Publications

2

Jul, 2020

Global sales of oral antibiotics formulated for children

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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, which includes samples of pharmacy wholesalers and retailers. The focus was on sales of child-appropriate oral formulations of Access antibiotics in the 2017 World Health Organization’s WHO Model list of essential medicines for children. Sales volumes are expressed using a standard unit (i.e. one tablet, capsule, ampoule or vial or 5 mL of liquid). Sales were analysed by antibiotic, WHO region and antibiotic formulation.

Findings Globally, 17.7 billion standard units of child-appropriate oral antibiotic formulations were sold in 2015, representing 24% of total antibiotic sales of 74.4 billion units (both oral and parenteral) in the database. The top five child-appropriate Access antibiotics by sales volume were amoxicillin, amoxicillin with clavulanic acid, trimethoprim–sulfamethoxazole, cefalexin and ampicillin. The proportion of the top five sold for use as a syrup varied between 42% and 99%. Dispersible tablets represented only 22% of all child-appropriate oral formulation sales and made up only 15% of sales of 10 selected Access antibiotics on the model list for children.

Conclusion Globally most child-appropriate oral antibiotics were not sold as dispersible tablets in 2015, as recommended by WHO. There is a clear need for novel solid forms of antibiotics suitable for use in children.

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21

Apr, 2020

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

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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, late–onset sepsis (LOS). Optimised use to maximise efficacy while minimising toxicity and resistance selection is imperative to ensure vancomycin‘s continued efficacy.

Methods NeoVanc is a European, open-label, Phase IIb, randomised, controlled, non-inferiority trial comparing an optimised vancomycin regimen to a standard vancomycin regimen when treating LOS known/suspected to be caused by Gram-positive organisms (excluding Staphylococcus aureus) in infants aged ≤ 90 days. Three hundred infants will be recruited and randomised in a 1:1 ratio. Infants can be recruited if they have culture confirmed (a positive culture from a normally sterile site and at least one clinical/laboratory criterion) or clinical sepsis (presence of any ≥ 3 clinical/laboratory criteria) in the 24 h before randomisation. The optimised regimen consists of a vancomycin loading dose (25 mg/kg) followed by 5 ± 1 days of 15 mg/kg q12h or q8h, dependent on postmenstrual age (PMA). The standard regimen is a 10 ± 2 day vancomycin course at 15 mg/kg q24h, q12h or q8h, dependent on PMA. The primary endpoint is a successful outcome at the test of cure visit (10 ± 1 days after the end of vancomycin therapy). A successful outcome consists of the patient being alive, having successfully completed study vancomycin therapy and having not had a clinical/microbiological relapse/new infection requiring treatment with vancomycin or other anti-staphylococcal antibiotic for > 24 h. Secondary endpoints include clinical/microbiological relapse/new infection at the short-term follow-up visit (30 ± 5 days after the initiation of vancomycin), evaluation of safety (renal/hearing), vancomycin PK and assessment of a host biomarker panel over the course of vancomycin therapy.

Discussion Based on previous pre-clinical data and a large meta-analysis of neonatal, PK/pharmacodynamic data, NeoVanc was set up to provide evidence on whether a loading dose followed by a short vancomycin course is non-inferior, regarding efficacy, when compared to a standard, longer course. If non-inferiority is demonstrated, this would support adoption of the optimised regimen as a way of safely reducing vancomycin exposure when treating neonatal, Gram-positive LOS.

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4

Feb, 2020

ISF/ESCMID Sepsis Award 2020

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Aislinn Cook, a research fellow at St. George’s University of London in the Paediatric Infectious Diseases Research Group, is the winner of the ISF/ESCMID Sepsis Award 2020! The International Sepsis Forum (ISF) is a non-profit public American charity with the mission to improve outcomes for patients with sepsis. Aislinn was awarded this prize for her ECCMID2020 abstract on the NeoAMR Global Neonatal Sepsis Observational Study (NeoOBS). NeoOBS was launched in July 2018 by the Global Antibiotic R&D Partnership in collaboration with Penta, St George’s University of London, University of Antwerp, MRC-Clinical trials Unit at University College London and 19 hospitals mainly in resource limited settings. The objective of the study is to assess mortality rates of hospitalised infants being treated with significant sepsis, as well as describing clinical presentation and recovery, sepsis management and microbiological epidemiology. This global multi-centre prospective study will complete recruitment at the end of this month. Data collected will be used to inform the design of future antibiotic treatment trials for neonatal sepsis.

