Rethinking Carbapenems: A Pharmacokinetic Approach for Antimicrobial Selection in Infected Necrotizing Pancreatitis

作者：Christina Maguire, Deepak Agrawal, Mitchell J. Daley, Elizabeth Douglass, Dusten T. Rose · 发表于：Annals of Pharmacotherapy · 年份：2020 · DOI：10.1177/1060028020970124 · 被引用次数：18 · 研究领域：Pancreatitis Pathology and Treatment、Gallbladder and Bile Duct Disorders、Abdominal vascular conditions and treatments

Objective: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP. Data Sources: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms. Study Selection and Data Extraction: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design. Data Synthesis: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa. Relevance to Patient Care and Clinical Practice: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing...