29,869 results match your criteria Antimicrobial agents and chemotherapy[Journal]


Efficacy and improved resistance potential of a cofactor-independent InhA inhibitor of in a C3HeB/FeJ mouse model.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 USA.

AN12855 is a direct, cofactor-independent inhibitor of InhA in In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency compared to isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline anti-tuberculosis agent isoniazid. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02071-18DOI Listing
February 2019
1 Read

Activity of a long-acting injectable bedaquiline formulation in a paucibacillary mouse model of latent tuberculosis infection.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Janssen R&D, a division of Janssen Pharmaceutica NV, Beerse, Belgium.

The potent anti-tuberculosis activity and long half-life of bedaquiline make it an attractive candidate for long-acting/extended release formulations for treatment of latent tuberculosis infection (LTBI). Our objective was to evaluate a long-acting injectable (LAI) bedaquiline formulation in a validated paucibacillary mouse model of LTBI. Following immunization with rBCG30, BALB/c mice were challenged by aerosol infection with H37Rv. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.00007-19DOI Listing
February 2019
1 Read

In Vitro Evaluation of the Drug Interaction Potential of Doravirine.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Merck & Co., Inc., Kenilworth, NJ, USA

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 infection. studies were conducted to assess the potential for drug interactions with doravirine via major drug-metabolizing enzymes and transporters. Kinetic studies confirmed that cytochrome P450 (CYP) 3A plays a major role in the metabolism of doravirine, with ∼20-fold higher catalytic efficiency for CYP3A4 versus CYP3A5. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02492-18DOI Listing
February 2019

Population Pharmacokinetics of Doravirine and Exposure-Response in Individuals with HIV-1.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Merck & Co., Inc., Kenilworth, NJ, USA.

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV-1). A population pharmacokinetic (PK) model was developed for doravirine using pooled data from densely sampled Phase 1 trials and from sparsely sampled Phase 2b and Phase 3 trials evaluating doravirine administered orally as a single entity or as part of a fixed-dose combination of doravirine/lamivudine/tenofovir disoproxil fumarate. A one-compartment model with linear clearance from the central compartment adequately described the clinical PK of doravirine. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02502-18DOI Listing
February 2019
1 Read

Conjugal Transfer, Whole Genome Sequencing, and Plasmid Analysis of Four -bearing Isolates from U.S. Patients.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Centers for Disease Control and Prevention, Atlanta, GA, USA.

Four clinical isolates bearing gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to plasmids were stable in conjugants after multiple passages on non-selective media. was located on an IncX4 (n=3) or IncN (n=1) plasmid. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02417-18DOI Listing
February 2019

Pharmacokinetic Interactions Between the HCV Inhibitors Elbasvir and Grazoprevir and HIV Protease Inhibitors Ritonavir, Atazanavir, Lopinavir, or Darunavir in Healthy Participants.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Merck & Co., Inc., Kenilworth, NJ, USA.

The combination of the hepatitis C virus (HCV) NS5A inhibitor elbasvir and NS3/4A protease inhibitor grazoprevir is a potent, once-daily therapy indicated for the treatment of chronic HCV infection in individuals coinfected with human immunodeficiency virus-1 (HIV). We explored the pharmacokinetic interactions of elbasvir and grazoprevir with ritonavir and ritonavir-boosted HIV protease inhibitors in three phase 1 trials. Drug-drug interaction trials in healthy participants were conducted to evaluate the effect of ritonavir on the pharmacokinetics of grazoprevir ( = 10) and the potential 2-way pharmacokinetic interaction of elbasvir ( = 30) or grazoprevir ( = 39) when coadministered with ritonavir-boosted atazanavir, lopinavir, or darunavir. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02142-18DOI Listing
February 2019

Dynamics of resistance plasmids in extended spectrum β-lactamase-producing Enterobacteriaceae during post-infection colonization.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

Extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) are a major cause of bloodstream infections and the colonization rate of EPE in the gut microbiota of individuals lacking prior hospitalization or comorbidities is increasing. In this study we performed an in-depth investigation of the temporal dynamics of EPE and their plasmids during one year by collecting fecal samples from three patients initially seeking medical care for urinary tract infections. In two of the patients the same strain that caused the UTI was found at all consecutive samplings from the gut microbiota and no other EPEs were detected, while in the third patient the UTI strain was only found in the initial UTI sample. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02201-18DOI Listing
February 2019

Role of Viscoelasticity in Bacterial Killing by Antimicrobials in Differently Grown Biofilms.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, P.O Box 196, 9700 AD, Groningen, The Netherlands

colonizes the sputum of most adult cystic fibrosis patients, forming hard to eradicate biofilms, in which bacteria are protected in their self-produced EPS-matrix. EPS provides biofilms with viscoelastic properties, causing time-dependent relaxation after stress-induced deformation, according to multiple characteristic time-constants. These time-constants reflect different biofilm (matrix) components. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01972-18DOI Listing
February 2019
1 Read

Select β-lactam combinations exhibit synergy against .

