Keeping the horse with the cart: are we underdosing tazobactam even when using continuous-infusion ceftolozane/tazobactam for effectively preventing resistance development by ESBL-producing Enterobacterales?

ABSTRACT: Ceftolozane/tazobactam is widely used against extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, yet FDA-approved dosing relies on intermittent infusion and a fixed 2:1 ratio that assumes adequate β-lactamase inhibition. Tazobactam's faster and variable clearance raises concerns for subtherapeutic exposure. This study evaluated whether continuous infusion (CI) improves pharmacokinetic target attainment and whether current dosing adequately covers both components. We conducted an analysis of 139 hospitalized adults receiving CI ceftolozane/tazobactam with therapeutic drug monitoring (TDM). Free steady-state concentrations (fCss) and observed clearance were calculated and assessed across kidney function strata. Population pharmacokinetic modeling and Monte Carlo simulati

SUBMITTER: Pai MP 

PROVIDER: S-EPMC12691610 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature