Antibiotics needed to treat multidrug-resistant infections in neonates


Authors: CM Williams PCM, Qazi SA, Agarwal R, Velaphi S, Bielicki JA, Nambiar S, Giaquinto C, Bradley J, Noel GJ, Ellis S, O’Brien S, Balasegaram M & Sharland M

Manuscripts published online first in: Bulletin of the World Health Organization

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


Authors: Hill L.F, Clements M.N, Turner M.A, Donà D, Lutsar I, Jacqz-Aigrain E, Heath P.T, Roilides E, Rawcliffe L, Alonso-Diaz C, Baraldi E, Dotta A, Ilmoja M, Mahaveer A, Metsvaht T, Mitsiakos G,  Papaevangelou V, Sarafidis K, Walker A.S, Sharland M, on behalf of the NeoVanc Consortium

Published in: The Lancet

Global estimates of the relative pediatric consumption and cost of oral amoxicillin and amoxicillin plus clavulanic acid


Authors: G. A. Levine, M. Sharland, S. Ellis, Y. Ferrisse, C. Loze, Y. Hsia, G. Fink, J. Bielicki; for the PediCAP project

Published in: ECCMID 2021



Background: Amoxicillin and co-amoxiclav are commonly used antibiotics for community-acquired infections in young children. Both are classified as Access antibiotics for pediatric respiratory infections in the WHO EMLc.

Harmonising regulatory approval for antibiotics in children


Authors: Phoebe C M Williams, John Bradley, Emmanuel Roilides, Linus Olson, Sheldon Kaplan, Irja Lutsar, Carlo Giaquinto, Daniel K Benjamin, Mike Sharland

Published in: The Lancet

Introduction: Antimicrobial resistance represents a substantial threat to the Sustainable Development Goals (SDGs), with a large impact on the health of children worldwide. However, very few paediatric trials for new antibiotics have been done to inform the optimal treatment of multidrug-resistant infections in children.

Global sales of oral antibiotics formulated for children


Authors: Li G, Jackson C, Bielicki J, Ellis S, Hsiac Y, Sharland M

Published in: Bulletin of the World Health Organization, July 2020

Objective To investigate international consumption patterns of child-appropriate oral formulations of antibiotics by formulation type, with a focus on dispersible tablets, using data from a global sales database.

Methods Antibiotic sales data for 2015 covering 74 countries and regional country groups were obtained from the MIDAS® pharmaceutical sales database,

A comparison of five paediatric dosing guidelines for antibiotics


Authors: Mathur S, Jackson C, Urus H, Ziarko I, Goodbun M, Hsia Y, Ellis S, Sharland M.

Published in: Bulletin of the World Health Organization, April 2020

Objective To compare dosing guidance in the paediatric formularies of high-income countries and emerging economies for 32 commonly prescribed antibiotics on the World Health Organization’s (WHO’s) 2017 Model List of Essential Medicines for Children.

Interim pharmacokinetic analysis of a multi-centre randomised open label phase IIb study in neonates to validate the meta-analysis population pharmacokinetic model used to simulate an optimised dosing regimen in neonates and infants aged < 90 days: the NeoVanc trial


Authors: L. Hill, E. Jacqz-Aigrain, V. Elie, W. Zhao, M. Clements, M. Turner, I. Lutsar, P. Heath, E. Roilides, S. Walker, M. Sharland

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Background: Vancomycin remains one of the most widely prescribed antibiotics for Gram-positive neonatal late onset sepsis (LOS),

An optimised dosing regimen vs. a standard dosing regimen of vancomycin for the treatment of late onset sepsis due to Gram-positive microorganisms in infants less than 90 days: the NeoVanc trial


Authors: L. Hill, M. Clements, M. Turner, I. Lutsar, E. Jacqz-Aigrain, P. Heath, E. Roilides, S. Walker, M. Sharland

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Background: Vancomycin remains one of the most widely prescribed antibiotics for Gram-positive neonatal late onset sep- sis (LOS). Robust neonatal clinical outcome data comparing different vancomycin dosing regimens is lacking.

Application of WISCA (Weighted Incidence Syndromic Combination Antibiogram) to guide empiric therapy in oncological paediatric patients with febrile neutropenia


Authors: E. Barbieri, D. Bottigliengo, P. Costenaro, A. Marzollo, M. Petris, M. Pierobon, G. Biddeci, C. Giaquinto, A. Biffi, D. Donà

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Background: Febrile neutropenia (FN) is an acute potentially life-threatening oncological complication which should be treated promptly with antibiotics. With the spread of antibiotic resistance,

Antibiotic treatment for paediatric outpatients with community-acquired pneumonia: findings from 10 years of prescribing habits in Italy


Authors: P. Costenaro, A. Cantarutti, E. Barbieri, A. Scamarcia, A. Oletto, P. Sacerdoti, R. Lundin, L. Cantarutti, C. Giaquinto, D. Dona’

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Background: Despite national and international efforts to promote appropriate antibiotic prescribing, Italian paediatric antimicrobial prescription rates are among the highest in Europe,

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


Authors: Hill LF, Turner MA, Lutsar I, et al; NeoVanc Consortium.

Published in: Trials. 2020;21(1):329

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,

Implementation and impact of pediatric antimicrobial stewardship programs: a systematic scoping review


Authors: Donà D, Barbieri E, Daverio M, Lundin R, Giaquinto C, Zaoutis T, Sharland M

Published in: Antimicrob Resist Infect Control.2020;9:3

Background Antibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic misuse increases the risk of toxicity, raises healthcare costs, and selection of resistance.

