# P-1361. High Dose Daptomycin Shows Non-Inferior Outcome Compared to Linezolid in Patients with Daptomycin and Vancomycin Resistant Enterocci Bloodstream Infection

## TL;DR

High-dose daptomycin is as effective as linezolid for treating bloodstream infections caused by daptomycin-resistant VRE, despite resistance in lab tests.

## Contribution

This study demonstrates that high-dose daptomycin is non-inferior to linezolid in treating daptomycin-resistant VRE bloodstream infections.

## Key findings

- High-dose daptomycin (≥11 mg/kg) showed no significant difference in mortality compared to linezolid.
- Daptomycin-resistant VRE bloodstream infections had a 47.5% 28-day mortality rate.
- Higher Charlson Comorbidity Index and Pitt bacteremia score were linked to increased mortality.

## Abstract

Vancomycin-resistant Enterococcus (VRE), causes severe nosocomial infections and increase healthcare costs. Guidelines recommend high-dose daptomycin or linezolid for VRE bloodstream infections (BSI). Daptomycin-resistant VRE, emerging recently, limits treatment options. This study analyzes clinical characteristics, prognostic factors, and daptomycin and linezolid outcomes in daptomycin-resistant VRE BSI.Table 1.Baseline Characteristics of Included SubjectsNote: Continuous variables are presented as median (IQR); categorical variables as number (%).Table 2.Multivariable Logistic Regression Analysis of 28-day Mortality

Baseline Characteristics of Included Subjects

Note: Continuous variables are presented as median (IQR); categorical variables as number (%).

Multivariable Logistic Regression Analysis of 28-day Mortality

We conducted a prospective cohort study with retrospective analysis at National Taiwan University Hospital system from 2010 to 2024, enrolling hospitalized adults with VRE BSI treated with linezolid or daptomycin (≥ 8 mg/kg). Post hoc minimum inhibitory concentration (MIC) testing for daptomycin was performed by broth microdilution via the Sensititre system which MIC ≥ 8 mg/L indicated resistance.

The primary outcome was 28-day in-hospital mortality; the secondary outcome was recurrent bacteremia defined as same pathogen detected in blood after completed at least 10 days of treatment.Survival Analysis of 28-day Mortality Categorized by Patients Receiving Linezolid, Daptomycin at 8-11mg/kg Compared to Daptomycin > 11mg/kg

Survival Analysis of 28-day Mortality Categorized by Patients Receiving Linezolid, Daptomycin at 8-11mg/kg Compared to Daptomycin > 11mg/kg

Of 2,230 VRE BSI episodes, 120 isolates met inclusion criteria. Median patient age was 67.3 years (IQR: 55.2–78.4); 57.5% were male. Primary bloodstream infections (45.8%) and urinary tract infections (43.3%) were main sources. Daptomycin treated 101 patients (84.1%), linezolid 19 (15.8%). The 28-day mortality rate was 47.5%. Multivariable analysis showed higher Charlson Comorbidity Index (aOR, 1.30; P=0.02), elevated Pitt bacteremia score (aOR, 1.35; P< 0.01), and lower platelet count (aOR, 0.98; P< 0.01) linked to increased mortality. Compared to daptomycin >11 mg/kg, 8–11 mg/kg doses raised mortality (aOR, 3.30; P=0.04); no difference was seen with high-dose daptomycin vs. linezolid (aOR, 2.02; P=0.39). Recurrent bacteremia occurred in 11 patients, with similar rates in daptomycin and linezolid groups (15.6% vs. 18.2%; P=0.82).

Daptomycin-resistant VRE BSI had high mortality. Higher Charlson Comorbidity Index, Pitt bacteremia score, and lower platelet count predicted mortality. High-dose daptomycin (≥11 mg/kg) may be at least comparable to linezolid in treating daptomycin-resistant VRE BSI, despite in vitro resistance.

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