Antimicrobial resistance: Researching new options for patients with unmet medical needs

Antimicrobial Resistance (AMR) occurs when drugs designed to treat infections caused by bacteria, viruses, parasites and fungi no longer work. Since antimicrobial agents enable almost all modern healthcare, AMR significantly compromises our ability to live together in a safe and prosperous way.

The University of Liverpool’s Antimicrobial Pharmacodynamics and Therapeutics (APT) laboratory has built up a wide-ranging body of work to help tackle this global challenge.

The Laboratory’s 20-plus members work together to discover and develop new antibiotics and use them in a precise and sustainable way. APT’s research directly helps patients in the NHS and globally.

Professor William Hope, who leads the APT Laboratory said: “We have extensive infrastructure, expertise and track record in developing new antibiotics for AMR. We primarily help turn new compounds that have shown to work in a test tube into human medicines.”

New antibiotics

Recent examples of the APT Laboratory’s work to provide new options for patients with unmet medical needs related to AMR include:

• Development of teixobactins: a new class of antibiotics that can potentially be used to treat multidrug resistant Gram positive infections
• Development of olorofim (in collaboration with F2G Ltd): the first new antifungal agent for three decades, Olorofim is in Phase II clinical trials and has activity against multidrug resistant fungi
• Development of new beta lactamase (enzymes produced by bacteria that break open the beta-lactam ring, inactivating the beta-lactam antibiotic) inhibitors: including enmetazobactam (Allecra Therapeutics) and ANT2681. Enmetazobactam has been demonstrated to be effective in a Phase III clinical trial.
• Development of tebipenem (Spero Therapeutics), a highly effective antibiotic that can be given by mouth. Tebipenem has been demonstrated to be effective in a Phase III clinical trial and a New Drug Application has been submitted to the US FDA.
• Development of new treatment options for premature babies with sepsis in collaboration with GARDP
• Development of new experimental systems that can be used to develop new antibiotics for premature babies that have infection in the brain (Duke University and the US FDA).

The APT Laboratory has active research programs with multiple sponsors developing new antibiotics for multi- and extremely drug resistant pathogens that include Pfizer, Phico, Spero Therapeutics, Bugworks, and Bioversys. The lab is a partner in the iiCON consortium, developing new experimental models to aid in the development of new antibiotics.

Precision Therapy

The APT research group leads the NIHR AMR laboratories (opened by Dame Sally Davies in January 2020) alongside the Liverpool School of Tropical Medicine, which contain state-of-the art infrastructure for bioanalysis, microbial sequencing and pharmacogenomics.

It also has an active collaboration with Pfizer to advance precision dosing of antibiotics as a standard of care in the NHS, and helps doctors and their patients understand whether they are well positioned to maximally benefit from an antibiotic – this requires integrating information from the antibiotic, the patient and the microbe.

Active programs in global health

We have active programs in global health to find innovative solutions to the treatment of schistosomiasis, cryptococcal meningitis and neonatal sepsis.

Training the next generation of researchers and clinician scientists

APT teaches undergraduates, PhD scholars, postdoctoral fellows and clinician-scientists at all stages of clinical and research training. Providing training in laboratory medicine, mathematical modelling, clinical infectious diseases and clinical pharmacology. The Laboratory also has established links with leading researchers in other disciplines such as computer science, engineering and chemistry.

Providing national and international leadership in the fight against AMR

APT’s Professor Shampa Das is a member of EUCAST Steering Committee, which is the European organisation responsible for defining breakpoints for all antibiotics (for example, designating whether a microorganism is susceptible or resistant to an antibiotic), and is Co-Chair of the ASM-ESCMID Joint Conference on Drug development to meet the challenge of AMR.

Professor William Hope is Co-Lead, NIHR Infectious Diseases National Specialty Group, and chairs the Antimicrobial Resistance Scientific Steering group, which is currently developing a national strategy for clinical AMR research.