High target attainment for β-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Abstract

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of β-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum β-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0mL/min/1.73m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of β-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.