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
