Swedish multicentre study of target attainments with β-lactams in the ICU: which MIC parameter should be used?

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 (MIC(WCS))—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 MIC(ECOFF) (epidemiological cut-off value). In the calculations we compared the MIC(ECOFF) and the MIC(WCS). RESULTS: The proportion of patients with target attainment failure for all antibiotics using 100%T(>MIC) was 45% (95% CI, 37%–53%) for MIC(WCS) and 23% (95% CI, 16%–31%) for MIC(ECOFF). 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 MIC(WCS) and MIC(ECOFF), respectively. CONCLUSIONS: MIC(WCS) can overestimate target attainment failure. The use of MIC(WCS) could be one reason for the difficulties in establishing a relationship between target failure and mortality in other studies. Based on findings herein, the MIC(ECOFF), which is based on the MIC of the causative pathogen, should be considered a more suitable alternative. When no pathogen is detected, the MIC(ECOFF) of likely pathogens according to infection type should be used.