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Peri-operative Pharmacokinetics of Cefazolin Prophylaxis During Valve Replacement Surgery

Ahmad Alli, Fathima Paruk, Claire Roger, Jeffrey Lipman, Daren Calleemalay, Steven C. Wallis, Juan Scribante, Guy A. Richards, Jason A. Roberts

Abstract

There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens.

Introduction

The risk of post-operative surgical site infection (SSI) is high following major cardiac surgery [1, 2]. Sternal wound infections, (including mediastinitis), endocarditis or prosthetic implant infections are of particular concern following cardiac surgery and are associated with poor patient outcomes and escalating costs of care [3]. The occurrence of mediastinitis in particular is a severe complication with mortality rates reported to be as high as 47% [4]. As such, effective antimicrobial prophylaxis is crucial.

Materials and method

This was a prospective, PK study with convenience sampling conducted in the cardiothoracic theatres of Charlotte Maxeke Johannesburg Academic Hospital, a quaternary academic training and referral center for cardiothoracic patients in South Africa. The University of the Witwatersrand Human Research Ethics Committee approved the study (clearance certificate No. M140662). Written informed consent was obtained from each participant.

Results

Sixteen patients were included in the study with an equal number of males and females.

Discussion

In this population PK study in patients undergoing CPB surgery, we found that the current regimen of cefazolin (2 g 4-hourly) was insufficient to achieve the PK/PD target of 100% fT>MIC for relevant pathogens during the first 4 hours of open cardiac surgery in patients with normal renal function and serum albumin concentrations. In line with the pharmacodynamics of beta-lactams, our dosing simulations showed that increasing the dose and/or increasing dosing frequency resulted in improvements in the PTA and FTA.

Conclusions

The dosing regimen of intravenous administration of 2g cefazolin 4-hourly, was inadequate for achieving target drug exposures for a standard patient, undergoing valve surgery receiving CPB, with a serum creatinine (SeCr) level of 50 μmol/L and an albumin concentration of 35 g/L. The efficacy of regimens with either a higher dosage or increased frequency or the use of continuous infusions needs to be explored in this population. In order to ensure successful prophylaxis, existing dosing regimens need to be re-evaluated and individualised, particularly taking patient factors such as renal function into account.

Citation: Alli A, Paruk F, Roger C, Lipman J, Calleemalay D, Wallis SC, et al. (2023) Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery. PLoS ONE 18(9): e0291425. https://doi.org/10.1371/journal.pone.0291425

Editor: Andrea Ballotta, IRCCS Policlinico S.Donato, ITALY

Received: December 22, 2021; Accepted: August 17, 2023; Published: September 20, 2023

Copyright: © 2023 Alli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Figshare repository: Title: Alli, Ahmad (2023). Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery. figshare. Dataset. DOI: https://doi.org/10.6084/m9.figshare.23691003.v1.

Funding: The author(s) received no specific funding for this work.

Competing interests: J.L. has received grants from Pfizer and MSD J.A.R. has received investigator-initiated grants from, or has consulted for, bioMérieux, Astellas, MSD, Accelerate Diagnostics and Cardeas Pharma. C.R. has received grants from Pfizer and MSD.

 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291425#sec025

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