Standard ceftriaxone achieves target at low MICs in suspected sepsis patients

Treatment with standard ceftriaxone dose delivers adequate target attainment at low minimum inhibitory concentrations (MICs) in hospitalized patients with suspected sepsis, according to a Thai study.

“Appropriate drug exposure is as crucial as proper selection and timely antibiotic administration in sepsis treatment,” the researchers said.

In this study, the researchers examined the pharmacokinetics (PK) of ceftriaxone in sepsis patients who received ceftriaxone 2 g every 12 or 24 h. They collected blood samples (11‒14 samples per patient) within the first 24 h after administration and estimated PK parameters from unbound plasma concentrations using a nonlinear mixed-effects modelling approach.

The research team also assessed the probability of target attainment (PTA) of standard and high-dose ceftriaxone at various MICs using Monte Carlo simulations.

In the population PK analysis of 238 concentration‒time data points from 20 patients, ceftriaxone PK was best described by a two-compartment model. Glomerular filtration rate (GFR), serum albumin, and body weight had a substantial impact on clearance, volume of distribution, and intercompartment clearance, respectively.

In simulations, standard ceftriaxone dose (2 g intravenously every 24 h, 30-min infusion) demonstrated adequacy for pathogens with MIC ≤1 mg L⁻¹. However, target attainment decreased at higher MIC values, specifically with GFR >130 mL·min⁻¹. Notably, twice-daily dosing produced higher exposures.

“PTA decreased with higher MICs and higher renal function, with higher dose regimens showing numerically greater exposures,” the researchers said. “These findings may help guide future studies on dosing optimization.”