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

  • H. WokseppEmail author
  • A. Hällgren
  • S. Borgström
  • F. Kullberg
  • A. Wimmerstedt
  • A. Oscarsson
  • P. Nordlund
  • M-L. Lindholm
  • J. Bonnedahl
  • L. Brudin
  • B. Carlsson
  • T. Schön
Original Article


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% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) 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 m2. 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.


Minimum Inhibitory Concentration International Normalize Ratio Intensive Care Unit Patient Therapeutic Drug Monitoring Continuous Renal Replacement Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank the participants and the clinical staff of the study.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • H. Woksepp
    • 1
    • 2
    Email author
  • A. Hällgren
    • 3
  • S. Borgström
    • 4
  • F. Kullberg
    • 5
  • A. Wimmerstedt
    • 6
  • A. Oscarsson
    • 7
    • 8
  • P. Nordlund
    • 9
  • M-L. Lindholm
    • 4
  • J. Bonnedahl
    • 10
  • L. Brudin
    • 11
  • B. Carlsson
    • 12
  • T. Schön
    • 13
    • 14
  1. 1.Department of Clinical MicrobiologyKalmar County HospitalKalmarSweden
  2. 2.Department of Medicine and OptometryLinnaeus UniversityKalmarSweden
  3. 3.Department of Clinical and Experimental Medicine, Faculty of Health SciencesLinköping UniversityLinköpingSweden
  4. 4.Department of Anaesthesia & Intensive CareKalmar County HospitalKalmarSweden
  5. 5.Department of Anaesthesia & Intensive CareCentral HospitalVäxjöSweden
  6. 6.Department of Infectious DiseasesCentral HospitalVäxjöSweden
  7. 7.Department of Medicine and HealthLinköping UniversityLinköpingSweden
  8. 8.Department of Anaesthesiology and Intensive CareLinköping University HospitalLinköpingSweden
  9. 9.Department of Anaesthesia and Intensive CareRyhov HospitalJönköpingSweden
  10. 10.Department of Infectious DiseasesKalmar County HospitalKalmarSweden
  11. 11.Department of Clinical PhysiologyKalmar County HospitalKalmarSweden
  12. 12.Department of Clinical Pharmacology and Department of Medical and Health SciencesLinköping UniversityLinköpingSweden
  13. 13.Department of Clinical Microbiology and Department of Infectious DiseasesKalmar County HospitalKalmarSweden
  14. 14.Department of Medical MicrobiologyLinköping UniversityLinköpingSweden

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