Article
Chemistry, Medicinal
Yuanyuan Dai, Wenjiao Chang, Xin Zhou, Wei Yu, Chen Huang, Yunbo Chen, Xiaoling Ma, Huaiwei Lu, Rujin Ji, Chaoqun Ying, Peipei Wang, Zhiying Liu, Qingfeng Yuan, Yonghong Xiao
Summary: The study evaluated the administration regimen of ceftazidime/avibactam for bloodstream infections caused by Enterobacteriaceae and Pseudomonas aeruginosa. Different dosage regimens were optimized based on efficacy evaluations to guide individualized treatment for better clinical responses.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Infectious Diseases
Valentin al Jalali, Peter Matzneller, Anh Duc Pham, Wisse van Os, Michael Woelfl-Duchek, Maria Sanz-Codina, Andreas Vychytil, Birgit Reiter, Thomas Stimp, Markus Zeitlinger
Summary: This study investigated the pharmacokinetics of CAZ/AVI in patients undergoing APD and found similar PK profiles of the drug in plasma and peritoneal dialysate, indicating the suitability of a fixed-dose combination. Monte Carlo simulations showed that even a low dose of CAZ/AVI achieved a high probability of target attainment for treating infections in APD patients.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Microbiology
Thomas P. Lodise, J. Nicholas O'Donnell, Stephen Balevic, Xing Liu, Kenan Gu, Jomy George, Shruti Raja, Jeffrey T. Guptill, Smitha Zaharoff, Nyssa Schwager, Vance G. Fowler, Alison Wall, Katherine Wiegand, Henry F. Chambers
Summary: This study described the pharmacokinetic (PK) characteristics of ceftazidime-avibactam (CZA) and aztreonam (ATM) in combination and assessed the association between ATM exposure and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations. The study found that CZA-ATM administration reduced ATM clearance and did not exacerbate AST/ALT elevations. Continuous infusion of ATM should be used with caution.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Annabel Werumeus Buning, Caspar J. Hodiamont, Natalia M. Lechner, Margriet Schokkin, Paul W. G. Elbers, Nicole P. Juffermans, Ron A. A. Mathot, Menno D. de Jong, Reinier M. van Hest
Summary: This study aimed to describe the population pharmacokinetics of ceftazidime in critically ill patients with Pseudomonas aeruginosa infection, and found that patient characteristics and treatment methods can affect drug clearance, suggesting the use of loading doses for patients with proven or suspected P. aeruginosa infection.
Article
Microbiology
Christian M. Gill, Elif Aktas, Wadha Alfouzan, Lori Bourassa, Adrian Brink, Carey-Ann D. Burnham, Rafael Canton, Yehuda Carmeli, Marco Falcone, Carlos Kiffer, Anna Marchese, Octavio Martinez, Spyros Pournaras, Harald Seifert, Abrar K. Thabit, Maria Virginia Villegas, Lars F. Westblade, David P. Nicolau
Summary: In this study, high in vitro potency of ceftazidime and cefepime among carbapenem-resistant Pseudomonas aeruginosa isolates was found, with 6 g/day required to achieve optimal pharmacodynamic profiles. These findings should be considered in the clinical setting and for the application of CLSI susceptibility breakpoints.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Jiaxin Yu, Wei Zuo, Hongwei Fan, Jiayu Wu, Luyao Qiao, Benyu Yang, Wenxi Li, Yang Yang, Bo Zhang
Summary: Ceftazidime-avibactam (C-A) was found to be an effective therapy for severe carbapenem-resistant gram-negative bacterial infections, and clinical response was correlated with the time of C-A initiation. A dosage >3.75g/d C-A was associated with prolonged survival for patients in continuous renal replacement therapy (CRRT). Randomized controlled trials or multicenter studies are needed to confirm these findings.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Microbiology
Lin Wang, Weiyi Shen, Rong Zhang, Jiachang Cai
Summary: This study identified a novel ceftazidime-avibactam-resistant KPC-2 variant, KPC-123, in a Citrobacter koseri isolated from a patient in a Chinese hospital. The KPC-123 variant showed high-level resistance to ceftazidime and ceftazidime/avibactam, but remained susceptible to carbapenems. Whole-genome sequencing and genomic analysis revealed the transfer and in vivo evolution of the bla(KPC)-carrying plasmid. Active surveillance is needed to prevent and control the dissemination of ceftazidime/avibactam resistance.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Zeyu Huang, Yijia Han, Xiaotuan Zhang, Yao Sun, Yuzhan Lin, Luozhu Feng, Tieli Zhou, Zhongyong Wang
Summary: This study demonstrates that the combination of CZA and NAC effectively inhibits the growth of CZA-resistant clinical Enterobacterales strains. It also inhibits biofilm formation in vitro and reduces bacterial burden in a mouse thigh infection model. The combination is biocompatible and primarily increases cell membrane permeability to cause bacterial death.
