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    29010 results match your criteria Antimicrobial agents and chemotherapy[Journal]

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    Novel zinc attenuating compounds as potent broad spectrum antifungal agents withandefficacy.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Pcovery, Ole Maaløes vej 3, 2200 Copenhagen N, Denmark
    An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here, we report the identification and characterization of two novel zinc-attenuating compounds ZAC307 and ZAC989, which exhibit broad-spectrumantifungal activity andefficacy in a fungal kidney burden candidiasis model.The compounds were identified serendipitously as part of a drug discovery process aimed at finding novel inhibitors of the fungal plasma membrane proton ATPase, Pma1. Read More

    Prediction model for anti-malarial activities of hemozoin inhibitors using physicochemical properties.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
    The rapid spread of strains of malaria parasites resistant to several drugs has threatened global malaria control. Hence, the aim of this study was to predict the anti-malarial activity of chemical compounds possessing anti-hemozoin formation activity as a new means of anti-malarial drug discovery. After the initialanti-hemozoin formation high-throughput screening (HTS) of 9,600 compounds, a total of 224 hit compounds were identified as hemozoin inhibitors. Read More

    The Pharmacokinetics of 2000 mg Ertapenem in Tuberculosis Patients.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
    Ertapenem is a carbapenem antibiotic with activity againstDose simulations in a hollow fiber infection model showed that 2000 mg once daily is an appropriate dose to be tested in clinical studies. Before using this dose in a phase II study, the aim of this prospective pharmacokinetic study is to confirm the pharmacokinetics of 2000 mg once daily in TB patients. Twelve TB patients received a single intravenous dose of 2000 mg ertapenem as 30-min infusion. Read More

    Inactivation of Plasmepsin 2 and 3 sensitizesto the antimalarial drug piperaquine.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Centre de recherche en infectiologie du CHU de Québec-Université Laval, Québec City, Québec, Canada
    Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treatmalaria in multiple Southeast Asian countries is now increasingly failing in Cambodia where artemisinin resistance is nearly fixed which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification ofis a molecular marker of PPQ resistance however whether these enzymes play a role in the mechanism of resistance is currently unknown. We here show that inactivatingorindividually in the 3D7reference strain results in hyper-susceptibility to PPQ. Read More

    The coexistence of twogenes on an IncF plasmid as revealed by nanopore sequencing.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
    In a carbapenem-resistantclinical isolate of sequence type 167, two copies ofwere found on a 144,225-bp IncF self-transmissible plasmid of the F36:A4:B- type. Bothgenes were located in 11,065-bp regions flanked by two copies of ISThe two regions were identical in sequence but were present at different locations on the plasmid, suggesting a duplication of the same region. This study highlights the complex genetic contexts of. Read More

    pSTM6-275, a conjugative IncHI2 plasmid ofthat confers antibiotic and heavy metal resistance under changing physiological conditions.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Veterinary Biosciences, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
    Detailed annotation of an IncHI2 plasmid, pSTM6-275, fromserotype,4,5,12:i:- TW-Stm6 revealed a composite structure including antimicrobial resistance genes on mobile genetic elements. The plasmid was thermosensitive for transfer toand conferred reduced susceptibility to antibiotics, copper sulphate and silver nitrate. Metal ion susceptibility was dependent on physiological conditions, giving an insight into the environments where this trait might confer a fitness advantage. Read More

    Efficacy of systemically administered polymyxins in mouse burn wound infection caused by multidrug-resistant Gram-negative pathogens: A proof-of-concept study.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.
    The efficacy of subcutaneously administered polymyxins against burn wound infections caused by,, andwas examined in a murine infection model. Subcutaneously administered colistin and polymyxin B achieved a >2-logreduction in the bacterial load forandinfections, while wound infections bywere less responsive (<1-logreduction). This study highlights the potential therapeutic benefits of parenteral polymyxins for treating burn wound infections. Read More

    A Phase 1 Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Oral Doses of DS-2969b, a Novel GyrB Inhibitor.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Daiichi Sankyo Pharma Development, Basking Ridge NJ, USA.
    DS-2969b is a novel GyrB inhibitor in development for the treatment ofinfection (CDI). The aim of this study was to assess the safety, tolerability, pharmacokinetics, and effects on normal gastrointestinal microbiota of multiple daily oral ascending doses of DS-2969b in healthy subjects. The study enrolled three sequential ascending dose cohorts (60 mg, 200 mg, and 400 mg). Read More

    Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, Ohio United States of America
    Ceftazidime-avibactam is a "second generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carbapenemases and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Read More

    Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    From Gilead Sciences, Inc., Foster City, California, USA
    Sofosbuvir and ribavirin exert their anti-hepatitis C virus (HCV) activity following metabolic activation in the liver. However, intrahepatic concentrations of the pharmacologically active nucleotide metabolites in humans are poorly characterized due to the inaccessibility of tissue and technical challenges with measuring nucleotide levels. A clinical study assessing the efficacy of sofosbuvir and ribavirin administered prior to liver transplant to prevent HCV reoccurrence provided a unique opportunity to quantify nucleotide concentrations in human liver. Read More

    assessment of antifungal drugs and sulfamethoxazole/trimethoprim against clinical isolates of.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria (UFSM), RS, Brazil
    Conidiobolomycosis is an infection for which there are no sufficient clinical ordata to support a consensus about the optimal treatment and, consequently, cases of therapeutic success and failure have been described for all forms of therapy (1-3).…. Read More

    Omadacycline: comparativeactivity against dog and cat bite wound isolates.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    From The R. M. Alden Research Lab, Culver City, CA.
    Omadacycline was tested against 125 isolates recovered from infected cat and dog bites in humans. Its activity was similar to other compounds in the tetracycline class and was active against strains exhibiting tetracycline resistance. Against anaerobic isolates, resistance to tetracyclines was more prominent, and omadacycline was the most active of the group. Read More

    Targeting the nonmevalonate pathway inincreases susceptibility to certain β-lactam antibiotics.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium
    The non-mevalonate pathway is the sole pathway for isoprenoid biosynthesis inand possibly a novel target for the development of antibacterial chemotherapy. The goal of the present study was to evaluate the essentiality of, the second gene of the non-mevalonate pathway, inand to determine whether interfering with the non-mevalonate increases susceptibility towards antibiotics. To this end, a rhamnose-inducible conditionalknock-down mutant ofK56-2 (K56-2) was constructed, by using a plasmid which enables the delivery of a rhamnose-inducible promotor in the chromosome. Read More

    Pharmacodynamics of Voriconazole for Invasive Pulmonary Scedosporiosis.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool
    is a medically important fungal pathogen that causes a wide range of infections in humans. There are relatively few antifungal agents that are active againstspp. Little is known about the pharmacodynamics of voriconazole againstBoth static and dynamicmodels of invasive scedosporiosis were developed. Read More

    andEfficacy of a Novel and Long Acting Fungicidal Azole, PC1244 onInfection.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Pulmocide Ltd, London, UK.
    The antifungal effects of the novel triazole, PC1244, designed for topical or inhaled administration, againsthave been tested in a range ofandstudies. PC1244 demonstrated potent antifungal activities against clinicalisolates (N=96) with a MIC range of 0.016--0. Read More

    A next-generation sequencing and bioinformatics protocol for Malaria drug Resistance marker Surveillance (MaRS).
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States of America.
    The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug resistant parasites. To take advantage of this technology an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance incalledlariaesistanceurveillance (MaRS), was developed. TADS relies on PCR enriching genomic regions, specifically target genes of interest, prior to deep sequencing. Read More

    Determinants of extreme ß-lactam tolerance in thecomplex.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Department of Genome Sciences, University of Washington, Seattle, WA, USA
    Slow-growing bacteria are insensitive to killing by antibiotics, a trait known as antibiotic tolerance. In this study, we characterized the genetic basis of an unusually robust ß-lactam (meropenem) tolerance seen inspecies. We identified tolerance genes under three different slow-growth conditions by extensive transposon mutant screening (Tn-seq) followed by single mutant validation. Read More

