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Jan-Willem Alffenaar, Onno W Akkerman, Richard Anthony, Simon Tiberi, Scott Heysell, M P Grobusch, Frank Cobelens, Dick van Soolingen
Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M...
October 20, 2016: Expert Review of Anti-infective Therapy
Keertan Dheda, Kwok Chiu Chang, Lorenzo Guglielmetti, Jennifer Furin, H Simon Schaaf, Dumitru Chesov, Aliasgar Esmail, Christoph Lange
Globally there is a burgeoning epidemic of drug mono-resistant tuberculosis (TB), multi-drug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least 1 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 aminoglycocide. This trend cannot be ignored because DR-TB is associated with greater morbidity compared to drug-sensitive TB, it accounts for almost 25% of global TB mortality, is extremely costly to treat, consuming 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...
October 15, 2016: Clinical Microbiology and Infection
Martin Dedicoat
No abstract text is available yet for this article.
October 2016: International Journal of Tuberculosis and Lung Disease
Narendran Gopalan, Padmapriyadarsini Chandrasekaran, Soumya Swaminathan, Srikanth Tripathy
Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy...
2016: AIDS Research and Therapy
R Cariem, V Cox, V de Azevedo, J Hughes, E Mohr, L Triviño Durán, N Ndjeka, J Furin
Multidrug-resistant tuberculosis (MDR-TB) is a serious public health problem, but the new drugs bedaquiline (BDQ) and delamanid offer hope to improve outcomes and minimise toxicity. In Khayelitsha, South Africa, patients are routinely started on BDQ in the out-patient setting. This report from the field describes BDQ use in the out-patient setting at the Nolungile Clinic. The clinic staff overall report a positive experience using the drug. Challenges have been based largely on the logistics of drug supply and delivery...
September 2016: Public Health Action
Santiago Ramón-García, Rubén González Del Río, Angel Santos Villarejo, Gaye D Sweet, Fraser Cunningham, David Barros, Lluís Ballell, Alfonso Mendoza-Losana, Santiago Ferrer-Bazaga, Charles J Thompson
While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug...
September 28, 2016: Scientific Reports
Stewart T Cole
Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials...
November 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
T Maitre, A Aubry, V Jarlier, J Robert, N Veziris
The emergence of drug-resistant tuberculosis (TB) compromises global tuberculosis control. The incidence of multidrug-resistant strains (MDR) defined as resistant to the two main antituberculosis drugs, rifampicin and isoniazid, was raised in the 1990s. Ten percent of these strains have developed additional resistance to the main second-line antituberculosis drugs: fluoroquinolones and aminoglycosides. These strains are defined as extensively drug-resistant (XDR). The prognosis of MDR-TB and XDR-TB is poor due to limited therapeutic resources...
September 13, 2016: Médecine et Maladies Infectieuses
Nesri Padayatchi, Sharana Mahomed, Marian Loveday, Kogieleum Naidoo
No abstract text is available yet for this article.
October 2016: Expert Opinion on Pharmacotherapy
Ji-Hye Byun, Jae-A Park, Hye-Rim Kang, Ju-Young Shin, Eui-Kyung Lee
BACKGROUND: No clear evidence on the comparative effectiveness of delamanid (DLM) and bedaquiline (BDQ) has been published. OBJECTIVE: This study aims to estimate the incremental effectiveness of DLM versus BDQ in patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: We developed a Markov model based on a cohort with MDR-TB, which consisted of success, failure, loss to follow-up, and death. The cohort simulation was conducted assuming each patient was 36 years old and, lived until age 82, and that the cycle length was 1 year...
November 2016: Clinical Drug Investigation
H Simon Schaaf, Stephanie Thee, Louvina van der Laan, Anneke C Hesseling, Anthony J Garcia-Prats
INTRODUCTION: Increasing numbers of children with drug-resistant tuberculosis are accessing second-line antituberculosis drugs; these are more toxic than first-line drugs. Little is known about the safety of new antituberculosis drugs in children. Knowledge of adverse effects, and how to assess and manage these, is important to ensure good adherence and treatment outcomes. AREAS COVERED: A Pubmed search was performed to identify articles addressing adverse effects of second-line antituberculosis drugs; a general search was done for the new drugs delamanid and bedaquiline...