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21287

() is a nontuberculous mycobacterium that causes invasive pulmonary infections in patients with structural lung disease. is intrinsically resistant to several classes of antibiotics and an increasing number of strains isolated from patients exhibit resistance to most antibiotics considered for treatment of infections by this mycobacterium. Therefore, there is an unmet need for new regimens with improved efficacy to treat this disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02613-18DOI Listing
February 2019

Pharmacokinetics of albendazole, albendazole sulfoxide and albendazole sulfone determined from plasma, blood, dried blood spots and Mitra® samples of hookworm-infected adolescents.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland

Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood micro-sampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02489-18DOI Listing
February 2019
2 Reads

and intracellular activity of imipenem combined with tedizolid, rifabutin, and avibactam against .

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, F-75006 Paris, France

infections are difficult to treat due to resistance to many antibiotics. , tedizolid combined with imipenem displayed a moderate synergistic effect (FIC index of 0.41) but no bactericidal activity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01915-18DOI Listing
February 2019

Circulation of plasmids harboring resistance genes to quinolones and/or extended spectrum cephalosporins in multiple serotypes from swine in the United States.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, United States.

Nontyphoidal (NTS) poses a major public-health risk worldwide that is amplified by the existence of antimicrobial resistant strains, especially to quinolones and extended-spectrum cephalosporins (ESC). Little is known on the dissemination of plasmids harboring the acquired genetic determinants that confer resistance to these antimicrobials across NTS serotypes from livestock in the United States.NTS isolates (n=183) from U. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02602-18DOI Listing
February 2019

Dose Optimization of Colistin Combinations against Carbapenem-Resistant from Chinese Hospital-acquired Pneumonia Patients Using PK/PD Model.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China

Colistin-based combination therapy has become an important strategy to combat the carbapenem-resistant (CRAB). However, the optimal dosage regimen selection for the combination with the maximum efficacy is challenging. Checkerboard assay was employed to evaluate the synergy of colistin in combination with meropenem, rifampicin, fosfomycin and minocycline against nine carbapenem-resistant (Minimum inhibitory concentration of meropenem [MIC]≥32 mg/L) isolated from Chinese hospital-acquired pneumonia (HAP) patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01989-18DOI Listing
February 2019
1 Read

Optimization of methionyl tRNA-synthetase inhibitors for treatment of infection.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Department of Medicine and Department of Biochemistry, University of Washington, Seattle, Washington, USA

Cryptosporidiosis is one of the leading causes of moderate to severe diarrhea in children in low-resource settings. The therapeutic options for cryptosporidiosis are limited to one drug, nitazoxanide, which unfortunately has poor activity in the most needy populations of malnourished children and HIV infected persons. This paper describes the discovery and early optimization of a class of imidazopyridine-containing compounds with potential for treating infections. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02061-18DOI Listing
February 2019
1 Read

Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study.

Antimicrob Agents Chemother 2019 02 11. Epub 2019 Feb 11.

Division of Infectious Diseases, Carver College of Medicine, University of Iowa, USA.

Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS) and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety and tolerability of oxfendazole were evaluated in healthy volunteers in this Phase 1 first-in-human (FIH) study. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02255-18DOI Listing
February 2019
1 Read

Bacterial Cytological Profiling (BCP) as a tool to study mechanism of action of antibiotics that are active against .

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand

An increasing number of multidrug-resistant (MDR-) infections have been reported worldwide, posing a threat to public health. The establishment of methods to elucidate the mechanism of action (MOA) of -specific antibiotics is needed to develop novel antimicrobial therapeutics with activity against MDR- We previously developed bacterial cytological profiling (BCP) to understand the MOA of compounds in and Given how distantly related is to these species, it was unclear to what extent it could be applied. Here we implemented bacterial cytological profiling (BCP) as an antibiotic MOA discovery platform for We found that the BCP platform can distinguish among six major antibiotic classes and can also sub-classify antibiotics that inhibit the same cellular pathway but have different molecular targets. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02310-18DOI Listing
February 2019

Characterization of hypermutator isolates from patients with cystic fibrosis in Australia.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University (Parkville campus), Parkville, Victoria 3052, Australia

Hypermutable isolates (hypermutators) have been identified in patients with cystic fibrosis (CF). Hypermutators display a greatly increased mutation rate, an enhanced ability to become resistant to antibiotics during treatment and are associated with reduced lung function in patients. Their prevalence has been established amongst patients with CF, but has not been determined for patients with CF in Australia. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02538-18DOI Listing
February 2019
1 Read

Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient.

