Population pharmacokinetics and optimized prophylaxis dosing of cefazolin during transcatheter aortic valve implantation.

Abstract

Background: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical valve replacement for aortic stenosis. Infective endocarditis, most often caused by enterococci, is a significant post-procedural complication. Cefazolin has been the most frequently utilized agent for TAVI procedural prophylaxis, although recent guidelines suggest addition of an agent with enterococcal activity. Optimizing antimicrobial prophylaxis is important but little is known about antibiotic pharmacokinetics (PK) in this procedure.

Objectives: To define the population PK profile of prophylactic cefazolin in TAVI procedures and determine appropriateness for use.

Methods: Adult patients receiving cefazolin prophylaxis for TAVI were enrolled. Serum was collected at four timepoints periprocedurally for analysis of cefazolin concentrations. Population PK analysis and Monte Carlo simulation was performed. Fractional target attainment (FTA) against MIC distributions for common pathogens was performed.

Results: Three hundred and fifty-nine plasma cefazolin concentrations (188 total, 171 unbound) from 50 participants were used for model development. PTA for a 2 g dose of cefazolin and a procedure of 2 h duration was >90% for organisms with an MIC up to 8 mg/L. FTA was 100% for MSSA at all examined procedure durations and estimated glomerular filtration rate levels. FTAs for Staphylococcus epidermidis and Enterococcus faecalis, based on limited MIC data, were predominantly subthreshold.

Conclusions: This study found a 2 g dose of cefazolin achieved target exposure for MSSA but was subthreshold for other pathogens.