    Susceptibility of clinical isolates ofto metronidazole and secnidazole-anstudy.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham
    Nitroimidazoles (metronidazole [MTZ] and tinidazole [TNZ]) are the only drugs recommended for treating(TV) infection. MTZ resistance occurs in 4%-10% of cases of vaginal trichomoniasis (1, 2), and TNZ resistance in 1% of patients (2). Emerging nitroimidazole-resistant trichomoniasis is concerning because few alternatives to standard therapy exist. Read More

    andactivities of DS-2969b, a novel GyrB inhibitor, against.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Department of Microbiology, and Department of Medicinal Chemistry, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India, Daiichi Sankyo Co., Ltd., Tokyo, Japan
    DS-2969b is a novel GyrB inhibitor, which is currently under clinical development for treatment ofinfection (CDI). In this study, theandactivities of DS-2969b were evaluated. DS-2969b inhibited the supercoiling activity ofDNA gyrase. Read More

    The In Vitro Activity of Omadacycline and Comparators Against Anaerobic Bacteria.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Micromyx, Inc. 4717 Campus Drive, Kalamazoo, MI 49008.
    Omadacycline (OMC), a broad-spectrum aminomethylcycline, has shown clinical efficacy in anaerobic acute bacterial skin and skin structure infections (ABSSSI) and in animal models of intra-abdominal anaerobic infections. Here, the in vitro activity of OMC against clinically-relevant anaerobes was similar to tigecycline, with MICvalues of 1 to 8 μg/mL againstspp, 0.5 μg/mL against,spp. Read More

    Anidulafungin pharmacokinetics in ascites and pleural effusion of critically ill patients.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Anidulafungin concentrations were quantified with high pressure liquid chromatography (HPLC) and UV detection in ascites and in pleural effusion of ten adult critically ill patients. Samples were collected from ascites and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulafungin levels in ascites (0. Read More

    activity of lascufloxacin againstwith mutations in the quinolone resistance-determining regions (QRDRs).
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
    Lascufloxacin showed potent activity againstwith GyrA or ParC mutation (first-step mutants). The frequency of selecting resistant strains tended to be lower for lascufloxacin than levofloxacin and garenoxacin after drug exposure in first-step mutants, but was similar in the comparison between lascufloxacin and moxifloxacin. The increase in MIC was smaller for lascufloxacin than for levofloxacin, garenoxacin, and moxifloxacin when clinical strains with only ParC mutation were exposed to the corresponding drug. Read More

    Interaction between TLR9-CpG-ODNs and HBV virions leads to entry inhibition in hepatocytes and reduction of IFNα production by pDC.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    INSERM, U1052, CNRS, UMR_5286, Cancer Research Center of Lyon (CRCL), Lyon, France
    We previously reported that TLR9 CpG-oligonucleotides could inhibit the establishment of HBV infections in hepatocytes. Our aim was to uncover the underlying mechanisms of this inhibition. HepaRG, RPMI-B lymphoblastoma and primary plasmacytoid dendritic cells exposed to HBV and TLR9 ligands/agonists in various configurations were used. Read More

    High rate of association of 16S rRNA methylases and carbapenemases in Enterobacteriaceae recovered from hospitalized children, Angola.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, INSERM European Unit (IAME, France), University of Fribourg, Switzerland.
    Acquired 16S rRNA methylases (RMTase) conferring pandrug resistance to aminoglycosides were searched among enterobacterial isolates recovered in Angola. A total of 36 hospitalized children were screened for rectal colonization using the SuperAminoglycoside medium selective. Twenty-two pan-aminoglycoside-resistant enterobacterial isolates were recovered, all of them producing RMTases, namely RmtB, ArmA, and RmtC. Read More

    Species identification and-antifungal susceptibility ofspecies complex clinical isolates: a French multicentre study.
    Antimicrob Agents Chemother 2018 Feb 12. Epub 2018 Feb 12.
    EA Dynamyc 7380 UPEC, ENVA, Faculté de Médecine de Créteil, Créteil, France
    Background: sectionis a species complex currently comprising 14 cryptic species of whose prevalence in clinical samples as well as antifungal susceptibility are poorly known.

    Objectives: The aims were to investigateclinical isolates at the species level and to perform antifungal susceptibility by reference and commercial methods.