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Baylor College of Medicine, Houston, Texas.

The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70kg (weight based vs non-weight based) to achieve an area under the curve (AUC) ≥400mg*L/hour and a trough concentration < 20mg/L is not known. Population pharmacokinetic analysis determined that vancomycin should be weight based dosed using fat free mass, with appropriate adjustment for kidney dysfunction. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02359-18DOI Listing
February 2019

AmpI functions as an iron exporter to alleviate β-lactam-mediated ROS stress in .

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan

is an organism with a remarkable capacity for drug resistance with several antibiotic resistance determinants in its genome. genome codes for L1 and L2 responsible for intrinsic β-lactam resistance. The Smlt3721 gene (denoted ), located downstream of the gene, encodes an inner membrane protein. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02467-18DOI Listing
February 2019
1 Read

Whole genome sequencing for drug resistance profile prediction in .

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland

Whole genome sequencing allows rapid detection of drug-resistant isolates. However, the availability of high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data has thus far been limited.We determined drug resistance profiles of 176 genetically diverse clinical isolates from Democratic Republic of the Congo, Ivory Coast, Peru, Thailand and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD BACTEC MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02175-18DOI Listing
February 2019
2 Reads

Impact of Pre-existing Hepatitis C Virus Genotype 6 NS3, NS5A and NS5B Polymorphisms on Their In Vitro Susceptibility to Inhibition by Direct-Acting Antiviral Agents.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA.

HCV genotype (GT)-6 is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with HCV GT-6a where high response rates to direct-acting antivirals (DAAs) have been achieved. However, GT-6 is highly diverse with 29 reported subtypes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02205-18DOI Listing
February 2019
1 Read

Activity of Tebipenem (SPR859) Against Penicillin-Binding Proteins of Gram-negative and Gram-positive Bacteria.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Centre d'Étude et de Valorisation de la Diversité Microbienne (CEVDM), Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1.

Tebipenem (SPR859) is the microbiologically active form of SPR994, tebipenem-pivoxil, an orally available carbapenem with activity against extended spectrum β-lactamase (ESBL) producing Measurement of the relative binding of SPR859 to the bacterial cell targets revealed that it is a potent inhibitor of multiple penicillin-binding proteins (PBPs), but primarily a Gram-negative PBP2 inhibitor, similar to other compounds in this class. These data support further clinical development of SPR994. Read More

View Article

Download full-text PDF

Source
http://aac.asm.org/lookup/doi/10.1128/AAC.02181-18
Publisher Site
http://dx.doi.org/10.1128/AAC.02181-18DOI Listing
February 2019
5 Reads

In vitro antimicrobial activity of diacerein on 76 .

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Henan Eye Institute, Henan Eye Hospital, Zhengzhou, 450003, China.

Bacterial keratitis is an aggressive infectious corneal disease. With the continuing rise in antibiotic resistance and a decline in the discovery of new antibiotics, new antimicrobial drugs are now required. In the present study, we determined the antibacterial activity of diacerein, an anti-inflammatory drug, against 76 Gram-positive cocci isolated from bacterial keratitis patients in vitro and anti- activity in mouse bacterial keratitis model in vivo. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01874-18DOI Listing
February 2019
2 Reads

A FASII inhibitor prevents staphylococcal evasion of daptomycin by inhibiting phospholipid decoy production.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

MRC Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Rd, London, SW7 2AZ, UK.

Daptomycin is a treatment of last resort for serious infections caused by drug-resistant Gram-positive pathogens such as methicillin-resistant We have shown recently that can evade daptomycin by releasing phospholipid decoys that sequester and inactivate the antibiotic, leading to treatment failure. Since phospholipid release occurs via an active process, we hypothesised that it could be inhibited, thereby increasing daptomycin efficacy. To identify opportunities for therapeutic interventions that block phospholipid release, we first determined how the host environment influenced the release of phospholipids and inactivation of daptomycin by The addition of certain host-associated fatty acids to the growth medium enhanced phospholipid release. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02105-18DOI Listing
February 2019

Negative impact of carbapenem methylation on the reactivity of β-lactams for cysteine acylation revealed by quantum calculations and kinetic analyses.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Univ. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.