Standardising neonatal and pediatric anitibiotic clinical trial design and conduct: the PENTA-ID network review


Authors: Folgori L, Lutsar I, Standing JF, et al.

Published in: BMJ Open. 2019; 9:e032592

Abstract: 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.

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network


Authors: Li G, Bielicki JA, Ahmed ASMNU, et al.

Published in: Arch Dis Child.2091;0:1-6

Objective To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middleincome country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).

Differential susceptibility of Staphylococcus epidermidis biofilms to vancomycin, daptomycin and linezolid between clinical Isolates from neonates and adults


Authors:Simitsopoulou M, Kadiltzoglou P, Kyrpitzi D, Roilides E.

Published in: Int J Biol Med Res.2019;10(1):6591-6596

Abstract This study aimed to compare the effects of vancomycin, linezolid and daptomycin against planktonic cells and biofilms of 32 bloodstream isolates derived from neonates and adults of three hospitals. Staphylococcus epidermidis biofilm formation was spectrophotometrically assessed following safranin staining.

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants


Authors: Jacqz-Aigrain E, Leroux S, Thomson AH, et al.

Published in: J Antimicrob Ther 2019; 74(8):2128-2138

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,

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries.


Authors: Hsia Y, Lee BR, Versporten A, et al; GARPEC and Global-PPS networks.

Published in: Lancet Glob Health. 2019;7(7):e861-e871

Background Improving the quality of hospital antibiotic use is a major goal of WHO’s global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally.

Hard to study, hard to treat: putting children at the centre of antibiotic research and development


Authors: Balasegaram M, Pécoul B, Gray G, Sharland M, Swaminathan S.

Published in: Lancet Infect Dis. 2019;19(6):573-574

Abstract Newborn babies, infants, and children are substantially affected by antimicrobial resistance. Globally, infectious diseases remain a major cause of morbidity and mortality in children, and an estimated 214 000 newborn babies died from drug-resistant bacterial infections in 2015

R&D for children’s antibiotics – a wake-up call


Authors: O’Brien S, Sharland M, Zaoutis T

Published in: AMR CONTROL 2019-2020; online edition

Abstract It is time to prioritize children’s needs in the context of antimicrobial resistance (AMR). Children, especially babies and young infants, are particularly vulnerable to the rise in drug-resistant infection and need treatments that are adapted to their specific needs. Yet, there are almost no clinical trials looking into children’s antibiotics.

The use of polymyxins to treat carbapenem resistant infections in neonates and children


Authors: Thomas R, Velaphi S, Ellis S, et al.

Published in: Expert Opin Pharmacother. 2019;20(4):415-422. 

Introduction The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units.

Effects of an antimicrobial stewardship intervention on perioperative antibiotic prophylaxis in pediatrics


Authors: Donà D, Luise D, La Pergola E, et al.

Published in: Antimicrob Resist Infect Control. 2019;8:13. 

Purpose This study aims to determine the effectiveness of anAntimicrobial Stewardship Program based on a Clinical Pathway (CP) to improve appropriateness in perioperative antibiotic prophylaxis (PAP).

Materials and Methods This pre-post quasi-experimental study was conducted in a 12 month period (six months before and six months after CP implementation),

High rates of prescribing antimicrobials for prophylaxis in children and neonates: results from the antibiotic resistance and prescribing in European children point prevalence survey


Authors: Hufnagel M, Versporten A, Bielicki J, et al.; for ARPEC Project Group.

Published in: J Pediatric Infect Dis Soc. 2018. doi: 10.1093/jpids/piy019.

Background This study was conducted to assess the variation in prescription practices for systemic antimicrobial agents used for prophylaxis among pediatric patients hospitalized in 41 countries worldwide.

Methods Using the standardized Antibiotic Resistance and Prescribing inEuropean Children Point Prevalence Survey protocol,

The impact of clinical pathways on antibiotic prescribing for acute otitis media and pharyngitis in the emergency department


Authors: Dona D, Baraldi M, Brigadoi G, et al.

Published in: Pediatr Infect Dis J. 2018;37(9):901-907.

Background Although Italian pediatric antimicrobial prescription rates are among the highest in Europe, little action has been taken to improve the appropriateness of antimicrobial prescriptions. The primary aim of this study was to assess changes in antibiotic prescription before and after acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis Clinical Pathway (CP) implementation;

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


Authors: Germovesk E, Lutsar I, Kipepr K, et al.; for NeoMero Consortium

Published in: J Antimicrob Chemother. 2018;73(7):1908-1916

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.

Surveillance for control of antimicrobial resistance


Authors: Tacconelli E, Sifakis F, Harbarth S, et al; for EPI-Net COMBACTE-MAGNET Group

Published in: Lancet Infect Dis. 2018;18(3):e99-e106.

Abstract Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions,

Effects of clinical pathway implementation on antibiotic prescription for pediatric community-acquired pneumonia


Authors: Donà D, Zingarella S, Gastaldi A, et al.

Published in: PLoS One. 2018;13(2):e0193581. 

Background Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

Materials and Methods The CP was implemented on 10/01/2015.

Pharmacodynamics of vancomycin for CoNS infection: experimental basis for optimal use of vancomycin in neonates


Authors: Ramos-Martin R , Johnson A, Livermore J, et al.

Published in: J Antimicrob Ther 2016;71(4):992-1002

Objectives CoNS are the most common cause of neonatal late-onset sepsis. Information on the vancomycin

pharmacokinetics/pharmacodynamics against CoNS is limited. The aim of this study was to characterize vancomycin

pharmacokinetic/pharmacodynamic relationships for CoNS and investigate neonatal optimal dosage