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Amanda K Debes, Robert H Gilman, Carolyne Onyango-Makumbi, Andrea Ruff, Richard Oberhelman, David W Dowdy
BACKGROUND: The objective of this analysis was to assess the cost-effectiveness of TB diagnosis using Microscopic Observation Drug Susceptibility (MODS), Xpert MTB/RIF (Xpert), and empiric treatment for all patients, in addition to current clinical diagnostic practices in children less than 5 years of age in a national tuberculosis (TB) referral hospital in Uganda. METHODS: A decision analysis was conducted from the healthcare perspective, with a primary outcome of incremental cost effectiveness expressed as cost per year of life gained (YLG)...
October 3, 2016: Pediatric Infectious Disease Journal
Samuel G Schumacher, Maarten van Smeden, Nandini Dendukuri, Lawrence Joseph, Mark P Nicol, Madhukar Pai, Heather J Zar
Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography...
October 13, 2016: American Journal of Epidemiology
A Jayakumar, R M Savic, C K Everett, D Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid
The Xpert® MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle thresholds (Ct), which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert Ct trajectory and drug exposure during TB treatment to evaluate the potential utility of Xpert Ct for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB consecutively enrolled at ten international clinical trial sites participating in Study 29X, a CDC-sponsored TB Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses up to 20 mg/kg...
October 12, 2016: Journal of Clinical Microbiology
Sabine Hofmann-Thiel, Nikolay Molodtsov, Uladzimir Antonenka, Harald Hoffmann
Abbott RealTime MTB (RT MTB) is a new automated nucleic acid amplification test for the detection of Mycobacterium tuberculosis complex (MTBC) in clinical specimens. In combination with RealTime MTB INH/RIF Resistance (RT MTB INH/RIF), which can be applied to RT MTB positive specimens as add-on assay, the tests also indicate genetic markers of resistance to isoniazid and rifampicin. We aimed to evaluate the diagnostic sensitivity and specificity of RT MTB using different types of respiratory and extra-pulmonary specimens and to compare performance characteristics directly with the FluoroType MTB assay...
October 12, 2016: Journal of Clinical Microbiology
P Naidoo, R Dunbar, E du Toit, M van Niekerk, S B Squire, N Beyers, J Madan
SETTING: Cape Town, South Africa, where Xpert(®) MTB/RIF was introduced as a screening test for all presumptive tuberculosis (TB) cases. OBJECTIVE: To compare laboratory costs of smear/culture- and Xpert-based tuberculosis (TB) diagnostic algorithms in routine operational conditions. METHODS: Economic costing was undertaken from a laboratory perspective, using an ingredients-based costing approach. Cost allocation was based on reviews of standard operating procedures and laboratory records, timing of test procedures, measurement of laboratory areas and manager interviews...
October 2016: International Journal of Tuberculosis and Lung Disease
Simon Walusimbi, Brendan Kwesiga, Rashmi Rodrigues, Melles Haile, Ayesha de Costa, Lennart Bogg, Achilles Katamba
BACKGROUND: Microscopic Observation Drug Susceptibility (MODS) and Xpert MTB/Rif (Xpert) are highly sensitive tests for diagnosis of pulmonary tuberculosis (PTB). This study evaluated the cost effectiveness of utilizing MODS versus Xpert for diagnosis of active pulmonary TB in HIV infected patients in Uganda. METHODS: A decision analysis model comparing MODS versus Xpert for TB diagnosis was used. Costs were estimated by measuring and valuing relevant resources required to perform the MODS and Xpert tests...
October 10, 2016: BMC Health Services Research
Michele M Kim, Rozhin Penjweini, Xing Liang, Timothy C Zhu
Photodynamic therapy (PDT) is an effective non-ionizing treatment modality that is currently being used for various malignant and non-malignant diseases. In type II PDT with photosensitizers such as benzoporphyrin monoacid ring A (BPD), cell death is based on the creation of singlet oxygen ((1)O2). With a previously proposed empirical five-parameter macroscopic model, the threshold dose of singlet oxygen ([(1)O2]rx,sh]) to cause tissue necrosis in tumors treated with PDT was determined along with a range of the magnitude of the relevant photochemical parameters: the photochemical oxygen consumption rate per light fluence rate and photosensitizer concentration (ξ), the probability ratio of (1)O2 to react with ground state photosensitizer compared to a cellular target (σ), the ratio of the monomolecular decay rate of the triplet state photosensitizer (β), the low photosensitizer concentration correction factor (δ), and the macroscopic maximum oxygen supply rate (g)...
