiline (BDQ) and Delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
Methods
This was a retrospective cohort study based on routinely collected programme data. In clinic, treatment regimens are designed based on culture-drug sensitivity test patterns, previous drug-exposures and are provided for 20-22 months. The BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February2016-February2018 were included.
Result
Of the 70 patients included, the median (IQR) age was 25(22-32) years and 56% were females. All except one were fluoroquinolone resistant. The median(IQR) duration of exposure to BDQ and DLM was 77(43-96) weeks. Thirty-nine episodes of serious-adverse-events(SAEs) were reported among 30(43%) patients, including five instances of QTc prolongation-assessed as possibly related to BDQ and/or DLM. Majority(69%) had culture conversion before 24 weeks of treatment. In 61(87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49(70%) patients.
Conclusion
The successful treatment outcomes of this cohort show that regimens including concomitant bedaquiline and delamanid for longer than 24 weeks are effective and can be safely administered on ambulatory basis. National TB programmes globally should scale up access to life saving DR-TB regimens with new drugs.
Journal Article > ResearchFull Text
PLOS One. 11 July 2011; Volume 7 (Issue 7); DOI:10.1371/journal.pone.0040781
Isaakidis P, Varghese B, Mansoor H, Cox HS, Ladomirska J, et al.
PLOS One. 11 July 2011; Volume 7 (Issue 7); DOI:10.1371/journal.pone.0040781
Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.