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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/28533249/the-myxobacterial-metabolite-soraphen-a-inhibits-hiv-1-by-reducing-virus-production-and-altering-virion-composition
#1
Eric Fleta-Soriano, Katarína Smutná, Javier P Martinez, Cristina Lorca Oró, S Kashif Sadiq, Gilles Mirambeau, Carmen Lopez-Iglesias, Marta Bosch, Albert Pol, Mark Brönstrup, Juana Diez, Andreas Meyerhans
Soraphen A is a myxobacterial metabolite that blocks the acetyl-CoA carboxylase of the host, and was previously identified as a novel HIV inhibitor. Here we report that Soraphen A acts by reducing virus production and altering the gp120 virion content, impacting entry capacity and infectivity. These effects are partially reversed by addition of palmitic acid, suggesting inhibition of HIV Env palmitoylation as one of the mechanisms of antiviral action.
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533248/impact-of-hiv-1-integrase-l74f-v75i-mutations-from-a-clinical-isolate-on-resistance-to-second-generation-integrase-strand-transfer-inhibitors
#2
Atsuko Hachiya, Karen A Kirby, Yoko Ido, Urara Shigemi, Masakazu Matsuda, Reiko Okazaki, Junji Imamura, Stefan G Sarafianos, Yoshiyuki Yokomaku, Yasumasa Iwatani
A novel HIV-1 integrase mutation pattern, L74F/V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F/V75I to N155H or G140S/Q148H increased resistance levels to second-generation INSTIs, dolutegravir (>385-, 100-fold, respectively) and cabotegravir (153-, 197-fold, respectively). These findings are important for developing an accurate interpretation system of INSTI resistance and the rational design of next-generation INSTIs...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533247/first-detection-of-a-fosfomycin-resistance-gene-fosa7-in-salmonella-enterica-serovar-heidelberg-isolated-from-broiler-chickens
#3
Muhammad A Rehman, Xianhua Yin, Marissa G Persaud-Lachhman, Moussa S Diarra
We previously described Salmonella Heidelberg harbouring a chromosomal gene cluster similar to the glutathione S-transferase gene, a putative fosA conferring resistance to fosfomycin. Here we show that this new gene named fosA7 confers resistance to fosfomycin. Introduction of fosA7 into fosfomycin susceptible Salmonella Enteritidis, resulted in a substantial increase in the fosfomycin MIC. This finding increases awareness of antibiotic resistance in Salmonella Heidelberg from broiler related to the food safety and public health...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533246/5-aminopyrazole-4-carboxamide-based-compounds-prevent-the-growth-of-cryptosporidium-parvum
#4
Wenlin Huang, Ryan Choi, Matthew A Hulverson, Zhongsheng Zhang, Molly C McCloskey, Deborah A Schaefer, Grant R Whitman, Lynn K Barrett, Rama Subba Rao Vidadala, Michael W Riggs, Dustin J Maly, Wesley C Van Voorhis, Kayode K Ojo, Erkang Fan
Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) is a promising target for drug development against cryptosporidiosis. We report a series of low nanomolar CpCDPK1 5-aminopyrazole-4-carboxamide (AC) scaffold inhibitors that also potently inhibit C. parvum growth in vitro Correlation between anti-CpCDPK1 and C. parvum growth inhibition, as previously reported for pyrazolopyrimidines, was not apparent. Nonetheless, lead AC-compounds exhibited a substantial reduction of parasite burden in the neonatal mouse cryptosporidiosis model when dosed at 25 mg/kg...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533245/clonal-dissemination-of-oxa-232-carbapenenase-producing-klebsiella-pneumoniae-in-neonates
#5
Dandan Yin, Dong Dong, Ke Li, Lei Zhang, Jianliang Liang, Yang Yang, Nana Wu, Yiyan Bao, Chuanqing Wang, Fupin Hu
Five OXA-232 carbapenemase-producing Klebsiella pneumoniae were isolated from neonates, belonging to the pandemic clone ST15, and co-produced blaCTX-M-15 and blaSHV-1 genes. All isolates were resistant to ertapenem (MIC>32μg/mL) and meropenem (4-8μg/mL), susceptible or intermediate to impenem (1-2μg/mL). The blaOXA-232 was located on a ColE-type transformable plasmid of 6,141 bp. To our best knowledge, this is the first report of OXA-232 carbapenemase among clinical isolates in China.
