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https://www.readbyqxmd.com/read/27927856/the-long-term-mortality-of-tuberculosis-meningitis-patients-in-new-york-city-a-cohort-study
#1
Christopher Vinnard, Liza King, Sonal Munsiff, Aldo Crossa, Kentaro Iwata, Jotam Pasipanodya, Douglas Proops, Shama Ahuja
BACKGROUND: Tuberculosis meningitis (TBM) is the most devastating clinical presentation of infection with M. tuberculosis; delayed initiation of effective anti-tuberculosis (TB) therapy is associated with poor treatment outcomes. Our objective was to determine the relationship between drug resistance and 10-year mortality among TBM patients. METHODS: We conducted a retrospective cohort study of 324 patients with culture-confirmed TBM, susceptibility results reported for isoniazid and rifampin, and initiation of at least two anti-TB drugs, reported to the TB registry in New York City, NY (US) between January 1, 1992 and December 31, 2001...
December 7, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27914363/new-insights-into-the-sar-and-drug-combination-synergy-of-2-quinolin-4-yloxy-acetamides-against-mycobacterium-tuberculosis
#2
Bruno Couto Giacobbo, Kenia Pissinate, Valnês Rodrigues-Junior, Anne Drumond Villela, Estêvão Silveira Grams, Bruno Lopes Abbadi, Fernanda Teixeira Subtil, Nathalia Sperotto, Rogério Valim Trindade, Davi Fernando Back, Maria Martha Campos, Luiz Augusto Basso, Pablo Machado, Diógenes Santiago Santos
2-(Quinolin-4-yloxy)acetamides have been described as potent and selective in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Herein, a new series of optimized compounds were found to demonstrate highly potent antitubercular activity, with minimum inhibitory concentration (MIC) values against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains in the submicromolar range. Furthermore, the most active compounds had no apparent toxicity to mammalian cells, and they showed intracellular activities similar to those of isoniazid and rifampin in a macrophage model of Mtb infection...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27906006/integrated-therapy-for-hiv-and-tuberculosis
#3
REVIEW
Weerawat Manosuthi, Surasak Wiboonchutikul, Somnuek Sungkanuparph
Tuberculosis (TB) has been the most common opportunistic infection and cause of mortality among HIV-infected patients, especially in resource-limited countries. Clinical manifestations of TB vary and depend on the degree of immunodeficiency. Sputum microscopy and culture with drug-susceptibility testing are recommended as a standard method for diagnosing active TB. TB-related mortality in HIV-infected patients is high especially during the first few months of treatment. Integrated therapy of both HIV and TB is feasible and efficient to control the diseases and yield better survival...
May 12, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27902737/a-comparison-of-the-sensititre-mycotb-plate-the-bactec-mgit-960-and-a-microarray-based-molecular-assay-for-the-detection-of-drug-resistance-in-clinical-mycobacterium-tuberculosis-isolates-in-moscow-russia
#4
Elena Y Nosova, Danila V Zimenkov, Anastasia A Khakhalina, Alexandra I Isakova, Ludmila Y Krylova, Marina V Makarova, Ksenia Y Galkina, Maria A Krasnova, Svetlana G Safonova, Vitaly I Litvinov, Dmitry A Gryadunov, Elena M Bogorodskaya
BACKGROUND: The goal of this study was to compare the consistency of three assays for the determination of the drug resistance of Mycobacterium tuberculosis (MTB) strains with various resistance profiles isolated from the Moscow region. METHODS: A total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the rpoB, katG, inhA, ahpC, gyrA, gyrB, rrs, eis, and embB genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol...
