Background: Therapeutic drug monitoring (TDM) has been suggested to optimize antimicrobial target attainment, typically using 100%T>MIC, in β-lactam treatment in the ICU. The MIC parameter used in this equation is mostly the worst case scenario MIC (MICWCS)-the highest MIC the empirical treatment should cover. However, the impact of the MIC parameter used in pharmacokinetic/pharmacodynamic calculations has been poorly investigated.
Objectives: To assess the influence of target attainment rates for two different MIC parameters using actual MICs of the causative pathogens as the primary reference.
Methods: In a Swedish multicentre study of target attainment for 138 ICU patients treated with β-lactams, the causative pathogen was isolated and subjected to reference MIC testing. Whenever the strain belonged to the WT distribution, we assigned it to the category MICECOFF (epidemiological cut-off value). In the calculations we compared the MICECOFF and the MICWCS.
Results: The proportion of patients with target attainment failure for all antibiotics using 100%T>MIC was 45% (95% CI, 37%-53%) for MICWCS and 23% (95% CI, 16%-31%) for MICECOFF. When the target 50%T>4×MIC was used, corresponding attainment failures were 57% (95% CI, 49%-66%) and 25% (95% CI, 17%-32%) for MICWCS and MICECOFF, respectively.
Conclusions: MICWCS can overestimate target attainment failure. The use of MICWCS could be one reason for the difficulties in establishing a relationship between target failure and mortality in other studies. Based on findings herein, the MICECOFF, which is based on the MIC of the causative pathogen, should be considered a more suitable alternative. When no pathogen is detected, the MICECOFF of likely pathogens according to infection type should be used.
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.