Great work Aislinn!

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10

Jan, 2020

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

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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. The primary aim of this systematic review is to summarize the current state of evidence of the implementation and outcomes of pediatric antimicrobial stewardship programs (ASPs) globally.

Methods MEDLINE, Embase and Cochrane Library databases were systematically searched to identify studies reporting on ASP in children aged 0-18 years and conducted in outpatient or in-hospital settings. Three investigators independently reviewed identified articles for inclusion and extracted relevant data.

Results Of the 41,916 studies screened, 113 were eligible for inclusion in this study. Most of the studies originated in the USA (52.2%), while a minority were conducted in Europe (24.7%) or Asia (17.7%). Seventy-four (65.5%) studies used a before-and-after design, and sixteen (14.1%) were randomized trials. The majority (81.4%) described in-hospital ASPs with half of interventions in mixed pediatric wards and ten (8.8%) in emergency departments. Only sixteen (14.1%) studies focused on the costs of ASPs. Almost all the studies (79.6%) showed a significant reduction in inappropriate prescriptions. Compliance after ASP implementation increased. Sixteen of the included studies quantified cost savings related to the intervention with most of the decreases due to lower rates of drug administration. Seven studies showed an increased susceptibility of the bacteria analysed with a decrease in extended spectrum beta-lactamase producers E. coli and K. pneumoniae; a reduction in the rate of P. aeruginosa carbapenem resistance subsequent to an observed reduction in the rate of antimicrobial days of therapy; and, in two studies set in outpatient setting, an increase in erythromycin-sensitive S. pyogenes following a reduction in the use of macrolides.

Conclusions Pediatric ASPs have a significant impact on the reduction of targeted and empiric antibiotic use, healthcare costs, and antimicrobial resistance in both inpatient and outpatient settings. Pediatric ASPs are now widely implemented in the USA, but considerable further adaptation is required to facilitate their uptake in Europe, Asia, Latin America and Africa.

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30

Dec, 2019

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

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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. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators.
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18

Nov, 2019

European Antibiotic Awareness Day

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Today, 18th of November, is European Antibiotic Awareness Day (EADD), that marks the start of the World Antibiotic Awareness Week (WAAW). WAAW aims to increase global awareness of antibiotic resistance, as well as  encourage best practices among the general public, health workers and policy makers to stop the spread of antibiotic resistance. The latest data from the European Centre for Disease Prevention and Control highlights that across the European Union, the number of patients infected by resistant bacteria is increasing. Emphasising the major threat antibiotic resistance continues to pose to public health. Infections caused by antibiotic resistant bacteria can be life-threatening, especially for those most vulnerable in society, such as children and especially newborns. However, until recently, the increasing trend in drug-resistant infections in infants and children has gone relatively unrecognized. In the last few years Penta has been involved in several European and global initiatives aimed at better characterising the use of antibiotics in children and infants, understanding the scale of resistance and investigating the best treatment regimens. At Penta, we are continuing to actively expand our activities in this important area and accelerate the development of treatments for infants and children. #KeepAntibioticsWorking #WakeUpToAMR

2

Oct, 2019

A look back at European Researchers’ Night

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Bacteria are steadily becoming less and less responsive to currently available antibiotics. Together with members of the public, we explored the hot topic of ‘antimicrobial resistance’ at the European Researchers’ Night on 27 September 2019 in Padua, Italy. Every year in the EU alone, an estimated 33,000 people die as a result of infections that cannot be treated with antimicrobial drugs. Sure enough, the World Health Organization (WHO) has placed the growth of antimicrobial resistance on its list of top five threats to global health in 2019.

A total of 57 people took part in the interactive WHO online survey, and the results proved eye-opening! 21% of respondents believed that antibiotics were effective against viruses or all microorganisms. Meanwhile, only one third of people interviewed knew that the overuse of antibiotics leads to higher levels of resistance in microbes, and not in the human body itself.

 

 

It’s clear there is still much work to be done to fill the knowledge gaps on this critical issue. Scientific and academic institutions need to continue strengthening their efforts to make people aware that every one of us is responsible for halting the rise in antimicrobial resistance. Wash your hands properly, always seek for medical advice before taking an antibiotic and remember that drug resistance is becoming a problem not only in people, but also in animals, especially those used for food production, as well as in the environment. Without the proper action today, there will be no cure tomorrow!

