Abstract：
OBJECTIVE: Acinetobacter baumannii is classified by the centre for Disease Control and Prevention (CDC) as an \"urgent threat\" due to its ability to acquire and develop resistance to multiple classes of antibiotics. As a result, it is one of the most concerning pathogens in healthcare settings, with increasing incidence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) associated with high morbidity and mortality rates. Therefore, there are ongoing efforts to find novel treatment options, one of which is cefiderocol. We aim to review available evidence on cefiderocol use for severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumannii.
METHODS: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol.
CONCLUSIONS: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol\'s entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes.
CONCLUSIONS: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.
METHODS: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol.
CONCLUSIONS: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol\'s entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes.
CONCLUSIONS: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.
摘要：
背景：鲍曼不动杆菌被疾病控制和预防中心（CDC）归类为“紧急威胁”，因为它能够获得和发展对多种抗生素的耐药性。因此,它是医疗机构中最令人担忧的病原体之一，与高发病率和死亡率相关的碳青霉烯类耐药鲍曼不动杆菌（CRAB）感染的发生率增加。因此,正在努力寻找新的治疗方案，其中之一是塞菲德罗。我们旨在审查头孢地洛用于碳青霉烯耐药鲍曼不动杆菌引起的严重医院内性肺炎的现有证据。方法：2017年至2023年进行了全面审查，涵盖了Pubmed等数据库的文章，Scopus,和Embase,以及ECCMID2023的会议记录。主要重点是鲍曼不动杆菌和头孢地洛引起的严重医院内肺炎。
结论：头孢地洛，通过铁载体转运途径靶向周质间隙青霉素结合蛋白（PBPs），对多重耐药革兰氏阴性杆菌有希望。其治疗CRAB肺炎的有效性仍存在争议。CREDIBLE试验报告，头孢地罗与最佳治疗相比，死亡率更高，而其他队列研究显示结果不同。患者的差异和药代动力学因素可能是这些差异的基础。推荐的头孢地洛给药方案可能达不到所需的药代动力学目标，尤其是危重病人和肺部感染。在临床断点中忽略了阻碍头孢地洛通过铁转运蛋白进入细菌的肺因素。优化的给药或组合方案可以增强感染部位暴露和结果。
结论：需要进一步的研究来确定最佳的头孢地洛剂量和给药（单与单双重疗法,连续vs.间歇输注)，重症鲍曼不动杆菌医院获得性肺炎。
结论：头孢地洛，通过铁载体转运途径靶向周质间隙青霉素结合蛋白（PBPs），对多重耐药革兰氏阴性杆菌有希望。其治疗CRAB肺炎的有效性仍存在争议。CREDIBLE试验报告，头孢地罗与最佳治疗相比，死亡率更高，而其他队列研究显示结果不同。患者的差异和药代动力学因素可能是这些差异的基础。推荐的头孢地洛给药方案可能达不到所需的药代动力学目标，尤其是危重病人和肺部感染。在临床断点中忽略了阻碍头孢地洛通过铁转运蛋白进入细菌的肺因素。优化的给药或组合方案可以增强感染部位暴露和结果。
结论：需要进一步的研究来确定最佳的头孢地洛剂量和给药（单与单双重疗法,连续vs.间歇输注)，重症鲍曼不动杆菌医院获得性肺炎。
