Patients undergoing major head and neck surgery are at risk of developing surgical site infections.

Antibiotic prophylaxis reduces the incidence of surgical site infections significantly; however, there is no agreement on the optimal type and duration of the antibiotic regimen.

A systematic review and meta-analysis of the literature in Medline, Cochrane, and Embase was performed, following the PRISMA guidelines.

The conclusion is that cefazolin, amoxicillin–clavulanate, and ampicillin–sulbactam are the antibiotics of choice, whereas clindamycin monotherapy increases the risk of infection in comparison to standard antibiotics and thus should be avoided. The latter finding is in contrast to current guidelines.

24–48 h of prophylaxis is appropriate, also in patients with an increased risk of infection.