STUDY DESIGN: A rabbit model was used to test the efficacy of cefazolin administered in various therapeutic regimens in preventing iatrogenic Staphylococcus aureus infections during spinal instrumentation. OBJECTIVE: To assess the efficacy of various prophylactic therapeutic regimens of cefazolin in preventing iatrogenic S. aureus infections during spinal instrumentation. SUMMARY OF BACKGROUND DATA: Previous studies have not dealt specifically with the occurrence of iatrogenic S. aureus infections during spinal instrumentation in a prospective fashion. METHODS: Twenty New Zealand White rabbits underwent a posterior approach to the lumbar spine. Fifteen of the animals then had double-braided 26-gauge surgical wire placed around bilateral L3-L4 and L4-L5 facet joints. A standardized volume of a 103 S. aureus/mL of solution was then inoculated onto the fusion-hardware site in all rabbits. The rabbits were divided into four groups receiving various antibiotic dose regimens. Five days after surgery, the animals were killed, and cultures were obtained. RESULTS: All of the rabbits receiving no antibiotic had fusion sites infected with S. aureus. None of the animals who received prophylactic cefazolin produced cultures that grew S. aureus. A specimen from one fusion site cultured Staphylococcus epidermidis, which is not sensitive to cefazolin. Analysis of these data using Fisher's exact test resulted in a P value of 0.008 when results in antibiotic groups were compared with those in a group receiving no antibiotics and a P value of 0.0003 when all groups were compared. CONCLUSIONS: This model was valid and reproducible for the study of spinal instrumentation and infection. In addition, the data support the efficacy and use of prophylactic intravenous antibiotics in preventing infection in spinal instrumentation and fusion surgery.