Observational studyThe Journal of antimicrobial chemotherapy2026
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.
Observational study in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOnco-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.
objectivesTo 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.
methodsThis 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.
resultsA 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.
conclusionsCI 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.
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