30,990 results match your criteria Antimicrobial agents and chemotherapy[Journal]


Ethionamide population pharmacokinetic model and target attainment in multidrug-resistant tuberculosis.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Infectious Disease Pharmacokinetics Laboratory, College of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA

Ethionamide (ETA), an isonicotinic acid derivative, is part of multidrug-resistant tuberculosis (MDR-TB) regimen. The current guidelines deprioritized ETA due to potential less effectiveness compared to other agents. Our aim was to develop a population pharmacokinetic (PK) model and simulate ETA dosing regimens to assess target attainment. Read More

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http://dx.doi.org/10.1128/AAC.00713-20DOI Listing

CRISPR/Cas9-mediated carbapenemase genes and plasmids curing in carbapenem-resistant Enterobacteriaceae.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Center for Discovery and Innovation, Hackensack-Meridian Health, Nutley, NJ, USA

Combating plasmid-mediated carbapenem resistance is essential to control and prevent the dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Here we conducted a proof-of-concept study to demonstrate CRISPR/Cas9-mediated resistance gene and plasmid curing can effectively re-sensitize CRE to carbapenems. A novel CRISPR/Cas9-mediated plasmid-curing system (pCasCure) was developed and electrotransferred into various clinical CRE isolates. Read More

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http://dx.doi.org/10.1128/AAC.00843-20DOI Listing

Clinical trials of repurposed antivirals for SARS-CoV-2.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. Read More

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http://dx.doi.org/10.1128/AAC.01101-20DOI Listing

Characterization of large deletion mutants of selected for isoniazid resistance.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA

Large Genomic Deletions (6 to 63 kbp, LGDs) were observed in isoniazid-resistant () mutants derived from four strains. These LGDs had no growth defect in vitro, but could be defective for intracellular growth, and showed varying sensitivities towards oxidative stress despite lacking The LGDs region comprises 74 genes, mostly of unknown function, that may be important for intracellular growth and protection against oxidative stress. Read More

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http://dx.doi.org/10.1128/AAC.00792-20DOI Listing

Use of a fluorescence-based assay to measure membrane potential changes in high throughput.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Texas A&M University, Department of Biology, College Station, TX, USA

Bacterial membrane potential is difficult to measure using classical electrophysiology techniques due to the small cell size and the presence of the peptidoglycan cell wall. Instead, chemical probes are often used to study membrane potential changes in conditions of interest. Many of these probes are fluorescent molecules that accumulate in a charge-dependent manner, and the resulting fluorescence change can be analyzed via flow cytometry or using a fluorescence microplate reader. Read More

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http://dx.doi.org/10.1128/AAC.00910-20DOI Listing

Monoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B Virus.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA

Human influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (mAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe infections with influenza B virus. Read More

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http://dx.doi.org/10.1128/AAC.00284-20DOI Listing

Spread of ST45 producing GES-5 carbapenemase or GES-1 extended-spectrum β-lactamase in newborns and infants.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Dept Molecular Microbiology, National Medicines Institute, 00-725 Warsaw, Poland.

GES-type extended-spectrum β-lactamases (ESBLs), like GES-1, mutate by Gly170Asn/Ser substitutions into carbapenem-hydrolyzing variants, of which GES-5 is relatively more frequent (1, 2).…. Read More

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http://dx.doi.org/10.1128/AAC.00595-20DOI Listing

Intracellular Tenofovir and Emtricitabine Concentrations in Younger and Older Women with HIV Receiving Tenofovir Disoproxil Fumarate/Emtricitabine.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

UNC School of Medicine, Chapel Hill, NC.

The altered immune states of aging and HIV infection may affect intracellular metabolism of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC); increased cellular senescence decreases FTC-triphosphate (FTCtp) concentrations. The effects of age and inflammation on the ratio of intracellular metabolites (IM; tenofovir diphosphate [TFVdp], FTCtp) to their endogenous nucleotides (EN; dATP and dCTP, respectively), a potential treatment efficacy marker, was assessed among participants of the Women's Interagency HIV Study (WIHS), who ranged from 25-75 years. Samples from women receiving TDF/FTC with viral load <200 copies/mL were dichotomized by age at collection into two groups (≤45 years, ≥60 years). Read More

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http://dx.doi.org/10.1128/AAC.00177-20DOI Listing

Population Pharmacokinetics of Praziquantel in Pregnant and Lactating Filipino Women infected with .