The Ldt L,D-transpeptidase mediates resistance to most β-lactam antibiotics in by replacing classical peptidoglycan polymerases. The catalytic Cys of Ldt is rapidly acylated by β-lactams belonging to the carbapenem class but not by penams and cephems. We previously reported quantum calculations and kinetic analyses for Ldt and showed that the inactivation profile is not determined by differences in drug binding ( values in the 50-80 mM range). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02039-18DOI Listing
February 2019

Clinical and Molecular Characteristics of Positive Methicillin-resistant Causing Bloodstream Infections.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Republic of Korea

The increasing use of chlorhexidine for methicillin-resistant (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by -positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02157-18DOI Listing
February 2019
1 Read

Viability Screen of LOPAC Reveals Tyrosine Kinase Inhibitor Tyrphostin A9 as a Novel Partner Drug for Artesunate Combinations to Target the Ring Stage.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Laboratory of Molecular and Cellular Parasitology, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

The emergence of artemisinin-resistant poses a major threat to current frontline artemisinin combination therapies. Artemisinin resistance is widely associated with mutations in the PfKelch13 propeller region leading to delayed parasite clearance and increased survival of early ring stage parasites. There is therefore a need to discover novel drugs that are effective against artemisinin-resistant In view of this, our study aims to identify compounds from the Library of Pharmacologically Active Compounds (LOPAC) that could increase the efficacy of artesunate and be used as a potential partner drug for treatment against artemisinin-resistant falciparum malaria. Read More

View Article

Download full-text PDF

Source
http://aac.asm.org/lookup/doi/10.1128/AAC.02389-18
Publisher Site
http://dx.doi.org/10.1128/AAC.02389-18DOI Listing
February 2019
2 Reads

Iron Chelator Deferasirox Reduces Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, 14214, United States of America.

, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02152-18DOI Listing
February 2019
2 Reads

"Resurrecting old β-lactams": the potent inhibitory activity of temocillin against multi-drug resistant spp. isolates from the United States.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106

spp. are opportunistic human pathogens that infect persons with cystic fibrosis and the immunocompromised. spp. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02315-18DOI Listing
February 2019

Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Baylor College of Medicine, Department of Pediatrics, Renal Section.

This retrospective study included pediatric intensive care unit patients receiving continuous venovenous hemodiafiltration (CVVHDF) being treated with cefepime. Free drug concentration time above one and four times a presumed MIC of 8 mcg/mL were calculated. Four patients received doses ranging from 48 to 64 mg/kg/dose every six to twelve hours. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02006-18DOI Listing
February 2019

Abrogation of triazole resistance upon deletion of in a clinical isolate of .

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

University of Tennessee Health Science Center, Department of Clinical Pharmacy, Memphis, Tennessee, USA

has rapidly emerged as a healthcare-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four genes with the highest degree of homology to and among three triazole-resistant clinical isolates, as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete and in both a triazole-resistant clinical isolate and the susceptible reference strain, and observed MIC for all clinically available triazoles decreased as much as 128-fold in the deletion strains. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.00057-19DOI Listing
February 2019
1 Read

Impact of an antimicrobial stewardship intervention on within and between patient daptomycin resistance evolution in vancomycin-resistant .

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Vancomycin-resistant s (VRE) is a leading cause of hospital acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem, and has previously been described in this hospital. In response to increasing resistance, an antimicrobial stewardship intervention was implemented to reduce hospital-wide use of daptomycin. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01800-18DOI Listing
February 2019

Pooled population pharmacokinetic analysis of tribendimidine for the treatment of infections.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Swiss Tropical & Public Health Institute, Basel, Switzerland

Opisthorchiasis, caused by the food-borne trematode , affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao PDR, pharmacokinetic samples from 125 adult and adolescent patients treated with 400 mg tribendimidine were obtained following the design of an sparse sampling scheme at 20 min, 2, 7.75, 8 and 30 h after treatment, using dried blood spot sampling. Read More

View Article

Download full-text PDF

Source
http://aac.asm.org/lookup/doi/10.1128/AAC.01391-18
Publisher Site
http://dx.doi.org/10.1128/AAC.01391-18DOI Listing
February 2019
2 Reads

An Mechanistic Study of the Distribution of Lascufloxacin into the Epithelial Lining Fluid.