October 2016: Expert Opinion on Drug Safety
Suresh Mallikaarjun, Charles Wells, Carolyn Petersen, Anne Paccaly, Susan E Shoaf, Shiva Patil, Lawrence Geiter
Delamanid is a medicinal product approved for treatment of multidrug-resistant tuberculosis. Three studies were conducted to evaluate the potential drug-drug interactions between delamanid and antiretroviral drugs, including ritonavir, a strong inhibitor of CYP3A4, and selected anti-TB drugs, including rifampin, a strong inducer of cytochrome P450 (CYP) isozymes. Multiple-dose studies were conducted in parallel groups of healthy subjects. Plasma samples were analyzed for delamanid, delamanid metabolite, and coadministered drug concentrations, and pharmacokinetic (PK) parameters were determined...
October 2016: Antimicrobial Agents and Chemotherapy
Gina Gualano, Susanna Capone, Alberto Matteelli, Fabrizio Palmieri
Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials...
June 24, 2016: Infectious Disease Reports
Arnold Mafukidze, Elizabeth Harausz, Jennifer Furin
INTRODUCTION: Drug-resistant forms of tuberculosis are a major public health problem with a serious global impact. Although there have recently been two new drugs introduced for the treatment of drug-resistant TB (bedaquiline and delamanid), the current therapeutic armamentarium is limited. Because treatment of drug-resistant TB requires the use of a multidrug-regimen, there has been growing interest in the use of antibiotics developed for other infectious pathogens but that have shown efficacy in the treatment of TB...
July 18, 2016: Expert Review of Clinical Pharmacology
Hiroyuki Sasabe, Yoshihiko Shimokawa, Masakazu Shibata, Kenta Hashizume, Yusuke Hamasako, Yoshihiro Ohzone, Eiji Kashiyama, Ken Umehara
No abstract text is available yet for this article.
July 2016: Antimicrobial Agents and Chemotherapy
Stephen Patterson, Susan Wyllie, Suzanne Norval, Laste Stojanovski, Frederick Rc Simeons, Jennifer L Auer, Maria Osuna-Cabello, Kevin D Read, Alan H Fairlamb
There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg(-1) for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg(-1) than at 3 mg kg(-1) (5 or 10 day dosing)...
2016: ELife
Tejal Rawal, Shital Butani
After 50 years drought, several drugs are looming from the pipeline to combat tuberculosis. They will serve as a boon to the field that has been burdened with primitive, inadequate treatments and drug-resistant bacterial strains. From the decades, due to lack of interest and resources, the field has suffered a lot. Learning from the flaws, scientists have renovated their approaches to the finding of new antitubercular drugs. The first line drugs take about six months or more for the entire treatment. The second line remedy for resistant-tuberculosis requires daily injections which carry severe side effects...
January 2016: Indian Journal of Pharmaceutical Sciences
Giampietro Sgaragli, Maria Frosini, Simona Saponara, Federico Corelli
Ineffectively treated tuberculosis (TB) is associated with substantial morbidity and mortality. Cure of TB patients is hampered by the development of multidrug resistance in M. tuberculosis and the need of long-term treatment. The diarylquinoline derivative bedaquiline was approved in December 2012 under the accelerated-approval regulations of FDA as part of a combination therapy for treating adults with pulmonary MDR-TB for whom effective cures are not otherwise available. The bicyclic nitroimidazoles delamanid and its companion pretomanid inhibit mycolic acid synthesis via an unknown mechanism...
2016: Current Medicinal Chemistry
Chris Greening, F Hafna Ahmed, A Elaaf Mohamed, Brendon M Lee, Gunjan Pandey, Andrew C Warden, Colin Scott, John G Oakeshott, Matthew C Taylor, Colin J Jackson
5-Deazaflavin cofactors enhance the metabolic flexibility of microorganisms by catalyzing a wide range of challenging enzymatic redox reactions. While structurally similar to riboflavin, 5-deazaflavins have distinctive and biologically useful electrochemical and photochemical properties as a result of the substitution of N-5 of the isoalloxazine ring for a carbon. 8-Hydroxy-5-deazaflavin (Fo) appears to be used for a single function: as a light-harvesting chromophore for DNA photolyases across the three domains of life...
June 2016: Microbiology and Molecular Biology Reviews: MMBR
(no author information available yet)
[This corrects the article on p. 359 in vol. 8, PMID: 26604805.].
2016: Infection and Drug Resistance
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