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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/28416559/a-novel-non-antibiotic-nitroglycerin-based-catheter-lock-solution-for-the-prevention-of-intraluminal-central-venous-catheter-infections-in-cancer-patients
#1
Anne-Marie Chaftari, Ray Hachem, Ariel Szvalb, Mahnaz Taremi, Bruno Granwehr, George Michael Viola, Amin Sapna, Andrew Assaf, Numan Yazan, Pankil Shah, Ketevan Gasitashvili, Elizabeth Natividad, Ying Jiang, Rebecca Slack, Ruth Reitzel, Joel Rosenblatt, Elie Mouhayar, Issam Raad
Background: For long-term central lines (CL), the lumen is the major source of central line associated bloodstream infections (CLABSI). Current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel non-antibiotic catheter lock solution for the prevention of CLABSI.Patients and Methods: Between November 2015, and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheter (PICC) to receive the study lock solution...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416558/in-vitro-discordance-with-in-vivo-activity-humanized-exposures-of-ceftazidime-avibactam-aztreonam-and-tigecycline-alone-and-in-combination-against-new-delhi-metallo-%C3%AE-lactamase-producing-klebsiella-pneumoniae-in-a-murine-lung-infection-model
#2
M L Monogue, L M Abbo, R Rosa, J F Camargo, O Martinez, R A Bonomo, D P Nicolau
The management of infections with New Delhi Metallo-beta-lactamase-1 (NDM) producing bacteria remains clinically challenging given the multi-drug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM+ Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against a MDR K. pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in > 2 log10CFU bacterial reduction, therefore, no in vivo synergy was observed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416557/terbinafine-resistance-of-trichophyton-clinical-isolates-caused-by-specific-point-mutations-in-the-squalene-epoxidase-gene
#3
Tsuyoshi Yamada, Mari Maeda, Mohamed Mahdi Alshahni, Reiko Tanaka, Takashi Yaguchi, Olympia Bontems, Karine Salamin, Marina Fratti, Michel Monod
Terbinafine is one of the allylamine antifungal agents, whose target is squalene epoxidase (SQLE). This agent has been extensively used in the therapy of dermatophyte infections. The incidence of patients with tinea pedis or unguium tolerant to terbinafine treatment prompted us to screen terbinafine resistance of all Trichophyton clinical isolates from the laboratory of Centre Hospitalier Universitaire Vaudois collected over a three-year period, and to identify their mechanism of resistance. Among 2056 tested isolates, 17 (≈ 1%) showed reduced terbinafine susceptibility, all of which were found to harbor SQLE gene alleles with different single point mutations, leading to single amino acid substitutions at one of four positions (Leu(393), Phe(397), Phe(415) and His(440)) of the SQLE protein...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416556/colistin-resistant-mcr-1-positive-escherichia-coli-in-public-beaches-an-infectious-threat-emerging-in-recreational-waters
#4
Miriam R Fernandes, Fábio P Sellera, Fernanda Esposito, Caetano P Sabino, Louise Cerdeira, Nilton Lincopan
The emergence and rapid spread of colistin-resistant Escherichia coli carrying the mcr-1 gene has generated an urgent need to strengthen surveillance. We have performed a meticulous investigation of strains of this sort, resulting in the first identification of international clones of E. coli carrying IncX4 plasmid-mediated mcr-1 and blaCTX-M genes in recreational waters of public urban beaches in cities with high tourist turnover, highlighting a new environmental reservoir.
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416555/mycobacterium-tuberculosis-proteome-response-to-anti-tuberculosis-compounds-reveals-metabolic-escape-pathways-that-prolong-bacterial-survival
#5
Lia Danelishvili, Natalia Shulzhenko, Jessica J J Chinison, Lmar Babrak, Jialu Hu, Andriy Morgun, Gregory Burrows, Luiz E Bermudez
Tuberculosis (TB) continues to be one of the most common bacterial infectious diseases and the leading cause of death in many parts of the world. A major limitation of TB therapy is slow killing of infecting organism, increasing the risk for the development of tolerance phenotype and drug-resistance. Studies indicate that M. tuberculosis (Mtb) takes several days to be killed upon treatment with lethal concentrations of antibiotics both in vitro and in vivo To investigate how metabolic remodeling can enable transient bacterial survival during exposure with bactericidal concentrations of compounds, Mtb H37Rv strain was exposed to twice of the minimal inhibitory concentration of isoniazid, rifampicin, moxifloxacin, mefloquine or bedaquiline for 24h, 48h, 4 days, and 6 days, and the bacterial proteomic response was analyzed using the quantitative shotgun mass spectrometry...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416554/in-vitro-study-of-isapl1-mediated-mobilization-of-the-colistin-resistance-gene-mcr-1
#6
Laurent Poirel, Nicolas Kieffer, Patrice Nordmann
The plasmid-mediated mcr-1 gene encodes a phosphoethanolamine transferase conferring resistance to polymyxins. The mcr-1 gene is associated with insertion sequence ISApl1 (IS30 family). In-vitro mobilization assays demonstrated the functionality of the composite transposon structure ISApl1-mcr-1-ISApl1 Transposition generated a 2-bp duplication and occurred in AT-rich DNA regions. This is the first report demonstrating the mobility of the mcr-1 gene by transposition.