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool Health Partners Liverpool, UK.

An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite () spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in endemic areas. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. Read More

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http://dx.doi.org/10.1128/AAC.00566-20DOI Listing

The in vitro activity of tedizolid compared to linezolid and five other antimicrobial agents against 332 anaerobic isolates including group spp., , and spp.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

From the RM Alden Research Laboratory, , Santa Monica CA, 90291 and.

Tedizolid's anaerobic activity is unappreciated; it was active against all 332 anaerobic isolates at ≤2 μg/ml except and was more active than linezolid against sp. (MIC 1 μg/ml vs 2-4 μg/ml). Tedizolid was active against Gram-positive anaerobes (MIC clostridia 0. Read More

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http://dx.doi.org/10.1128/AAC.01088-20DOI Listing

Toward a single dose cure for Buruli ulcer.

Antimicrob Agents Chemother 2020 Jul 6. Epub 2020 Jul 6.

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

A single dose of TELACEBEC (Q203), a phase 2 clinical candidate for tuberculosis, eradicates in a mouse model of Buruli ulcer infection without relapse up to 19 weeks post treatment. Clinical use of Q203 could dramatically simplify the clinical management of Buruli ulcer, a neglected mycobacterial disease. Read More

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http://dx.doi.org/10.1128/AAC.00727-20DOI Listing

Non-stationary pharmacokinetics of caspofungin in ICU patients.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland

Standard dosing of caspofungin in critically ill patients has been reported to result in lower drug exposure, which can lead to subtherapeutic AUC/MIC ratios. The aim of the study was to investigate the population pharmacokinetics of caspofungin in a cohort of 30 ICU patients with a suspected invasive fungal infection, with a large proportion of patients requiring extracorporeal therapies including ECMO and CRRT. Caspofungin was administered as empirical antifungal therapy 70 mg i. Read More

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http://dx.doi.org/10.1128/AAC.00345-20DOI Listing

ANTILEISHMANIAL AMINOPYRAZOLES: STUDIES INTO MECHANISMS AND STABILITY OF EXPERIMENTAL DRUG RESISTANCE.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Belgium

Current antileishmanial treatment is hampered by limitations such as drug toxicity and the risk of treatment failure, which may be related to parasitic drug resistance. Given the urgent need for novel drugs, the Drugs for Neglected Diseases (DND) has undertaken a drug discovery program, which has resulted in the identification of aminopyrazoles - a highly promising antileishmanial chemical series. Multiple experiments have been performed to anticipate the propensity for resistance development. Read More

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http://dx.doi.org/10.1128/AAC.00152-20DOI Listing

In Vitro and In Vivo Activity, Tolerability and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus-2 Genital Infection.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612

Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the ano-genital area that may be transmitted through sexual encounters. Nucleoside analogs such as acyclovir (ACV) are currently prescribed clinically to curb this infection. But in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. Read More

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http://dx.doi.org/10.1128/AAC.00245-20DOI Listing
June 2020
4.476 Impact Factor

The FDA-approved drug Nelfinavir inhibits lytic cell-free, but not cell-associated non-lytic transmission of human adenovirus.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

Adenoviruses (AdVs) are prevalent and give rise to chronic and recurrent disease. The human AdV (HAdV) species B and C, such as HAdV-C2, C5 and B14, cause respiratory disease, and constitute a health threat for immuno-compromised individuals. HAdV-Cs are well known for lysing cells, owing to the E3 CR1-β-encoded adenovirus death protein (ADP). Read More

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http://dx.doi.org/10.1128/AAC.01002-20DOI Listing

Preclinical evaluation of acylhydrazone SB-AF-1002 as a novel broad-spectrum antifungal agent.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New York, USA

The incidence of invasive fungal infections is rising due to the increase in susceptible populations. Current clinically available drugs have therapeutic limitations due to toxicity, narrow spectrum of activity, and more importantly for the consistent rise of fungal species that are intrinsically resistant or develop resistance due to the prolonged therapy. Thus, there is an urgent need for new broad-spectrum antifungal agents with low toxicity and a novel mechanism of action. Read More

