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Author Irja Lutsar

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An optimised dosing regimen versus a standard dosing regimen of vancomycin for the treatment of late onset sepsis due to Gram-positive microorganisms in neonates and infants aged less than 90 days (NeoVanc): study protocol for a randomised controlled trial.

Louise F Hill, Mark A Turner, Irja Lutsar, Paul T Heath, Pollyanna Hardy, Louise Linsell, Evelyne Jacqz-Aigrain, Emmanuel Roilides, Mike Sharland, ,

BACKGROUND:Vancomycin has been used in clinical practice for over 50 years; however, validated, pharmacokinetic (PK) data relating clinical outcomes to different dosing regimens in neonates are lacking. Coagulase negative staphylococci (CoNS) are the most commonly isolated organisms in neonatal, late-onset sepsis (LOS). Optimised use to maximise efficacy while minimising toxicity ... Read more >>

Trials (Trials)
[2020, 21(1):329]

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Dynamics of hepatitis C epidemic among people living with HIV in Estonia

Kerstin Kase, Radko Avi, Karolin Toompere, Heli Rajasaar, Merit Pauskar, Pilleriin Soodla, Ene-Ly Jõgeda, Kai Zilmer, Irja Lutsar, Kristi Huik,

Abstract Background Estonia has a typical Eastern European HIV epidemic where the most frequent co-infection is chronic hepatitis C (HCV). We aimed to describe the changes in HCV prevalence, the distribution of HCV genotypes (GT), and HCV treatment in Estonian people living with HIV over 15 years. Methods We used ... Read more >>

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Dynamics of pertussis toxin IgG after symptomatic pertussis in children and adults.

Piia Jõgi, Hiie Soeorg, Marje Oona, Tanel Kaart, Karolin Toompere, Tereza Maskina, Iris Koort, Anneli Rätsep, Irja Lutsar, ,

BACKGROUND AND AIM:The knowledge of dynamics of pertussis toxin (PT)-IgG after pertussis and the appropriate diagnostic cut-off value is limited. We aimed to describe the dynamics of PT-IgG in children and adults up to three years after symptomatic pertussis. METHODS:Patients with persistent cough of unknown aetiology were prospectively enrolled 2012-2014. ... Read more >>

Vaccine (Vaccine)
[2020, 38(16):3196-3200]

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Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

Irja Lutsar, Corine Chazallon, Ursula Trafojer, Vincent Meiffredy de Cabre, Cinzia Auriti, Chiara Bertaina, Francesca Ippolita Calo Carducci, Fuat Emre Canpolat, Susanna Esposito, Isabelle Fournier, Maarja Hallik, Paul T Heath, Mari-Liis Ilmoja, Elias Iosifidis, Jelena Kuznetsova, Laurence Meyer, Tuuli Metsvaht, George Mitsiakos, Zoi Dorothea Pana, Fabio Mosca, Lorenza Pugni, Emmanuel Roilides, Paolo Rossi, Kosmas Sarafidis, Laura Sanchez, Michael Sharland, Vytautas Usonis, Adilia Warris, Jean-Pierre Aboulker, Carlo Giaquinto, ,

BACKGROUND:The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore ... Read more >>

PLoS ONE (PloS one)
[2020, 15(3):e0229380]

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Acute gastroenteritis hospitalizations after implementation of universal mass vaccination against rotavirus.

Kadri Kõivumägi, Karolin Toompere, Hiie Soeorg, Eveli Kallas, Ene-Ly Jõgeda, Kristi Huik, , Irja Lutsar,

BACKGROUND:Estonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aimed to describe changes in acute gastroenteritis (AGE) hospitalization during RV seasons before (2007-2013) and after (2015-2018) RV UMV and compare patient profile of hospitalized AGE patients aged 0-18 years during first two consecutive RV seasons 2015 vs 2016. ... Read more >>

Vaccine (Vaccine)
[2020, 38(13):2879-2886]

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Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

Petter Andersen, Aleksandr Ianevski, Hilde Lysvand, Astra Vitkauskiene, Valentyn Oksenych, Magnar Bjoras, Kaidi Telling, Irja Lutsar, Uga Dumpis, Yasuhiko Irie, Tanel Tenson, Anu Kantele, Denis Kainov,

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of ... Read more >>

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Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Laura Folgori, Irja Lutsar, Joseph F Standing, A Sarah Walker, Emmanuel Roilides, Theoklis E Zaoutis, Hasan Jafri, Carlo Giaquinto, Mark A Turner, Mike Sharland,

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), ... Read more >>

BMJ Open (BMJ open)
[2019, 9(12):e032592]

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GAPPS (Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies) a critical appraisal system for antimicrobial PKPD studies - development and application in pediatric antibiotic studies.

Silke Gastine, Asia N Rashed, Yingfen Hsia, Charlotte Jackson, Charlotte I S Barker, Shrey Mathur, Stephen Tomlin, Irja Lutsar, Julia Bielicki, Joseph F Standing, Mike Sharland,

Introduction: There are limited data on optimal dosing of antibiotics in different age groups for neonates and children. Clinicians usually consult pediatric formularies or online databases for dose selection, but these have variable recommendations, are usually based on expert opinion and are not graded based on the existing pharmacokinetic-pharmacodynamic (PKPD) ... Read more >>

Expert Rev Clin Pharmacol (Expert review of clinical pharmacology)
[2019, 12(12):1091-1098]

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Medicines prescription patterns in European neonatal units.

Inge Mesek, Georgi Nellis, Jana Lass, Tuuli Metsvaht, Heili Varendi, Helle Visk, Mark A Turner, Anthony J Nunn, Jennifer Duncan, Irja Lutsar,

Background Hospitalized neonates receive the highest number of drugs compared to all other age groups, but consumption rates vary between studies depending on patient characteristics and local practices. There are no large-scale international studies on drug use in neonatal units. Objective We aimed to describe drug use in European neonatal ... Read more >>

Int J Clin Pharm (International journal of clinical pharmacy)
[2019, 41(6):1578-1591]

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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.

Evelyne Jacqz-Aigrain, Stéphanie Leroux, Alison H Thomson, Karel Allegaert, Edmund V Capparelli, Valérie Biran, Nicolas Simon, Bernd Meibohm, Yoke-Lin Lo, Remedios Marques, José-Esteban Peris, Irja Lutsar, Jumpei Saito, Hidefumi Nakamura, Johannes N van den Anker, Mike Sharland, Wei Zhao,

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 ... Read more >>

J. Antimicrob. Chemother. (The Journal of antimicrobial chemotherapy)
[2019, 74(8):2128-2138]

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Stable level of HIV transmitted drug resistance in Estonia despite significant scale-up of antiretroviral therapy.

Pilleriin Soodla, Kristi Huik, Merit Pauskar, Lize Cuypers, Kristel Van Laethem, Heli Rajasaar, Eveli Kallas, Helen Lepa, Anna Velts-Lindh, Ene-Ly Jõgeda, Irja Lutsar, Radko Avi,

BACKGROUND:Due to the widespread use of non-nucleoside reverse transcriptase inhibitors (NNRTI) as part of first-line therapies to curb the human immunodeficiency virus (HIV) epidemic in Eastern-European countries, transmitted drug resistance (TDR) is of serious concern in this region. Therefore, TDR and its associated risk factors were investigated among newly diagnosed ... Read more >>

Infect. Genet. Evol. (Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases)
[2019, 75:103901]

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The concordance of the limiting antigen and the Bio-Rad avidity assays in persons from Estonia infected mainly with HIV-1 CRF06_cpx.

Kristi Huik, Pilleriin Soodla, Merit Pauskar, S Michele Owen, Wei Luo, Gary Murphy, Ene-Ly Jõgeda, Eveli Kallas, Heli Rajasaar, Radko Avi, Silvina Masciotra, Irja Lutsar, ,

BACKGROUND:Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of ... Read more >>

PLoS ONE (PloS one)
[2019, 14(5):e0217048]

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Genetic Relatedness of Staphylococcus haemolyticus in Gut and Skin of Preterm Neonates and Breast Milk of Their Mothers.