September 23, 2016: Journal of Photochemistry and Photobiology. B, Biology
Laura C Luciani-Giacobbe, María V Ramírez-Rigo, Yamila Garro-Linck, Gustavo A Monti, Ruben H Manzo, María E Olivera
One of the main obstacles to the successful treatment of tuberculosis is the poor and variable oral bioavailability of rifampicin (RIF), which is mainly due to its low hydrophilicity and dissolution rate. The aim of this work was to obtain a hydrophilic new material that allows a very fast dissolution rate of RIF and therefore is potentially useful in the development of oral solid dosage forms. The acid form of carboxymethylcellulose (CMC) was co-processed with RIF by solvent impregnation to obtain CMC-RIF powder, which was characterized by polarized optical microscopy, powder x-ray diffraction, DSC-TGA, hot stage microscopy, (13)C and (15)N solid-state NMR and FT-IR spectroscopy...
October 6, 2016: European Journal of Pharmaceutical Sciences
Alessandro Menozzi, Manuel Dall'Aglio, Fausto Quintavalla, Luca Dallavalle, Valentina Meucci, Simone Bertini
BACKGROUND: A clinical trial was conducted in order to assess the efficacy of rifaximin, a broad-spectrum antibiotic with negligible gastrointestinal absorption, in comparison with metronidazole, a commonly employed antimicrobial drug, in dogs with chronic enteropathy. Twenty-four pet dogs were randomly enrolled into two different groups: MET group (10 dogs) and RIF group (14 dogs). Dogs of MET group received metronidazole 15 mg/kg q12h for 21 days by oral route, whereas dogs of RIF group, were given rifaximin 25 mg/kg q12h for 21 days by oral route...
October 6, 2016: BMC Veterinary Research
Junjie Huang, Min Sun, Zitong Wang, Qiaoxia Zhang, Jin Lou, Yun Cai, Weihong Chen, Xin Du
BACKGROUND: 9 treatments for acute promyelocytic leukemia (APL) have been compared in many randomized controlled trials (RCT). The conclusions have been inconsistent and the purpose of this study is to conduct a network meta-analysis. RESULTS: Rankings of event-free survival are ATRA+RIF (81.2%), ATRA+ATO (69.6%), ATO (50.6%). Rankings of complete remission are ATRA+RIF (79.3%), ATRA+ATO (64.8%), RIF (60.3%), ATO (55.9%). Rankings of avoiding differentiation syndromes are CT (84...
October 4, 2016: Oncotarget
Ida Pam Ombura, Noel Onyango, Susan Odera, Florence Mutua, Joshua Nyagol
BACKGROUND: Although prevention and control of spread of multi-drug resistant tuberculosis strains is a global challenge, there is paucity of data on the prevalence of DR-TB in patients diagnosed with TB in referral hospitals in Kenya. The present study assessed patients' characteristics and prevalence of drug resistant TB in sputa smear positive TB patients presenting to Coast Provincial General Hospital (CPGH) in Mombasa, Kenya. METHODS: Drug resistance was evaluated in 258 randomly selected sputa smear TB positive cases between the periods of November 2011 to February 2012 at the CPGH-Mombasa...
2016: PloS One
Ahmad Qasem, Mitra Safavikhasraghi, Saleh A Naser
BACKGROUND: Most recently we reported that RHB‑104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn's disease (CD)-associated with Mycobacterium avium subspecies paratuberculosis (MAP) (Alcedo et al. in Gut Pathog 14:32, 2016). The combination exhibited unique synergistic antimicrobial growth activity. The proprietary RHB-104 capsule formulation contains active ingredients (63.3 % Clarithromycin (CLA), 6.7 % Clofazimine (CLO) and 30 % Rifabutin (RIF))...
2016: Gut Pathogens
Heba Abdelwahab, Julia S Martin Del Campo, Yumin Dai, Camelia Adly, Sohby El-Sohaimy, Pablo Sobrado
A novel mechanism of rifampicin (Rif) resistance has recently been reported in Nocardia farcinica. This new mechanism involves the activity of rifampicin monooxygenase (RifMO), a flavin-dependent monooxygenase that catalyzes the hydroxylation of Rif, which is the first step in the degradation pathway. Recombinant RifMO was overexpressed and purified for biochemical analysis. Kinetic characterization revealed that Rif binding is necessary for effective FAD reduction. RifMO exhibits only a 3-fold coenzyme preference for NADPH over NADH...
