目的:描述连续输注(CI)头孢他啶-阿维巴坦的药代动力学/药效学(PK/PD)行为以及一系列危重肾脏患者的微生物学结果,这些患者接受了碳青霉烯耐药革兰氏阴性(CR-GN)血流感染(BSI)和/或呼吸机相关性肺炎(VAP)的治疗。
方法:肾功能不同程度的危重患者接受CI头孢他啶-阿维巴坦治疗,我们对2021年4月至2022年3月期间接受治疗药物监测的患者进行了回顾性评估.头孢他啶和阿维巴坦浓度在稳态下测定,并计算游离分数(fCss)。当头孢他啶的Css/MIC比值≥4(相当于100%fT>4xMIC)和阿维巴坦的Css/CT比值>1(相当于100%fT>CT为4.0mg/L)同时达到时,头孢他啶-阿维巴坦的联合PK/PD目标被认为是最佳的(如果仅达到两者之一,则为准最佳,如果两者均未实现,则为次优)。评估了头孢他啶-阿维巴坦PK/PD靶标与微生物学结果之间的关系。
结果:10例记录有CR-GN感染的患者(5个BSI,4VAP,检索到1个BSI+VAP)。头孢他啶-阿维巴坦的联合PK/PD靶点在8例和2例中均为最优和准最优,分别。两名患者发生微生物衰竭(一名患有VAP,一个带有BSI+VAP),其中一人产生了头孢他啶-阿维巴坦耐药性。都接受了肾脏替代疗法,尽管达到了最佳的联合PK/PD目标并接受了磷霉素联合治疗,但仍失败。
结论:CI给药可以使大多数CR-GN感染的危重肾脏患者实现头孢他啶-阿维巴坦的最佳联合PK/PD目标,并可能有助于将微生物失效的风险降至最低。
OBJECTIVE: To describe the pharmacokinetic/pharmacodynamic (PK/PD) behaviour of continuous infusion (CI) ceftazidime-avibactam and the microbiological outcome in a
case series of critically ill renal patients treated for documented carbapenem-resistant Gram-negative (CR-GN) bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP).
METHODS: Critically ill patients with different degrees of renal function who were treated with CI ceftazidime-avibactam for documented CR-GN infections, and who underwent therapeutic drug monitoring from April 2021 to March 2022, were retrospectively assessed. Ceftazidime and avibactam concentrations were determined at steady-state, and the free fraction (fCss) was calculated. The joint PK/PD target of ceftazidime-avibactam was considered as optimal when both Css/MIC ratio for ceftazidime ≥4 (equivalent to 100%fT>4xMIC) and Css/CT ratio for avibactam >1 (equivalent to 100% fT>CT of 4.0 mg/L) were simultaneously achieved (quasi-optimal if only one of the two was achieved, and suboptimal if neither of the two was achieved). The relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed.
RESULTS: Ten patients with documented CR-GN infections (5 BSIs, 4 VAP, 1 BSI+VAP) were retrieved. The joint PK/PD targets of ceftazidime-avibactam were optimal and quasi-optimal in eight and two cases, respectively. Microbiological failure occurred in two patients (one with VAP, one with BSI+VAP), one of whom developed ceftazidime-avibactam resistance. Both underwent renal replacement therapy, and failed despite attaining optimal joint PK/PD target and receiving fosfomycin co-treatment.
CONCLUSIONS: CI administration may enable optimal joint PK/PD targets of ceftazidime-avibactam to be achieved in most critical renal patients with CR-GN infections, and may help to minimize the risk of microbiological failure.