Antimicrobial Pharmacodynamics and Therapeutics (APT) Group

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News

Dr Enas Newire has a new first author publication, entitled 'Identification of a Type IV-A CRISPR-Cas System Located Exclusively on IncHI1B/IncFIB Plasmids in Enterobacteriaceae'.  https://www.frontiersin.org/articles/10.3389/fmicb.2020.01937/full  


Tuesday 12 May 2020 | 4:00 PM - 5:30 PM BST

Global Antibiotic Research and Development Partnership (GARDP) REVIVE webinar presented by Dr Shampa Das "Probability of target attainment analyses for dose selection in antimicrobial drug development"

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In this webinar, Shampa Das will give an overview of her work in studying the probability of target attainment for dose selection.

Topics discussed will include:

  • An overview of what is meant by the probability of target attainment (PTA)
  • How it is calculated and what data is used for this
  • How PTA is used for decision making during drug development

The presentation will be followed by a Q&A session.

Register here.


Dr Shampa Das was successfully awarded funding as part of the COVID-19 Strategic Research Funding Call, March 2020.

Working closely with other academics in the UoL and LSTM Covid-19 partnership & the University of Florida, the APT group have been funded to conduct hollow fibre infection model studies to examine dose selection of therapeutics targeting Covid-19.

The hollow fibre infection model (HFIM) is a state-of-the-art in vitro model system used to study the exposure response relationships of anti-infectives to design optimal dosing regimens. The therapeutics currently being trialled for COVID-19 have little or no data to support dosage selection. New therapeutics are considered for clinical use based on limited in vitro data.


Members of the APT team will be speaking/presenting posters at the 30th European Congress of Clinical Microbiology & Infectious Diseases (ECCMID)
Paris, France
18-21 April 2020

ECCMID, as the world’s premier Clinical Microbiology & Infectious Diseases event, brings together experts from many fields to present their latest findings, guidelines and experiences to an audience of over 13,000 colleagues.

  • Shampa Das will be giving an oral presentation on ‘Aminoglycosides revisited’ in a session titled Antimicrobial Susceptibility Testing with EUCAST methods and breakpoints.’ Saturday 18 April 08.30 – 12.30, Hall A2.
  • Christopher Darlow will be giving a poster presentation titled ‘Pharmacodynamics of amikacin and fosfomycin combination therapy in neonatal sepsis modelled in a hollow fibre infection model’ Tuesday 21 April, poster stand P4289.
  • Adam Johnson will be giving a poster presentation titled ‘Pharmacodynamic analysis of meropenem in combination with a novel ß-lactamase inhibitor ANT2681 against New Dehli metallo ß-lactamase-producing Escherichia coli’ Tuesday 21 April, poster stand P3707.

CEIDR launch

L-R: Professor Dame Sally Davies, Professor Dame Janet Beer, Professor David Lalloo, Professor William Hope and Professor Louise Kenny.

Centre of Excellence in Infectious Diseases Research (CEIDR) - Next important phase in infectious diseases research in Liverpool launched.

Professor Dame Sally Davies, former Chief Medical Officer and current UK Special Envoy on Antimicrobial Resistance, visited Liverpool 22 January 2020 to help launch an ambitious new programme of AMR research at the University of Liverpool and Liverpool School of Tropical Medicine (LSTM).

As part of an ambitious new chapter for their Centre of Excellence in Infectious Diseases Research (CEIDR), the two institutions are stepping up efforts to tackle the AMR crisis and its impact on human health in Liverpool, the UK and globally.

During her visit, Dame Sally unveiled a plaque marking CEIDR’s new £3.5m National Institute for Health Research (NIHR) Antimicrobial Resistance Laboratories. These state-of-the art laboratories will provide the infrastructure needed for Liverpool researchers to develop personalised antimicrobial therapies to prevent and treat AMR.

Dame Sally Davies & Prof William Hope

Professor Dame Sally Davies & Professor William Hope celebrate the foundation of the Dame Sally Davies Chair in antimicrobial research awarded to Professor William Hope.

Professor William Hope, Dame Sally Davies Chair in Antimicrobial Resistance at the University of Liverpool, has been appointed as CEIDR’s new academic Centre Director. With expertise covering drugs and antimicrobials, diagnostics, vector control products and vaccines, Dr Fiona Marston will continue to lead the centre’s well-established industrial partnership programme under the new name of CEIDR Innovations.

Read our full press release.


Crytococcus

Current treatment for fungal meningitis is fuelling drug resistance

Our research shows a common first-line treatment approach for cryptococcal meningitis in low-income countries is being compromised by the emergence of drug resistance.


William Hope is speaking at the Colston Research Society Symposium on Antimicrobial resistance - in Bristol 14th November -‘Individualisation of antimicrobial therapy to prevent and treat AMR’.


