Cefazolin prophylaxis in minimally invasive gynecologic surgery – are dosage and timing appropriate? Prospective study using resampling simulation

Objective: Cefazolin is a widely used antimicrobial prophylactic agent, however the appropriate dosage, timing, pharmacology and microbial coverage have not been well-established for gynecologic procedures. We aimed to describe serum concentrations and pharmacokinetics of Intravenous cefazolin given to women prior to scheduled minimally invasive gynecologic surgeries, and to determine whether appropriate antimicrobial coverage had been achieved in short time from prophylactic administration to surgical start time. Methods: A prospective cohort analysis study, using a resampled dataset, of women undergoing scheduled gynecological surgeries in a university affiliated tertiary medical center. IV cefazolin (1 or 2 gr) was administered prior to incision to women weighing <80 kg (Group A) and ≥80 kg (Group B), respectively. Cefazolin serum levels were obtained at the time of skin incision (Time 0) and 30 min later (Time 30), measured by high-pressure liquid chromatography (HPLC). Appropriate antimicrobial coverage was defined when cefazolin serum levels were above minimal inhibitory concentrations (MIC) for Enterobacteriaceae. Results: Overall, 21 women were included. The mean time interval between drug administration and incision did not differ between the two groups (18 ± 10 min vs. 11 ± 10 min, respectively, p = .0.25). A hierarchical mixed linear regression model, using a simulation of multiple random bootstrap resampling (n = 1,000), revealed that cefazolin serum levels exceeded MIC, regardless of the timing of administration in the sampling intervals. Mean cefazolin serum levels in time 0 and time 30 min were not affected by BMI in patients receiving 1 gr. Conclusion: A single dose of IV cefazolin given shortly prior to skin incision provides serum concentrations above minimal inhibitory concentrations for susceptible pathogens in most women undergoing scheduled minimally invasive gynecologic surgery.