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Christen Ravn, Ulrika Furustrand Tafin, Bertrand Bétrisey, Søren Overgaard, Andrej Trampuz
Background and purpose - Antibiotic treatment of patients before specimen collection reduces the ability to detect organisms by culture. We investigated the suppressive effect of antibiotics on the growth of non-adherent, planktonic, and surface-related biofilm bacteria in vitro by using sonication and microcalorimetry methods. Patients and methods - Biofilms of Staphylococcus aureus, S. epidermidis, Escherichia coli, and Propionibacterium acnes were formed on porous glass beads and exposed for 24 h to antibiotic concentrations from 1 to 1,024 times the minimal inhibitory concentration (MIC) of vancomycin, daptomycin, rifampin, flucloxacillin, or ciprofloxacin...
October 24, 2016: Acta Orthopaedica
Pierre Dehoux, Jean Christophe Marvaud, Amr Abouelleil, Ashlee M Earl, Thierry Lambert, Catherine Dauga
BACKGROUND: Clostridium bolteae and Clostridium clostridioforme, previously included in the complex C. clostridioforme in the group Clostridium XIVa, remain difficult to distinguish by phenotypic methods. These bacteria, prevailing in the human intestinal microbiota, are opportunistic pathogens with various drug susceptibility patterns. In order to better characterize the two species and to obtain information on their antibiotic resistance genes, we analyzed the genomes of six strains of C...
October 21, 2016: BMC Genomics
K V Shur, M V Zaychikova, N E Mikheecheva, K M Klimina, O B Bekker, S N Zhdanova, O B Ogarkov, V N Danilenko
We report a draft genome sequence of Mycobacterium tuberculosis strain B9741 belonging to Beijing B0/W lineage isolated from a HIV patient from Siberia, Russia. This clinical isolate showed MDR phenotype and resistance to isoniazid, rifampin, streptomycin and pyrazinamide. We analyzed SNPs associated with virulence and resistance. The draft genome sequence and annotation have been deposited at GenBank under the accession NZ_LVJJ00000000.
December 2016: Genomics Data
Petar Duvnjak, Mario Laguna
The use of live attenuated intravesicular Bacillus Calmette-Guerin (BCG) therapy is a generally accepted safe and effective method for the treatment of superficial transitional cell carcinoma (TCC) of the bladder. Although rare, < 5% of patient's treated with intravesicular BCG therapy may develop potentially serious complications, including localized infections to the genitourinary tract, mycotic aneurysms and osteomyelitis. We present here a case of a 63-year-old male who developed left coronary and multiple peripheral M...
August 2016: Journal of Radiology Case Reports
Aliya Yamin, Ethan Bornstein, Rachel Hensel, Omar Mohamed, Russell R Kempker
Background.  Despite the low and decreasing prevalence of tuberculosis (TB) in the United States, there remain certain high-risk groups with high incidence rates. The targeted screening and treatment of latent TB infection (LTBI) among these high-risk groups are needed to achieve TB elimination; however, by most accounts, LTBI treatment completion rates remain low. Methods.  We retrospectively studied all patients accepting treatment for LTBI at the Fulton County Health Department TB clinic over 2 years...
October 2016: Open Forum Infectious Diseases
Aurélie Chauffour, Jérôme Robert, Nicolas Veziris, Alexandra Aubry, Vincent Jarlier
BACKGROUND: The treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks...
October 2016: PLoS Neglected Tropical Diseases
Yu Huang, Qingqing Wu, Shuiyang Xu, Jieming Zhong, Songhua Chen, Jinghang Xu, Liping Zhu, Haibo He, Xiaomeng Wang
With 25% of the global burden, China has the highest incidence of drug-resistant tuberculosis (TB) in the world. However, surveillance data on extensively drug-resistant TB (XDR-TB) from China are scant. To estimate the prevalence of XDR-TB in Zhejiang, Eastern China, 30 of 90 TB treatment centers in Zhejiang were recruited. Patients with suspected TB who reported to the clinics for diagnosis were requested to undergo a smear sputum test. Positive sputum samples were tested for drug susceptibility. Data on anti-TB drug resistance from 1999 to 2008 were also collected to assess drug resistance trends...
October 18, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Parham Sendi, Werner Zimmerli
No abstract text is available yet for this article.
October 13, 2016: Clinical Microbiology and Infection
Luc Dirix, Helen Swaisland, Henk M W Verheul, Sylvie Rottey, Karin Leunen, Guy Jerusalem, Christian Rolfo, Dorte Nielsen, L Rhoda Molife, Rebecca Kristeleit, Judith de Vos-Geelen, Morten Mau-Sørensen, Patricia Soetekouw, Carla van Herpen, Anitra Fielding, Karen So, Wendy Bannister, Ruth Plummer
PURPOSE: The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA-mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. METHODS: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors...
October 10, 2016: Clinical Therapeutics
Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination. METHODS:  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. METHODS:  We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Soumya Swaminathan, Jotam G Pasipanodya, Geetha Ramachandran, A K Hemanth Kumar, Shashikant Srivastava, Devyani Deshpande, Eric Nuermberger, Tawanda Gumbo
BACKGROUND:  The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. METHODS:  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Malkeet Kumar, Kawaljit Singh, Krupa Naran, Fahreta Hamzabegovic, Daniel F Hoft, Digby F Warner, Peter Ruminski, Getahun Abate, Kelly Chibale
Efflux pumps are considered a major potential contributor to the development of various forms of resistance in Mycobacterium tuberculosis leading to the emergence of multidrug-resistant tuberculosis (TB). Verapamil (VER) and tricyclic chemosensitizers such as the phenothiazines are known to possess efflux pump inhibition properties and have demonstrated significant efficacy in various TB disease models. Novel hybrid molecules based on fusion of the VER substructure with various tricyclic, as well as nontricyclic, chemosensitizer cores or their structural motifs are described...
October 14, 2016: ACS Infectious Diseases
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
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
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
Bintou A Ahidjo, Mariama C Maiga, Elizabeth A Ihms, Mamoudou Maiga, Alvaro A Ordonez, Laurene S Cheung, Sarah Beck, Bruno B Andrade, Sanjay Jain, William R Bishai
Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone's antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response...
September 8, 2016: JCI Insight
Eric F Egelund, Ramiro Isaza, Abdullah Alsultan, Charles A Peloquin
This report describes the pharmacokinetic profiles of chronically administered oral isoniazid and rifampin in one adult male and one adult female Asian elephant ( Elephas maximus ) that were asymptomatically infected with Mycobacterium tuberculosis . Rifampin's half-life was reduced when compared to previous single-dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both elephants experienced delayed absorption of isoniazid and rifampin as compared to previous pharmacokinetic studies in this species...
September 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
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
S Tevell, B Hellmark, Å Nilsdotter-Augustinsson, B Söderquist
Further knowledge about the clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different coagulase-negative staphylococci (CoNS) may facilitate interpretation of microbiological findings and improve treatment algorithms. Staphylococcus capitis is a CoNS with documented potential for both human disease and nosocomial spread. As data on orthopaedic infections are scarce, our aim was to describe the clinical and microbiological characteristics of PJIs caused by S. capitis...
September 29, 2016: European Journal of Clinical Microbiology & Infectious Diseases
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