antimicrobial agents
PharmacologyPharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing EnterobacteriaceaeEnterobacteriaceae that produce metallo-β-lactamases (MBLs) are an emerging threat to public health. The metallo-β-lactamase inhibitor (MBLi) ANT2681 inhibits the enzymatic activity of MBLs through interaction with the dinuclear zinc ion cluster present in the active site that is common to these enzymes. ANT2681 is being codeveloped, with meropenem as the partner β-lactam, as a novel combination therapy for infections caused by...
Editor's Pick Mechanisms of ResistanceStructural Recognition of Spectinomycin by Resistance Enzyme ANT(9) from Enterococcus faecalisSpectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT(9) family or by enzymes of the dual-specificity ANT(3ʺ)(9) family, which also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3ʺ...
Experimental TherapeuticsMinocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris BiofilmsCandida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10...
SusceptibilityRetrospective Analysis of Antimicrobial Susceptibility Profiles of Nocardia Species from a Tertiary Hospital and Reference Laboratory, 2011 to 2017Nocardia species are found worldwide and are opportunistic pathogens of both immunocompromised and immunocompetent hosts. Recent updates to the taxonomy of this genus have indicated that there are more than 90 recognized species of Nocardia with 54 species reported to be clinically relevant.
MinireviewFact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic InteractionsMany antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common...
SusceptibilityA Whole-Cell Screen Identifies Small Bioactives That Synergize with Polymyxin and Exhibit Antimicrobial Activities against Multidrug-Resistant BacteriaThe threat of diminished antibiotic discovery has global health care in crisis. In the United States, it is estimated each year that over 2 million bacterial infections are resistant to first-line antibiotic treatments and cost in excess of 20 billion dollars.
Clinical TherapeuticsPopulation Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIVThis study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling.
PharmacologySafety, Tolerability, and Pharmacokinetics of Oral Nafithromycin (WCK 4873) after Single or Multiple Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult SubjectsNafithromycin (WCK 4873), a novel lactone-ketolide, was administered to healthy adult subjects in 2 randomized, double-blind, placebo-controlled, phase 1 studies. In the first-in-human study, single ascending oral doses of nafithromycin (100 to 1,200 mg) were administered to subjects under fasted or fed conditions, with effects of food on bioavailability of nafithromycin studied at the dose levels of 400 and 800 mg.
Clinical TherapeuticsDaily Dosing for Bedaquiline in Patients with TuberculosisThe bedaquiline regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in adults is a loading dose of 400 mg QD for 2 weeks followed by 200 mg thrice weekly (TIW) for 22 weeks. Most TB antibiotics administered with bedaquiline are given QD.
Experimental TherapeuticsTherapeutic Efficacy of LN-1-255 in Combination with Imipenem in Severe Infection Caused by Carbapenem-Resistant Acinetobacter baumanniiThe carbapenem-hydrolyzing class D β-lactamases (CHDLs) are the main mechanism of carbapenem resistance in Acinetobacter baumannii. CHDLs are not effectively inactivated by clinically available β-lactam-type inhibitors. We have previously described the in vitro efficacy of the inhibitor LN-1-255 in combination with carbapenems.