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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/28717043/tandem-amplification-of-sccmec-can-drive-high-level-methicillin-resistance-in-mrsa
#1
Laura A Gallagher, Simone Coughlan, Nikki S Black, Pierce Lalor, Elaine M Waters, Bryan Wee, Mick Watson, Tim Downing, J Ross Fitzgerald, Gerard T A Fleming, James P O'Gara
Hospital-associated methicillin-resistant Staphylococcus aureus strains typically express high level, homogenous (HoR) β-lactam resistance, whereas community-associated MRSA (CA-MRSA) more commonly express low level heterogeneous (HeR) resistance. Expression of the HoR phenotype typically requires both increased expression of the mecA gene, carried on the Staphylococcus cassette chromosome SCCmec element, and additional mutational event(s) elsewhere on the chromosome. Here the oxacillin concentration in a chemostat culture of the CA-MRSA strain USA300 was increased from 8 μg/ml to 130 μg/ml over 13 days to isolate highly oxacillin resistant derivatives...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717042/modeling-the-kinetics-of-the-permeation-of-antibacterial-agents-into-growing-bacteria-and-its-interplay-with-efflux
#2
Wright W Nichols
A mathematical model of the passive permeation of a novel solute into bacteria is developed that explicitly accounts for intracellular dilution through growth. A bacterial cell envelope permeability coefficient of >10(-8) cm(2)s(-1) approx., is predicted to ensure passive permeation into rapidly replicating bacterial cells. The relative importance of the permeability coefficients of the cytoplasmic and outer membranes of Gram-negative bacteria in determining the overall envelope permeability coefficient is analyzed quantitatively...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#3
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717040/flucloxacillin-results-in-suboptimal-voriconazole-plasma-concentrations
#4
Eline W Muilwijk, Bart G J Dekkers, Stefanie Henriet, Paul E Verweij, Bregje Witjes, Astrid M L Oude Lashof, Geert H Groeneveld, Johannes van der Hoeven, Jan Willem C Alffenaar, Frans G M Russel, Frank van de Veerdonk, Roger J M Brüggemann
Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and gram-positive infections (e.g. patients with chronic granulomatous disease or post-influenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin resulting in subtherapeutic voriconazole plasma concentrations in more than 50% of patients, posing a severe threat if not managed properly.
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717039/deletion-of-sigb-causes-increased-sensitivity-to-para-aminosalicylic-acid-and-sulfamethoxazole-in-mycobacterium-tuberculosis
#5
Shan-Shan Yang, Yang-Bo Hu, Xu-De Wang, Yun-Rong Gao, Kun Li, Xian-En Zhang, Shi-Yun Chen, Tian-Yu Zhang, Jing Gu, Jiao-Yu Deng
Although the de novo folate biosynthesis pathway has been well studied in bacteria, little is known about its regulation. In this study, the sigB gene in Mycobacterium tuberculosis (M. tb) was deleted. Subsequent drug susceptibility tests revealed that M. tb ΔsigB was more sensitive to para-aminosalicylic acid (PAS) and sulfamethoxazole (SMX). Comparative transcriptional analysis was performed and down-regulation of pabB was observed in the sigB deleted strain, which was further verified by qRT-PCR and Western blot assay...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717038/a-human-biofilm-disrupting-monoclonal-antibody-potentiates-antibiotic-efficacy-in-rodent-models-of-both-staphylococcus-aureus-and-acinetobacter-baumannii-infections
#6
Yan Q Xiong, Angeles Estellés, L Li, W Abdelhady, R Gonzales, Arnold S Bayer, Edgar Tenorio, Anton Leighton, Stefan Ryser, Lawrence M Kauvar