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http://dx.doi.org/10.1128/AAC.00946-20DOI Listing

Pharmacist-driven Implementation of Fast Identification and Antimicrobial Susceptibility Testing Improves Outcomes for Patients with Gram-negative Bacteremia and Candidemia.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Department of Pharmacy, Peninsula Regional Medical Center, Salisbury, Maryland

Bloodstream infections (BSI) are associated with increased morbidity and mortality, especially when caused by gram-negative or fungal pathogens. The objective of this study was to assess the impact of fast ID/AST with the Accelerate Pheno ™ system (AXDX) from May 2018 to December 2018 on antibiotic therapy and patient outcomes. A pre-post quasi-experimental study of 200 patients (100 pre-AXDX implementation and 100 post-AXDX implementation) was conducted. Read More

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http://dx.doi.org/10.1128/AAC.00578-20DOI Listing

Efficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of .

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

Pyrazolones are heterocyclic compounds with interesting biological properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cyclic AMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan , the etiological agent of Chagas disease (CD), a major Neglected Tropical Disease. phenotypic screening identified a 4-bromophenyl-dihydropyrazole dimer as anti- hit and 17 novel pyrazolone analogues with variations on the phenyl ring were investigated in a panel of phenotypic laboratory models. Read More

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http://dx.doi.org/10.1128/AAC.00414-20DOI Listing

Computational chemogenomics drug repositioning strategy enables the discovery of Epirubicin as a new repurposed hit for and .

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Laboratory of Tropical Diseases-Prof. Dr. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas-UNICAMP, Campinas, SP, Brazil

Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks and time-to-market. Herein we have used this strategy to identify novel antimalarial hits. Read More

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http://dx.doi.org/10.1128/AAC.02041-19DOI Listing

A roadblock-and-kill mechanism of action model for the DNA-targeting antibiotic ciprofloxacin.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom.

Fluoroquinolones - antibiotics that cause DNA damage by inhibiting DNA topoisomerases - are clinically important, but their mechanism of action is not yet fully understood. In particular, the dynamical response of bacterial cells to fluoroquinolone exposure has hardly been investigated, although the SOS response, triggered by DNA damage, is often thought to play a key role. Here we investigate growth inhibition of the bacterium by the fluoroquinolone ciprofloxacin at low concentrations. Read More

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http://dx.doi.org/10.1128/AAC.02487-19DOI Listing

Prolonged exposure to β-lactam antibiotics reestablishes susceptibility of daptomycin-nonsusceptible to daptomycin.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

School of Pharmacy, University of Wisconsin-Madison, Doherty Applied Microbial Genomics, Dept. of Microbiology & Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia

Daptomycin-nonsusceptible () often exhibit gain-in-function mutations in the gene (involved in positive surface charge maintenance). Standard β-lactams, although relatively inactive against MRSA, may prevent emergence of mutations and DAP-NS. We determined if β-lactams might also impact DAP-NS isolates already possessing an mutation to revert them to DAP-susceptible () phenotypes, and if so, whether this is associated with specific penicillin-binding protein () targeting. Read More

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http://dx.doi.org/10.1128/AAC.00890-20DOI Listing

Semimechanistic Modeling of Eravacycline Pharmacodynamics Using Time-Kill Data with MIC Incorporated in an Adaptive Resistance Function.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food & Drug Administration (FDA)

Effective bacterial infection eradication requires not only potent antibacterial agents, but also proper dosing strategies. Current practices generally utilize point estimates of the effect of the therapeutic agents even though the actual kinetics of exposure are much more complex and relevant. Here, we use a full time course of the observed effects to develop a semi-mechanistic pharmacokinetic-pharmacodynamic model for eravacycline against multiple Gram-negative bacterial pathogens. Read More

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http://dx.doi.org/10.1128/AAC.01308-20DOI Listing

Unraveling the gentamicin drug product complexity reveals variation in microbiological activities and nephrotoxicity.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Former employees of Achaogen Inc., South San Francisco, California, USA.