William Hope and Shampa Das are both presenting at British Society for Antimicrobial Chemotherapy (BSAC) conference -‘Meeting the Challenges of Gram-Negative Infection Management’ on 19th November 2019 in London. William on ‘PK-PD challenges for Gram-negative infections’ and Shampa ‘Advances in betalactamase inhibition in difficult to treat infections’.


Dr Kat Stott one of our clinical PhD fellows, returns to Liverpool this month from Malawi. Kat has had a very successful 2 years in Malawi recruiting patients with cryptococcal meningitis to a pharmacokinetic-pharmacodynamic (PK-PD) substudy of the Ambition-cm trial (ISRCTN72509687). Ambition-cm examines whether a novel drug regimen for cryptococcal meningitis may be non-inferior to standard of care. Together with the local study team, Kat has successfully reached her recruitment target of 65 patients. Samples are awaiting shipment back to the University of Liverpool for PK analysis and whole genome sequencing, and to Duke University in North Carolina for pathogen phenotyping and transcriptomic analysis. Further samples will stay in Malawi and undergo immunological analyses at the Malawi-Liverpool Wellcome Trust Clinical Research Programme, to examine the impact of host immunity on PD outcomes.


Spero Therapeutics: Exciting independent review committee recommendation announced on positive interim PK data from SPR994 ADAPT-PO Phase 3 Clinical Trial


Dr Shampa Das appointed to European Antimicrobial Resistance research steering group

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Dr Shampa Das, Senior Lecturer in Antimicrobial Pharmacodynamics (PD) from the University’s Department of Molecular and Clinical Pharmacology, has been appointed to join the European Committee on Antimicrobial Susceptibility Testing (EUCAST) Steering Committee as a PK/PD expert.

EUCAST was launched in 1997 in order determine, review and revise European clinical breakpoints, the concentration of an antibiotic which defines where a bacterium is susceptible or resistant, in close collaboration with the European Medicines Agency (EMA) and European Centre for Disease Prevention and Control (ECDC).

Dr Das will be a member of EUCAST’s Steering Committee. She has previously been employed as a Director of Clinical Pharmacology at the Antibiotics Unit, AstraZeneca. She has vast experience with drug development, preclinical PK/PD and clinical support to aid optimal dose selection, as well as extensive experience with the regulatory process.

Of the appointment Dr Das said: “I am proud and privileged to have been appointed to this prestigious position. A critical aspect of preventing emergence of resistance is to ensure that antibiotics are dosed correctly.

“EUCAST is a highly respected organisation and I am delighted to be able to support them in promoting education and training in antimicrobial susceptibility testing.”

More information about EUCAST can be found here http://www.eucast.org/organization/


2019 ASM/ESCMID Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance September 3-6, 2019 | Boston, Massachusetts

ASM ESCMID POSTER PRESENTATIONS

  • Pharmacodynamics of SPR206 in Murine Models of Infection Against Multi‐Drug Resistant (MDR) Gram‐Negative Bacteria
    L. Mcentee, A. Johnson, N. Farrington, A. Kirb1, T. Lister, T. Parr, N. Cotroneo, S. Das, W. Hope;
  • Pharmacokinetic and Pharmacodynamic Analysis of Cefepime and AAI101 against Multidrug‐Resistant Enterobacteriaceae
    A. Johnson, N. Farrington, L. McEntee, P. Knechtle, S. Biondi, S. Shapiro, S.Das, W. Hope;
  • Phase III Dose Selection for Tebipenem‐Pivoxil Hydrobromide, a Novel Oral Carbapenem
    S. Das, M. Laura, A. Johnson, N. Farrington, S. Gore, A. Kirby, A. Jai2, D.Melnick, T. Parr, W. Hope;
  • Development of an Experimental Model of Bacterial Meningoencephalitisto Facilitate Antimicrobial Drug Development for Neonates
    N. Farrington, L. McEntee, A. Johnson, A. Kirby, S. Gore, R. Greenberg, S.Das, W. Hope;

Nikki Farrington received a travel award to attend based on the scientific quality of her abstract.

William Hope & Shampa Das are also moderating the following sessions:

  • Pre-Clinical and Clinical Considerations for the Development of Antifungal Agents
  • Lecture: Creating a Sustainable Antibiotics R&D Ecosystem
  • Keynote Lecture: Investor Sentiment: How Did We Get Grand Ballroom Here and is There a Way Out?
  • Pre-Clinical and Clinical Considerations for the Development of Antifungal Agents
  • Keynote Lecture: Beta-Lactamase Inhibitors: A Journey of Discovery

University joins new antimicrobial resistance consortium

Our researchers have joined a new consortium to help in the development of novel antibacterial agents to battle antimicrobial resistance in gram-negative bacteria.

