0000000000241084

AUTHOR

Irja Lutsar

showing 5 related works from this author

Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-i…

2022

Summary Background Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. Methods NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged …

medicine.medical_specialtyTime FactorsPopulationEquivalence Trials as TopicLoading doseArticlelaw.inventionGram-positiveRandomized controlled triallawVancomycinIntensive careInternal medicineIntensive Care Units NeonatalSepsisDevelopmental and Educational PsychologyClinical endpointMedicineHumansDosingeducationInfusions Intravenouseducation.field_of_studybusiness.industryInfant NewbornInfantdosingUnited KingdomAnti-Bacterial AgentsEuropeRegimenTreatment OutcomeSpainRelative riskPediatrics Perinatology and Child Healthsepsibusiness
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Novel activities of safe-in-human broad-spectrum antiviral agents

2018

According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley feve…

0301 basic medicineviruksetviruses030106 microbiologyAPPROVED DRUGSHEPATITIS-C VIRUSINFLUENZA-A VIRUSBioinformaticsAntiviral AgentsArticle03 medical and health sciencesBroad spectrumVirologyHumansRNA VirusesvirusesCELL-CULTUREPharmacologyZIKA VIRUS-INFECTIONviral diseasesECHOVIRUS 1ta1183DNA VirusesDrug Repositioningta1182MOUSE MODELLIVER-TRANSPLANTATION3. Good healthDrug repositioning030104 developmental biology317 PharmacyVirus DiseasesvirustauditENTRY3111 BiomedicineViral diseaseINHIBITORSAntiviral Research
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O26 Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young Inf…

2019

BackgroundIn the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.MethodsA ‘meta-model’ using NONMEM with 4894 concentrations from 1631 neonates was built and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming at reaching a target AUC0-24 of 400 mg*h/L at steady state in at least 80% of neonates.ResultsA two-compartment model best fitted the data. Current weight, post-menstrual age (PMA) and serum creatinine were the significant covariates for clearance (CL). After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg twice dail…

education.field_of_studyCreatininePediatricsmedicine.medical_specialtybusiness.industryMaintenance dosePopulationLoading doseNONMEMchemistry.chemical_compoundchemistryPharmacokineticsMeta-analysisPediatrics Perinatology and Child HealthmedicineVancomycineducationbusinessmedicine.drugArchives of Disease in Childhood
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Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.

2019

Abstract Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if &lt…

0301 basic medicinePediatricsvancomycininfusion procedures0302 clinical medicinenewbornMedicinePharmacology (medical)Randomized Controlled Trials as Topiceducation.field_of_studyMaintenance doseAnti-Bacterial Agents3. Good healthInfectious Diseasesdrug maintenance doseResearch DesignArea Under CurveData Interpretation Statisticalcreatinine testsVancomycinMonte Carlo Methodmedicine.drugMicrobiology (medical)medicine.medical_specialty030106 microbiologyPopulationGestational AgeMicrobial Sensitivity TestsLoading doseRS03 medical and health sciencesPharmacokineticsdrug loading dose030225 pediatricsHumanssteady stateeducationPharmacologyDose-Response Relationship Drugbusiness.industryBody WeightInfant NewbornPostmenstrual AgeinfantNONMEMRegimen[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologieregimen[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologiebusinessserum
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Do We Know When, What and For How Long to Treat?

2012

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric C…

Microbiology (medical)medicine.medical_specialtyRespiratory tract infectionsbusiness.industryRespiratory infectionDiseasemedicine.diseasePneumoniaInfectious DiseasesAntibiotic resistanceCommunity-acquired pneumoniaPediatrics Perinatology and Child HealthEpidemiologymedicineEtiologybusinessIntensive care medicinePediatric Infectious Disease Journal
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