The gentamicin drug product is a complex mixture of numerous components, many of which have not individually undergone safety and efficacy assessments. This is in contrast to the majority of medicines that require rigorous characterizations of trace impurities and are dosed as single components. In gentamicin, four components, known as gentamicin congeners C1, C1a, C2, and C2a, comprise the majority of the mixture. Read More

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http://dx.doi.org/10.1128/AAC.00533-20DOI Listing

HIV-1 Integrase Inhibitors that are active against Drug-Resistant Integrase Mutants.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.

The current recommended first-line therapy for HIV-1 infected patients is a second generation integrase (IN) strand transfer inhibitor (INSTI), either Dolutegravir (DTG) or Bictegravir (BIC), in combination with two nucleoside reverse transcriptase inhibitors (NRTIs). Both DTG and BIC potently inhibit most INSTI-resistant IN mutants selected by first-generation INSTIs. BIC has not been reported to select for resistance in treatment-naïve patients and DTG has selected for a small number of resistant viruses in treatment-naïve patients. Read More

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http://dx.doi.org/10.1128/AAC.00611-20DOI Listing

Genomic Profiling of Evolving Daptomycin Resistance in a Patient with Recurrent Sepsis.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Chan Zuckerberg Biohub, San Francisco, CA, USA

is a novel staphylococcal species associated with invasive disease. We report the first case of daptomycin/vancomycin-resistant initially speciated as , that developed from repeated treatment with daptomycin for a complex vascular graft infection. Whole genome sequencing of longitudinally collected isolates identified acquisition of MprF S337L, a mutation predicted to increase surface charge and repel cationic molecules. Read More

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http://dx.doi.org/10.1128/AAC.00961-20DOI Listing

Population pharmacokinetics and target attainment of cefepime in critically ill patients and guidance for initial dosing.

Antimicrob Agents Chemother 2020 Jun 29. Epub 2020 Jun 29.

Infectious Disease Pharmacokinetics Laboratory, Emerging Pathogens Institute, University of Florida, Gainesville, FL.

Cefepime is commonly used in the intensive care unit (ICU) to treat bacterial infections. The time the free cefepime concentration above the minimum inhibitory concentration (T) should be optimized to increase the efficacy of the regimen. We aim to optimize the exposure of cefepime in ICU patients using population pharmacokinetic (PK) modeling and simulations. Read More

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http://dx.doi.org/10.1128/AAC.00745-20DOI Listing

Correction for Softley et al., "Structure and Molecular Recognition Mechanism of IMP-13 Metallo-β-Lactamase".

Antimicrob Agents Chemother 2020 Jun 23;64(7). Epub 2020 Jun 23.

Biomolecular NMR and Center for Integrated Protein Science Munich at Department Chemie, Technical University of Munich, Garching, Germany

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http://dx.doi.org/10.1128/AAC.01077-20DOI Listing

Erratum for Reitzel et al., "Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective for Eradication of Candida auris Biofilms".

Antimicrob Agents Chemother 2020 Jun 23;64(7). Epub 2020 Jun 23.

Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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http://dx.doi.org/10.1128/AAC.01014-20DOI Listing

Correction for Rodríguez López et al., "Small-Molecule Morphogenesis Modulators Enhance the Ability of 14-Helical β-Peptides To Prevent Candida albicans Biofilm Formation".

Antimicrob Agents Chemother 2020 Jun 23;64(7). Epub 2020 Jun 23.

Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.

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http://dx.doi.org/10.1128/AAC.00841-20DOI Listing
June 2020
4.476 Impact Factor

IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Infectious Diseases Unit, Internal Medicine Department, Hospital Universitario Puerta de Hierro-Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana, Madrid, Spain.

Evidence to support the use of steroids in COVID-19 pneumonia is lacking. We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality. We performed a single-center retrospective cohort study in a University hospital in Madrid, Spain, during March 2020. Read More

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http://dx.doi.org/10.1128/AAC.01168-20DOI Listing

First report of -, -, and co-harboring foodborne .

