# Therapeutic drug monitoring-guided optimization of isavuconazole dose for ICU patients with refractory pulmonary aspergillosis: case report

## TL;DR

This case report shows how adjusting isavuconazole doses using drug monitoring helped an ICU patient with a difficult fungal infection.

## Contribution

The study presents a real-world example of TDM-guided dose optimization for isavuconazole in ICU patients.

## Key findings

- A prolonged loading regimen achieved pharmacokinetic steady state in a treatment-resistant patient.
- TDM-guided dosing was associated with a favorable clinical outcome without severe side effects.
- More research is needed to refine ICU-specific dosing guidelines for isavuconazole.

## Abstract

Isavuconazole (ISA) is recommended as the first-line therapy for pulmonary aspergillosis. In intensive care unit (ICU) patients, ISA exhibits enhanced clearance and a larger volume of distribution but lower plasma concentrations, indicating the need for plausible dose adjustment. However, current evidence regarding off-label ISA dosing regimens for ICU patients is restricted to pharmacokinetic prediction modeling, with no published clinical studies available to date. In this case, a prolonged ISA-loading dosing regimen was applied to address previous standard ISA treatment failures; thereby, pharmacokinetic steady state was achieved with serial therapeutic drug monitoring (TDM)-guided dose optimization. This study illustrated a favorable clinical course associated with TDM-guided dosing adjustment, with no severe adverse reactions. Given the limited sample size, it is critical to investigate the clinical scenario further to adequately provide references for ISA dosing guidelines and TDM strategies for ICU practice.