Many serious bacterial infections are antibiotic-refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high affinity human monoclonal antibody against a DNABII epitope conserved across both gram-positive and gram-negative bacterial species. In the current study, the efficacy of TRL1068 for disruption of biofilm was demonstrated in vitro in the absence of antibiotics by scanning electron microscopy...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717037/impact-of-a-carbapenem-antimicrobial-stewardship-program-on-patient-outcomes
#7
Valerie Xue Fen Seah, Rina Yue Ling Ong, Ashley Shi Yuan Lim, Chia Yin Chong, Natalie Woon Hui Tan, Koh Cheng Thoon
Antimicrobial stewardship programs (ASPs) aim to improve appropriate antimicrobials use. However, concerns of the negative consequences from accepting ASP interventions exist, particularly when de-escalation or discontinuation of broad-spectrum antibiotics are recommended. Hence, we sought to evaluate the impact on clinical outcomes when ASP interventions for inappropriate carbapenem use were accepted or rejected by primary providers.We retrospectively reviewed all carbapenem prescriptions deemed inappropriate according to institutional guidelines with ASP interventions between July 2011 and December 2014...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717036/transmission-of-resistant-gram-negative-bacteria-to-healthcare-worker-gowns-and-gloves-during-care-of-nursing-home-residents-in-va-community-living-centers
#8
Natalia Blanco, Lisa Pineles, Alison D Lydecker, J Kristie Johnson, John D Sorkin, Daniel J Morgan, Mary-Claire Roghmann
Objective: To estimate the risk of transmission of antibiotic resistant Gram-negative bacteria (RGNB) to gowns and gloves (G&G) worn by healthcare workers (HCWs) when providing care to nursing home residents and to identify types of care and resident characteristics associated with transmission.Methods: A multi-center, prospective observational study was conducted enrolling residents and HCWs from VA nursing homes. Perianal swabs to detect RGNB were collected from residents. HCWs wore G&G during usual care activities and at the end of the interaction the G&G were swabbed in a standardized manner...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28717035/neurotoxic-concentration-of-piperacillin-during-continuous-infusion-in-critically-ill-patients
#9
Marie-Charlotte Quinton, Sandra Bodeau, Loay Kontar, Yoann Zerbib, Julien Maizel, Michel Slama, Kamel Masmoudi, Anne-Sophie Lemaire-Hurtel, Youssef Bennis
This retrospective cohort study included 53 patients admitted in ICU, of average age 69 years, without neurologic disorder before initiation of piperacillin continuous infusion at standard dose and who underwent piperacillin serum concentration monitoring. Among them, 23 developed neurologic disorder for which the piperacillin causality was chronologically and semiologically suggestive. A concentration threshold of 157.2 mg/L independently predicted neurotoxicity with 96.7% specificity and 52.2% sensitivity and may constitute a limitation when targeting less susceptible pathogens...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696242/metallo-%C3%AE-lactamases-dim-1-ndm-1-vim-2-and-a-16s-rrna-methyltransferase-rmtb4-rmtf2-producing-pseudomonas-aeruginosa-in-nepal
#10
Tatsuya Tada, Kayo Shimada, Kazuhito Satou, Takashi Hirano, Bharat M Pokhrel, Jeevan B Sherchand, Teruo Kirikae
A total of 11 multidrug-resistant Pseudomonas aeruginosa clinical isolates were obtained in Nepal. Four of these isolates harbored genes encoding one or more carbapenemases (DIM-1, NDM-1 and/or VIM-2), and five harbored genes encoding a 16S rRNA methyltransferase (RmtB4 or RmtF2). A novel RmtF variant, RmtF2, had a substitution (K65E) compared with RmtF. To our knowledge, this is the first report describing carbapenemase- and 16S rRNA methyltransferase-co-producing P. aeruginosa clinical isolates in Nepal.