Antimicrob Agents Chemother 2019 Feb 4. Epub 2019 Feb 4.

Watarase Research Center, Kyorin Pharmaceutical Co., Ltd.

The present study aimed to clarify the mechanism underlying the high distribution of lascufloxacin in epithelial lining fluid (ELF). Involvement of transporters was examined by transcellular transport across Calu-3 and transporter-overexpressing cells; the binding of lascufloxacin to ELF components was examined by an organic solvent-water partitioning system that employed pulmonary surfactant and phospholipids. Transcellular transport across the transporter-overexpressing cells indicated lascufloxacin to be a substrate of both P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP); therefore, its transport across Calu-3 cells was inhibited by P-gp and BCRP inhibitors. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02208-18DOI Listing
February 2019
1 Read

Retraction for Liu and Chen, "Translation Elongation Factor 4 (LepA) Contributes to Tetracycline Susceptibility by Stalling Elongating Ribosomes".

Antimicrob Agents Chemother 2019 Feb 29;63(2). Epub 2019 Jan 29.

School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, China.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02581-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355579PMC
February 2019

Correction for Schmidt-Malan et al., " Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli".

Antimicrob Agents Chemother 2019 Feb 29;63(2). Epub 2019 Jan 29.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02563-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355576PMC
February 2019
1 Read

Erratum for Withey et al., "Conjugated Linoleic Acid Reduces Cholera Toxin Production and by Inhibiting Vibrio cholerae ToxT Activity".

Antimicrob Agents Chemother 2019 Feb 29;63(2). Epub 2019 Jan 29.

Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02493-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355574PMC
February 2019

A pharmacokinetic-pharmacodynamic assessment of the hepatic and bone-marrow toxicities of the new trypanoside fexinidazole.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Thailand

Fexinidazole is a novel oral treatment for , human African trypanosomiasis: -HAT. Fexinidazole also has activity against the causative agent of Chagas disease. During the course of a dose ranging assessment in chronic indeterminate Chagas disease, delayed neutropenia and significant increases in hepatic transaminases were observed and clinical investigations were suspended. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02515-18DOI Listing
January 2019
1 Read

Arylacetamide deacetylase (AADAC) gene polymorphism and HIV infection affect the exposure of Rifapentine: a population pharmacokinetics analysis.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.

Rifapentine is a rifamycin used to treat tuberculosis. As for rifampicin, plasma exposures of rifapentine are associated with treatment response. While concomitant food intake and HIV infection explain part of the pharmacokinetic variability associated with rifapentine, few studies have evaluated the contribution of genetic polymorphisms. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01964-18DOI Listing
January 2019
1 Read
4.476 Impact Factor

Inhibition of yeast-to-hypha transition and virulence of by 2-alkylaminoquinoline derivatives.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Integrative Microbiology Research Centre, College of Agriculture, South China Agricultural University, Guangzhou 510642, China

A rapid increase in infection and drug resistance has caused an emergent need for new clinical strategies against this fungal pathogen. In this study, we evaluated the inhibitory activity of a series of 2-alkylaminoquinoline derivatives against isolates. A total of 28 compounds were assessed for their efficacy in inhibiting the yeast-to-hypha transition, which is considered one of the key virulence factors in Several compounds showed strong activity to decrease the morphological transition and virulence of cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01891-18DOI Listing
January 2019
1 Read

Dalbavancin Alone and in Combination with Ceftaroline against Four Different Phenotypes of in a PK/PD Model.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy & Health Sciences, Detroit, MI, USA

Glycopeptides such as vancomycin have been used as the first line therapy against MRSA infections for over half a century. Reduced susceptibility and emergence of resistance to first generation glycopeptides has led to development of second generation lipoglycopeptide derivatives such as dalbavancin which hold broader ranges of activity and enhanced pharmacokinetic properties. We evaluated the MIC values for a total of 100 isolates including 25 MRSA, 25 hVISA, 25 daptomycin non-susceptible (DNS) MRSA and 25 VISA strains against dalbavancin, ceftaroline and vancomycin alone and in combination. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01743-18DOI Listing
January 2019
1 Read

Efficacy of Tedizolid Against Enterococci and Staphylococci, including strains, in a Mouse Peritonitis Model.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.

In a mouse peritonitis model, tedizolid was comparable to linezolid and daptomycin against an strain (VAN, AMP), an strain, and an MRSA strain with and without Against a (B)+ tedizolid was inferior to linezolid and daptomycin, despite ∼ 4-fold lower MIC. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02627-18DOI Listing
January 2019

Pharmacological, Toxicological and Dose-Range Assessment of OG716, a Novel Lantibiotic for the Treatment of Associated Infection (CDI).