2016: PloS One
https://www.readbyqxmd.com/read/27902411/non-typeable-haemophilus-influenzae-biofilm-production-and-severity-in-lower-respiratory-tract-infections-in-a-tertiary-hospital-in-mexico
#5
Michel Fernando Martínez-Reséndez, Juan Manuel González-Chávez, Elvira Garza-González, Lorena Nefertiti Castro-Fuentes, Jessica Lizzeth Gutiérrez-Ferman, Gabriela Echániz-Aviles, Adrián Camacho-Ortíz, María Noemí Carnalla-Barajas, Araceli Soto-Noguerón, Héctor Jesús Maldonado-Garza, Cristina Liliana Hernández-Balboa, Jorge M Llaca-Díaz, Samantha Flores-Treviño
Non-typeable Haemophilus influenzae (NTHi) is a common opportunistic bacterial pathogen that primarily infects the respiratory mucosa. This study was conducted to assess clinical and microbiological data related to disease severity in patients with lower respiratory tract infections caused by NTHi in a tertiary care hospital in Mexico. NTHi isolates were subjected to serotyping, antimicrobial susceptibility evaluation, and analyses of β-lactamase production, genetic relatedness, and biofilm formation. Clinical and demographic data were retrieved from patients' records...
October 17, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27874159/evaluation-of-genexpert-mtb-rif-for-detection-of-mycobacterium-tuberculosis-complex-and-rpo-b-gene-in-respiratory-and-non-respiratory-clinical-specimens-at-a-tertiary-care-teaching-hospital-in-saudi-arabia
#6
Ali M Somily, Mazin A Barry, Hanan A Habib, Fawzia E Alotaibi, Fahad A Al-Zamil, Mohammed A Khan, Mohammed S Sarwar, Nawab D Bakhash, Abdulkarim A Alrabiaah, Zahid A Shakoor, Abiola C Senok
To assess the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), against smear microscopy and culture method for diagnosis of MTB infection. Methods: This is a retrospective analysis of 103 respiratory and 137 non-respiratory patient specimens suspected of tuberculosis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia performed between April 2014 and March 2015. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test...
December 2016: Saudi Medical Journal
https://www.readbyqxmd.com/read/27872078/polymyxin-b-in-combination-with-rifampin-and-meropenem-against-polymyxin-b-resistant-kpc-producing-klebsiella-pneumoniae
#7
John Diep, David M Jacobs, Rajnikant Sharma, Jenna Covelli, Dana R Bowers, Thomas A Russo, Gauri G Rao
Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing K. pneumoniae and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae The rate and extent of killing with polymyxin B (1-128mg/L), rifampin (2-16mg/L), and meropenem (10-120mg/L) were evaluated against polymyxin B-susceptible (PB(S)) and -resistant (PB(R)) clinical isolates using 48h static time-kills...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872065/in-vitro-susceptibility-testing-of-bedaquiline-against-mycobacterium-avium-complex
#8
Barbara A Brown-Elliott, Julie V Philley, David E Griffith, Foram Thakkar, Richard J Wallace
We performed bedaquiline broth microdilution susceptibilities using Clinical Laboratory Standards Institute (CLSI) guidelines on 103 respiratory isolates of Mycobacterium avium complex (MAC), including multidrug resistant isolates. Approximately 90% of isolates had bedaquiline minimal inhibitory concentrations (MICs) ≤0.008 μg/mL and 102/103 isolates had MICs ≤0.015 μg/mL. Bedaquiline has excellent potential for use in patients with MAC, although for reasons of its metabolism by the cytochrome P450 system, it should not be given with rifampin...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27865404/formulation-studies-of-inha-inhibitors-and-combination-therapy-to-improve-efficacy-against-mycobacterium-tuberculosis
#9
Susan E Knudson, Jason E Cummings, Gopal R Bommineni, Pan Pan, Peter J Tonge, Richard A Slayden
Previously, structure-based drug design was used to develop substituted diphenyl ethers with potency against the Mycobacterium tuberculosis (Mtb) enoyl-ACP reductase (InhA), however, the highly lipophilic centroid compound, SB-PT004, lacked sufficient efficacy in the acute murine Mtb infection model. A next generation series of compounds were designed with improved specificity, potency against InhA, and reduced cytotoxicity in vitro, but these compounds also had limited solubility. Accordingly, solubility and pharmacokinetics studies were performed to develop formulations for this class and other experimental drug candidates with high logP values often encountered in drug discovery...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865403/propidium-monoazide-and-xpert-mtb-rif-to-quantify-mycobacterium-tuberculosis-cells