2016: PloS One
Neha S Shah, S Y Grace Lin, Pennan M Barry, Yi-Ning Cheng, Gisela Schecter, Ed Desmond
Background.  Data from international settings suggest that isolates of Mycobacterium tuberculosis with rpoB mutations testing phenotypically susceptible to rifampin (RIF) may have clinical significance. We analyzed treatment outcomes of California patients with discordant molecular-phenotypic RIF results. Methods.  We included tuberculosis (TB) patients, during 2003-2013, whose specimens tested RIF susceptible phenotypically but had a rpoB mutation determined by pyrosequencing. Demographic data were abstracted from the California TB registry...
September 2016: Open Forum Infectious Diseases
Víctor M Ayala-García, Luz I Valenzuela-García, Peter Setlow, Mario Pedraza-Reyes
: Aag from B. subtilis has been implicated in in vitro removal of hypoxanthine and alkylated bases from DNA. The regulation of expression of aag in B. subtilis, and the resistance to genotoxic agents and mutagenic properties of an Aag-deficient strain were studied here. A strain with a transcriptional aag-lacZ fusion expressed low levels of β-galactosidase during growth and early sporulation but exhibited increased transcription during late stages of this developmental process. Notably, aag-lacZ expression was higher inside the forespore than in the mother cell compartment and this expression was abolished in a sigG-deficient background suggesting a forespore-specific mechanism of aag transcription...
October 3, 2016: Journal of Bacteriology
Zhenyu Li, Aiping Li, Jining Gao, Hong Li, Xuemei Qin
Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress...
2016: Frontiers in Pharmacology
Fuguo Shi, Xiaobing Li, Hong Pan, Li Ding
Rifampicin (RIF) is used in regimens for infections caused by Mycobacteria accompanied by serious adverse reactions. Rifampicin-quinone (RIF-Q) is a major autoxidation product of RIF. It is not clear whether RIF-Q plays a role in RIF induced adverse reactions. Investigation of the systemic exposure of RIF-Q is helpful to better understand the role of RIF-Q in RIF induced adverse reactions. In this study, a simple and reproducible high performance liquid chromatography-mass spectrometry (LC-MS) method involving a procedure to prevent the RIF from oxidation for simultaneous quantification of RIF and RIF-Q in rat plasma has been developed and validated, and applied to elucidate the systemic exposure of RIF-Q in rats...
September 26, 2016: Journal of Pharmaceutical and Biomedical Analysis
Somayyeh Safari, Azita Faramarzi, Azam Agha-Rahimi, Mohammad Ali Khalili
The aim was to report a healthy live birth using re-vitrified-warmed cleavage-stage embryos derived from supernumerary warmed embryos after frozen embryo transfer (ET) in a patient with recurrent implantation failure (RIF). The case was a 39-year-old female with a history of polycystic ovarian syndrome and adenomyosis, along with RIF. After ovarian hyperstimulation, 33 cumulus-oocyte complexes were retrieved and fertilized with conventional in vitro fertilization and intracytoplasmic sperm injection. Because of the risk of ovarian hyperstimulation syndrome, 16 grade B and C embryos were vitrified...
September 2016: Clinical and Experimental Reproductive Medicine
R Pushkin, Maria Iglesias-Ussel, Keedy Kara, C MacLauchlin, D R Mould, R Berkowitz, S Kreuzer, R Darouiche, D Oldach, P Fernandes
BACKGROUND:  Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described. METHODS:  In a phase 2 open-label randomized study, we evaluated oral FA/RIF versus standard of care (SOC) IV antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at re-implantation (week 12) for subjects with 2-stage exchange; and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively...
September 28, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Yanan Li, Yuling Wang, Zhi Zhang, Huixia Gao, Haibin Wang, Jinfeng Cao, Shumin Zhang, Yuzhen Liu, Jianhua Lu, Zungui Xu, Erhei Dai
Ethambutol (EMB) is an essential first-line drug for tuberculosis (TB) treatment. Nucleotide substitutions at embB codon 306 have been proposed as a potential marker for EMB resistance and a predictor for broad drug resistance in clinical Mycobacterium tuberculosis (MTB) isolates. However, discordant findings about the association between embB306 mutation and EMB resistance were reported. The Hebei province is located in the Beijing-Tianjin-Hebei integration region; however, little information about the genetic diversity of embB locus is available in this area...
September 26, 2016: Antimicrobial Agents and Chemotherapy
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