Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala,Sweden.
Clinical Microbiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
J Antimicrob Chemother. 2023 Dec 1;78(12):2895-2901. doi: 10.1093/jac/dkad327.
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.
To assess the influence of target attainment rates for two different MIC parameters using actual MICs of the causative pathogens as the primary reference.
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.
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.
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.
治疗药物监测（TDM）已被建议用于优化 ICU 中β-内酰胺治疗的抗菌目标达标率，通常使用 100%T>MIC。该方程中使用的 MIC 参数大多是最坏情况下的 MIC（MICWCS）——经验性治疗应覆盖的最高 MIC。然而，用于药代动力学/药效学计算的 MIC 参数的影响尚未得到充分研究。
使用实际病原体 MIC 作为主要参考，评估两种不同 MIC 参数的目标达标率的影响。
在一项针对 138 名 ICU 患者接受β-内酰胺治疗的目标达标率的瑞典多中心研究中，分离出病原体并进行参考 MIC 检测。只要菌株属于 WT 分布，我们就将其归为 MICECOFF（流行病学临界值）类别。在计算中，我们比较了 MICECOFF 和 MICWCS。
对于所有抗生素，使用 100%T>MIC 时，MICWCS 导致目标达标失败的患者比例为 45%（95%CI，37%-53%），而 MICECOFF 为 23%（95%CI，16%-31%）。当使用目标 50%T>4×MIC 时，MICWCS 和 MICECOFF 分别对应达标失败率为 57%（95%CI，49%-66%）和 25%（95%CI，17%-32%）。
MICWCS 可能高估了目标达标失败率。MICWCS 的使用可能是其他研究中未能建立目标失败与死亡率之间关系的原因之一。基于本文的发现，基于病原体 MIC 的 MICECOFF 应该被认为是更合适的替代方案。当未检测到病原体时，应使用根据感染类型推测的可能病原体的 MICECOFF。
