Falcone Marco, Viale Pierluigi, Tiseo Giusy, Pai Manjunath
a Department of Public Health and Infectious Diseases , "Sapienza" University of Rome , Rome , Italy.
b Infectious Diseases Unit, Department of Medical and Surgical Sciences , Hospital S. Orsola-Malpighi, University of Bologna , Bologna , Italy.
Expert Opin Drug Metab Toxicol. 2018 Mar;14(3):331-340. doi: 10.1080/17425255.2018.1434142. Epub 2018 Jan 31.
Ceftazidime-avibactam (CAZ-AVI) is a combination of a third-generation cephalosporin and a non-β-lactam, β-lactamase inhibitor, recently approved for urinary tract infections and complicated abdominal infections. Moreover, it represents a treatment option for patients with hospital acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR) bacteria. Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ-AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics (PD) in this field. Expert opinion: In vitro and in vivo data about PK/PD of CAZ-AVI confirm that penetration of CAZ-AVI in the epithelial lining fluid (ELF) represents approximately 30% of the plasma concentrations. Clinical studies documented that CAZ-AVI 2000 mg/500 mg every 8 h is the optimal dose regimen to achieve the PK/PD target attainment in patients with HAP. Thus, CAZ-AVI could represent an option both to treat HAP caused by Gram-negative bacilli (GNB) displaying resistance to most of the antibiotics and to reduce the use of carbapenems, limiting the onset of resistance profiles among GNB. Additional information about specific patients populations, such as critically-ill subjects or pediatric patients, are needed for a more individualized use of CAZ-AVI.
头孢他啶-阿维巴坦（CAZ-AVI）是第三代头孢菌素与一种非β-内酰胺类β-内酰胺酶抑制剂的组合，最近被批准用于治疗尿路感染和复杂性腹腔感染。此外，它也是医院获得性肺炎（HAP）患者的一种治疗选择，尤其是由多重耐药（MDR）细菌引起的HAP。涵盖领域：本综述聚焦于CAZ-AVI在HAP中的药代动力学（PK）以及评估该领域PK/药效学（PD）的临床前和临床研究。专家观点：关于CAZ-AVI的PK/PD的体外和体内数据证实，CAZ-AVI在上皮衬液（ELF）中的渗透量约为血浆浓度的30%。临床研究表明，每8小时给予2000mg/500mg的CAZ-AVI是在HAP患者中实现PK/PD目标达成的最佳剂量方案。因此，CAZ-AVI既可以作为治疗由对大多数抗生素耐药的革兰氏阴性杆菌（GNB）引起的HAP的一种选择，也可以减少碳青霉烯类药物的使用，限制GNB耐药谱的出现。为了更个体化地使用CAZ-AVI，还需要关于特定患者群体（如重症患者或儿科患者）的更多信息。