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Laboratory of Food Microbiology and Hygiene, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Japan

Carbapenem and colistin antibiotics are often the last resort treatment for severe infections caused by multidrug-resistant bacteria (1-3).…. Read More

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http://dx.doi.org/10.1128/AAC.00882-20DOI Listing

Povidone Iodine: Properties, Mechanisms of Action and Role in Infection Control and Decolonization.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Pole de microbiologie, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain UCLouvain, Brussels, Belgium.

Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant (MRSA) infections. The two most commonly used agents for decolonization are intranasal mupirocin 2% ointment and chlorhexidine wash but the increasing emergence of resistance and treatment failure has underscored the need for alternative therapies. This article discusses povidone iodine (PVP-I) as an alternative decolonization agent and is based on literature reviewed during an Expert's workshop on resistance and MRSA decolonization. Read More

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http://dx.doi.org/10.1128/AAC.00682-20DOI Listing

Rapidly-correcting Frameshift Mutations in the Gene Produce Reversible Ethambutol Resistance and Small Colony Variant Morphology.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Center for Emerging Pathogens, Department of Medicine, New Jersey Medical School, Rutgers University, Newark, New Jersey

We have identified a previously unknown mechanism of reversible high-level ethambutol (EMB)-resistance in that is caused by a reversible frameshift mutation in the gene. A frameshift mutation in produces small colony variant (SCV) phenotype, but this mutation does not change the minimal inhibitory drug concentrations (MICs) of any drug in wild-type However, the same mutation in a low level EMB resistant double mutant (MIC=8μg/ml) produces an SCV with an EMB MIC of 32μg/ml. Reversible-resistance is indistinguishable from a drug-persistent phenotype because further culture of these SCV mutants results in rapid reversion of the frameshifts, reestablishing the correct open reading frame, returning the culture to normal colony size and reversing the EMB MIC back to the 8μg/ml MIC of the parental strain. Read More

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http://dx.doi.org/10.1128/AAC.00213-20DOI Listing

New scheme of intermittent benznidazole administration in patients chronically infected with : Clinical, parasitological and serological assessment after three years of follow-up.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Hospital Interzonal General de Agudos "Eva Perón"; San Martín, Buenos Aires, Argentina.

In a pilot study, we showed that intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by qPCR at the end of treatment. Herein, a three-year post-treatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg/day in two daily doses every 5 days. Read More

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http://dx.doi.org/10.1128/AAC.00439-20DOI Listing

Genetic Basis of Azole and Echinocandin Resistance in Clinical in Japan.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Division of Clinical Research, Medical Mycology Research Center, Chiba University, Chiba, Japan.

Infections caused by have gained worldwide concern especially if associated with increasing echinocandin and azole resistance. In this study, we analyzed the molecular mechanisms of azole and echinocandin resistance in obtained from hospitalized patients in Japan from 1997 to 2019. All isolates were checked phenotypically for resistance, genotypically to detect mutations in , , and hot spot 1 (HS1), HS2, and HS3 of and HS1 and HS2 of and were genotyped by multilocus sequence typing (MLST). Read More

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http://dx.doi.org/10.1128/AAC.00783-20DOI Listing

Urinary creatinine clearance and Pharmacokinetics studies: If we can measure it why do we estimate it?

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Serviço de Medicina Intensiva, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

In a recent issue of , Aréchiga-Alvarado …. Read More

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http://dx.doi.org/10.1128/AAC.00980-20DOI Listing

How to optimally combine genotypic and phenotypic drug-susceptibility testing methods for pyrazinamide.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Emerging Bacterial Pathogens Unit, IRCCS Ospedale San Raffaele, Milano, Italy

False susceptible phenotypic drug-susceptibility testing (DST) results for pyrazinamide due to mutations with MICs close to the critical concentration (CC) confound the classification of resistance mutations, leading to an underestimate of the specificity of genotypic DST. This could be minimised by basing treatment decisions on well-understood mutations and by adopting an area of technical uncertainty for phenotypic DST rather than only testing the CC, as is current practice for the complex. Read More

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http://dx.doi.org/10.1128/AAC.01003-20DOI Listing

NADPH-cytochrome P450 reductase Ccr1 is a target of Tamoxifen and participates in its antifungal activity via regulating cell wall integrity in fission yeast.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Department of Microbial and Biochemical Pharmacy, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China

