Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics

Abstract

Appropriate surgical antimicrobial prophylaxis (SAP) is an important measure in preventing surgical site infections (SSIs). Although antimicrobial pharmacokinetics–pharmacodynamics (PKPD) is integral to optimizing antibiotic dosing for the treatment of infections, there is less research on preventing infections postsurgery. Whereas clinical studies of SAP dose, preincision timing, and redosing are informative, it is difficult to isolate their effect on SSI outcomes. Antimicrobial PKPD aims to explain the complex relationship between antibiotic exposure during surgery and the subsequent development of SSI. It accounts for the many factors that influence the PKs and antibiotic concentrations in patients and considers the susceptibilities of bacteria most likely to contaminate the surgical site. This narrative review examines the relevance and role of PKPD in providing effective SAP. The dose–response relationship i.e., association between lower dose and SSI in cefazolin prophylaxis is discussed. A comprehensive review of the evidence for an antibiotic concentration–response (SSI) relationship in SAP is also presented. Finally, PKPD considerations for improving SAP are explored with a focus on cefazolin prophylaxis in adults and outstanding questions regarding its dose, preincision timing, and redosing during surgery.