The PNEUDOS Study Program: defining novel and individualised antimicrobial dosing regimens for treatment of pneumonia in ICU

National Health and Medical Research Council

Pneumonia is the most common infection in ICU patients and occurs in10% of all ICU admissions. Unfortunately, treatment outcomes for ICU patients with pneumonia remain poor despite recent therapeutic advances. Optimised antimicrobial dosing is an intervention that can significantly reduce mortality in this patient population. Previous studies of important antimicrobials used in ICU patients have quantified major differences in pharmacokinetics between ICU and non-ICU patients with pneumonia. For pneumonia, the infection site is best described as the epithelial lining fluid (ELF) in the lung. Although optimal antimicrobial therapy should be considered a priority for ICU patients with pneumonia to improve patient outcomes, the dosing regimens that can achieve therapeutic concentrations at the infection site (i.e., ELF) in these patients remain unknown.

The PNEUmonia DOSing in critically ill patients (PNEUDOS) Study Program aims to address significant knowledge gaps in the management of pneumonia for critically ill patients in the ICU. The PNEUDOS Study Program utilises a stepwise research design to define novel and individualised dosing regimens that can maximise antimicrobial efficacy by achieving therapeutic concentrations in both blood and ELF of ICU patients with pneumonia. This Study Program focuses on benzylpenicillin, ceftriaxone, meropenem, and piperacillin/tazobactam and consists of four studies that will be conducted in stages.

  • Phase 1: INTENSIVE-PNEUDOS (NCT04986254) - involves intensive pharmacokinetic sampling and recruiting patients from 6 ICUs across Australia, Belgium, France, Hong Kong and Malaysia
  • Phase 2: SPARSE-PNEUDOS - involves sparse pharmacokinetic sampling in a larger cohort of ICU patients from different countries (e.g., Australia, France, Greece, Malaysia, Portugal, Switzerland, and US)
  • Phase 3: PNEUDOS-MODSIM - pharmacokinetic modelling and simulation work to design optimised antimicrobial dosing regimens based on data from Phase 1 and Phase 2
  • Phase 4: PNEUDOS-VALIDATION RCT - evaluate safety, efficacy and tolerability of antimicrobial dosing regimens developed in Phase 3

Project members

Jason Roberts

Professor Jason Roberts

Acting Director
UQ Centre for Clinical Research
NHMRC Leadership Fellow
The University of Queensland
Pharmacist Consultant
Royal Brisbane & Women’s Hospital

Professor Jan De Waele

European Collaboration Co-Lead
Critical Care Physician
Ghent University Hospital

Professor Jeffrey Lipman

Critical Care Research, Translation and Training Lead
Emeritus Professor
UQ Centre for Clinical Research

Professor Jean-Yves Lefrant

European Collaboration Co-Lead
ICU Physician and Chair of AZUREA Research
University of Nîmes

Dr Mohd Hafiz Abdul-Aziz

Clinical dosing studies workstream lead
Postdoctoral Research Fellow
UQ Centre for Clinical Research

Associate Professor Cornelia Landersdorfer

Research Lead for Scientists
NHMRC Career Development Fellow
Monash University

Cheryl Fourie

Industry Fellow
UQ Centre for Clinical Research

Dr Steve Wallis

Head of Bioanalysis
UQ Centre for Clinical Research

Dr Jayesh Dhanani

Intensive Care Specialist - RBWH, PhD Candidate
Dr Menino Cotta

Dr Menino Cotta

UQ Development Fellow, School of Pharmacy, Faculty of Health and Behavioural Sciences