    Methods: Eighty-two clinicalisolates were collected from 8 French university hospitals. Read More

    High genetic plasticity in multidrug resistant ST3-IncHI2 plasmids revealed by sequence comparison and phylogenetic analysis.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.
    We report a novel fusion plasmid pP2-3T co-integrating ST3-IncHI2 with IncFII plasmid backbone mediating multidrug resistance and virulence. Phylogenetic analysis and comparative genomic revealed that pP2-3T and other MDR ST3-IncHI2 plasmids clustered together representing a unique IncHI2 lineage that exhibited high conservation in backbones of plasmid, but possessed highly genetic plasticity in variable regions via acquiring numerous ARGs and fusing with other plasmids. Surveillance studies should be taken to monitor multiresistance IncHI2 plasmids among Enterobacteriaceae. Read More

    Time to Multidrug-Resistant Tuberculosis Treatment Initiation in Association with Treatment Outcomes in Shanghai, China.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Road, Shanghai, China
    In high TB-burden countries like China, the diagnosis of multidrug-resistant tuberculosis (MDR-TB) using conventional drug susceptibility testing (DST) takes months, making treatment delay inevitable. Poor outcomes of MDR-TB might be associated with delayed, even inappropriate treatment. The purpose of this study was to investigate the time to MDR-TB treatment initiation, and to assess the association between early treatment and treatment outcomes. Read More

    Short proline-rich lipopeptide potentiates minocycline and rifampicin against multidrug- and extensively drug-resistant.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada
    A series of 16 short proline-rich lipopeptides (SPRLPs) were constructed to mimic longer naturally-existing proline-rich antimicrobial peptides. Antibacterial assessment revealed that lipopeptides containing hexadecanoic acid (C16) possess optimal antibacterial activity relative to others with shorter lipid component. SPRLPs were further evaluated for their potential to serve as adjuvants in combination with existing antibiotics to enhance antibacterial activity against drug-resistantOut of sixteen prepared SPRLPs, C12-PRP was found to significantly potentiate the antibiotics minocycline and rifampicin against multidrug- and extensively drug-resistant (MDR/XDR)clinical isolates. Read More

    Establishment and validation ofas a novel model organism to studyinfection, pathogenesis and treatment.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
    : Treatment ofinfections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited due to a lack of a practicalmodel of infection.: To establish a simplemodel forinfection, virulence, and drug testing inlarvae.: We inoculated larvae with, and followed histopathology, CFU count and mortality with and without antibiotic treatment. Read More

    Identification of Anti-Lead Compounds with Putative Immunomodulatory Activity.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil
    In substitution for the current Chagas disease treatment with several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, the balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, where a pro-inflammatory microenvironment modulated by IL-10 is shown to be relevant to potentiate anti-drug activity. This study aimed to identify the potential immunomodulatory activity of the anti-K777, Pyronaridine (PYR) and Furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected subjects (NI) and chronic Chagas disease patients (CD). Read More

    Prophylactic anti-heparanase activity by PG545 is anti-viraland protects against Ross River virus disease in mice.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia
    Recently we reported on the efficacy of pentosan polysulfate (PPS), a heparan sulfate mimetic, to reduce the recruitment of inflammatory infiltrates and protect the cartilage matrix from degradation in Ross River virus (RRV) infected PPS--treated mice. Herein, we describe both prophylactic and therapeutic treatment with PG545, a low molecular weight heparan sulfate mimetic, for arthritogenic alphaviral infection. We first assessed anti-viral activity, through a 50% plaque reduction (IC) assay. Read More

    Drug susceptibility profiling and genetic determinants of drug resistance in.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland
    Studies on drug susceptibility ofare very few and involve limited number of strains. The purpose of this study was to determine drug susceptibility profiles ofisolates representing a spectrum of species genotypes (subtypes) with two different methodologies, i.e. Read More

    Compounds with potential activity against.
    Antimicrob Agents Chemother 2018 02 5. Epub 2018 Feb 5.
    Barcelona Biomedical Research Park, Centre for Genomic Regulation, Biomolecular Screening & Protein Technologies Unit, 88 Dr.aiguider, 08003 Barcelona, Spain
    The high acquisition of drug resistance bynecessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high throughput screening of compounds against thiol-deficientstrains and subsequent validations with thiol-deficientstrains, revealed that Δand Δmutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su), Δand Δmutants had increased susceptibility to bacitracin (Ba) and Δ, Δ, and Δmutants had increased susceptibility to fusaric acid (Fu). Read More

    Penetration of cefotaxime into cerebrospinal fluid in neonates and young infants.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China
    : Cefotaxime is the first-line treatment for meningitis in neonates and young infants. However, limited data on cefotaxime cerebrospinal fluid (CSF) concentrations in neonates and young infants were available. The aim of the present study is to evaluate the penetration of cefotaxime into CSF in neonates and young infants. Read More

