Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications. We determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent. There were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam. All tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.

中文翻译：

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临床症状和治疗部位预测碳青霉烯类保留疗法在头孢曲松不敏感的大肠杆菌血流感染中的效用

Cefiderocol、ceftazidime-avibactam、ceftolozane-tazobactam、静脉内磷霉素和plazomicin代表潜在的碳青霉烯保护剂，用于产生超广谱β-内酰胺酶或AmpCβ-内酰胺酶的大肠杆菌感染。然而，可用数据在预测可以替代的碳青霉烯类治疗量和现实世界的禁忌症方面是有限的。我们确定了 2015 年至 2016 年在单一卫生网络中的头孢曲松非敏感大肠杆菌菌血症未选择队列中可替代的碳青霉烯类治疗天数 (DOT) 和常见禁忌症，以考虑抗生素敏感性和感染部位. 个体患者数据用于计算每个药剂的 DOT 和替代。有 108 次大肠杆菌菌血症发作，导致 67 次。2 个碳青霉烯 DOT/100 患者天的抗菌治疗。头孢他啶-阿维巴坦可用于替代 36.2 DOT/100 患者-天（54%）的住院根治性治疗，头孢唑烷-他唑巴坦替代 34.7 DOT/100 患者-天（52%），头孢地考替代 27.1 DOT/100 患者-天（ 40%)，磷霉素为 23.3 DOT/100 患者日 (35%)，plazomicin 为 27.1 DOT/100 患者日 (40%)。非尿路感染源是磷霉素 (25)、plazomicin (26) 和头孢地洛尔 (26) 最常见的禁忌症。在门诊胃肠外抗菌治疗 (OPAT) 计划中的使用占 DOT 的 40%，如果稳定性数据允许用于头孢他啶-阿维巴坦和头孢洛扎烷-他唑巴坦，所有这些都可以被替代。所有测试的药物都可以用来替代大量的碳青霉烯类疗法。