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Multidrug resistant

Anthony J Garcia-Prats, Penelope C Rose, Heather R Draper, James A Seddon, Jennifer Norman, Helen M McIlleron, Anneke C Hesseling, H Simon Schaaf
BACKGROUND: Currently recommended treatment for multidrug-resistant (MDR) tuberculosis (TB) includes 4-8 months of an injectable medication, which is poorly tolerated. We evaluated the impact of co-administering lidocaine on pain and pharmacokinetics of intramuscular injections of amikacin in children with MDR-TB. METHODS: Children 8-18 years of age, receiving amikacin for MDR-TB treatment in Cape Town, South Africa, were eligible for this randomized crossover trial...
March 14, 2018: Pediatric Infectious Disease Journal
Irene Galani, Konstantina Nafplioti, Marianthi Chatzikonstantinou, Maria Souli
PURPOSE: The aim of this study was to evaluate the in vitro activity of double-carbapenem combinations against OXA-48-producing Klebsiella pneumoniae clinical isolates. METHODOLOGY: Double combinations of ertapenem, meropenem and imipenem were evaluated for synergy and bactericidal activity using the time-kill methodology. All antibiotics were tested at 10 mg l-1 and at a sub-inhibitory concentration of 0.5× minimum inhibitory concentration (MIC) for isolates with a carbapenem MIC≤8 mg l-1 ...
March 21, 2018: Journal of Medical Microbiology
Omer Karasahin, Zıya Yildiz, Onur Unal, Umit Arslan
We report a case of infective endocarditis secondary to healthcare-associated bloodstream infection caused by an uncommon etiologic agent, multidrug-resistant Enterobacter cloacae . The patient was treated with a combination of antimicrobial therapy and surgery, but could not be saved. With this case, we discuss the prevalence, risk factors, treatment options, and outcomes of the rarely encountered Enterobacter cloacae -associated infective endocarditis.
2018: IDCases
Li Liu, Mingxing Miao, Yang Chen, Zhongjian Wang, Binbin Sun, Xiaodong Liu
This study investigated alterations in the function and expression of P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) at the blood-brain barrier (BBB) of acute liver failure (ALF) mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl- S -glutathione, respectively...
2018: Frontiers in Pharmacology
Marilia N N Lima, Cleber C Melo-Filho, Gustavo C Cassiano, Bruno J Neves, Vinicius M Alves, Rodolpho C Braga, Pedro V L Cravo, Eugene N Muratov, Juliana Calit, Daniel Y Bargieri, Fabio T M Costa, Carolina H Andrade
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target...
2018: Frontiers in Pharmacology
Chih-Hsun Tai, Chi-Hao Shao, Chen-You Chen, Shu-Wen Lin, Chien-Chih Wu
Background: Treatment options are limited for infections due to multidrug-resistant Gram-positive pathogens. Daptomycin is a lipopeptide antibiotic with concentration-dependent killing characteristic and dose-dependent post-antibiotic effect. To achieve optimized pharma-codynamic effect, some experts advocated using a high dose of daptomycin (≥9 mg/kg) for severe infections. However, the safety of high-dose therapy in patients with renal impairment remains unknown. This study was aimed to evaluate the safety of daptomycin in patients with severe renal impairment...
2018: Therapeutics and Clinical Risk Management
A Gramegna, B C Millar, F Blasi, J S Elborn, D G Downey, J E Moore
INTRODUCTION: Pulmonary exacerbations in people with Cystic Fibrosis (CF), with chronic Gram-negative pathogens, are associated with reduced survival. These pathogens are usually treated with repeated courses of systemic antibiotics. However there is a linked emergence of multidrug resistant (MDR) pathogens. Ceftolozane/tazobactam is a new cephalosporin/beta-lactamase inhibitor combination that has been demonstrated to have good activity against MDR Pseudomonas aeruginosa. MATERIAL & METHODS: In this study ceftolozane/tazobactam was compared to other commonly used intravenous antibiotics against 193 non-fermenting Gram-negative bacteria isolated from CF sputum specimens, including P...