    Posaconazole MIC distributions forSC by four methods: Impact ofmutations on estimation of epidemiological cutoff values (ECVs/ECOFFs).
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
    Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and non-mutant strains (harboring or not harboring mutations, respectively). Posaconazole MIC distributions forSC were collected from 26 laboratories (Australia, Canada, Europe, India, South/North America, Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. Read More

    Development of echinocandin resistance infollowing short-term exposure to caspofungin for empiric therapy.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Mycology Reference Laboratory, Mubarak Al-Kabeer Hospital, Kuwait.
    Isolation of two echinocandin-resistantstrains from endotracheal secretions of a patient, following short-term exposure to caspofungin, is described. Both strains exhibited resistance to echinocandins by Etest and reference broth microdilution, showing a homozygous S645P mutation within hot-spot (HS)-1 region ofand belonging to a unique multilocus sequence type. Otherisolates collected from the same intensive care unit patients within a 60-day-period were susceptible to echinocandins and contained wild-typesequences. Read More

    transfer and microevolution of avian native IncA/C-carrying plasmid pRH-1238 during a broiler chicken infection study.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    German Federal Institute for Risk Assessment (BfR), Department for Biological Safety, Berlin, Germany
    The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE) in wildlife and livestock animals poses an important safety concern for public health. With ourbroiler chicken infection study we investigated transfer and experimental microevolution of the-carrying IncA/Cplasmid (pRH-1238) introduced by avian native() Corvallis, without inducing antibiotic selection pressure. We evaluated dependency of the time point of inoculation on donor [Corvallis (12-SA01738)] and a plasmid-freespp. Read More

    Pharmacokinetics and safety of intravenous Murepavadin infusion in healthy adult subjects administered as Single and Multiple ascending doses.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    POLYPHOR Ltd, Allschwil, Switzerland.
    Murepavadin is the first in class of Outer Membrane Protein Targeting Antibiotics (OMPTA) which is a pathogen specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targetingMurepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A was a double-blind, randomized, placebo-controlled, single ascending dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin and 2 subjects were randomized to placebo. Read More

    Antifungal susceptibility of thecomplex: comparison of twomethods.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic.
    Cryptic species ofincluding thespecies complex, are increasingly reported as a cause of invasive aspergillosis. Their identification is clinically relevant as these species frequently have intrinsic resistance to common antifungals. We evaluated susceptibilities of 90 environmental and clinical isolates from thespecies complex, identified by DNA sequencing of the calmodulin gene, to seven antifungals (voriconazole, posaconazole, itraconazole, amphotericin B, anidulafungin, micafungin and caspofungin) using the reference European Committee on Antimicrobial Susceptibility testing (EUCAST) method. Read More

    Synergy between pyrvinium pamoate and azoles against.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Dermatology, Zhongshan Hospital Fudan University, Shanghai,200032, China.
    The black yeastcauses phaeohyphomycosis in both immunocompetent individuals and immunosuppressed patients, resulting in localized cutaneous and subcutaneous infections to more severe systemic forms such as neurotropic infections (1-3).…. Read More

    andActivity of DS86760016, a Novel Leucyl-tRNA Synthetase Inhibitor for Gram-Negative Pathogens.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Microbiology, and Department of Pharmacokinetics and Metabolism, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India
    The emergence of multidrug-resistant (MDR) Gram-negative bacilli is a major concern in the treatment of nosocomial infections. Antibacterial agents with novel modes of action can be useful as these pathogens have become resistant to almost all existing standard-of-care agents. GSK2251052, a leucyl-tRNA synthetase inhibitor, has a novel mode of action against Gram-negative bacteria. Read More

    Safety of Anti-Staphylococcal Penicillins versus Cefazolin: A Systematic Review and Meta-Analysis.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ.
    Recent studies and experience suggest that cefazolin might be as equally effective as anti-staphylococcal penicillins for methicillin-susceptible(MSSA) with a better safety profile and lower cost. The objective of these meta-analyses was to compare the safety of anti-staphylococcal penicillins and cefazolin. PubMed, EMBASE, International Pharmaceutical Abstracts databases and websites for clinical trial registries through June 23, 2017 were searched. Read More

