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    29307 results match your criteria Antimicrobial agents and chemotherapy[Journal]

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    Tet38 Efflux Pump Contributes to Fosfomycin Resistance in .
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
    Fosfomycin inhibits MurA following uptake by the GlpT transporter of glycerol-3-phosphate in In , plasmid overexpression of the Tet38 efflux pump and a mutant resulted in increased MICs and decreased accumulation of fosfomycin, with MICs affected by glycerol-3-phosphate. In contrast, a mutant had a lower MIC and increased accumulation of fosfomycin, suggesting that Tet38 acts as an efflux transporter of fosfomycin. Read More

    Identification of 14 alpha-lanosterol demethylase (CYP51) in species.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Mycotic and Parasitic Agents and Mycobacteria, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    spp. cause infections (scedosporiosis) in both immunocompetent and immunocompromised individuals and may persistently colonise the respiratory tract in patients with cystic fibrosis (CF). They are less susceptible against azoles when compared with other moulds such as , suggesting the presence of resistance mechanisms. Read More

    Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Merck & Co., Inc., Kenilworth, NJ, USA.
    Doravirine is a novel non-nucleoside reverse transcriptase inhibitor in development for use with other antiretroviral therapies to treat human immunodeficiency virus 1 (HIV-1) infection. Doravirine metabolism predominantly occurs via cytochrome P450 3A with <10% of elimination occurring via the renal pathway. As severe renal impairment can alter the pharmacokinetics (PK) of metabolically eliminated drugs, the effect of severe renal impairment on doravirine PK was assessed. Read More

    Population Pharmacokinetics and Safety of Solithromycin Following Intravenous and Oral Administration in Infants, Children, and Adolescents.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Duke Clinical Research Institute, Durham, NC, USA
    Solithromycin is a novel fluoroketolide antibiotic, which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age 6 years [range 4 days - 17 years]) were administered intravenous (IV) or oral (capsules or suspension) solithromycin (IV 6-8 mg/kg; capsules/suspension 14-16 mg/kg on Day 1 and 7-15 mg/kg on Days 2-5). Read More

    Molecular confirmation of the linkage between gene coding region and its intrinsic voriconazole and fluconazole resistance.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas - Universidad Nacional del Litoral. Santa Fe (Argentina).
    is the most prevalent causative agent of Mucormycosis, an increasingly reported opportunistic fungal infection. These mucormycetes are intrinsically resistant to - and -active antifungal azole drugs such as fluconazole and voriconazole, respectively. Despite of its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. Read More

    The Prevalence of a Cefazolin Inoculum Effect Associated with Gene Types Among Methicillin-Susceptible Isolates from Four Major Medical Centers in Chicago.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Pharmacy Practice, Midwestern University, Downers Grove, IL, USA.
    Cefazolin efficacy with high inoculum methicillin-susceptible (MSSA) infections remains in question due to therapeutic failure inferred from an inoculum effect. This study investigated the local prevalence of a cefazolin inoculum effect (CInE) and its association with staphylococcal gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, Illinois contributed MSSA isolates. Read More

    Phase I Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants (PROOF).
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
    The pharmacokinetics (PK), safety, and tolerability of two repeated dosing regimens of oral fosfomycin tromethamine were evaluated in 18 healthy adult subjects. Subjects received 3 g every other day (QOD) for 3 doses then every day (QD) for 7 doses, or vice versa, in a phase I, randomized, open-label, two-period crossover study. Serial blood (n=11) and urine samples (n=4 collection intervals) were collected before and up to 24 hours after dosing on Days 1 and 5 along with pre-dose concentrations on Days 3 and 7. Read More

    activity of ceftazidime-avibactam against carbapenem-resistant and hypervirulent isolates.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Public Health Research Institute Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
    Carbapenem-resistant and hypervirulent (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin and tigecycline are highly active against CR-hvKp isolates (MIC90 ≤ 1μg/ml), including KPC-2-producing ST11 CR-hvKp. Read More

    - and -acting factors influence expression of the -encoded efflux pump of and levels of gonococcal susceptibility to substrate antimicrobials.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA
    The gonococcal NorM efflux pump exports substrates with a cationic moiety including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The gene is part of a four gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (Ts) between the -10 and -35 hexamers; the majority of gonococcal strains analyzed herein contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly-T tract, the same transcriptional start site (TSS) was used for expression of Interestingly, the T-6 tract correlated with a higher level of both expression and gonococcal resistance to NorM substrates BE and EB. Read More