Article
Microbiology
Luozhu Feng, Yining Zhao, Zhuocheng Yao, Xiaodong Zhang, Shufang Zheng, Lijiang Chen, Ying Zhang, Lingbo Wang, Tieli Zhou, Jianming Cao
Summary: This study developed a rapid ResaCeftazidime-avibactam Enterobacterales NP test, which can detect the susceptibility of Enterobacterales to CZA within a short period of time with high accuracy and consistency. This method is economical and convenient, and may be used for the rapid screening and timely treatment of CZA-resistant strains in clinical settings.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Review
Infectious Diseases
Wright W. Nichols, Sushmita D. Lahiri, Patricia A. Bradford, Gregory G. Stone
Summary: This article reviews the resistance to ceftazidime/avibactam and its primary pharmacology, which is thematically linked with recent reviews of the basic in vitro and in vivo translational biology of the combination (J Antimicrob Chemother 2022; 77: 2321-40 and 2341-52). Single-step exposures to 8x MIC of ceftazidime/avibactam resulted in frequencies of resistance in Enterobacterales or Pseudomonas aeruginosa.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Li Xue, Qi Hui, Jin Fei, Yao Bu-Fan, Wu Yue-E, Qi Yu-Jie, Kou Chen, Wu Xi-Rong, Luo Xiao-Jing, Shen Yan-Hua, Zheng Xu, Wang Yong-Hong, Xu Fang, Jiao Wei-Wei, Li Jie-Qiong, Xiao Jing, Dong Yi-Ning, Du Bin, Shi Hai-Yan, Xu Bao-Ping, Shen A-Dong, Zhao Wei
Summary: By conducting a population pharmacokinetic study and recommending a model-based dosage regimen, this study aimed to optimize sepsis therapy in neonates and young infants using ceftazidime. Through Monte Carlo simulation, evidence-based dosage regimens were proposed based on developmental pharmacokinetic-pharmacodynamic analysis, covering the entire range of this vulnerable population.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Infectious Diseases
Joan Gomez-Junyent, Oscar Murillo, Heidi H. Yu, Mohammad A. K. Azad, Hasini Wickremasinghe, Raul Rigo-Bonnin, Eva Benavent, Javier Ariza, Jian Li
Summary: The study demonstrated that continuous infusion of ceftazidime displayed concentration-dependent antibiofilm activity against P. aeruginosa biofilm, especially when combined with colistin. The use of high-dosage regimens of continuous infusion ceftazidime with colistin was supported for biofilm-associated infections caused by ceftazidime-susceptible P. aeruginosa.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Infectious Diseases
Karoline Knudsen List, Mette Kolpen, Kasper Norskov Kragh, Godefroid Charbon, Stine Radmer, Frank Hansen, Anders Lobner-Olesen, Niels Frimodt-Moller, Frederik Boetius Hertz
Summary: The study evaluated the efficacy of mecillinam in combination with either avibactam or ceftazidime/avibactam against carbapenemase-producing clinical isolates. The combination substantially reduced MICs and showed significant log-CFU reductions in time-kill and in vivo experiments, indicating a notable effect on most types of CPEs, both in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Silvia Corcione, Ilaria De Benedetto, Nour Shbaklo, Giulia Torsello, Tommaso Lupia, Gabriele Bianco, Rossana Cavallo, Luca Brazzi, Giorgia Montrucchio, Francesco Giuseppe De Rosa
Summary: The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains poses a significant challenge to healthcare systems. Ceftazidime/avibactam (C/A) has been a first-line treatment, but C/A-resistant strains are increasing, especially among pneumonia patients or those with prior suboptimal blood exposure to C/A. A retrospective study was conducted on patients admitted to an ICU for COVID-19, with the primary purpose of studying C/A-resistant strains and describing the characteristics of the population. The study found a single clone of C/A-resistant KPC-Kp isolates with a D179Y mutation in the bla(KPC-2) gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Roxane Rohani, Marc H. Scheetz, Helen K. Donnelly, Alvaro Donayre, Mengjia Kang, Estefani Diaz, Kay Dedicatoria, Alan R. Hauser, Egon A. Ozer, Sophia Nozick, Chao Qi, Anna E. Pawlowski, Michael N. Neely, Alexander Misharin, Richard G. Wunderink, Nathaniel J. Rhodes
Summary: Critical illness affects the attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets. This study aimed to quantify PK/PD attainment in patients with hospital-acquired pneumonia. The results showed that individualized treatment is required to achieve suggested PK/PD targets.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)