Invasive fungal diseases are a leading cause of mortality among immune-compromised populations. Treatment is notoriously difficult due to the limited number of antifungal drugs as well as the emergence of drug resistance. Tamoxifen (TAM), a selective estrogen receptor modulator frequently used for treatment of breast cancer, has been found to have antifungal activities, and may be a useful addition to treat fungal infectious diseases. Read More

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http://dx.doi.org/10.1128/AAC.00079-20DOI Listing

Prevalence of Aminoglycoside Resistance Genes and Molecular Characterization of a Novel Gene among Clinical Isolates of Complex from a Chinese Teaching Hospital.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China

complex are important opportunistic human pathogens capable of causing a wide variety of infections. During recent decades, the aminoglycoside-resistant complex isolates have increasingly been reported and become a major concern. Here we employed high-throughput sequencing in combination with specific PCR assays to investigate the prevalence of aminoglycoside resistance genes among 170 isolates of the complex collected from a teaching hospital in Wenzhou, China. Read More

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http://dx.doi.org/10.1128/AAC.00852-20DOI Listing

Pharmacodynamics of Fosfomycin Against Carbapenem-resistant .

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Department of Pharmacy, Department of Microbiology, Department of Infectious DiseasesSingapore General Hopsital, Singapore; Outram Road, Singapore 169608

The increase of carbapenem-resistant Enterobacterales (CRE) and lack of therapeutic options due to scarcity of new antibiotics has sparked interest towards the use of intravenous fosfomycin against systemic CRE infections. We aimed to investigate the pharmacodynamics of fosfomycin against carbapenem-resistant and Time-kill studies and population analysis profiles were performed with eight clinical CRE isolates, which were exposed to fosfomycin concentrations ranging from 0.25 to 2048mg/L. Read More

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http://dx.doi.org/10.1128/AAC.00536-20DOI Listing

Activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole against multidrug resistant .

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA

The production of a metallo-(L1) and serine-(L2) β-lactamase precludes the use of β-lactams for the treatment of infections. Pre-clinical data suggest cefiderocol is the first approved β-lactam with reliable activity against but data against strains resistant to current first -line agents are limited and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, and trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical isolates. Read More

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http://dx.doi.org/10.1128/AAC.00559-20DOI Listing

Characterization of Amikacin Drug Exposure and Nephrotoxicity in an Animal Model.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204

Despite excellent activity, aminoglycosides are used conservatively to treat multidrug resistant bacterial infections due to their associated nephrotoxicity. Aminoglycosides are known to accumulate in the kidneys, but the quantitative relationship between drug exposures and nephrotoxicity is not well established. To bridge the knowledge gap, the objective of this study was to develop an animal model with clinically relevant conditions to mimic human disease progression. Read More

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http://dx.doi.org/10.1128/AAC.00859-20DOI Listing

Genomic Analysis Reveals Antibiotic Susceptible Clones and Emerging Resistance in (Saskatchewan, Canada).

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Department of Biochemistry, Microbiology and Immunology; Vaccine and Infectious Disease Organization - International Vaccine Centre, University of Saskatchewan, Saskatoon SK, Canada

Whole genome sequencing was used to identify mutations in antibiotic resistance-conferring genes, to compare susceptibility predictions with minimum inhibitory concentrations and to ascertain strain types in 99 isolates of Genotypes associated with susceptibility as well as MIC creep or emerging resistance were noted. Phylogenomic analysis revealed three distinctive clades and putative gonococcal transmission linkages involving a tetracycline resistant outbreak and the clonal spread of susceptible isolates in men. Read More

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http://dx.doi.org/10.1128/AAC.02514-19DOI Listing

Transcription Factor Rpn4 Mediates Fluconazole Resistance Through Regulation of Ergosterol Biosynthesis and Plasma Membrane Permeability.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal

The ability to acquire azole resistance is an emblematic trait of the fungal pathogen Understanding the molecular basis of azole resistance in this pathogen is crucial to design more suitable therapeutic strategies. This study shows that the transcription factor (TF) CgRpn4 is a determinant of azole drug resistance. RNA-sequencing during fluconazole exposure revealed that CgRpn4 regulates expression of 212 genes, activating 80 genes and repressing, likely in an indirect fashion, 132 genes. Read More