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696241/ethambutol-partitioning-in-tuberculous-pulmonary-lesions-explains-its-clinical-efficacy
#11
Matthew Zimmerman, Jodi Lestner, Brendan Prideaux, Paul O'Brien, Isabela Freedman, Chao Chen, Jillian Dietzold, Isaac Daudelin, Firat Kaya, Landry Blanc, Pei-Yu Chen, Steven Park, Padmini Salgame, Jansy Sarathy, Véronique Dartois
Clinical trials and practice have shown that ethambutol is an important component of the first line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against non-growing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. Here we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into TB lesions. First we utilized novel in vitro lesion pharmacokinetic assays and predicted good penetration of the drug into lesions...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696240/biofilms-formed-by-isolates-from-recurrent-vulvovaginal-candidiasis-patients-are-heterogeneous-and-insensitive-to-fluconazole
#12
Leighann Sherry, Ryan Kean, Emily McKloud, Lindsay E O'Donnell, Rebecca Metcalfe, Brian L Jones, Gordon Ramage
Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC from a patient cohort to identify the causative organisms associated with VVC. Biofilm forming capacity and antifungal sensitivity profiles were also assessed. We report a shifting prevalence of Candida species with heterogeneous biofilm forming capacity, both of which are associated with altered antifungal drug sensitivity.
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696239/the-adverse-effects-and-choice-of-injectable-agents-in-mdr-tb-amikacin-or-capreomycin
#13
Amber Arnold, Graham S Cooke, Onn Min Kon, Martin Dedicoat, Marc Lipman, Angela Loyse, Irina Chis Ster, Thomas S Harrison
Background: The prolonged use of injectable agents in an MDR-TB regimen is recommended by the WHO despite association with ototoxicity and nephrotoxicity.Objective: We undertook this study to look at the relative adverse effects of capreomycin and amikacin.Methods: We reviewed the case notes of 100 consecutive patients treated at 4 MDR-TB treatment centres in the UK.Results: The median total duration of treatment with an injectable agent was 178 (IQR 109-192, n=73) days for those with MDR-TB, 179 (104-192, n=12) days for those with MDR-TB plus fluoroquinolone resistance and 558 (324-735, n=8) days for those with XDR-TB...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696238/the-sterilizing-effect-of-ertapenem-clavulanate-in-a-hollow-fiber-model-of-tuberculosis-and-implications-on-clinical-dosing
#14
Sander P van Rijn, Shashikant Srivastava, Mireille A Wessels, Dick van Soolingen, Jan-Willem C Alffenaar, Tawanda Gumbo
Carbapenems are now being explored for treatment of multi-drug resistant tuberculosis (MDR-TB), especially in conjunction with clavulanate. Clinical use is constrained by the need for multiple parenteral doses per day, and lack of knowledge of the optimal dose for sterilizing effect. Our objective was to identify the ertapenem exposure associated with optimal sterilizing effect and then design a once a day dose for clinical use. We utilized the hollow fiber system model of tuberculosis in a 28-day exposure-response study of 8 different ertapenem doses in combination with clavulanate...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696237/persistent-loss-of-hbv-markers-in-serum-without-cellular-immunity-by-combination-of-peg-ifn-plus-etv-therapy-in-humanized-mice
#15
Takuro Uchida, Michio Imamura, C Nelson Hayes, Nobuhiko Hiraga, Hiromi Kan, Masataka Tsuge, Hiromi Abe-Chayama, Yizhou Zhang, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama
Nucleot(s)ide analogues and peg-interferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long term loss of HBsAg in human hepatocyte chimeric mice...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696236/combination-therapy-with-isavuconazole-and-micafungin-for-treatment-of-experimental-invasive-pulmonary-aspergillosis
#16
Vidmantas Petraitis, Ruta Petraitiene, Matthew W McCarthy, Laura L Kovanda, Myo H Zaw, Kaiser Hussain, Naima Shaikh, Bo Bo W Maung, Navjot K Sekhon, William W Hope, Thomas J Walsh
Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. We hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-D-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole and the echinocandin micafungin, may result in improved outcome in experimental IPA in persistently neutropenic rabbits. Treatment groups included isavuconazole (ISA) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg/day, micafungin at 2 mg/kg/day (MFG2), or combinations of (ISA20+MFG2), (ISA40+MFG2), (ISA60+MFG2), and untreated rabbits (UC)...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696235/evaluation-of-combination-drug-therapy-for-treatment-of-antibiotic-resistant-inhalation-anthrax-in-a-murine-model
#17
H S Heine, S V Shadomy, A E Boyer, L Chuvala, R Riggins, A Kesterson, J Myrick, J Craig, M G Candela, J R Barr, K Hendricks, W A Bower, H Walke, G L Drusano
Bacillus anthracis is considered a likely agent to be used as a bioweapon and use of a strain resistance to the first-line antimicrobial treatments is a concern. We determined treatment efficacy against a ciprofloxacin-resistant (C(r)) strain of B. anthracis (C(r) Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7-35 LD50 of B. anthracis C(r) Ames spores. Commencing at 36 hours (h) post-exposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacinalone (control groups), or ciprofloxacin combined with two antimicrobials including meropenem/linezolid, meropenem/clindamycin, meropenem/rifampin, meropenem/doxycycline, penicillin/linezolid, penicillin/doxycycline, rifampin/linezolid, or rifampin/clindamycin at appropriate dosing intervals(6 or 12 hours) for the respective antibiotics...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696234/role-of-daptomycin-on-wound-healing-in-a-mrsa-burn-infected-animal-model
#18
Oriana Simonetti, Guendalina Lucarini, Fiorenza Orlando, Elisa Pierpaoli, Roberto Ghiselli, Mauro Provinciali, Pamela Castelli, Mario Guerrieri, Roberto Di Primio, Annamaria Offidani, Andrea Giacometti, Oscar Cirioni
Prolonged hospitalization and antibiotic therapy are risk factors for the development of methicillin-resistant S. aureus (MRSA) infections in thermal burn patients. We used a rat model to study the in vivo efficacy of daptomycin in the treatment of burn wound infections by S. aureus and we evaluated the wound healing process through morphological and immunohistochemical analysis. A copper bar heated in boiling water was applied on paraspinal site of each rat resulting in two full thickness burns. A small gauze was placed over each burn and inoculated with 5x10(7) cfu of S...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696233/comparison-of-omadacycline-and-tigecycline-pharmacokinetics-in-the-plasma-epithelial-lining-fluid-and-alveolar-cells-in-healthy-adult-subjects
#19
Mark H Gotfried, Karolyn Horn, Lynne Garrity-Ryan, Stephen Villano, Evan Tzanis, Surya Chitra, Amy Manley, S Ken Tanaka, Keith A Rodvold
The steady-state concentrations of omadacycline and tigecycline in plasma, epithelial lining fluid (ELF), and alveolar cells (AC) concentrations were obtained in 58 healthy adult subjects. Subjects were administered either omadacycline as 100 mg intravenously (IV) every 12 hours for two doses followed by 100 mg IV every 24 hours for three doses or tigecycline as an initial dose of 100 mg IV followed by 50 mg IV every 12 hours for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28696232/community-composition-determines-activity-of-antibiotics-against-multispecies-biofilms
#20
Sarah Tavernier, Aurélie Crabbé, Mayram Tuysuz, Liesbeth Stuer, Silke Henry, Petra Rigole, Inne Dhondt, Tom Coenye
In young cystic fibrosis (CF) patients, Staphylococcus aureus is typically the most prevalent organism, while in adults, Pseudomonas aeruginosa is the major pathogen. More recently, it was observed that also Streptococcus anginosus plays an important role in exacerbations of respiratory symptoms. These species are often co-isolated from CF lungs, yet little is known about whether antibiotic killing of one species is influenced by the presence of others. In the present study, we compared the activity of various antibiotics against S...
July 10, 2017: Antimicrobial Agents and Chemotherapy
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