#10
Xavier A Kayigire, Sven O Friedrich, Miriam N Karinja, Lize van der Merwe, Neil A Martinson, Andreas H Diacon
Propidium monoazide (PMA) penetrates non-viable cells with compromised membranes. PMA has been proposed to improve the specificity of Xpert MTB/RIF (Xpert) for the detection of viable Mycobacterium tuberculosis. This study assessed the effect of PMA on Xpert cycle thresholds (CT) of M. tuberculosis made non-viable under antibiotic pressure. In vitro, we measured the difference between CT with and without PMA (ΔCT) in liquid cultures treated with one of six anti-tuberculosis drugs (isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, moxifloxacin) and found significant ΔCT only with isoniazid and ethambutol for pan-susceptible M...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27858342/physiologically-based-pharmacokinetic-pbpk-modeling-of-pitavastatin-and-atorvastatin-to-predict-drug-drug-interactions-ddis
#11
Peng Duan, Ping Zhao, Lei Zhang
BACKGROUND: The disposition of statins varies and involves both metabolizing enzymes and transporters, making predictions of statin drug-drug interactions (DDIs) challenging. Physiologically based pharmacokinetic (PBPK) models have, however, demonstrated ability to predict complex DDIs. OBJECTIVE: In this study, PBPK models of two statins (pitavastatin and atorvastatin) were developed and applied to predict pitavastatin and atorvastatin associated DDIs. METHOD: Pitavastatin and atorvastatin PBPK models were developed using in vitro and human pharmacokinetic data in a population-based PBPK software (SimCYP(®)) by considering the contribution of both metabolizing enzymes and transporters to their overall pharmacokinetics...
November 17, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27856528/in-vivo-hepatic-enhancer-elements-in-the-human-abcg2-locus
#12
Rachel J Eclov, Mee J Kim, Robin P Smith, Xiaomin Liang, Nadav Ahituv, Deanna L Kroetz
ABCG2 encodes the mitoxantrone resistance protein (MXR, BCRP), an ATP-binding cassette (ABC) efflux membrane transporter. Computational analysis of the ~300 kb region of DNA surrounding ABCG2 (chr4:88911376-89220011, hg19) identified 30 regions with potential cis-regulatory capabilities. These putative regulatory regions were tested for their enhancer and suppressor activity in a human liver cell line using luciferase reporter assays. The in vitro enhancer and suppressor assays identified four regions that decreased gene expression and five regions that increased expression >1...
November 17, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27855070/pharmacokinetics-of-the-first-line-antituberculosis-drugs-in-ghanaian-children-with-tuberculosis-with-and-without-hiv-coinfection
#13
Sampson Antwi, Hongmei Yang, Anthony Enimil, Anima M Sarfo, Fizza S Gillani, Daniel Ansong, Albert Dompreh, Antoinette Orstin, Theresa Opoku, Dennis Bosumtwe, Lubbe Wiesner, Jennifer Norman, Charles A Peloquin, Awewura Kwara
Although human immunodefiency virus (HIV) coinfection is the most important risk factor for poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with tuberculosis (TB) with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide and ethambutol for at least 4 weeks had blood samples collected at pre-dose, 1, 2, 4, and 8-hours post-dose...
November 14, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27855069/activity-of-tedizolid-in-methicillin-resistant-staphylococcus-epidermidis-experimental-foreign-body-associated-osteomyelitis
#14
Kyung-Hwa Park, Kerryl E Greenwood-Quaintance, Audrey N Schuetz, Jayawant N Mandrekar, Robin Patel
We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin, against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia and a stainless-steel wire with precolonized MRSE biofilm was implanted. Following a one-week infection period, 92 rats received either no treatment (n=17) or 14 days of intraperitoneal tedizolid (n=15), tedizolid plus rifampin (n=15), rifampin (n=15), vancomycin plus rifampin (n=15), or vancomycin (n=15)...
November 14, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27855064/rifampin-based-combination-therapy-is-active-in-foreign-body-osteomyelitis-after-prior-rifampin-monotherapy
#15
Cassandra L Brinkman, Suzannah M Schmidt-Malan, Jayawant N Mandrekar, Robin Patel
Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with débridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than one round of rifampin monotherapy (2)...
