Ann E. Eakin
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View article: US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institutes of Health Co-Sponsored Public Workshop Summary—Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea
US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institutes of Health Co-Sponsored Public Workshop Summary—Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea Open
There is an unmet need for developing drugs for the treatment of gonorrhea due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug-resista…
View article: SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies
SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies Open
The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medica…
View article: SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster
SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster Open
The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 along with its high number of mutations in the spike gene has raised alarm about the effectiveness of current medical countermeasures. To address this concern, we meas…
View article: SARS-CoV-2 Delta Variant Displays Moderate Resistance to Neutralizing Antibodies and Spike Protein Properties of Higher Soluble ACE2 Sensitivity, Enhanced Cleavage and Fusogenic Activity
SARS-CoV-2 Delta Variant Displays Moderate Resistance to Neutralizing Antibodies and Spike Protein Properties of Higher Soluble ACE2 Sensitivity, Enhanced Cleavage and Fusogenic Activity Open
The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. Here, we compared B.1…
View article: SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity
SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity Open
The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. The spike proteins of…
View article: Key Substitutions in the Spike Protein of SARS-CoV-2 Variants Can Predict Resistance to Monoclonal Antibodies, but Other Substitutions Can Modify the Effects
Key Substitutions in the Spike Protein of SARS-CoV-2 Variants Can Predict Resistance to Monoclonal Antibodies, but Other Substitutions Can Modify the Effects Open
Therapeutic antibodies are effective in preventing severe disease from SARS-CoV-2 infection (COVID-19), but their effectiveness may be reduced by virus variants with mutations affecting the spike protein. To help predict resistance to ther…
View article: Ternary complex structure of human hgprtase, prpp, mg 2+ , and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding
Ternary complex structure of human hgprtase, prpp, mg 2+ , and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding Open
Site-directed mutagenesis was used to replace Lys68 of the human hypoxanthine phosphoribosyltransferase (HGPRTase) with alanine to exploit this less reactive form of the enzyme to gain additional insights into the structure activity relati…
View article: Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model
Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model Open
Background MBL-producing strains of Enterobacteriaceae are a major public health concern. We sought to define optimal combination regimens of ceftazidime/avibactam with aztreonam in a hollow-fibre infection model (HFIM) of MBL-producing st…
View article: In Vivo Activity of Amodiaquine against Ebola Virus Infection
In Vivo Activity of Amodiaquine against Ebola Virus Infection Open
During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an E…
View article: Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents
Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents Open
In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial …
View article: Generating Robust and Informative Nonclinical <i>In Vitro</i> and <i>In Vivo</i> Bacterial Infection Model Efficacy Data To Support Translation to Humans
Generating Robust and Informative Nonclinical <i>In Vitro</i> and <i>In Vivo</i> Bacterial Infection Model Efficacy Data To Support Translation to Humans Open
In June 2017, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial …
View article: Pharmacokinetic Data Are Predictive of <i>In Vivo</i> Efficacy for Cefixime and Ceftriaxone against Susceptible and Resistant <i>Neisseria gonorrhoeae</i> Strains in the Gonorrhea Mouse Model
Pharmacokinetic Data Are Predictive of <i>In Vivo</i> Efficacy for Cefixime and Ceftriaxone against Susceptible and Resistant <i>Neisseria gonorrhoeae</i> Strains in the Gonorrhea Mouse Model Open
There is a pressing need for drug development for gonorrhea. Here we describe a pharmacokinetic (PK)/pharmacodynamic (PD) analysis of extended-spectrum cephalosporins (ESC) against drug-susceptible and drug-resistant gonococcal strains in …
View article: Faculty Opinions recommendation of The multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity.
Faculty Opinions recommendation of The multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity. Open
The multiple antibiotic resistance (mar) operon of Escherichia coli is a paradigm for chromosomally encoded antibiotic resistance in enteric bacteria.The locus is recognised for its ability to modulate efflux pump and porin expression via …
View article: Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus
Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus Open
In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepa…
View article: Pharmacodynamic Profiling of a Siderophore-Conjugated Monocarbam in Pseudomonas aeruginosa: Assessing the Risk for Resistance and Attenuated Efficacy
Pharmacodynamic Profiling of a Siderophore-Conjugated Monocarbam in Pseudomonas aeruginosa: Assessing the Risk for Resistance and Attenuated Efficacy Open
The objective of this study was to investigate the risk of attenuated efficacy due to adaptive resistance for the siderophore-conjugated monocarbam SMC-3176 in Pseudomonas aeruginosa by using a pharmacokinetic/pharmacodynamic (PK/PD) appro…
View article: Pharmacokinetics/pharmacodynamics of a β-lactam and β-lactamase inhibitor combination: a novel approach for aztreonam/avibactam
Pharmacokinetics/pharmacodynamics of a β-lactam and β-lactamase inhibitor combination: a novel approach for aztreonam/avibactam Open
PK/PD evaluations for aztreonam/avibactam in HFIM yielded a single target across strains with a wide MIC range. This integrated approach could be easily applied for forecasting clinically efficacious doses for β-lactam/β-lactamase inhibito…