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XDR Tuberculosis in childrens

Emanuele Pontali, Dina Visca, Rosella Centis, Lia D'Ambrosio, Antonio Spanevello, Giovanni Battista Migliori
PURPOSE OF REVIEW: Multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR)-TB epidemics are key obstacles towards TB control and elimination. RECENT FINDINGS: Diagnosis of MDR/XDR-TB is difficult and requires several weeks. New diagnostic tools are being tested and proposed allowing for shorter time to diagnosis and reduced delays in starting an adequate treatment regimen. MDR/XDR-TB treatment strategies are currently on an evolving stage...
February 20, 2018: Current Opinion in Pulmonary Medicine
Csaba Ködmön, Martin van den Boom, Phillip Zucs, Marieke Johanna van der Werf
BackgroundConfirming tuberculosis (TB) in children and obtaining information on drug susceptibility is essential to ensure adequate treatment. We assessed whether there are gaps in diagnosis and treatment of multidrug-resistant (MDR) TB in children in the European Union and European Economic Area (EU/EEA), quantified the burden of MDR TB in children and characterised cases. Methods : We analysed surveillance data from 2007 to 2015 for paediatric cases younger than 15 years. Results : In that period, 26 EU/EEA countries reported 18,826 paediatric TB cases of whom 4,129 (21...
November 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
Thandi Kapwata, Natashia Morris, Angela Campbell, Thuli Mthiyane, Primrose Mpangase, Kristin N Nelson, Salim Allana, James C M Brust, Pravi Moodley, Koleka Mlisana, Neel R Gandhi, N Sarita Shah
BACKGROUND: KwaZulu-Natal province, South Africa, has among the highest burden of XDR TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR TB patients and proximity to health facilities in KwaZulu-Natal. METHODS: We recruited adults and children with XDR TB diagnosed in KwaZulu-Natal...
2017: PloS One
Lia D'Ambrosio, Rosella Centis, Simon Tiberi, Marina Tadolini, Margareth Dalcolmo, Adrian Rendon, Susanna Esposito, Giovanni Battista Migliori
The new drugs delamanid and bedaquiline are increasingly used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). As evidence is lacking, the World Health Organization recommends their use under specific conditions in adults, delamanid only being recommended in children ≥6 years of age. No systematic review has yet evaluated the efficacy, safety and tolerability of the new drugs in children. A search of peer-reviewed, scientific evidence was performed, to evaluate the efficacy/effectiveness, safety, and tolerability of delamanid or bedaquiline-containing regimens in children with confirmed M/XDR-TB...
July 2017: Journal of Thoracic Disease
Justine B Nasejje, Henry Mwambi, Keertan Dheda, Maia Lesosky
BACKGROUND: Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate...
July 28, 2017: BMC Medical Research Methodology
Aravind Swaminathan, Philipp du Cros, James A Seddon, Shamsiya Mirgayosieva, Rajabov Asladdin, Zulfiya Dusmatova
BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy...
June 12, 2017: BMC Infectious Diseases
Hyun Jung Kim, Hyung Ho Yoon, Byung Wook Eun, Youngmin Ahn, Sungweon Ryoo, Hee Jin Kim
The incidence of drug-resistant tuberculosis (DR-TB) in pediatric populations is a critical indicator of national TB management and treatment strategies. Limited data exist regarding the rate of pediatric DR-TB. In this study, we aimed to analyze the status of DR-TB in Korean children from 2007 to 2013. We analyzed specimens submitted to the Korean Institute of Tuberculosis using Mycobacterium tuberculosis culture and drug susceptibility tests (DSTs) from January 2007 through December 2013. Specimens from patients ≤ 19 years of age were included...
June 2017: Journal of Korean Medical Science
Lesley Scott, Pedro da Silva, Catharina C Boehme, Wendy Stevens, Christopher M Gilpin
PURPOSE OF REVIEW: Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation...
March 2017: Current Opinion in HIV and AIDS
Susanna Esposito, Samantha Bosis, Marina Tadolini, Sonia Bianchini, Giovanni Battista Migliori, Nicola Principi
RATIONAL: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are emerging problems in several countries. These infections require long and expensive treatment regimens. Recently, 2 new drugs, bedaquiline and delamanid, have been approved in several countries for use in adults with severe, difficult-to-treat MDR-TB, and it has been suggested that they could also be administered to children with MDR-TB and limited treatment options. However, no study has been completed on their efficacy...
November 2016: Medicine (Baltimore)
K Dheda, K C Chang, L Guglielmetti, J Furin, H S Schaaf, D Chesov, A Esmail, C Lange
BACKGROUND: Globally there is a burgeoning epidemic of drug monoresistant tuberculosis (TB), multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least one major TB drug, including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly, almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycoside. This trend cannot be ignored because drug-resistant TB is associated with greater morbidity compared to drug-susceptible TB, accounts for almost 25% of global TB mortality, is extremely costly to treat, consumes substantial portions of budgets allocated to national TB programmes in TB-endemic countries and is a major threat to healthcare workers, who are already in short supply in resource-poor settings...
March 2017: Clinical Microbiology and Infection
Ira Shah, Forum Shah
BACKGROUND: The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. AIM: To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. METHODS: A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B...