Hiie Soeorg, Hanna Kadri Metsvaht, Evamaria Elisabet Keränen, Imbi Eelmäe, Mirjam Merila, Mari-Liis Ilmoja, Tuuli Metsvaht, Irja Lutsar,

BACKGROUND:Staphylococcus haemolyticus is a common colonizer and cause of late-onset sepsis (LOS) in preterm neonates. By describing genetic relatedness, we aimed to determine whether mother's breast milk (BM) is a source of S. haemolyticus colonizing neonatal gut and skin and/or causing LOS. METHODS:S. haemolyticus was isolated from stool and skin ... Read more >>

Pediatr. Infect. Dis. J. (The Pediatric infectious disease journal)
[2019, 38(3):308-313]

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Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010⁻2018.

Aleksandr Ianevski, Eva Zusinaite, Nastassia Shtaida, Hannimari Kallio-Kokko, Miia Valkonen, Anu Kantele, Kaidi Telling, Irja Lutsar, Pille Letjuka, Natalja Metelitsa, Valentyn Oksenych, Uga Dumpis, Astra Vitkauskiene, Kestutis Stašaitis, Christina Öhrmalm, Kåre Bondeson, Anders Bergqvist, Rebecca J Cox, Tanel Tenson, Andres Merits, Denis E Kainov,

With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and ... Read more >>

Viruses (Viruses)
[2019, 11(3):]

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Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010-2018

Aleksandr Ianevski, Eva Zusinaite, Nastassia Shtaida, Hannumari Kallio-Kokko, Miia Valkonen, Anu Kantele, Kaidi Telling, Irja Lutsar, Pille Letjuka, Natalja Metelitsa, Valentyn Oksenych, Uga Dumpis, Astra Vitkauskiene, Kestutis Stašaitis, Christina Öhrmalm, Kåre Bondeson, Anders Bergqvist, Rebecca Cox, Tanel Tenson, Andres Merits, Denis Kainov,

With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and ... Read more >>

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Drug prescription pattern in European neonatal units

Inge Mesek, Georgi Nellis, Jana Lass, Tuuli Metsvaht, Heili Varendi, Helle Visk, Mark Turner, Anthony Nunn, Jennifer Duncan, Irja Lutsar,

ABSTRACT Background Hospitalized neonates receive the highest number of drugs compared to all other age groups, but consumption rates vary between studies depending on patient characteristics and local practices. There are no large scale international studies on drug use in neonatal units. We aimed to describe drug use in European ... Read more >>

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Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): a randomised controlled trial

Irja Lutsar, Corine Chazallon, Ursula Trafojer, Vincent Meiffredy de Cabre, Cinzia Auriti, Chiara Bertaina, Francesca Ippolita Calo Carducci, Fuat Emre Canpolat, Susanna Esposito, Isabelle Fournier, Maarja Hallik, Paul Heath Frcpch, Mari-Liis Ilmoja, Elias Iosifidis, Jelena Kuznetsova, Laurence Meyer, Tuuli Metsvaht, George Mitsiakos, Zoi Dorothea Pana, Fabio Mosca, Lorenza Pugni, Emmanuel Roilides, Paolo Rossi, Kosmas Sarafidis, Laura Sanchez, Michael Sharland, Vytautas Usonis, Adilia Warris, Jean-Pierre Aboulker, Carlo Giaquinto, ,

Abstract Background The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, were single centre or country, insufficiently powered, evaluated antibiotics not in ... Read more >>

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External evaluation of population pharmacokinetic models for vancomycin in neonates

Tõnis Tasa, Riste Kalamees, Jaak Vilo, Irja Lutsar, Tuuli Metsvaht,

Abstract Introduction Numerous vancomycin population pharmacokinetic (PK) models of neonates have been published. We aimed to comparatively evaluate a set of these models by quantifying their model-based and Bayesian concentration prediction performances using an external retrospective dataset, and estimate their attainment rates in predefined therapeutic target ranges. Methods Implementations of ... Read more >>

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Genetic relatedness of Gram-negative bacteria colonizing gut and skin of neonates and mother's own milk.

Ülle Parm, Jelena Štšepetova, Imbi Eelmäe, Mirjam Merila, Mari-Liis Ilmoja, Tuuli Metsvaht, Irja Lutsar, Hiie Soeorg,

OBJECTIVE:We described colonization of mother's own milk with Gram-negative bacteria and its relationship with neonatal colonization. STUDY DESIGN:Gram-negative bacteria isolated from weekly collected stool, skin and mother's own milk of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were genotyped. Colonization-related factors were determined by logistic regression. RESULTS:Gram-negative bacteria were ... Read more >>

J Perinatol (Journal of Perinatology)
[2018, 38(11):1503-1511]

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Multidrug resistant Pseudomonas aeruginosa in Estonian hospitals.