    Biochemical and Structural Basis of Triclosan Resistance in a Novel Enoyl-Acyl Carrier Protein Reductase.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Applied Bioscience, Dong-A University, Busan 49315, Republic of Korea
    Enoyl-acyl carrier protein reductase (ENR), such as FabI, FabL, FabK and FabV, catalyzes the last reduction step in bacterial type II fatty acid biosynthesis. Previously, we reported metagenome-derived ENR homologs resistant to triclosan (TCL) and highly similar to 7-α hydroxysteroid dehydrogenase (7-AHSDH). These homologs are commonly found in Epsilonproteobacteria, a class that contains several human pathogenic bacteria, including the genera and Herein, we report the biochemical and predicted structural basis of TCL resistance in a novel 7-AHSDH-like ENR. Read More

    Clonal background, resistance gene profile, and porin gene mutations modulate susceptibility to imipenem/relebactam in diverse .
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, 630 W 168th Street, New York, NY 10032, United States
    Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While harboring account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether CRE species and antibiotic resistance genotype influence response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem(IMI)/cilastatin. Read More

    Potency of solithromycin against fast and slow growing chlamydial organisms.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112
    Evidence is provided that solithromycin is a bactericidal against not only fast growing chlamydial organisms but also those slowed by IFNγ At sub-lethal concentrations, Sol impedes homotypic fusion of -containing vacuoles and reduces secretion of the type III secretion (T3S) effector, IncA. Sol may therefore represent a potential new clinical treatment for infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation. Read More

    Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Institute for Biomedical Sciences, Georgia State University, Atlanta, GA
    Morbidity and mortality resulting from influenza-like disease are a threat especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics are urgently needed that are efficacious against major drivers of influenza-like disease including influenza viruses and respiratory syncytial virus (RSV). Using a dual-pathogen high throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified -hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses and IAVs of human, avian, and swine origin. Read More

    and Evaluation of APX001A/APX001 and other Gwt1 inhibitors against .
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
    Cryptococcal meningitis (CM), caused primarily by , is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated the and activity of several compounds including APX001A and its prodrug APX001, currently in clinical development for invasive fungal infections. Read More

    Colistin does not potentiate ceftazidime-avibactam killing of carbapenem-resistant or suppress emergence of ceftazidime-avibactam resistance.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
    We tested ceftazidime-avibactam and colistin against 24 carbapenem-resistant (CRE) by time-kills. Ceftazidime-avibactam (0.25x, 1x, 4x MIC) was bactericidal against 8%, 21%, and 88% of isolates, respectively. Read More

    "Emergence of azole resistant from immunocompromised hosts in India".
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Rachna Seth, MD, Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.
    This prospective study shows that the rate of azole resistant (ARAF) in Indian immunocompromised patient population with invasive aspergillosis (IA) is low, 6/706 (0.8%). This lower rate supports the continued use of voriconazole as the first line of treatment. Read More

    Multiple drug resistant chloramphenicol resistance requires an inner membrane permease.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Departments of Microbiology, Genome Sciences, and Medicine, University of Washington, Seattle, WA.
    is a Gram negative organism that is a cause of hospital acquired multidrug resistant (MDR) infections. has a unique cell surface compared to many other Gram-negative pathogens in that it can live without LPS and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of MDR, we screened a transposon library for mutants with defective permeability barrier function, as defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate, 5-Bromo-4-chloro-3-indolyl phosphate (XP). Read More

    The effect of the novel antifungal drug F901318 (Olorofim) on the growth and viability of .
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    F2G Ltd., Manchester M30 0LX, United Kingdom.
    F901318 (olorofim) is a novel antifungal drug that is highly active against species. Belonging to a new class of antifungals called the orotomides, F901318 targets dihydroorotate dehydrogenase (DHODH) in the pyrimidine biosynthesis pathway. In this study, the antifungal effects of F901318 against were investigated. Read More

