Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.

中文翻译：

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ICU抗生素治疗的时机

在重症监护病房 (ICU) 的患者中，严重或危及生命的感染很常见。ICU 中的大多数感染起源于细菌或真菌，需要抗菌治疗来解决临床问题。抗生素是感染重症患者治疗的基石。然而，抗生素通常未得到最佳施用，导致较差的患者结果，包括更高的死亡率。脓毒症和感染性休克等危及生命的感染患者使用抗生素的时机现在被认为是该人群生存的最重要决定因素之一。延迟对严重感染进行抗生素治疗的个体的死亡率可能会增加一倍或更多。此外，适当的抗生素治疗的时机，一种基于体外易感性对致病病原体有活性的物质，也会影响存活。因此，不仅早期经验性抗生素给药很重要，而且这些药物的选择也很关键。抗生素输注的持续时间，特别是对于 β-内酰胺类药物，也会通过增加致病病原体的抗菌药物暴露来影响抗生素疗效。然而，由于抗生素耐药性不断增加，需要根据微生物学结果积极降级抗菌药物，以抵消早期广谱抗生素治疗的压力。在这篇综述中，我们研究了影响抗生素优化的时间相关变量，因为它与 ICU 中危及生命的感染的治疗有关。除了强调 ICU 中抗生素使用时机的重要性之外，我们还希望提供一种抗菌药物的方法，同时最大限度地减少这些药物的不必要使用。这种方法将越来越多地与分子微生物学测试和人工智能/机器学习的进步联系起来。这些进展应有助于在较早的时间点确定需要经验性抗生素治疗的患者以及所需的特定抗生素，以避免不必要地使用广谱抗生素。