Liverpool lead Dr Shampa Das, Senior Lecturer in Antimicrobial Pharmacodynamics, said: “A critical aspect of preventing emergence of resistance is to ensure that antibiotics are dosed correctly. We will use experimental infection models with mathematical computation to explore the relationship between the amount of drug given, antimicrobial effect and prevention of resistance emergence and use this to optimise the clinical dose regimen.”


Unique Liverpool Summer School welcomes delegates from around the world.

ESCMID Summer School

The University of Liverpool and the Liverpool School of Tropical Medicine (LSTM) welcomed delegates from 26 countries to this year’s European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Summer School.

ESCMID is a non-profit organization whose mission is to improve the diagnosis, treatment and prevention of infection-related diseases. Every year the organisation runs a week-long programme that covers a broad range of topics in clinical microbiology and infectious diseases.

This year the 18th ESCMID Summer School took place in Liverpool between 29 June – 5 July. The Summer School Co-ordinators this year were Professor William Hope from the University of Liverpool and Professor Nick Beeching from LSTM. The event was sponsored by Liverpool based Centre of Excellence in Infectious Diseases Research (CEIDR).


£300k awarded for new translational research projects by CEIDR.

The Liverpool Centre of Excellence in Infectious Diseases Research (CEIDR) has awarded £300,000 to support seven new collaborative translational projects from its Translational Pump Priming (CEIDR TPP) fund.


£3.54m boost for Liverpool based Antimicrobial Resistance research.

The University of Liverpool and the Liverpool School of Tropical Medicine (LSTM) have been awarded £3.54m for a research project that aims to develop a ‘personalised health’ approach to prevent and treat antimicrobial resistance (AMR).


We have developed a new treatment option for Multi-Drug Resistant Infections.


MRC Showcase Day

Dr Sara Boyd & Dr Christopher Darlow presented at the North West England MRC Fellowship Scheme in Clinical Pharmacology and Therapeutics Annual Showcase on 15 May 2019, Hilton Hotel, Manchester Airport, UK.

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Dr Christopher Darlow: 'Determining an optimal new combination of antibiotics for neonatal sep-sis in a low-to-middle –income setting'

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Dr Sara Boyd: 'Pharmacodynamics for multidrug-resistant Gram-negative infections'


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Sonia Luque (Honorary Staff member) presenting at ECCMID (16/4/19)– title ‘Population pharmacokinetics and pharmacodynamics of anidulafungin against Candida albicans in a cohort of critically ill patients’.

Laura McEntee Poster

Laura McEntee presenting poster at ECCMID (15/4/19) title ‘Pharmacodynamics of ertapenem’ in ‘Preclinical PD assessment of antibacterial agents’ session.


Registration now open for ESCMID Summer School in Liverpool.

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Registration is now open for this prestigious week long course dedicated to postgraduate and continuing medical education, being hosted by the University of Liverpool and the Liverpool School of Tropical Medicine.

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) is a non-profit organization whose mission is to improve the diagnosis, treatment and prevention of infection-related diseases. Every year the organisation runs a week-long programme that covers a broad range of topics in clinical microbiology and infectious diseases.

This year will see the 18th ESCMID Summer School taking place in Liverpool between 29 June – 5 July. The course will interest young MDs at the end of their specialty training as well as biologists, pharmacists, PhD students and postdoctoral fellows working in the infection field. The scientific programme of classical lectures is complimented by interactive workshops.

The ESCMID Summer School Co-ordinators this year are Professor William Hope from the University of Liverpool and Professor Nick Beeching from LSTM.

Since its founding in 1983, ESCMID has evolved to become Europe’s leading society in clinical microbiology and infectious diseases with members from all European countries and all continents. For more than 30 years, ESCMID has been an influential component in the professional lives of microbiologists and infectious disease specialists and now reaches more than 7,000 individual and 30,000 affiliated members around the world. ESCMID, based in Basel, Switzerland, welcomes new colleagues from all nations.

Of the course Professor William Hope, said: “It is an honour to be hosting the ESCMID Summer School which is one of the best and comprehensive courses that defines the state-of-the-art in clinical infectious diseases and microbiology.”

Dr Nick Beeching, said: “We are delighted to host this prestigious course in Liverpool, with the chance for trainees to interact with Faculty members from all over Europe.”

More details about the course and how to register can be found here.