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533244/a-population-pharmacokinetic-model-of-gentamicin-in-paediatric-oncology-patients-to-facilitate-personalised-dosing
#6
C C Llanos-Paez, C E Staatz, R Lawson, S Hennig
To ensure safe and effective dosing of gentamicin in children therapeutic drug monitoring (TDM) is recommended. TDM utilising Bayesian forecasting software is recommended, but is unavailable as no population model exists that describes the pharmacokinetics of gentamicin in paediatric oncology patients. This study aimed to develop and externally evaluate a population pharmacokinetic model of gentamicin to support personalised dosing in paediatric oncology patients. A non-linear mixed effect population pharmacokinetic model was developed from retrospective data...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533243/roles-of-ramr-and-tet-a-mutations-in-conferring-tigecycline-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-clinical-isolates
#7
Sheng-Kang Chiu, Li-Yueh Huang, Hsi Chen, Yu-Kuo Tsai, Ci-Hong Liou, Jung-Chung Lin, L Kristopher Siu, Feng-Yee Chang, Kuo-Ming Yeh
Tigecycline is regarded as a last-resort treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, but increasing numbers of tigecycline-resistant K. pneumoniae isolates have been reported. Tigecycline resistance mechanisms are underdetermined in CRKP. This study aimed to elucidate mechanisms underlying tigecycline resistance in 16 tigecycline- and carbapenem-resistant K. pneumoniae (TCRKP) isolates. Mutations in tigecycline resistance determinant genes (ramR, acrR, oqxR, tet(A), tet(L), tet(X), tet(M), rpsJ) were assessed by PCR amplicon sequencing, and mutations in ramR and tet(A) exhibited high prevalences individually (81%) and in combination (63%)...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533242/coadministration-of-liposomal-amphotericin-b-and-contrast-medium-does-not-increase-risk-of-kidney-injury
#8
John C O'Horo, Douglas R Osmon, Omar M Abu Saleh, Jasmine R Marcelin, Kamel A Gharaibeh, Abdurrahman M Hamadah, Amelia K Barwise, Bryce M Kayhart, Jennifer S McDonald, Robert J McDonald, Nelson Leung
Intravenous radiographic contrast medium and amphotericin B are commonly required in the care of patients with fungal infections. Both interventions have proposed nephrotoxicity through similar mechanisms. We systematically examined patients who received coadministration of liposomal amphotericin B (AmBisome; GE Healthcare) and intravenous contrast medium within a 24-hour period and compared them with patients who underwent non--contrast medium studies. We found 114 cases and 85 controls in our study period...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533241/arr-cb-a-rifampin-resistance-determinant-found-active-or-cryptic-in-clostridium-bolteae
#9
Jean-Christophe Marvaud, Thierry Lambert
Clostridium bolteae, which belongs to the Clostridium clostridioforme complex is a member of the human gut microbiota. Recent analysis of seven genomes of C. bolteae revealed the presence of an arr-like gene. Among these strains only 90A7 was found to be resistant to rifampin in the absence of alteration in RpoB. Cloning of arr-cb from 90A7 in Escherichia coli combined with directed mutagenesis demonstrated that Arr-cb is functional but that a Q127→R variant present in 90A9 and 90B3 was inactive. qRT-PCR analysis indicated that arr-cb was silent in the four remaining strains due to a defective transcription...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533240/heterocycle-thiazole-compounds-exhibit-antifungal-activity-through-increase-in-the-production-of-reactive-oxygen-species-in-cryptococcus-neoformans-cryptococcus-gattii-species-complex
#10
Nívea Pereira de Sá, Caroline Miranda de Lima, Cleudiomar Inácio Lino, Paulo Jorge Sanches Barbeira, Ludmila de Matos Baltazar, Daniel Assis Santos, Renata Barbosa de Oliveira, Eleftherios Mylonakis, Beth Burgwyn Fuchs, Susana Johann
Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, sub-acute, or chronic systemic infection, involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazoles 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533239/plasmodium-falciparum-and-p-vivax-demonstrate-contrasting-chloroquine-resistance-reversal-phenotypes
#11
Grennady Wirjanata, Irene Handayuni, Pak Prayoga, Leo Leonardo, Dwi Apriyanti, Leily Trianty, Ruland Wandosa, Basbak Gobay, Enny Kenangalem, Jeanne Rini Poespoprodjo, Rintis Noviyanti, Dennis E Kyle, Qin Cheng, Ric N Price, Jutta Marfurt
High-grade chloroquine (CQ) resistance has emerged in both P. falciparum and P. vivax The aim of the present study was to investigate phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility.Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 P. falciparum and 34 P. vivax clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533238/posaconazole-induced-hypertension-and-hypokalemia-in-vivo-11%C3%AE-hydroxysteroid-dehydrogenase-inhibition
#12
George R Thompson, Diana Chang, Rebecca R Wittenberg, Ian McHardy, Alison Semrad
We describe a case of apparent mineralocorticoid excess (AME) secondary to posaconazole and suggest the biochemical mechanism. Clinical and laboratory investigation confirmed 11β-hydroxysteroid dehydrogenase inhibition and withholding therapy led to a resolution of all clinical and laboratory abnormalities. A lower dose of posaconazole was later restarted and avoided recurrence of this syndrome. Additional studies are necessary to determine the frequency of posaconazole induced AME and whether other azole antifungals can be associated with this phenomenon...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533237/antimicrobial-resistance-risks-of-cholera-prophylaxis-for-united-nations-peacekeepers
#13
Amber Kunkel, Joseph A Lewnard, Virginia E Pitzer, Ted Cohen
More than five years after a United Nations peacekeeping battalion introduced cholera to Haiti, over 150,000 peacekeepers continue to be deployed annually from cholera endemic countries. The United Nations has thus far declined to provide antimicrobial chemoprophylaxis to peacekeepers, a policy based largely on concerns that the risks of drug resistance generation and spread would outweigh the potential benefits of preventing future cholera importations. In this study, we sought to better understand the relative benefits and risks of cholera chemoprophylaxis for peacekeepers in terms of antibiotic resistance...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533236/antibacterial-and-antibiofilm-activities-of-a-novel-synthetic-cyclic-lipopeptide-against-cariogenic-streptococcus-mutans-ua159
#14
Kyung R Min, Adriana Galvis, Brandon Williams, Ramanjaneyulu Rayala, Predrag Cudic, Dragana Ajdic
Despite continuous efforts to control cariogenic dental biofilms, very few effective antimicrobial treatments exist. In this study, we characterized the activity of a novel synthetic cyclic lipopeptide 4 (CLP-4), derived from fusaricidin, against the cariogenic pathogen Streptococcus mutans UA159. We determined CLP-4's minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), spontaneous resistance frequency, and we performed time-kill assays. Additionally, we assessed CLP-4's potential to inhibit biofilm formation (MBIC) and eradicate pre-formed biofilms (MBEC)...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533235/the-tet39-determinant-and-the-msre-mphe-genes-in-acinetobacter-plasmids-are-each-part-of-discrete-modules-flanked-by-inversely-oriented-pdif-xerc-xerd-sites
#15
Grace A Blackwell, Ruth M Hall
The tet39 tetracycline resistance determinant and the macrolide resistance genes msrE and mphE were found in an 18.2 kb plasmid, pS30-1, recovered from a GC2 Acinetobacter baumannii isolate from Singapore, that conferred resistance to tetracycline and erythromycin. pS30-1 also contains mobA and mobC genes encoding MOBQ family proteins but attempts to mobilise pS30-1 utilising a co-resident conjugative repAci6 plasmid were unsuccessful. Eight pdif sites, consisting of inversely-oriented binding sites for the XerC and XerD recombinases separated by 6 bp, were detected in pS30-1...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533234/differential-activity-of-the-oral-glucan-synthase-inhibitor-scy-078-against-wild-type-and-echinocandin-resistant-strains-of-candida-spp