    A Novel Rabbit Spirometry Model of Type E Botulism and its Use for the Evaluation of Post-symptom Antitoxin Efficacy.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel
    Botulinum neurotoxins (BoNTs), the most poisonous substances known in nature, pose significant concern to health authorities. The only approved therapeutic for botulism is antitoxin. While administered to patients only after symptom onset, antitoxin efficacy is evaluated in animals mostly in relation to time post-intoxication regardless of symptoms. Read More

    The Novel Fungal Cyp51 Inhibitor VT-1598 is Efficacious in Experimental Models of Central Nervous System Coccidioidomycosis Caused byand.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    University of Texas Health Science Center at San Antonio, San Antonio, TX.
    Coccidioidal meningitis can cause significant morbidity, and lifelong antifungal therapy is often required. VT-1598 is a fungal-specific Cyp51 inhibitor that has potentactivity againstspecies. We evaluated theefficacy of VT-1598 in murine models of CNS coccidioidomycosis causedandInfection was introduced via intracranial inoculation, and therapy began 48 hours post-inoculation. Read More

    Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics Vaborbactam and Meropenem Alone and in Combination Following Single and Multiple Doses in Healthy Adult Subjects.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    The Medicines Company, San Diego, CA
    Meropenem-vaborbactam is a fixed combination of the novel β-lactamase inhibitor vaborbactam and the carbapenem antibiotic meropenem developed for the treatment of serious infections caused by drug-resistant gram-negative bacteria. The safety, tolerability and pharmacokinetics (PK) of vaborbactam and meropenem following single and multiple ascending doses of each study drug administered alone or combined were evaluated in 76 healthy adult subjects in a randomized, placebo-controlled, double-blind study. Subjects were enrolled in 1 of 5 dose cohorts (receiving 250-2000 mg vaborbactam and/or 1000-2000 mg meropenem) alone or in combination. Read More

    Evolution of theaminoglycoside mutational resistome in vitro and in the cystic fibrosis setting.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca, Spain.
    Inhaled administration of high doses of aminoglycosides is a key maintenance treatment ofchronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of step-wise high-level tobramycin resistance developmentand compared the results with those of isogenic pairs of susceptible-resistant clinical isolates. Resistance development correlated withmutationsandmutations, conferring polymyxin resistance, were also frequently selectedIn contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed inevolution experiments. Read More

    Azole resistance ofisolates from the environment and the clinic in Switzerland.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Institute of Microbiology, University of Lausanne and University Hospital Center, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland
    is an ubiquitous opportunistic pathogen. This fungus can acquire resistance to azole antifungals due to mutations in the azole target (). Recently,mutations typical for environmental azole resistance acquisition (for example TR34/L98H) have been described. Read More

    Towards understanding the "proline-centric" design of a peptide-mediated macrolide resistance mechanism.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    London Research and Development Centre, Agriculture and Agri-Food Canada, London Ontario Canada
    A novel macrolide resistance mechanism has recently been recovered from agricultural soil using functional metagenomics and high-resolution proteomics (1).…. Read More

    Optimization of a meropenem plus tobramycin combination dosage regimen against hypermutable and non-hypermutablemechanism-based modeling and the hollow-fiber infection model.
    Antimicrob Agents Chemother 2018 Feb 5. Epub 2018 Feb 5.
    Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
    Hypermutableare prevalent in patients with cystic fibrosis and rapidly become resistant to antibiotic monotherapies. Combination dosage regimens have not been optimized against such strains using mechanism-based modeling (MBM) and the hollow-fiber infection model (HFIM).The PAO1 wild-type strain and its isogenic hypermutable PAOΔstrain (MIC1. Read More

    The emergence and spread ofmutations associated with artemisinin resistance inparasites in twelve Thai provinces from 2007 - 2016.
    Antimicrob Agents Chemother 2018 Jan 29. Epub 2018 Jan 29.
    Bureau of Vector Borne Diseases, Department of Disease Control, Ministry of Public Health (MOPH), Nonathaburi, Thailand.
    Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated) malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS), which manifest as slow parasite clearance in patients and reduced ring-stage susceptibility to artemisinins in survival assays. Thekelch 13 gene mutations associated with artemisinin resistant parasites are now wide-spread in the GMS. Read More

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