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

• Published in: European journal of clinical microbiology & infectious diseases 2017-03, Vol.36 (3), p.553-563
• Main Authors: Woksepp, H., Hällgren, A., Borgström, S., Kullberg, F., Wimmerstedt, A., Oscarsson, A., Nordlund, P., Lindholm, M-L., Bonnedahl, J., Brudin, L., Carlsson, B., Schön, T.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; beta-Lactams - administration & dosage; beta-Lactams - pharmacokinetics; beta-Lactams - pharmacology; Biomedical and Life Sciences; Biomedicine; Chromatography, Liquid; Farmakologi; Female; Glomerular Filtration Rate; Humans; Intensive Care Units; Internal Medicine; Male; Mass Spectrometry; Medical Microbiology; Microbial Sensitivity Tests; Middle Aged; Original Article; Pharmacology; Prospective Studies; Serum - chemistry; Young Adult
• ISSN: 0934-9723; 1435-4373; 1435-4373
• DOI: 10.1007/s10096-016-2832-4

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 ≥18 years 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% f T >MIC ). MIC ECOFF was used as the target and, when available, the actual MIC (MIC ACTUAL ) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m 2 . The rate of patients reaching 100% f T > MIC ACTUAL was higher (89%, 31/35) compared to the same patients using MIC ECOFF (60%, p  = 0.002). In total, 55% (61/111) reached 100% f T > MIC ECOFF . Increased renal clearance was independently associated to not reaching 100% f T > MIC ECOFF . On repeated sampling, >77% of patients had stable serum drug levels around the MIC ECOFF . 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.