27

Sep, 2019

Let’s talk about antimicrobial resistance: Penta at European Researchers’ Night

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Penta will be at the European Researchers’ Night in Padua on 27 September, 2019. For this edition we have chosen the theme of ‘antimicrobial resistance’ (AMR). With the help of flyers and an educational video we hope to illustrate to the public what ‘AMR’ is, how it develops and spreads, and raise awareness on how much this problem is threatening global health. Our team will point out some simple yet extremely important practices that can help limit the rise of resistance.

Antimicrobials are one of the most important fields of activity for Penta; we are involved in several European and global initiatives aimed at better characterizing the use of antibiotics among children and neonates, the scale of resistance in this population and at investigating optimal treatment regimens for common neonatal infections.

The European Researchers’ Night is an initiative that, since 2005, has brought together researchers and the general public in different European cities on the same date in late summer: the fourth Friday in September. The event is a unique opportunity to invite the public to explore the world of research, to open a space for meeting and starting a dialogue with citizens and to encourage young people to pursue scientific careers. People of all ages will have the opportunity to visit research facilities that are usually not open to the public, use the latest technologies with the guidance of researchers, participate in experiments, competitions, demonstrations and simulations, exchange ideas and, most of all, have fun!

25

Sep, 2019

Uniting against antibiotic resistance: ‘5 by 25’

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Our friends at GARDP are calling upon the global community to support its goal to develop and deliver five new treatments by 2025 in response to the growing burden of antibiotic resistant infections.

Antibiotics have radically transformed our world by making previously incurable illnesses treatable. As a result, not only has our wellbeing significantly improved, but millions of lives have been saved. However, this remarkable progress is threatened by the spread of antibiotic resistance and requires an urgent global response.

We need solutions that will deliver for global public health. No one country or sector can do it alone. The GARDP model of public-private partnerships is key to preventing the world form entering a post-antibiotic era. Only together can we tackle this impending crisis!

GARDP invite you to join them at this year’s World Health Summit in Berlin to learn how their ‘5 BY 25’ goal will accelerate the development and delivery of five new and improved treatments to address antibiotic-resistant infections that pose the greatest threat to health and development. These new treatments will focus on the priority pathogens identified by the World Health Organization, and current unmet needs for diseases and key populations.

If you are interested in attending please write to ‘contact@gardp.org‘ by 17 October 2019.

 

Event details:

Date: Monday 28 October, 2019
Time: 14.00 –15:30
Venue: Saal 2 – America, Kosmos, Karl-Marx-Allee 131a, Berlin, Germany

28

May, 2019

Article – “R&D for children’s antibiotics: a wake-up call” published in AMR Control

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We are delighted to see an article on children’s antibiotics, co-authored by GARDP R&D Director, Dr Seamus O’Brien, Penta’s Chief Scientific Officer, Prof. Theo Zakoutlis and Prof. Mike Sharland, from St. George’s, University of London, published in AMR Control, as governments have been discussing AMR at the World Health Assembly.

In R&D for children’s antibiotics: a wake-up call the authors explain how AMR has a disproportionate effect on children, jeopardizing the attainment of the Sustainable Development Goals and universal health coverage. The article highlights research that must serve as an urgent wake-up call. This includes a study showing how, in Europe, infants under the age of 1-year-old bear the highest burden of AMR and a study which finds an estimated 214,000 neonatal sepsis deaths a year result from drug-resistant infections.

It outlines how children, particularly babies and young infants, need medicines that are adapted in terms of dosing, formulation. Yet, how lack of evidence means that such treatments are often simply not available. It reviews how the very few active clinical trials are limited in scope, do not recruit enough patients and do not focus on the most life-threatening infections.

The authors then highlight the work the partners are doing together – including the development of a global children’s antibiotic platform, which aims to accelerate paediatric development of antibiotic treatments, including clinical trials designed to meet regulatory requirements, and also trials to inform treatment guidelines. It also links to wider initiatives such as conect4children and the European Clinical Research Alliance on Infectious Diseases (ECRAID), for which Penta is paediatric partner.

GARDP, Penta, and St George’s call upon governments, researchers, industry – anyone with an interest in tackling AMR in children – to join them.

Read the full article here!