#16
Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Mariana Castanheira
SCY-078 (formerly MK-3118) is a novel orally active inhibitor of fungal β- (1, 3)-glucan synthase (GS). SCY-078 is a derivative of enfumafungin and is structurally distinct from the echinocandin class of antifungal agents. We evaluated the in vitro activity of this compound against wild-type (WT) and echinocandin-resistant isolates containing mutations in the FKS genes of Candida spp. Against 36 Candida spp. FKS mutants tested, 30 (83.3%) were non-WT to 1 or more echinocandins and only 9 (25.0%) were non-WT (MIC, >WT-upper limit) to SCY-078...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533233/epidemic-emergence-in-the-united-states-of-escherichia-coli-sequence-type-131-h30-2000-2009
#17
James R Johnson, Stephen Porter, Paul Thuras, Mariana Castanheira
The H30 subclone of Escherichia coli sequence type 131 (ST131) has become the leading antimicrobial-resistance E. coli lineage in the U.S., and often exhibits resistance to one or both of two key antimicrobial classes for treating Gram-negative infections, extended-spectrum cephalosporins (ESCs) and fluoroquinolones (FQs). However, the timing of and reasons for its recent emergence are inadequately defined. Accordingly, from E. coli clinical isolates collected systematically across the U.S. by the SENTRY Antimicrobial Surveillance Programs in 2000, 2003, 2006, and 2009, 234 isolates were selected randomly, stratified by year, within three resistance categories: (i) ESC-reduced susceptibility, regardless of FQ phenotype (hereafter, ESC-RS), (ii) FQ-resistant, ESC-susceptible (hereafter, FQ-R), and (iii) FQ-susceptible, ESC-susceptible (hereafter, FQ-S)...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533232/potentiation-of-antibiotic-activity-by-a-novel-cationic-peptide-potency-and-spectrum-of-activity-of-spr741
#18
David Corbett, Andrew Wise, Tara Langley, Kirsty Skinner, Emily Trimby, Stephen Birchall, Alain Dorali, Stephanie Sandiford, Jennifer Williams, Peter Warn, Martti Vaara, Troy Lister
Novel approaches to the treatment of multi-drug resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacy of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii Of 35 antibiotics tested, the MICs of eight were reduced 32- to 8,000-fold against E...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28507118/colistin-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-mediated-by-chromosomal-integration-of-plasmid-dna
#19
Astrid V Cienfuegos-Gallet, Liang Chen, Barry N Kreiswirth, J Natalia Jiménez
Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant-K. pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB Nineteen isolates belonged to ST512 (or its SLV) and harbored a novel 8.1-Kb hsdMSR insertion, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting the colistin resistance is mediated by chromosomal integration of plasmid DNA...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28507117/pharmacokinetics-of-levofloxacin-in-multidrug-and-extensively-drug-resistant-tuberculosis-patients
#20
Natasha Van't Boveneind-Vrubleuskaya, Tatiana Seuruk, Kai van Hateren, Tridia van der Laan, Jos G W Kosterink, Tjip S van der Werf, Dick van Soolingen, Susan van den Hof, Alena Skrahina, Jan-Willem C Alffenaar
Pharmacodynamics are important in treatment of especially multidrug- and extensively resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to minimal inhibitory concentration (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter to predict the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of treatment regimen at a dose of 15 mg/kg once daily...
May 15, 2017: Antimicrobial Agents and Chemotherapy
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