    Risk factors for gastrointestinal colonization and acquisition of carbapenem-resistant Gram-negative bacteria among patients in intensive care units in Thailand.
    Antimicrob Agents Chemother 2018 Jun 11. Epub 2018 Jun 11.
    Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.
    This study was conducted to investigate the prevalence and risk factors for carbapenem-resistant Gram-negative Bacteria (CR-GNB) colonization and acquisition among patients admitted to Intensive Care Units (ICUs) in two tertiary care hospitals in Northern Thailand. Rectal swab screening for CR-GNB was performed on patients at ICU admission and discharge. Phenotypes and genotypes of all isolates were determined. Read More

    Pentamidine for Prophylaxis against Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
    Background: pneumonia is a life-threatening opportunistic infection in children receiving immunosuppressive chemotherapy. Without prophylaxis, up to 25% of pediatric oncology patients receiving chemotherapy will develop pneumonia. Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against pneumonia. Read More

    Efficacy of Relebactam (MK-7655) in Combination with Imipenem/Cilastatin in Murine Infection Models.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Merck & Co., Inc., Kenilworth, NJ, USA.
    The World Health Organization has identified antimicrobial resistance as a global public health threat as the prevalence and spread of antibiotic resistance among bacterial pathogens worldwide are staggering. Carbapenems, such as imipenem and meropenem have been used to treat multidrug-resistant bacteria; however, since the development of resistance to carbapenems, β-lactam antibiotics in combination with β-lactamase inhibitors (BLI) has been one of the most successful strategies to enhance the activity of β-lactam antibiotics. Relebactam (REL) is a new BLI which has been found to inhibit Class A and Class C β-lactamases REL has been reported to restore imipenem's activity against both imipenem-resistant and Reported here are the efficacy studies of the imipenem-cilastatin (IMI)/REL combination in mouse models of disseminated and pulmonary infection caused by imipenem-resistant clinical isolates of and The combination was also evaluated in a delayed pulmonary model of infection. Read More

    Pharmacodynamic and immunomodulatory effects of micafungin on host responses against biofilms of in comparison to those of .
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Laboratory of Infectious Diseases, 3 Department of Pediatrics, Aristotle University School of Medicine, Hippokration Hospital, 54642 Thessaloniki, Greece
    Micafungin (MFG) demonstrates potent activity against biofilms of and , the most frequent opportunistic fungal pathogens. Little is known about its immunopharmacological effect on antibiofilm activity of phagocytic cells following exposure to biofilms. In this study, we investigated the effects of MFG on human neutrophil-mediated damage of and biofilms by XTT and the potential mechanisms underlying the immunomodulatory MFG activities on cultured monocyte-derived THP-1 cells in response to these biofilms by RT-PCR, sandwich and multiplex ELISA. Read More

    Evaluation of the Bactericidal Activity of Plazomicin and Comparators against Multidrug-resistant Enterobacteriaceae.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Micromyx, Kalamazoo, MI, USA
    The next-generation aminoglycoside plazomicin, in development for infections due to multi-drug resistant (MDR) Enterobacteriaceae, was evaluated alongside comparators for bactericidal activity in minimum bactericidal concentration (MBC) and time-kill (TK) assays against MDR Enterobacteriaceae isolates with characterized aminoglycoside and β-lactam resistance mechanisms. Overall, plazomicin and colistin were the most potent, with plazomicin demonstrating an MBC of 0.5/4 μg/mL and sustained 3-log kill against MDR , and spp. Read More

    Non-proteinogenic Amino Acid Containing Nucleotide Prodrug to Improve Oral Delivery of a Hepatitis C Virus Treatment.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Gilead Sciences, 333 Lakeside Drive, Foster City, California, USA.
    Delivery of pharmacologically active nucleoside triphosphate analogs to sites of viral infection is challenging. In prior work we identified a 2'--methyl-1'-cyano-7-deaza-adenosine -nucleotide analog with desirable selectivity and potency for the treatment of HCV infection. However, the prodrug selected for clinical development, GS-6620, required a high dose for meaningful efficacy and had unacceptable variability due to poor oral absorption as a result of suboptimal solubility, intestinal metabolism and efflux transport. Read More

    Effect of Linezolid plus Bedaquiline against in Log-Phase, Acid-Phase and Non-Replicating-Persister (NRP)-Phase in an Assay.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Institute for Therapeutic Innovation, College of Medicine, University of Florida, Orlando, Florida, United States of America.
    Tuberculosis is the ninth-leading cause of death worldwide. Treatment success is approximately 80% for susceptible strains and decreases to 30% for extensively resistant strains. Shortening therapy duration for () is a major goal, which can be attained with the use of combination therapy. Read More

    Efficacy of Meglumine Antimoniate under Low Polymerization State Orally Administrated in Murine Model of Visceral Leishmaniasis.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
    Progress towards the improvement of meglumine antimoniate (MA) commercially known as Glucantime®, a highly effective but also toxic antileishmanial drug, has been hindered by the lack of knowledge and control on its chemical composition. Here, MA was manipulated chemically with the aim of achieving an orally effective drug. MA compounds were synthesized from either antimony pentachloride (MA-SbCl) or potassium hexahydroxyantimonate (MA-KSb(OH)) and prepared under low polymerization state. Read More

    Primary fungal prophylaxis in hematological malignancy: A network meta-analysis of randomized controlled trials.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
    Several new anti-fungal agents have become available for primary fungal prophylaxis of neutropenia fever in haematological malignancy patients. Our aim was to synthesize all evidence on efficacy and enable an integrated comparison of all current treatments.We performed a systematic literature review to identify all publicly available evidence from randomized controlled trials (RCT). Read More

    PET-PCR for Detection of ene copy number.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, CGH, Atlanta, GA, United States
    Piperaquine is an important partner drug used in artemisinin-based combination therapies (ACTs). An increase in the and gene copy number has been associated with decreased susceptibility of to piperaquine in Cambodia. Here, we developed a photo- induced electron transfer real-time PCR (PET-PCR) assay to quantify the copy number of () that can be used in endemic countries to enhance molecular surveillance. Read More

    and activity of a novel catheter lock solution against bacterial and fungal biofilms.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Center for Medical Mycology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH
    Central line associated bloodstream infections (CLABSIs) are increasingly recognized to be associated with intralumenal microbial biofilms, and effective measures for the prevention and treatment of BSI remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL) containing trimethoprim (5 mg/ml) and ethanol (25%) and calcium Ethylenediaminetetraacetic acid (CA-EDTA) 3% for activity against bacterial and fungal biofilms using and (rabbit) catheter biofilm models. Biofilms were formed with bacterial (seven different species including vancomycin-resistant enterococcus, VRE) or fungal () species on catheter materials. Read More

    and intracellular activity of imipenem combined to rifabutin and avibactam against .
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    INSERM, U1138, LRMA, Equipe 12 du Centre de Recherche des Cordeliers, Paris, France
    Repurposing drugs may be useful as an add-on in the treatment of pulmonary infections, which are particularly difficult to cure. naturally produces a β-lactamase, Bla, which is inhibited by avibactam. The recommended regimens include imipenem, which is hydrolyzed by Bla and used without any β-lactamase inhibitor. Read More

    Artemisone and artemiside - potent pan-reactive antimalarial agents that also synergize redox imbalance in transmissible gametocyte stages.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa
    The emergence of resistance towards artemisinin combination therapies (ACTs) by the malaria parasite has the potential to severely compromise malaria control. Therefore, development of new artemisinins in combination with new drugs that impart activities towards both intraerythrocytic proliferative asexual and transmissible gametocyte stages, in particular those of resistant parasites, are urgently required. We define artemisinins as oxidant drugs through their ability to oxidize reduced flavin cofactors of flavin disulfide reductases critical for maintaining redox-homeostasis in the malaria parasite. Read More

    Few conserved amino acids in the small multidrug resistance transporter EmrE influence drug polyselectivity.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    University of Calgary, Department of Biological Sciences, 2500 University Dr. NW, Calgary, Alberta, Canada, T2N 1N4.
    EmrE is the archetypical member of the small multidrug resistance transporter family and confers resistance to a wide range of disinfectants and dyes known as quaternary cation compounds (QCCs). The aim of this study was to examine which conserved amino acids play an important role in substrate selectivity. Based on previous analysis of EmrE homologs, a total of 33 conserved residues were targeted for cysteine or alanine replacements within EmrE. Read More

    Efficacy of Plazomicin Alone or in Combination with Meropenem or Tigecycline against Enterobacteriaceae Isolates Exhibiting Various Resistance Mechanisms in an Immunocompetent Murine Septicemia Model.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA
    : Plazomicin is a next-generation aminoglycoside with potent activity against multidrug- and carbapenem-resistant Enterobacteriaceae. The objective of this study was to assess the efficacy of plazomicin exposure, alone and in combination with meropenem or tigecycline, against Enterobacteriaceae in the immunocompetent murine septicemia model.: ICR mice were inoculated intraperitoneally with bacterial suspensions. Read More

