Abstract

Background

In the ICU, early and appropriate antimicrobial therapy is important to lower infection-related mortality.

Objectives

Assess whether achieving early β-lactam free concentration above the MIC 100% of the time (fT_>MIC) is associated with positive outcomes in the ICU.

Methods

This retrospective study was conducted in ICU patients admitted to UF Health Shands Hospital between 2016 and 2018. Adult patients who received β-lactam therapy and had drug concentration measured were included. Data collected included demographics, β-lactam regimens and concentrations, sources of infection, cultures and susceptibilities, mortality, length of stay, resistance acquisition for 30 days and clinical outcome at end of therapy. Multiple regression and time-to-event (TTE) analyses were performed.

Results

Two-hundred and six patients were included. Clinical cure occurred in 71%, microbial eradication occurred in 58% and new resistance to the β-lactam received developed in 8% of patients. Hospital and 30 day mortalities were 17% and 14%, respectively. fT_>MIC and fT_>4×MIC were associated with clinical cure (P = 0.0303), microbial eradication (P = 0.0476) and suppression of resistance (P = 0.0043). Delay in measuring β-lactam concentration was associated with clinical failure (P = 0.0072), longer ICU stay (P < 0.0001) and higher mortality (P = 0.0387). In the TTE analysis, patients with 100% fT_>MIC had a significantly shorter ICU stay (P = 0.0297). Patients who had clinical cure and microbial eradication had drug concentrations measured earlier (P = 0.0025 and 0.0254, respectively).

Conclusions

This study highlights the importance of early measurement of β-lactam concentration and confirms the association between fT_>MIC and clinical cure, microbial eradication and emergence of resistance.

中文翻译：

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危重患者中β-内酰胺类药物的早期治疗监测及相关治疗结果。

摘要

背景

在ICU中，早期和适当的抗菌治疗对于降低感染相关的死亡率很重要。

目标

评估在100％的时间内超过MIC的早期β-内酰胺游离浓度（fT _{> MIC}）是否与ICU的阳性结果相关。

方法

这项回顾性研究是在2016年至2018年间对入选UF Health Shands医院的ICU患者进行的。纳入了接受β-内酰胺治疗并测定了药物浓度的成年患者。收集的数据包括人口统计学，β-内酰胺方案和浓度，感染源，培养物和药敏性，死亡率，住院时间，30天耐药性获得以及治疗结束时的临床结果。进行了多元回归和事件发生时间（TTE）分析。

结果

包括206名患者。71％的患者治愈了临床疾病，58％的患者清除了微生物，并且8％的患者对β-内酰胺产生了新的耐药性。住院死亡率和30天死亡率分别为17％和14％。fT _{> MIC}和fT _{> 4×MIC}与临床治愈（P  =  0.0303），根除微生物（P  =  0.0476）和抑制耐药性（P  =  0.0043）相关。延迟测量β-内酰胺浓度与临床失败（P  =  0.0072），ICU停留时间更长（P  <  0.0001）和较高的死亡率（P  = 0.0387）。在TTE分析中，具有100％fT _{> MIC}的患者的ICU住院时间明显缩短（P  =  0.0297）。进行临床治愈和根除微生物的患者的药物浓度测得较早（分别为P  =  0.0025和0.0254）。

结论

这项研究强调了早期测定β-内酰胺浓度的重要性，并证实了fT _{> MIC}与临床治愈，根除微生物和产生耐药性之间的关联。