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Oragenics, Inc. 13700 Progress Blvd, Alachua, FL 32608. USA

Lantibiotics present an attractive scaffold for the development of novel antibiotics. We report here a novel lantibiotic for the treatment of infection. The lead compounds were selected from a library of over 700 single and multiple substitution variants of the lantibiotic Mutacin 1140 (MU1140). Read More

View Article

Download full-text PDF

Source
http://aac.asm.org/lookup/doi/10.1128/AAC.01904-18
Publisher Site
http://dx.doi.org/10.1128/AAC.01904-18DOI Listing
January 2019
4 Reads

Population Pharmacokinetic Analyses for Plazomicin Using Pooled Data from Phase 1, 2, and 3 Clinical Studies.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA.

Plazomicin is an aminoglycoside with activity against multidrug-resistant Enterobacteriaceae. Plazomicin is dosed on a mg/kg basis and administered by 30-min intravenous infusion every 24 h, with dose adjustments for renal impairment and body weight (BW) ≥125% of ideal BW. A population pharmacokinetic analysis was performed to identify patient factors that account for variability in pharmacokinetics and to determine if dose adjustments are warranted based on covariates. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02329-18DOI Listing
January 2019
1 Read

Imidazole derivatives as promising agents for the treatment of Chagas disease.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Centro de Investigaciones Biológicas (CSIC). Ramiro de Maeztu, 9, 28040 Madrid, Spain.

More than 100 years later after being firstly described, Chagas disease remains endemic in 21 Latin American countries and has spread to other continents. Indeed, this disease, caused by the protozoan parasite , is no longer just a problem for the American continent but has become a global health threat. Current therapies, nifurtimox and benznidazole (Bz), are far from being adequate due to undesirable effects and their lack of efficacy in the chronic phases of the disease. Read More

View Article

Download full-text PDF

Source
http://aac.asm.org/lookup/doi/10.1128/AAC.02156-18
Publisher Site
http://dx.doi.org/10.1128/AAC.02156-18DOI Listing
January 2019
5 Reads

Novel Polymyxin Combination with Antiretroviral Zidovudine Exerts Synergistic Killing against NDM-producing MDR .

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Monash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.

Polymyxins are used as a last-line therapy against multidrug-resistant (MDR) New Delhi metallo-β-lactamase (NDM) producing However, polymyxin resistance can emerge with monotherapy; therefore, novel strategies are urgently needed to minimize the resistance and maintain their clinical utility. This study aimed to investigate the pharmacodynamics of polymyxin B in combination with the antiretroviral drug zidovudine against Three isolates were evaluated in static time-kill studies (0 - 64 mg/L) over 48 h. A one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model (IVM) was used to simulate humanized dosage regimens of polymyxin B (4 mg/L as continuous infusion) and zidovudine (as bolus dose thrice daily to achieve C = 6 mg/L) against BM1 over 72 h. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02176-18DOI Listing
January 2019
1 Read

DS86760016, a leucyl-tRNA synthetase inhibitor, with activity against .

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Department of Microbiology, and Department of Pharmacokinetics and Metabolism, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India.

DS86760016 is a new leucyl-tRNA-synthetase inhibitor in the preclinical development stage. DS86760016 showed potent activity against extended spectrum multidrug-resistant isolated from clinical samples and biofilms. In a murine catheter associated urinary tract infection model, DS86760016 treatment resulted in significant eradication of counts from kidney, bladder and catheter without developing drug-resistance. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02122-18DOI Listing
January 2019
4.476 Impact Factor

Molecular Epidemiology of Emerging Carbapenem Resistance in in Taiwan, 2010-2014.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.

This study investigated the molecular epidemiology of carbapenem-resistant and (ANAP). Clinical isolates of spp. collected by the biennial nationwide Taiwan Surveillance of Antimicrobial Resistance program from 2010-2014 were subjected to species identification, antimicrobial susceptibility testing, and PCR for detection of carbapenemase genes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02007-18DOI Listing
January 2019

synergism of rifabutin with clarithromycin, imipenem and tigecycline against the complex.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan.

Infections caused by the difficult-to-treat are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active against , especially against clarithromycin-resistant strains. However, exploring for potential synergy between rifabutin and available antimicrobials is currently limited. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02234-18DOI Listing
January 2019