Members of the APT team will be speaking/presenting posters at ECCMID (European Congress of Clinical Microbiology & Infectious Diseases), Amsterdam 13 - 16 April 2019:

  • William Hope speaking on - ‘Novel antifungals and how they might address some of the current treatment challenges’
  • William Hope co-chairing a session on ‘Issues in antifungal treatment’ with  Anna Skiada (Athens, Greece)
  • Shampa Das – presenting a poster –‘ Phase III dose selection for tebipenem’ in the ‘Recent research on the pharmacokinetics and safety of antibacterial agents’ session.
  • Laura McEntee – presenting a poster – ‘Pharmacodynamics of ertapenem’ in ‘Preclinical PD assessment of antibacterial agents’ session.
  • Sonia Luque (Honorary staff member) - presenting a poster – ‘Population pharmacokinetics and pharmacodynamics of anidulafungin against Candida albicans in a cohort of critically ill patients’.

Members of the APT team are attending the ‘Antimicrobial Resistance – preventing an antibiotic apocalypse  conference hosted by The Economist on March 26 2019 – Keynote speaker Dame Sally Davies.


Professor William Hope presented at the 'Superbugs and Superdrugs 2019' Confernence London, UK, 13 March 2019.  The slides are available for download.

Pharmacodynamics to Accelerate Antimicrobial Drug Development for AMR


At the recent British Ssociety for Antimicrobial Chemotherapy (BSAC) – Antimicrobial Chemotherapy Conference in London - 15th January 2019.

Dr Shampa Das, Senior Lecturer, Molecular and Clinical Pharmacology spoke on Tackling Beta-lactamase mediated resistance: A potted history of beta lactamase and lessons from recent development of beta-lactamase inhibiter combinations.

Beta-lactams have long been an essential tool in the armamentarium for the treatment of infections.  However, resistance to beta-lactams through the emergence of beta-lactamases is becoming a serious threat to their continued utility.  Beta-lactamase inhibitors were developed to overcome this problem, however, the spectrum of coverage against the different beta-lactamases and emerging resistance to beta-lactamase inhibitors is a continuing problem. The challenges of developing beta-lactam-beta-lactamase inhibitor combinations were discussed.

Adam Johnson, Senior Research Assistant, Molecular and Clinical Pharmacology ran an interactive workshop discussing the importance of HOLLOW FIBRE INFECTION MODEL (HFIM) use in pre-clinical research. Predominantly used to assess humanized Pharmacokinetic and Pharmacodynamic (PK-PD) relationships and the importance of this data in drug development for evaluation by regulatory agencies in approval decisions.


Research collaboration seeks to address deaths in newborns from sepsis.

The University of Liverpool has signed a collaborative research agreement with the Global Antibiotic Research and Development Partnership (GARDP) in a bid to develop new treatment options for newborns with sepsis. The research seeks to explore the correct dose and frequency of potential antibiotic combinations that could improve treatment outcomes in this vulnerable population. Read More.


Prof William Hope will speak at the 'Mycoses Study Group Education and Research Consortium (MSGERC) 2018 Biennial Meeting' 26th September 18 – Montana, USA on ‘New Treatments for Cryptococcosis ‘


Dr Sara Boyd, Adam Johnson and Laura McEntee attended the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) / American Society of Microbiology (ASM) Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance in Lisbon, September 2018.

Dr Sara Boyd, MRC Clinical Innovation Fellow, gave the Young Investigator Lecture at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) / American Society of Microbiology (ASM) Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance.  Her lecture was titled Metallobetalactamases (Epidemiology, Drug Design, Diagnosis and Treatment).

Sara Boyd at Conference

Adam Johnson presented a poster - Abstract Title: Pharmacokinetics and Pharmacodynamics of Tebipenem (SPR859) for Multidrug Resistant Enterobacteriaceae in a Hollow Fibre Infection Model

Laura McEntee presented a poster - Abstract Title: Pharmacokinetics and Pharmacodynamics of Tebipenem for Multidrug Resistant Enterobacteriaceae.


Laura McEntee

Laura McEntee attended the American Society of Microbiology (ASM) Microbe conference in Atlanta USA on 8th June 2018. Laura presented data on Spero's new compound and gave an oral and poster presentation entitled 'Pharmacokinetics and Pharmacodynamics of Tebipenem for Multi-drug Resistant Enterobacteriaceae'.


ESCMID/ASM Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance
Lisbon, Portugal
4 – 7 September 2018

Antimicrobial drug resistance remains a pressing public health problem. There has been a resurgence in interest in tackling AMR.

This conference focusses on the development of new antimicrobial agents for AMR. It is a multidisciplinary meeting that involves basic scientists, clinical academics, regulatory bodies, funding bodies and the pharmaceutical industry. Its scope
stretches from chemistry to clinical development, from neonates to adults, from bacteria to fungi – all with a global perspective.

The meeting is practical, interactive with plenty of time for networking. We will happily accept original data for poster and platform presentations. We are also especially interested in supporting young investigators and researchers from low to middle income countries.

http://www.escmid.org/Lisbon2018

ESCMID/ASM Conference Poster