Likelihood of aggressive PK/PD target attainment of continuous-infusion beta-lactams during the first week of treatment of febrile neutropenia: findings from a 1-year prospective, monocentric study in onco-haematological patients.

BACKGROUND

Onco-haematological patients with febrile neutropenia are at high risk of severe infections caused by multidrug-resistant pathogens. Continuous infusion (CI) of beta-lactams may improve pharmacokinetic/pharmacodynamic (PK/PD) target attainment, yet evidence in this population remains limited.

OBJECTIVES

To evaluate the likelihood of achieving an aggressive PK/PD target with CI beta-lactams during the first week of therapy in onco-haematological patients and to identify predictors of target non-attainment.

METHODS

This prospective observational study enrolled adult onco-haematological patients receiving CI beta-lactams for empirical or targeted treatment over a 1-year period. Steady-state plasma concentrations were measured between days 3 and 7. The aggressive PK/PD target was defined as a free steady-state concentration-to-MIC (or clinical breakpoint) ratio ≥4; for beta-lactam/beta-lactamase inhibitor combinations, a joint PK/PD target was applied. Multivariate logistic regression analysis identified factors associated with target attainment.

RESULTS

A total of 256 patients were included, 82 of whom (32.1%) received targeted therapy. Aggressive PK/PD target attainment was achieved in 85.4% of patients undergoing targeted treatment, compared with 57.5% of those treated empirically. Target non-attainment occurred most frequently with piperacillin/tazobactam and ceftazidime/avibactam. Augmented renal clearance (OR 12.29, P < 0.001), male sex (OR 3.79, P < 0.001) and age <65 years (OR 2.40, P = 0.025) independently predicted target non-attainment, whereas targeted therapy and meropenem use were associated with a higher attainment.

CONCLUSIONS

CI beta-lactams reliably achieve aggressive PK/PD targets during targeted therapy but not during empirical treatment in onco-haematological patients. Augmented renal clearance is a major determinant of underexposure, supporting the use of therapeutic drug monitoring to optimize dosing in this high-risk population.