aminoglycosides
SusceptibilityActivity of Plazomicin Tested against Enterobacterales Isolates Collected from U.S. Hospitals in 2016–2017: Effect of Different Breakpoint Criteria on Susceptibility Rates among AminoglycosidesPlazomicin was active against 97.0% of 8,783 Enterobacterales isolates collected in the United States (2016 and 2017), and only 6 isolates carried 16S rRNA methyltransferases conferring resistance to virtually all aminoglycosides. Plazomicin (89.2% to 95.9% susceptible) displayed greater activity than amikacin (72.5% to 78.6%), gentamicin (30.4% to 45.9%), and tobramycin (7.8% to 22.4%) against carbapenem-resistant and...
Mechanisms of ResistanceProduction of Norspermidine Contributes to Aminoglycoside Resistance in pmrAB Mutants of Pseudomonas aeruginosaEmergence of resistance to polymyxins in Pseudomonas aeruginosa is mainly due to mutations in two-component systems that promote the addition of 4-amino-4-deoxy-l-arabinose to the lipopolysaccharide (LPS) through upregulation of operon arnBCADTEF-ugd (arn) expression. Here, we demonstrate that mutations occurring in different...
Mechanisms of ResistanceIntegron-Derived Aminoglycoside-Sensing Riboswitches Control Aminoglycoside Acetyltransferase Resistance Gene ExpressionClass 1 integrons accumulate antibiotic resistance genes by site-specific recombination at aatI-1 sites. Captured genes are transcribed from a promoter located within the integron; for class 1 integrons, the first gene to be transcribed and translated normally encodes an aminoglycoside antibiotic resistance protein (either an acetyltransferase [AAC] or adenyltransferase [AAD]).
PharmacologyPopulation Pharmacokinetic Analyses for Plazomicin Using Pooled Data from Phase 1, 2, and 3 Clinical StudiesPlazomicin is an aminoglycoside with activity against multidrug-resistant Enterobacteriaceae. Plazomicin is dosed on a milligram-per-kilogram-of-body-weight basis and administered by a 30-min intravenous infusion every 24 h, with dose adjustments being made for renal impairment and a body weight (BW) of ≥125% of ideal BW.
PharmacologyPopulation Pharmacokinetics with Monte Carlo Simulations of Gentamicin in a Population of Severely Ill Adult Patients from Sub-Saharan Africa...In sub-Saharan Africa (SSA), gentamicin is commonly used for severe infections in non-intensive-care-unit (ICU) settings, but pharmacokinetic and pharmacodynamic data for this specific population are lacking. We performed a population pharmacokinetic study in an adult Mozambican non-ICU hospital population treated with gentamicin (n = 48) and developed a pharmacokinetic model using nonlinear mixed-effects modeling.
SusceptibilityIn Vivo Gentamicin Susceptibility Test for Prevention of Bacterial Biofilms in Bone Tissue and on ImplantsThe objective of this study was to set up an in vivo gentamicin susceptibility test for biofilm prevention in bone tissue and on implants. Twenty-five pigs were allocated to six groups.
Clinical TherapeuticsA Systematic Review of Single-Dose Aminoglycoside Therapy for Urinary Tract Infection: Is It Time To Resurrect an Old Strategy?Increasing bacterial resistance and poor patient adherence rates limit the effectiveness of conventional antibiotic therapies for urinary tract infection (UTI). The objective of this study was to investigate whether a single aminoglycoside dose adequately treated UTI.
SusceptibilityIn Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance StudyThe Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate the in vitro activities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from 2013 to 2017 from patients in Canadian hospitals as part of the CANWARD Surveillance Study. Plazomicin demonstrated potent in vitro activity against ...
Clinical TherapeuticsA Phase 1 Study To Assess the Pharmacokinetics of Intravenous Plazomicin in Adult Subjects with Varying Degrees of Renal FunctionPlazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infections. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single 7.5-mg/kg of body weight dose of plazomicin as a 30-min intravenous infusion.
Mechanisms of Action: Physiological EffectsStudies on Aminoglycoside Susceptibility Identify a Novel Function of KsgA To Secure Translational Fidelity during Antibiotic StressAntibiotic resistance has become a global crisis. Studies on the mechanism of bacterial tolerance to antibiotics will not only increase our conceptual understanding of bacterial death but also provide potential targets for novel inhibitors.