1. Bedaquiline resistance in drug-resistant tuberculosis HIV co-infected patients.
Eur Respir J. 2020 Jun 4;55(6):1902383. doi: 10.1183/13993003.02383-2019. Print 2020 Jun.
Nimmo C(1)(2)(3), Millard J(3)(4)(5), Brien K(3), Moodley S(3), van Dorp L(2), Lutchminarain K(6), Wolf A(7), Grant AD(3)(8), Balloux F(2), Pym AS(3), Padayatchi N(9), O’Donnell M(10)(11).
Genetic mutations linked to bedaquiline resistance were found before starting treatment and acquired during treatment in patients with drug-resistant TB and HIV in KwaZulu-Natal, South Africa. Routine bedaquiline resistance testing needs to be accelerated. http://bit.ly/2vnL4VY
Global tuberculosis (TB) control is threatened by drug resistance, with over 500 000 cases resistant to first line drugs in 2018 . Bedaquiline is a highly effective TB drug and has improved drug-resistant TB (DR-TB) outcomes in trial and programmatic settings [2, 3]. The World Health Organization (WHO) recommends its inclusion in most DR-TB regimens  and it is under further evaluation in clinical trials. There have been several reports of clinical bedaquiline resistance [5–8]. Resistance-associated variants (RAVs) in clinical isolates identified to date are almost exclusively caused by Rv0678 mutations which can raise Mycobacterium tuberculosis minimum inhibitory concentrations (MICs) for bedaquiline and clofazimine .
2. Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.
PLoS One. 2020 Jun 16;15(6):e0234651. doi: 10.1371/journal.pone.0234651. eCollection 2020.
Chavan VV(1), Dalal A(2), Nagaraja S(3), Thekkur P(4)(5), Mansoor H(1), Meneguim A(1), Paryani R(1), Singh P(1), Kalon S(1), Das M(1), Ferlazzo G(6), Isaakidis P(6).
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
3. Concordance of drug resistance profiles between persons with drug-resistant tuberculosis and their household contacts: a systematic review and meta-analysis.
Clin Infect Dis. 2020 May 25:ciaa613. doi: 10.1093/cid/ciaa613. Online ahead of print.
Chiang SS(1)(2), Brooks MB(3), Jenkins HE(4), Rubenstein D(1), Seddon JA(5)(6), van de Water BJ(3), Lindeborg MM(3), Becerra MC(3)(7), Yuen CM(3)(7).
BACKGROUND: Household contacts of patients with drug-resistant tuberculosis are at high risk for being infected with Mycobacterium tuberculosis and for developing tuberculosis disease. To guide regimen composition for the empirical treatment of tuberculosis infection and disease in these household contacts, we estimated drug resistance profile concordance between index patients with drug-resistant tuberculosis and their household contacts.
METHODS: We performed a systematic review and meta-analysis of studies published through July 24, 2018 and reported resistance profiles of drug-resistant tuberculosis index and secondary cases within their households. Using a random-effects meta-analysis, we estimated resistance profile concordance, defined as the percentage of secondary cases whose M. tuberculosis strains were resistant to the same drugs as strains from their index cases. We also estimated isoniazid/rifampin concordance, defined as whether index and secondary cases had identical susceptibilities for isoniazid and rifampin only.
RESULTS: We identified 33 eligible studies, which evaluated resistance profile concordance between 484 secondary cases and their household index cases. Pooled resistance profile concordance was 54.3% (95% confidence interval [CI]: 40.7-67.6, I2=85%). Pooled isoniazid/rifampin concordance was 82.6% (95% CI: 72.3-90.9; I2=73%). Concordance estimates were similar in a sub-analysis of 16 studies from high tuberculosis-burden countries. There were insufficient data to perform a sub-analysis among pediatric secondary cases.
CONCLUSION: Household contacts of drug-resistant TB patients should receive treatment for TB infection and disease that assumes that they, too, are infected with a drug-resistant M. tuberculosis strain. Whenever possible, drug susceptibility testing should be performed for secondary cases to optimize regimen composition.