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416553/pharmacokinetics-and-dialytic-clearance-of-ceftazidime-avibactam-in-a-critically-ill-patient-on-continuous-venovenous-hemofiltration
#7
Eric Wenzler, Kristen L Bunnell, Susan C Bleasdale, Scott Benken, Larry H Danziger, Keith A Rodvold
Ceftazidime-avibactam 1.25 g every 8 hours was used to treat multi-drug resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Pre-filter plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 hours along with post-filter and ultrafiltrate concentrations at hours 2 and 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were Cmax 61.10 and 14.54 mg/L, Cmin 31.96 and 8.45 mg/L, t1/2 6...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416552/in-vivo-pharmacodynamic-target-assessment-of-eravacycline-against-escherichia-coli-in-a-murine-thigh-infection-model
#8
Miao Zhao, Alexander J Lepak, Karen Marchillo, Jamie VanHecker, David R Andes
Eravacycline is a novel fluorocycline antibiotic with potent activity against a broad range of pathogens, including strains with tetracycline and other drug-resistance phenotypes. The goal of the studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated with efficacy in the murine thigh infection model. Six E. coli were utilized for the studies. MICs were determined using CLSI methods and ranged from 0.125 to 0.25 mg/L. A neutropenic murine thigh infection model was utilized for all treatment studies...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416551/comparative-pharmacodynamics-of-telavancin-and-vancomycin-in-the-neutropenic-murine-thigh-and-lung-infection-models-against-staphylococcus-aureus
#9
Alexander J Lepak, Miao Zhao, David R Andes
The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four S. aureus strains were included. The telavancin MIC ranged from 0.06 - 0.25 mg/L and vancomycin MIC from 1 - 4 mg/L. Plasma pharmacokinetics of escalating doses (1.25, 5, 20 and 80 mg/kg) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed penetration into the ELF mirrored the percent free fraction (not protein bound) in plasma for each drug...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416550/identification-and-optimization-of-thienopyridine-carboxamides-as-inhibitors-of-hiv-regulatory-complexes
#10
Robert L Nakamura, Mark A Burlingame, Shumin Yang, David C Crosby, Dale J Talbot, Kitty Chui, Alan D Frankel, Adam R Renslo
Viral regulatory complexes perform critical functions during virus replication and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA. These complexes are composed of many proteins and are dynamic, making them difficult to fully recapitulate in vitro Therefore we developed a cell-based reporter assay to monitor the assembly of viral complexes for inhibitor screening. We screened a small molecule library and identified multiple hits that inhibit the activity of the viral complexes...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416549/antiviral-activity-and-resistance-analysis-of-ns3-4a-protease-inhibitor-grazoprevir-and-ns5a-inhibitor-elbasvir-in-hepatitis-c-virus-gt4-replicons
#11
Ernest Asante-Appiah, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Robert Chase, David Nickle, Ping Qiu, Anita Howe, Frederick C Lahser
Although genotype (GT) 4-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents: grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor, in GT4 replicons prior to clinical studies in this genotype...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416548/pharmacokinetics-and-preliminary-safety-of-pod-intravaginal-rings-delivering-the-monoclonal-antibody-vrc01-n-for-hiv-prophylaxis-in-a-macaque-model
#12
Chunxia Zhao, Manjula Gunawardana, Francois Villinger, Marc M Baum, Mariana Remedios-Chan, Thomas R Moench, Larry Zeitlin, Kevin J Whaley, Ognian Bohorov, Thomas J Smith, Deborah J Anderson, John A Moss
The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known HIV-1 isolates in vitro, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other under-developed regions may be limited by the high cost and limited manufacturing capacity of conventionally produced antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01-N over a range of release rates have been developed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416547/simulating-intestinal-transporter-and-enzyme-activity-in-a-physiologically-based-pharmacokinetic-model-for-tenofovir-disoproxil-fumarate
#13
Darren M Moss, P Domanico, M Watkins, S Park, R Randolph, S Wring, J Hobson, S Rannard, M Siccardi, A Owen
Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir, has oral bioavailability (25%) limited by intestinal transport (p-glycoprotein), and intestinal degradation (carboxylesterase).….
