PMID- 34970142 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220101 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Antibacterial Activity and Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae. PG - 771910 LID - 10.3389/fphar.2021.771910 [doi] LID - 771910 AB - Objectives: 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 Klebsiella pneumoniae (BSIs-CRKP). Methods: 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. Results: The MIC(90) of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried bla (KPC-2) and bla (NDM-1). 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%. Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP. CI - Copyright (c) 2021 Yu, Chen, Shen, Ji, Ying, Liu, Xiong, Qiu and Xiao. FAU - Yu, Wei AU - Yu W AD - 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. FAU - Chen, Yunbo AU - Chen Y AD - 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. FAU - Shen, Ping AU - Shen P AD - 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. FAU - Ji, Jinru AU - Ji J AD - 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. FAU - Ying, Chaoqun AU - Ying C AD - 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. FAU - Liu, Zhiying AU - Liu Z AD - 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. FAU - Xiong, Luying AU - Xiong L AD - 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. FAU - Qiu, Yunqing AU - Qiu Y AD - 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. FAU - Xiao, Yonghong AU - Xiao Y AD - 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. LA - eng PT - Journal Article DEP - 20211214 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8712734 OTO - NOTNLM OT - Monte Carlo simulation OT - PK/PD OT - carbapenem-resistant Klebsiella pneumoniae OT - intermittent infusion OT - two-step infusion COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/01 06:00 MHDA- 2022/01/01 06:01 PMCR- 2021/12/14 CRDT- 2021/12/31 06:02 PHST- 2021/09/07 00:00 [received] PHST- 2021/11/22 00:00 [accepted] PHST- 2021/12/31 06:02 [entrez] PHST- 2022/01/01 06:00 [pubmed] PHST- 2022/01/01 06:01 [medline] PHST- 2021/12/14 00:00 [pmc-release] AID - 771910 [pii] AID - 10.3389/fphar.2021.771910 [doi] PST - epublish SO - Front Pharmacol. 2021 Dec 14;12:771910. doi: 10.3389/fphar.2021.771910. eCollection 2021.