March 17, 2018: Journal of Global Antimicrobial Resistance
João Perdigão, Carla Silva, Jaciara Diniz, Catarina Pereira, Diana Machado, Jorge Ramos, Hugo Silva, Fernanda Abilleira, Clarice Brum, Ana J Reis, Maíra Macedo, João L Scaini, Ana B Silva, Leonardo Esteves, Rita Macedo, Fernando Maltez, Sofia Clemente, Elizabeth Coelho, Sofia Viegas, Paulo Rabna, Amabélia Rodrigues, Nuno Taveira, Luísa Jordao, Afrânio Kritski, José Lapa E Silva, Igor Mokrousov, David Couvin, Nalin Rastogi, Isabel Couto, Arnab Pain, Ruth McNerney, Taane G Clark, Andrea von Groll, Elis R Dalla-Costa, Maria Lúcia Rossetti, Pedro E A da Silva, Miguel Viveiros, Isabel Portugal
Tuberculosis (TB) remains a major health problem within the Community of Portuguese Language Speaking Countries (CPLP). Despite the marked variation in TB incidence across its member-states and continued human migratory flux between countries, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and strain circulation between the countries still exists. To address this, we have assembled and analysed the largest CPLP M. tuberculosis molecular and drug susceptibility dataset, comprised by a total of 1447 clinical isolates, including 423 multidrug-resistant isolates, from five CPLP countries...
March 17, 2018: Infection, Genetics and Evolution
Nebiyu Hiruy, Muluken Melese, Dereje Habte, Degu Jerene, Zewdu Gashu, Genetu Alem, Ilili Jemal, Belay Tessema, Beza Belayneh, Pedro G Suarez
OBJECTIVES: This study compared the yield of TB among contacts of multidrug-resistant tuberculosis (MDR-TB) index cases with that of drug-sensitive TB (DS-TB) index cases in a program setting. METHODS: A comparative cross-sectional study was conducted among contacts of sputum-smear-positive new index DS-TB cases and MDR-TB index cases. After contacts were screened, we used GeneXpert for the diagnosis of TB. RESULTS: The study included 111 MDR-TB and 119 DS-TB index cases...
March 17, 2018: International Journal of Infectious Diseases: IJID
Anne E Robinson, Jeffrey P Henderson, Katherine A Henzler-Wildman
Membrane transporters are an important class of proteins which remain challenging to study. Transport assays are crucial to developing our understanding of such proteins as they allow direct measurement of their transport activity. However, currently available methods for monitoring liposomal loading of organic substrates primarily rely on detection of radioactively or fluorescently labeled substrates. The requirement of a labeled substrate significantly restricts the systems and substrates that can be studied...
March 17, 2018: Analytical Biochemistry
Shouhong Gao, Zhipeng Wang, Xinfang Xie, Chunhua You, Yang Yang, Yanhai Xi, Wansheng Chen
First-line anti-tuberculosis drugs are playing vital roles for curbing rapid spread of tuberculosis. Multidrug therapies are commonly applied in clinical to achieve better treatment outcomes. However, drug resistance and adverse reactions come along with this therapies and therapeutic drug monitoring is a feasible way to precaution them. For this reasons, a simple and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and single protein precipitation was developed and validated for simultaneously quantifying of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin in human plasma...
March 2018: Tuberculosis
Vahid Lohrasbi, Malihe Talebi, Abed Zahedi Bialvaei, Lanfranco Fattorini, Michel Drancourt, Mohsen Heidary, Davood Darban-Sarokhalil
Despite the low expensive and effective four-drug treatment regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) was introduced 40 years ago, TB continues to cause considerable morbidity and mortality worldwide. In 2015, the WHO estimated a total of 10.4 million new tuberculosis (TB) cases worldwide. Currently, the increased number of multidrug-resistant (MDR-TB), extensively-drug resistant (XDR-TB) and in some recent reports, totally drug-resistant TB (TDR-TB) cases raises concerns about this disease...
March 2018: Tuberculosis
Precious Bwalya, Tomoyuki Yamaguchi, Georgina Mulundu, Chie Nakajima, Grace Mbulo, Eddie Samuneti Solo, Yukari Fukushima, Kunda Kasakwa, Yasuhiko Suzuki
Pyrazinamide forms a core part of treatment for all types of tuberculosis (TB) in Zambia. Due to challenges associated with pyrazinamide testing, little information is available to indicate the frequency of resistance to this drug in Zambia. To determine the frequency of pyrazinamide (PZA) resistance and its correlation with mutation in pncA in Mycobacterium tuberculosis isolated from patients in Lusaka, Zambia, BACTEC MGIT M960 was used for phenotypic PZA susceptibility testing while sequencing was used to determine resistance-conferring mutations in the pncA...
