Prospective evaluation of therapeutic target attainment with a beta-lactam dosing nomogram in critically ill adult patients

BACKGROUND: Therapeutic drug monitoring (TDM) individualises antibiotic dosing, aiming for therapeutic exposures and minimising toxicity. However, TDM cannot always be performed due to resource requirements, and clinicians often dose according to guidelines. This study aimed to quantify the achievement of therapeutic exposures (concentrations) in a heterogeneous cohort of critically ill adults using nomogram-based antibiotic dosing. METHODS: This was a prospective, single-centre, cohort study of nomogram-based dosing of beta-lactams in critically ill adults. The primary outcome was the proportion of patients with therapeutic exposures, that is those above the efficacy threshold but below the toxic threshold. Secondary endpoints were exposures associated with toxicity, and the relationship between exposure and clinical outcomes. RESULTS: In 79 patients, therapeutic beta-lactam exposure was achieved in 82% (63/77) and 81% (35/43) of patients at days 1 to 3 and days 4 to 6, respectively. Piperacillin yielded the lowest therapeutic attainment, with 75% (24/32) and 71% (12/17) at days 1 to 3 and days 4 to 6, respectively, and the highest proportion of sub-therapeutic exposures: 25% (8/32) and 29% (5/17), respectively. Therapeutic tazobactam trough concentrations were achieved in 66% (21/32) and 65% (11/17) of patients at days 1 to 3 and days 4 to 6, respectively. CONCLUSIONS: In a single-centre heterogeneous population of critically ill adults with infection, initial dosing informed by a dosing nomogram for beta-lactams resulted in a high proportion of patients achieving therapeutic exposures.