May 2017: Paediatrics and International Child Health
Peter J Dodd, Charalambos Sismanidis, James A Seddon
BACKGROUND: After infection with Mycobacterium tuberculosis, children are at an increased risk of progression to tuberculosis disease; a condition that can be challenging to diagnose. New estimation approaches for children have highlighted the gap between incidence and notifications of M tuberculosis, and suggest there are more cases of isoniazid-resistant and multidrug-resistant (MDR) disease than are identified. No work has yet quantified the burden of drug-resistant infection, or accounted for other types of drug resistance or sampling uncertainty...
October 2016: Lancet Infectious Diseases
Samiksha Ghimire, Natasha Van't Boveneind-Vrubleuskaya, Onno W Akkerman, Wiel C M de Lange, Dick van Soolingen, Jos G W Kosterink, Tjip S van der Werf, Bob Wilffert, Daniel J Touw, Jan-Willem C Alffenaar
The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not the least important. This review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. A total of 37 studies on adult (32 studies) and paediatric (5 studies) MDR-TB patients were included. Among the 32 adult studies, 19 were on susceptibility of Mycobacterium tuberculosis isolates to levofloxacin by MIC, 1 was on susceptibility of M...
October 2016: Journal of Antimicrobial Chemotherapy
Giovanni Sotgiu, Lia D'Ambrosio, Rosella Centis, Simon Tiberi, Susanna Esposito, Simone Dore, Antonio Spanevello, Giovanni Battista Migliori
BACKGROUND: Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems. METHODS: A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB...
March 12, 2016: International Journal of Molecular Sciences
A Swaminathan, P du Cros, J A Seddon, S Quinnell, O I Bobokhojaev, Z Dusmatova, J Achar
BACKGROUND: Management of extensively drug-resistant tuberculosis (XDR-TB) and pre-XDR-TB is challenging, as effective drugs are lacking. Group 5 anti-tuberculosis drugs have an unclear role in the treatment of drug-resistant TB, and in children the efficacy, safety and effects of long-term use are not well described. We present clinical outcomes and adverse effects of a cohort of children with XDR-TB or pre-XDR-TB treated with Group 5 drugs in Tajikistan. METHODS: We conducted a retrospective analysis of eight children treated with one or more of the Group 5 drugs available under the Tajikistan National TB Programme-linezolid, amoxicillin-clavulanate, clofazimine and clarithromycin-given in combination with first- and second-line drugs...
April 2016: International Journal of Tuberculosis and Lung Disease
Luisa Galli, Laura Lancella, Silvia Garazzino, Marina Tadolini, Alberto Matteelli, Giovanni Battista Migliori, Nicola Principi, Alberto Villani, Susanna Esposito
Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the world. The number of cases of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), which are characterised by high mortality rates, is increasing. The therapeutic management of children with MDR- and XDR-TB is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life...
March 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Nicole Salazar-Austin, Alvaro A Ordonez, Alice Jenh Hsu, Jane E Benson, Mahadevappa Mahesh, Elizabeth Menachery, Jafar H Razeq, Max Salfinger, Jeffrey R Starke, Aaron M Milstone, Nicole Parrish, Eric L Nuermberger, Sanjay K Jain
Extensively drug-resistant (XDR) tuberculosis is becoming increasingly prevalent worldwide, but little is known about XDR tuberculosis in young children. In this Grand Round we describe a 2-year-old child from the USA who developed pneumonia after a 3 month visit to India. Symptoms resolved with empirical first-line tuberculosis treatment; however, a XDR strain of Mycobacterium tuberculosis grew in culture. In the absence of clinical or microbiological markers, low-radiation exposure pulmonary CT imaging was used to monitor treatment response, and guide an individualised drug regimen...
December 2015: Lancet Infectious Diseases
Karol Majewski, Małgorzata Rybczyńska, Karolina Wódz
STUDY AIM: Evaluation of detection and drug resistance of Mycobacterium tuberculosis in patients from the Łódzkie Voivodship in the period 2009 - 2013. MATERIAL AND METHODS: The data presented in the study include information obtained while diagnosing patients from the Łódzkie Voivodship in order to detect infections with Mycobacterium tuberculosis in the period 2009-2013. RESULTS: In 2009-2013 we analyzed clinical specimens for the purpose of detection of Mycobacterium tuberculosis...
2015: Przegla̧d Epidemiologiczny
Lia D'Ambrosio, Marina Tadolini, Rosella Centis, Raquel Duarte, Giovanni Sotgiu, Stefano Aliberti, Masoud Dara, Giovanni Battista Migliori
Multi-drug and extensively drug-resistant tuberculosis (MDR/XDR-TB) are considered a serious threat for TB control and elimination. The outcome of these patients is still largely unsatisfactory as of today, with treatment success rates being consistently below 50% at global level. The World Health Organization (WHO) recommends that management of MDR-TB cases is supported by a specialized team, including complementary medical professionals able to cover several perspectives (clinical, both for adults and children; surgical; radiological; public health; psychological; nursing, among others)...
March 2015: International Journal of Infectious Diseases: IJID
Petros Isaakidis, Mrinalini Das, Ajay M V Kumar, Christopher Peskett, Minni Khetarpal, Arun Bamne, Balkrishna Adsul, Mamta Manglani, Kuldeep Singh Sachdeva, Malik Parmar, Avinash Kanchar, B B Rewari, Alaka Deshpande, Camilla Rodrigues, Anjali Shetty, Lorraine Rebello, Peter Saranchuk
BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India...
2014: PloS One
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