Yu Wei, Chen Yunbo, Shen Ping, Ji Jinru, Ying Chaoqun, Liu Zhiying, Xiong Luying, Qiu Yunqing, Xiao Yonghong
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Pharmacol. 2021 Dec 14;12:771910. doi: 10.3389/fphar.2021.771910. eCollection 2021.
This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant (BSIs-CRKP). A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations. The MIC of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried and . A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%. TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.
本研究旨在探讨头孢他啶-阿维巴坦（CZA）和氨曲南-阿维巴坦（AZA）对耐碳青霉烯类血流感染（BSIs-CRKP）的活性及最佳治疗方案。从血液细菌耐药性调查协作系统（BRICS）项目中收集了318株非重复的BSIs-CRKP分离株。采用琼脂稀释法测定CZA和AZA的最低抑菌浓度（MIC）。通过PCR扩增碳青霉烯酶基因和多位点序列分型。进行蒙特卡洛模拟（MCS）以计算不同CZA或AZA给药方案的累积反应分数（CFR）。CZA和AZA的MIC分别为128/4和1/4 mg/L。分别有87.4%和3.5%的分离株携带 和 。共鉴定出68种ST型，其中29种为新型ST型。ST11占66.6%。进一步的MCS结果显示，采用两步输注疗法（第一步0.5小时快速输注，第二步3小时缓慢输注，TSIT）（2.5 g 0.5小时，每8小时3.75 g并3小时输注；3.75 g 0.5小时，每8小时2.5 g并3小时输注）时，CZA的CFR高于89%。AZA采用TSIT时的CFR高于96%。具备充分药代动力学条件的TSIT可能有助于提高CZA和AZA对BSIs-CRKP的治疗效果。
