Prospective randomized double-blinded trial comparing 2 anti-MRSA agents with supplemental coverage of cefazolin before lower extremity revascularization.

Surgical site infection results in significant morbidity after vascular reconstructions. Historical studies have demonstrated a reduction in surgical site infection with the use of antibiotic prophylaxis in vascular surgery.1 Over the following several decades’ comparisons, second- and third-generation cephalosporins have been made with Cefazolin, a first generation cephalosporin, with mixed results in differences in surgical site infection.2,3 Clearly the acquisition costs are greater with advanced generation cephalosporin’s, with unclear advantages in reduction of postoperative infections. Undoubtedly in the 21st century an evolving bacterial climate has occurred with resistant bacteria accounting for a consistent proportion of wound infections in the vascular patient.4 The University of South Florida reported in a cohort of 34 patients with complicated extra-cavity vascular surgical site infections nearly 1/2 had methicillin resistant (44%) isolates at the time of antibiotic bead implant procedures and less than 25% of sites producing Gram-negative isolates. This is in contrast to work from our institution that demonstrated nearly opposite isolate findings with respect to methicillin-resistant organisms and Gram-negative organisms with approximately 25% and 40%, respectively.5 These differences are dramatic and may be related to local regional differences in bacterial colonization or other geographical differences. Nevertheless, the proportion of Gram-positive organisms with resistance to first generation cephalosporins has skyrocketed. Fifteen years ago a direct comparison of a glycopedide (teicoplanin) with Cefazolin was made with no apparent reduction in incidence of surgical site infection.6 With this evolving microbial climate, we attempted to address this question several years ago with a prospective randomized trial comparing Cefazolin alone to Cefazolin with the addition of either vancomycin or daptomycin.7 The infection rate was lowest in those receiving a combination of Cefazolin and Daptomycin; however, sample size was small and other methodological issues were identified. With the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections4,5 compared with historical series, in addition to a single center design and enrollment challenges we felt a third arm with the current standard of care would be difficult to fulfill patient enrollment in a reasonable time frame. Therefore we sought to evaluate patients undergoing vascular operations with lower extremity incisions and directly compare whether one anti-MRSA agent was superior to the other in a prospective double-blinded fashion.