    Activities of oxadiazole antibacterials against and other Gram-positive bacteria.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Area of Biochemistry and Molecular Biology, University of La Rioja, Logroño, Spain
    The activities of four oxadiazoles were investigated with 210 methicillin-resistant (MRSA) strains. MIC and MIC values of 1-2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA. Read More

    Linezolid Kills Acid Phase and Non-replicative Persister Phase in a Hollow Fiber Infection Model.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Institute for Therapeutic Innovation, College of Medicine, University of Florida, Lake Nona, FL.
    The therapy of (MTB) infection is long and arduous. It has been hypothesized that the therapy duration is driven primarily by populations of organisms in different metabolic states that replicate slowly or not at all (Acid-phase and NRP-phase organisms). Linezolid is an oxazolidinone antimicrobial with substantial activity against Log-phase MTB. Read More

    Diversity of carbapenemase-producing isolates, France 2012-2013.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Bactériologie-Hygiene unit, Bicêtre Hospital, Assistance Publique des Hôpitaux de Paris
    With the dissemination of carbapenemase-producing (CPE) worldwide, carbapenem-hydrolyzing enzymes are increasingly reported among , the first hospital and community-acquired opportunistic pathogen. Here, we have performed an epidemiological survey of carbapenemase-producing (CP-) isolates received at the French National Reference Centre (F-NRC) in 2012 and 2013. Antimicrobial susceptibilities for last resort antibiotics and antimicrobial compounds commonly used to treat urinary tract infections were determined by broth microdilution. Read More

    Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from United States Hospitals and Comparative Activity of Aminoglycosides against Carbapenem-Resistant and Isolates Carrying Carbapenemase Genes.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    JMI Laboratories, North Liberty, IA 52317.
    Plazomicin and comparators agents were tested using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 United States hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC, 0.5/2 μg/ml) inhibited 99. Read More

    Model system identifies kinetic driver of Hsp90 inhibitor activity against African trypanosomes and .
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Hsp90 inhibitors, well-studied in the laboratory and clinic for antitumor indications, have promising activity against protozoan pathogens, including that causes African sleeping sickness, and malaria parasite To progress these experimental drugs toward clinical use we adapted an in vitro dynamic hollow-fiber system and deployed artificial pharmacokinetics to discover the driver of their activity: either concentration or time. Compounds from three major classes of Hsp90 inhibitors in development were evaluated against trypanosomes. In all circumstances tested Hsp90 inhibitors were concentration-driven. Read More

    Viability Screen of LOPAC Reveals Phosphorylation Inhibitor Auranofin as Potent Inhibitor of ST1, ST4 and ST7 Isolates.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Laboratory of Molecular and Cellular Parasitology, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
    is an enteric parasite with extensive global prevalence. Studies have linked infection with this protist with a variety of gastrointestinal disorders, including irritable bowel syndrome. Due to the polymorphic nature of , studies on the parasite could be complicated as results can be easily misinterpreted. Read More

    Pharmacokinetics of praziquantel in and infected school- and preschool- aged children.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel, aiming to control schistosomiasis. However, pharmacokinetic data, crucial to establish safe and effective dose for this age group, are sparse. The objective of this study was to establish and compare pharmacokinetic parameters of praziquantel in schistosomiasis infected preschool- and school-aged children. Read More

    Proposing as the origin of the plasmid-mediated resistance gene .
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Microbiología, Junin 956 Buenos Aires 1113, Argentina
    A putative gene in 14751 showed 99% nucleotide identity with plasmid-encoded Due to a single-nucleotide insertion translating to a truncated protein, 14751 does not confer fosfomycin resistance. Nonetheless, analysis of another genome deposit ( WCH1410) that could be recategorized as after phylogenetic analysis, revealed a 100% identical to the plasmid-borne Collectively, we suggest that represents the most probable origin of . Read More