November 14, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27852955/microbiological-efficacy-of-early-mrsa-treatment-in-cystic-fibrosis-in-a-randomised-controlled-trial
#16
Marianne Sponer Muhlebach, Valeria Beckett, Elena Popowitch, Melissa B Miller, Arthur Baines, Nicole Mayer-Hamblett, Edith T Zemanick, Wynton C Hoover, Jill M VanDalfsen, Preston Campbell, Christopher H Goss
OBJECTIVE: To evaluate microbiological effectiveness, that is, culture negativity of a non-blinded eradication protocol (Rx) compared with observation (Obs) in clinically stable cystic fibrosis participants with newly positive methicillin resistant Staphylococcus aureus (MRSA) cultures. DESIGN: This non-blinded trial randomised participants ages 4-45 years with first or early (≤2 positive cultures within 3 years) MRSA-positive culture without MRSA-active antibiotics within 4 weeks 1:1 to Rx or Obs...
November 15, 2016: Thorax
https://www.readbyqxmd.com/read/27849111/pharmacological-interventions-for-pruritus-in-adult-palliative-care-patients
#17
REVIEW
Waldemar Siemens, Carola Xander, Joerg J Meerpohl, Sabine Buroh, Gerd Antes, Guido Schwarzer, Gerhild Becker
BACKGROUND: This is an update of the original Cochrane review published in 2013 (Issue 6). Pruritus occurs in patients with disparate underlying diseases and is caused by different pathologic mechanisms. In palliative care patients, pruritus is not the most prevalent but is one of the most puzzling symptoms. It can cause considerable discomfort and affects patients' quality of life. OBJECTIVES: To assess the effects of different pharmacological treatments for preventing or treating pruritus in adult palliative care patients...
November 16, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27848902/the-impact-of-mass-gathering-on-the-burden-of-multidrug-resistant-mycobacterium-tuberculosis-in-al-madinah-al-monawarah-region-saudi-arabia
#18
Mogahid Elhassan, Hassan A Hemeg, Miskelyemen A Elmekki, Khalid A Turkistani, Ahmed A Abdul-Aziz
BACKGROUND: The pattern of Mycobacterium tuberculosis susceptibility to first line drugs and multidrug resistance in Al-Madinah Al-Munawarah, a seasonally overcrowded are during Hajj and Omrah, is not well studied. OBJECTIVE: This study aimed to investigate anti-TB drug resistance and its distribution among new cases in Al-Madinah Al-Monawarah. METHODS: Study subjects included 622 patients with first time confirmed TB referred to the central tuberculosis laboratory in Al-Madinah between January 2012 and December 2014...
November 15, 2016: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/27847376/relative-prevalence-and-antimicrobial-susceptibility-of-clinical-isolates-of-elizabethkingia-species-based-on-16s-rrna-gene-sequencing
#19
Mi-Soon Han, Hyunsoo Kim, Yangsoon Lee, Myungsook Kim, Nam Su Ku, Jun Yong Choi, Dongeun Yong, Seok Hoon Jeong, Kyungwon Lee, Yunsop Chong
Some of the previously reported clinical isolates of E. meningoseptica could be later named species of Elizabethkingia We determined the accuracy of species identification (with two MALDI-TOF MS and the VITEK 2 GN card), relative prevalence of three Elizabethkingia spp. in clinical specimens, and antimicrobial susceptibility of the species identified by 16S rRNA gene sequencing. Specimens for culture were collected from patients in a university hospital in Korea between 2009 and 2015. All 3 Elizabethkingia spp...
November 9, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27845276/3d-scaffold-with-effective-multidrug-sequential-release-against-bacteria-biofilm
#20
Rafaela García-Alvarez, Isabel Izquierdo-Barba, María Vallet-Regí
Bone infection is a feared complication following surgery or trauma that remains as an extremely difficult disease to deal with. So far, the outcome of therapy could be improved with the design of 3D implants, which combine the merits of osseous regeneration and local multidrug therapy so as to avoid bacterial growth, drug resistance and the feared side effects. Herein, hierarchical 3D multidrug scaffolds based on nanocomposite bioceramic and polyvinyl alcohol (PVA) prepared by rapid prototyping with an external coating of gelatin-glutaraldehyde (Gel-Glu) have been fabricated...
November 11, 2016: Acta Biomaterialia
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