Kaidi Telling, Mailis Laht, Age Brauer, Maido Remm, Veljo Kisand, Matti Maimets, Tanel Tenson, Irja Lutsar,

BACKGROUND:We aimed to identify the main spreading clones, describe the resistance mechanisms associated with carbapenem- and/or multidrug-resistant P. aeruginosa and characterize patients at risk of acquiring these strains in Estonian hospitals. METHODS:Ninety-two non-duplicated carbapenem- and/or multidrug-resistant P. aeruginosa strains were collected between 27th March 2012 and 30th April 2013. Clinical ... Read more >>

BMC Infect. Dis. (BMC infectious diseases)
[2018, 18(1):513]

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Association of IFNλ4 rs12979860 polymorphism with the acquisition of HCV and HIV infections among people who inject drugs.

Ene-Ly Jõgeda, Radko Avi, Merit Pauskar, Eveli Kallas, Tõnis Karki, Don Des Jarlais, Anneli Uusküla, Karolin Toompere, Irja Lutsar, Kristi Huik,

We investigated the presence of a single-nucleotide polymorphism designated rs12979860 in the interferon λ4 (IFNλ4) gene among 345 people who inject drugs (PWID) and 495 blood donors to evaluate associations between the rs12979860 genotypes and human immunodeficiency virus/hepatitis C virus (HIV/HCV). The rs12979860 TT genotype was over-represented among HIV+ PWID than HIV- ... Read more >>

J. Med. Virol. (Journal of medical virology)
[2018, 90(11):1779-1783]

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Higher intake of coagulase-negative staphylococci from maternal milk promotes gut colonization with mecA-negative Staphylococcus epidermidis in preterm neonates.

Hiie Soeorg, Sirli Treumuth, Hanna Kadri Metsvaht, Imbi Eelmäe, Mirjam Merila, Mari-Liis Ilmoja, Irja Lutsar, Tuuli Metsvaht,

OBJECTIVE:We aimed to determine factors associated with gut colonization of preterm neonates with coagulase-negative staphylococci (CoNS) from maternal milk (MM). STUDY DESIGN:CoNS isolated from weekly collected stool and MM of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were genotyped. Colonization-related factors were determined by Cox proportional hazards regression. RESULT:Gut ... Read more >>

J Perinatol (Journal of Perinatology)
[2018, 38(10):1344-1352]

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Do medical students feel prepared to prescribe antibiotics responsibly? Results from a cross-sectional survey in 29 European countries.

Oliver J Dyar, Dilip Nathwani, Dominique L Monnet, Inge C Gyssens, Cecilia Stålsby Lundborg, Céline Pulcini, ,

Background:In an era of antibiotic resistance, medical students must be prepared to prescribe antibiotics responsibly. Objectives:To assess self-reported preparedness among final-year medical students at European universities, using a comprehensive set of topics related to prudent antibiotic use. Methods:We conducted a cross-sectional, multicentre, web-based survey. All medical-degree students in their final ... Read more >>

J. Antimicrob. Chemother. (The Journal of antimicrobial chemotherapy)
[2018, 73(8):2236-2242]

Cited: 4 times

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Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

Eva Germovsek, Irja Lutsar, Karin Kipper, Mats O Karlsson, Tim Planche, Corine Chazallon, Laurence Meyer, Ursula M T Trafojer, Tuuli Metsvaht, Isabelle Fournier, Mike Sharland, Paul Heath, Joseph F Standing, ,

Background:Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives:To ... Read more >>

J. Antimicrob. Chemother. (The Journal of antimicrobial chemotherapy)
[2018, 73(7):1908-1916]

Cited: 1 time

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Evaluating Safety Reporting in Paediatric Antibiotic Trials, 2000-2016: A Systematic Review and Meta-Analysis.

Paola Pansa, Yingfen Hsia, Julia Bielicki, Irja Lutsar, A Sarah Walker, Mike Sharland, Laura Folgori,

BACKGROUND:There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children. OBJECTIVE:We performed a systematic review on the safety of antibiotic clinical ... Read more >>

Drugs (Drugs)
[2018, 78(2):231-244]

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