    Genetic and Biochemical characterization of OXA-519, a novel OXA-48-like β-lactamase.
    Antimicrob Agents Chemother 2018 Jun 4. Epub 2018 Jun 4.
    EA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Université Paris Sud, Université Paris Saclay, LabEx Lermit, Faculty of Medicine, Le Kremlin-Bicêtre, France
    A multidrug-resistant 1210 isolate with reduced carbapenem susceptibility revealed the presence of a novel plasmid-encoded gene, named The 60.7-kb plasmid (pOXA-519) was similar to the IncL-OXA-48 prototypical plasmid except for a ca. 2-kb deletion due to an IS insertion. Read More

    Miltefosine has post-antifungal effect and induces apoptosis in yeasts.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    Laboratório de Quimioterapia Antifúngica, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil
    spp. are common opportunistic fungal pathogens, particularly in HIV patients. The approved drug miltefosine (MFS) has potential as an alternative antifungal against cryptococcosis; however, the mechanism of action of MFS in is poorly understood. Read More

    Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    Center for Bioelectrics, Old Dominion University, Norfolk VA 23508, USA
    Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant , , , and in mature biofilms were reduced by 6 - 8 orders of magnitude with a PAD lock for 60 minutes. Read More

    Analysis of the tunicamycin biosynthetic gene cluster of reveals new insights into tunicamycin production and immunity.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, United Kingdom
    The tunicamycin biosynthetic gene cluster of consists of 14 genes () with a high degree of apparent translational coupling. Transcriptional analysis revealed that all of these genes are likely to be transcribed as a single operon from two promoters, p1 and p2. In frame deletion analysis revealed that just six of these genes () are essential for tunicamycin production in the heterologous host , while five () with likely counterparts in primary metabolism are not necessary, but presumably ensure efficient production of the antibiotic at the onset of tunicamycin biosynthesis. Read More

    Iron restriction to clinical isolates of by the novel chelator DIBI inhibits growth and increases sensitivity to azoles and in a murine model of experimental vaginitis.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    Louisiana State University Health Sciences Center School of Dentistry, 1100 Florida Ave. New Orleans, Louisiana, USA
    is an important opportunistic pathogen causing various human infections that are often treated with azole antifungals. The US CDC now regards developing candidal antifungal resistance as a threat, creating a need for new and more effective antifungal treatments. Iron is an essential nutrient for all living cells and there is growing evidence that interference with iron homeostasis of can improve its response to antifungals. Read More

    Clofazimine for the treatment of .
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA.
    pulmonary infection is global problem. Standard combination therapy consists of isoniazid 300 mg/day, rifampin 600 mg/day, and ethambutol 15 mg/kg/day for 18 months. Co-incubation of with different clofazimine concentrations over 7 days in test-tubes resulted in maximal kill (E) of 2. Read More

    Recommendations to address the difficulties encountered when determining linezolid resistance from whole genome sequencing data.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
    Mutations associated with linezolid resistance within the V domain of 23S rRNA are annotated using an numbering system. The 23S rRNA gene varies in length, nucleotide sequence and copy number between bacterial species. Consequently, this numbering system is not intuitive and can lead to confusion when locating mutation sites using whole genome sequencing data. Read More

    Disruption of Activates β-Lactamase Production in and Clinical Isolates.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    School of Cellular & Molecular Medicine, University of Bristol, Bristol, United Kingdom.
    The hyperproduction of chromosomally encoded β-lactamases is a key method of acquired resistance to ceftazidime, aztreonam, and when seen in backgrounds having reduced envelope permeability, carbapenems. Here we show that loss of Mpl, a UDP-muramic acid/peptide ligase, is a common and previously overlooked cause of chromosomally encoded β-lactamase hyperproduction in clinical isolates of and , important pathogens notorious for their β-lactam resistant phenotypes. Read More

    Anti-trypanosomal 8-hydroxyl naphthyridines are chelators of divalent transition metals.
    Antimicrob Agents Chemother 2018 May 29. Epub 2018 May 29.
    The Wellcome Trust Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
    Lack of information regarding the mechanisms of action (MoA) or specific molecular targets of phenotypically active compounds can prove a barrier to their development as chemotherapeutic agents. Here, we report the results of our orthogonal genetic, molecular and biochemical studies to determine the MoA of a novel 7-substituted 8-hydroxy-1,6-naphthyridine (8-HNT) series that display promising activity against and High-throughput loss-of-function genetic screens in highlighted two probable zinc transporters associated with resistance to these compounds. These transporters localized to the parasite Golgi. Read More

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