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416546/anti-influenza-activity-of-bacillus-subtilis-probiotic-strain
#14
Darya Starosila, Svetlana Rybalko, Ludmila Varbanetz, Naila Ivanskaya, Iryna Sorokulova
Among Bacillus bacteria, B. subtilis is the most productive species of antimicrobial compounds. In this study, we analyzed the activity of probiotic strain B. subtilis 3 against influenza virus. The antiviral effect of this strain has been demonstrated in vitro and in vivo New peptide P18 produced by probiotic strain was isolated, purified, chemically synthesized, and characterized. Cytotoxicity studies demonstrated no toxic effect of P18 on Madin-Darby canine kidney (MDCK) cells, even in the highest tested concentration (100 μg/mL)...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416545/dissemination-of-mcr-1-carrying-plasmids-among-colistin-resistant-salmonella-strains-from-humans-and-food-producing-animals-taiwan
#15
Chien-Shun Chiou, Ying-Tsong Chen, You-Wun Wang, Yen-Yi Liu, Hung-Chih Kuo, Yeuh-Hua Tu, Ann-Chi Lin, Ying-Shu Liao, Yu-Ping Hong
We detected the colistin-resistance gene mcr-1 in four Salmonella serovars isolated from humans and animals with diarrhea. The resistance gene was carried on different plasmids. One mcr-1-carrying conjugative plasmid, a variant of pHNSHP45, was disseminated among Salmonella isolates recovered from humans, pigs, and chickens.
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416544/deciphering-heteroresistance-to-colistin-in-a-klebsiella-pneumoniae-isolate-from-marseille-france
#16
Lucie Bardet, Sophie Baron, Thongpan Leangapichart, Liliane Okdah, Seydina M Diene, Jean-Marc Rolain
Here, we report the description of a colistin-heteroresistant Klebsiella pneumoniae fortuitously isolated from the stool sample of a patient with suspicion of tuberculosis in public hospital of Marseille, France. In the colistin-resistant subpopulation, a mutation in the mgrB gene leading to a premature Stop-codon was found, and the hypermucoviscous phenotype was lost. Susceptibility to other antibiotics remained unchanged. To our knowledge, this is the first identification of such a colistin-heteroresistant Klebsiella pneumoniae isolate in France...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416543/potential-toxicity-of-polymyxins-in-human-lung-epithelial-cells
#17
Maizbha U Ahmed, Tony Velkov, Yu-Wei Lin, Bo Yun, Cameron J Nowell, Fanfan Zhou, Qi Tony Zhou, Kim Chan, Mohammad A K Azad, Jian Li
Inhaled polymyxins are of considerable utility to achieve optimal exposure in the respiratory tract for the treatment of lung infections caused by multidrug-resistant Gram-negative pathogens. Current inhaled polymyxin therapy is empirical and often high doses are used which may lead to potential pulmonary adverse effects. This study aimed to investigate the effect of polymyxins on human lung epithelial cells (A549). Viability of A549 cells was examined after treatment with polymyxins using flow cytometry. Activation of caspase-3, -8, -9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential and mitochondrial oxidative stress induced by polymyxin B was evaluated...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416542/high-resolution-melting-analysis-for-the-rapid-detection-of-sequence-type-131-escherichia-coli
#18
Lucas B Harrison, Nancy D Hanson
IntroductionE. coli belonging to sequence type 131 clonal complex (ST131) have been associated with the global distribution of fluoroquinolone and β-lactam resistance. Whole genome sequencing and multi-locus sequence typing identify sequence type but are expensive when evaluating large numbers of samples. This study was designed to develop a cost-effective screening tool using high resolution melting (HRM) analysis to differentiate ST131 from non-ST-131 E. coli in large sample populations in the absence of sequence analysis...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416541/efflux-attenuates-the-anti-bacterial-activity-of-q203-in-mycobacterium-tuberculosis
#19
Jichan Jang, Ryangyeo Kim, Minjeong Woo, Jinsun Jeong, Da Eun Park, Guehye Kim, Vincent Delorme
New and improved treatments for tuberculosis (TB) are urgently needed. Recently, it has been demonstrated that verapamil, an efflux inhibitor, can reduce bacterial drug tolerance caused by efflux pump activity when administered in combination with available anti-tuberculosis agents. The aim of this study was to evaluate the effectiveness of verapamil in combination with the anti-tuberculosis drug candidate Q203, which has recently been developed and is currently under clinical trials as a potential anti-tuberculosis agent...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416540/in-vivo-efficacy-of-liposomal-amphotericin-b-against-wild-type-and-azole-resistant-aspergillus-fumigatus-isolates-in-two-different-immunosuppressed-models-of-invasive-aspergillosis
#20
Seyedmojtaba Seyedmousavi, Johan W Mouton, Willem J G Melchers, Paul E Verweij
Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported (AAC, 2013, 57, 4, 1866-1871) that the efficacy of liposomal amphotericin B (L-AmB) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus We here investigated the role of immune suppression, i.e. neutropenic and steroid-treated, on L-AmB efficacy in mice infected with a wild type (WT) and azole-resistant Aspergillus fumigatus harboring TR34/L98H mutation in cyp-51A gene.Survival of treated animals at day 14 in both immunosuppressed models was significantly better than that of non-treated controls...
April 17, 2017: Antimicrobial Agents and Chemotherapy
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