# Clinical outcomes with lower versus conventional dose polymyxin B regimens in dialysis dependent and non-dialysis patients with gram-negative sepsis: A real-world propensity-score matched cohort study

## TL;DR

This study found that lower doses of polymyxin B may lead to better outcomes in critically ill patients with gram-negative sepsis, especially those not on dialysis.

## Contribution

The study provides real-world evidence on the effectiveness of different polymyxin B dosing strategies in ICU patients with gram-negative sepsis.

## Key findings

- Low-dose polymyxin B was associated with significantly lower 28-day mortality compared to usual-dose regimens.
- Low-dose regimens improved vasopressor, ventilator, and ICU-free days compared to higher doses.
- Among dialysis-dependent patients, low-dose polymyxin B showed better microbiological clearance without significant survival differences.

## Abstract

Polymyxin B remains a key treatment option for infections caused by multidrug-resistant gram-negative bacilli, particularly in critically ill patients. However, its optimal dosing strategy recommendation remains uncertain, especially in those undergoing renal replacement therapy. This study aimed to compare the clinical and microbiological outcomes of low, usual and high dose polymyxin B in a real-world ICU population.

This 5-year retrospective cohort study included critically ill adult patients with gram-negative sepsis who received polymyxin B. Patients were categorized into low-, usual- and high-dose groups based on loading and total daily maintenance dose. Pairwise propensity score matching was performed to adjust for baseline differences. Primary outcome was 28-day all-cause mortality. Secondary outcomes included microbiological clearance, ventilator-free days, ICU-free days, and vasopressor-free days. Subgroup and sensitivity analyses were conducted, including within patients requiring dialysis. All the statistical analysis was performed using R software.

A total of 674 patients were included. After matching, usual-dose polymyxin B (61%) was associated with significantly higher 28-day mortality compared to the low-dose group (48.04%) (HR = 1.47;95% CI:[1.11–1.95];p = 0.007). Vasopressor, ventilator and ICU-free days were also significantly higher in the low-dose group were compared to the other groups. No significant survival advantage was observed with high-dose regimens. Among dialysis-dependent patients (n = 254), mortality did not differ significantly across dosing groups, though microbiological clearance was better with low dosing. Sensitivity and subgroup analysis also supported the results to be robust.

Low dose polymyxin B regimens were associated with lower mortality and comparable clinical outcomes compared to higher doses and may be feasible in critically ill patients with renal impairment. However, these findings should be interpreted cautiously given the observational design and residual confounding, warranting confirmation in future randomized trials.