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http://dx.doi.org/10.1128/AAC.00554-20DOI Listing

Bacteriophage-Antibiotic Combinations for with Varying Bacteriophage and Daptomycin Susceptibilities.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, United States

Concerns regarding increased prevalence of daptomycin (DAP)-resistant strains necessitate novel therapies for infections. Obligately lytic bacteriophages are viruses that target, infect, and kill bacterial cells. Limited studies have evaluated phage-antibiotic combinations against Following an initial screen of eight strains, three strains with varying DAP/phage susceptibility were selected for further experiments. Read More

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http://dx.doi.org/10.1128/AAC.00993-20DOI Listing

Modulation of monocyte activation and function during direct antiviral agents treatment in HIV coinfected patients.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain.

The activation phenotype and functional changes in monocyte subsets during HCV elimination in HIV/HCV-coinfected patients were evaluated. 22 HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antivirals (DAAs) therapy and 10 HIV-monoinfected patients were included. Activation phenotype (10 markers) and polyfunctionality (intracellular IL1α, IL1β, IL6, IL8, TNFα and IL10 production) in three monocyte subsets (classical, intermediate and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Read More

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http://dx.doi.org/10.1128/AAC.00773-20DOI Listing

Effectiveness of therapeutic drug monitoring guided vancomycin dosing in adult patients receiving extra corporeal membrane oxygenation.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Adult Intensive Care Services and Critical Care Research Group, the Prince Charles Hospital, Brisbane, Queensland, Australia.

Patients receiving extracorporeal membrane oxygenation (ECMO) are complex and drug dosing is complicated by significant pharmacokinetic alterations. We sought to describe the frequency of achievement of therapeutic vancomycin concentrations in critically ill patients receiving ECMO with therapeutic drug monitoring (TDM). In this retrospective observational study, we included all critically ill patients receiving TDM for vancomycin whilst on ECMO. Read More

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http://dx.doi.org/10.1128/AAC.01179-20DOI Listing

Risk factors associated with antibiotic treatment failure of Buruli ulcer.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Barwon Health, University Hospital Geelong, Geelong, Australia.

Combination antibiotic therapy is highly effective in curing Buruli ulcer (BU), caused by Treatment failures have been uncommonly reported with the recommended 56 days of antibiotics, and little is known about risk factors for treatment failure.We analysed treatment failures among BU patients treated for ≥56 days of antibiotics from a prospective observational cohort at Barwon Health, Victoria, from 1/1/1998-31/12/2018. Treatment failure was defined as culture positive recurrence within 12 months of commencing antibiotics that occurred: a) following failure to heal the initial lesion, or b) a new lesion developing at the original or new site. Read More

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http://dx.doi.org/10.1128/AAC.00722-20DOI Listing

Antifungal susceptibility of clinical yeast isolates from a large Canadian reference laboratory and application of whole genome sequence analysis to elucidate mechanisms of acquired resistance.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Public Health Ontario, 661 University Avenue, Toronto, ON, Canada M5G 1M1

To understand the epidemiology and susceptibility patterns of yeast infections in Ontario, we examined 4715 clinical yeast isolates submitted to our laboratory for antifungal susceptibility testing from 2014-2018. was the most frequently submitted species (43.0%) followed by (21. Read More

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http://dx.doi.org/10.1128/AAC.00402-20DOI Listing

activities of ravuconazole and isavuconazole against dematiaceous fungi.

Antimicrob Agents Chemother 2020 Jun 22. Epub 2020 Jun 22.

Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu 210042 People's Republic of China

The activities of 11 antifungals against 84 dematiaceous fungi were tested. For most tested fungal species, the MIC values of ravuconazole and isavuconazole were lower than those obtained with itraconazole, voriconazole and posaconazole. Ravuconazole and isavuconazole appear to be more efficient against most dematiaceous fungal infection than other triazoles. Read More

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http://dx.doi.org/10.1128/AAC.00643-20DOI Listing