© The Author(s) 2020. Published by Oxford University Press for the Infectious
Diseases Society of America. All rights reserved. For permissions, e-mail:
4. Isoniazid Preventive Therapy in Contacts of Multidrug-resistant Tuberculosis.
Am J Respir Crit Care Med. 2020 Jun 17. doi: 10.1164/rccm.201908-1576OC. Online ahead of print.
Huang CC(1)(2), Becerra MC(2), Calderon R(3), Contreras C(3), Galea J(4), Grandjean L(5)(6)(7), Lecca L(3), Yataco R(3), Zhang Z(1), Murray M(2)(8).
RATIONALE: The World Health Organization recommends the use of isoniazid alone or in combination with rifapentine to treat latent tuberculosis infection. The recent rise of drug-resistant tuberculosis has complicated the choice of latent tuberculosis infection treatment regimen.
OBJECTIVES: To evaluate the effects of isoniazid preventive therapy on contacts of multidrug-resistant tuberculosis patients Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index tuberculosis patients and 14,044 tuberculosis-exposed household contacts whom we followed for one year for the occurrence of incident tuberculosi disease. Although Peruvian national guidelines specify that isoniazid preventive therapy should be provided to contacts aged 19 and under, only half this group received isoniazid preventive therapy.
MEASUREMENTS AND MAIN RESULTS: Among 4,216 contacts under 19 years of age, 2,106
(50%) initiated isoniazid preventive therapy at enrollment. The protective effect of isoniazid was more extreme in contacts exposed to drug-sensitive (adjusted hazard ratio, 0.30 [95% confidence interval, 0.18-0.48]) and to multidrug-resistant tuberculosis (0.19 [0.05-0.66]) compared to those exposed to mono-isoniazid-resistant (0.80 [0.23-2.80]). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received isoniazid preventive therapy compared to 3% (8/273) of those who did not.
CONCLUSION: Household contacts who received isoniazid preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. Isoniazid may have a role in the management of latent multidrug-resistant tuberculosis infection.
|Tuberculosis and COVID-19 Publications|
1. Challenges in Tuberculosis Clinical Trials in the Face of the COVID-19 Pandemic: A Sponsor’s Perspective.
Trop Med Infect Dis. 2020 May 27;5(2):E86. doi: 10.3390/tropicalmed5020086.
The COVID-19 pandemic has caused unforeseen and extreme changes in societal and health system functioning not previously experienced in most countries in a lifetime. The impact of the pandemic on clinical trials can be especially profound given their complexities and operational requirements. The STREAM
Clinical Trial is the largest trial for MDR-TB ever conducted. Currently operating in seven countries, the trial had 126 participants on treatment and 312 additional participants in active follow up as of March 31, 2020. Areas of particular concern during this global emergency include treatment continuity,
supply chain management and participant safety monitoring. This commentary highlights some of the challenges faced due to the pandemic and the steps taken to protect the safety of trial participants and the integrity of the trial.
2. Responding to SARS-CoV-2 in South Africa: What can we learn from drug-resistant tuberculosis?
Eur Respir J. 2020 May 29:2001369. doi: 10.1183/13993003.01369-2020. Online ahead of print.
Ndjeka N(1)(2), Conradie F(3)(2), Meintjes G(4), Reuter A(5), Hughes J(6), Padanilam X(7), Ismail N(8), Kock Y(1), Master I(9), Romero R(10), Te Riele J(11), Enwerem M(12), Ferreira H(13), Maartens G(4).
Rapid adoption of new diagnostic tools, parallel process of research and implementation, decentralization of services, the use of personal protective equipment as well as strong partnership and collaboration could strengthen the fight against COVID-19.
The novel coronavirus strain, SARS-CoV-2, was first reported from China in December 2019 . As of the 14th May 2020, more than 4.4 million individuals have tested positive for SARS-COV-2 globally . More than 300,000 individuals have died globally due to SARS-COV-2 .