Pharmacokinetic/pharmacodynamic optimization of antimicrobial therapy in neutropenic sepsis: a comprehensive review.

Abstract

Neutropenic sepsis remains a life-threatening complication in patients undergoing cytotoxic chemotherapy or haematopoietic stem cell transplantation. A comprehensive literature search was conducted across PubMed, Embase, and the Cochrane Library through December 2025, focusing on clinical trials, observational studies, and population PK analyses involving neutropenic or febrile neutropenic patients in both adult and paediatric haematology and oncology populations. Pathophysiological changes in neutropenic sepsis-including augmented renal clearance, increased volume of distribution, and hypoalbuminemia-lead to substantial PK variability and frequent target non-attainment with standard dosing. Animal models consistently demonstrate that higher PK/PD targets are required in the absence of neutrophils. PK/PD-guided dose optimisation appears highly beneficial in neutropenic sepsis, although prospective randomised evidence specifically in this population remains limited. Integration of TDM, population PK modelling, and Bayesian dose adaptation into routine clinical practice represents a promising avenue towards improved outcomes, recognising that implementation will depend on locally available laboratory and pharmacy resources.