March 2018: Tuberculosis
Zhaohui Qiu, Jie Peng, Lingli Mou, Xiao Li, Fanqi Meng, Peng Yu
Multidrug resistance (MDR) of tumors occurs when tumor cells exhibit reduced sensitivity to a large number of unrelated drugs. The molecular mechanism of MDR commonly involves overexpression of the plasma membrane drug efflux pump P-glycoprotein (P-gp). Overexpression of P-gp may be induced by the selection and/or adaptation of cells during exposure to chemotherapeutic drugs, referred to as acquired P-gp-mediated MDR. This study aimed to establish a P-gp quantification method by Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry (UPLC-MS/MS) to better understand the regulation of P-gp expression and its relationship with the level of drug resistance...
March 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
P Petkov, R Marinova, V Kochev, N Ilieva, E Lilkova, L Litov
Antimicrobial peptides (AMPs) play crucial role as mediators of the primary host defence against microbial invasion. They are considered a promising alternative to antibiotics for multidrug resistant bacterial strains. For complete understanding of the antimicrobial defence mechanism, a detailed knowledge of the dynamics of peptide-membrane interactions, including atomistic studies on AMPs geometry and both peptide and membrane structural changes during the whole process is a prerequisite. We aim at clarifying the conformation dynamics of small linear AMPs in solution as a first step of in silico protocol for establishing a correspondence between certain amino-acid sequence motifs, secondary-structure elements, conformational dynamics in solution and the intensity and mode of interaction with the bacterial membrane...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Martin Mielke
Clinically relevant infections are the primary indication for the use of antimicrobial agents in human medicine. Consequently, the prevention of infections is the fundament of all measures to rationally reduce the use of antibiotics. A prevented infection must not be treated. For the prevention of several community-acquired infections, vaccines are available. In addition, several infections may be prevented on the basis of knowledge and responsible behavior. However, the prevention of nosocomial infections depends mainly on the responsibility of third parties in the context of medical procedures...
March 19, 2018: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0...
March 20, 2018: Archives of Toxicology
Vincent Lôme, Jean-Michel Brunel, Jean-Marie Pagès, Jean-Michel Bolla
Antibiotic resistance is now a worldwide therapeutic problem. Since the beginning of anti-infectious treatment bacteria have rapidly shown an incredible ability to develop and transfer resistance mechanisms. In the last decades, the design variation of pioneer bioactive molecules has strongly improved their activity and the pharmaceutical companies partly won the race against the clock. Since the 1980s, the new classes of antibiotics that emerged were mainly directed to Gram-positive bacteria. Thus, we are now facing to multidrug-resistant Gram-negative bacteria, with no therapeutic options to deal with them...
2018: Frontiers in Microbiology
Alessandro Russo, Simone Giuliano, Giancarlo Ceccarelli, Francesco Alessandri, Alessandra Giordano, Grazia Brunetti, Mario Venditti
Objectives: a significant cause of mortality in intensive care unit (ICU) is represented by multidrug-resistant (MDR) gram-negative bacteria, such as MDR Acinetobacter baumannii (MDR-AB) and Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). Aim of the present study was the comparison of clinical features, therapy and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. Methods: were retrospectively analyzed patients admitted to the intensive care unit (ICU) of a teaching hospital, from November 2010 to December 2015, who developed septic shock due to MDR-AB or KPC-Kp infection...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Francesca Forti, Dwayne R Roach, Marco Cafora, Maria E Pasini, David S Horner, Ersilia V Fiscarelli, Martina Rossitto, Lisa Cariani, Federica Briani, Laurent Debarbieux, Daniela Ghisotti
The alarming diffusion of multidrug resistant (MDR) bacterial strains requires investigations on non-antibiotic therapies. Amongst them, the use of bacteriophages (phages) as antimicrobial agents, namely phage therapy, is a promising treatment strategy with support by recent successful compassionate treatments in Europe and the U.S.A. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains of P. aeruginosa , including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance...
March 19, 2018: Antimicrobial Agents and Chemotherapy
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