Surgical site infections (SSIs) occur in 2%-5% of patients and are a costly nosocomial occurrence. The rate varies and is dependent upon the type of wound. Risk factors for SSI include immunodeficiency, chronic steroid use, diabetes mellitus, extremes of age, and inpatient status (Anesthesiology 2020;132:586-97). The timely administration of prophylactic antibiotic/s in appropriate dose/s is a goal of the Surgical Care Improvement Project (SCIP) ( This initiative is used as a quality measure for perioperative care in hospitals and health systems ( and to ensure a minimum inhibitory antimicrobial concentration at the surgical site to treat existing skin flora, namely streptococci, S. aureus, and coagulase-negative staphylococci (Infect Control Hosp Epidemiol 2008;29:996-1011). Clean-contaminated wounds may also be infected with gram-negative rods and enterococci. Other pathogens may be involved depending on the body cavity/viscus being operated on, adjacent mucosa, immune competence, and pathogens in the operative environment.

The chosen antibiotics should be active against likely microbes, have few systemic side effects, not impact the human biome, be inexpensive, and have an appropriate pharmacokinetic profile (rapid onset, sustained duration of action, and simple administration). Cefazolin, a first-generation cephalosporin, fits this profile and is the most widely used antibiotic for SSI prophylaxis (Surg Infect (Larchmt) 2013;14:73-156). Cefazolin has minimal to no cross reactivity and can safely be administered in patients allergic to penicillin (Anesth Analg 2018;127:642-9; JAMA Surg 2021;156:e210021). Current guidelines recommend against the use of cephalosporins in patients with documented penicillin anaphylaxis. However, even a patient with a history of anaphylaxis may tolerate penicillin, as hypersensitivity wanes over time, and a recent meta-analysis found that the vast majority of reported penicillin allergies are not associated with any increased risk of a hypersensitive reaction to cefazolin (Anesthesiology 2020;132:586-97; JAMA Surg 2021;156:e210021; JAMA 2017;318:82-3). Vancomycin may be used in patients with hypersensitivity to cefazolin. When gram-negative coverage is needed (e.g., genitourinary surgery, gynecologic surgery), vancomycin and gentamicin are appropriate options. Vancomycin accompanied with cefazolin is considered the antibiotic of choice for methicillin-resistant S. aureus (MRSA) colonization or infection. Alternatives to cefazolin allergy include vancomycin and clindamycin. For those allergic to vancomycin, daptomycin may be used.

“Surgical site infections (SSIs) occur in 2%-5% of patients and are a costly nosocomial occurrence. The rate varies and is dependent upon the type of wound. Risk factors for SSI include immunodeficiency, chronic steroid use, diabetes mellitus, extremes of age, and inpatient status.”

The Table lists the dosing of the commonly used antibiotics, including the intervals for redosing required for longer operations or during states of rapid metabolism, as in patients with burns (Surg Infect (Larchmt) 2013;14:73-156).

For most surgical procedures, the general principles for SSI antimicrobial prophylaxis remain the same. Some of the differences in care are summarized below.

Topical vancomycin has been shown to reduce SSI in head-injured trauma victims and other neurosurgical and spine procedures (Surg Neurol Int 2021;12:600; Surg Neurol Int 2016;7:S919-26).


Oral surgical procedures involving mucosal disruption are considered clean-contaminated and polymicrobial. They require metronidazole in addition to a cephalosporin or clindamycin (JAMA Otolaryngol Head Neck Surg 2019;145:610-6).

Orthopedic surgeries, with the exception of endoscopic procedures, usually involve the use of a foreign body. Thus, cefazolin is usually indicated since “the function of blood is to carry Ancef to the bone” (Surg Infect (Larchmt) 2013;14:73-156). Alternatives for patients at high risk for allergic reactions are clindamycin or vancomycin. Rare cases may require gram negative coverage with aminoglycosides, aztreonam, or fluoroquinolones (Anesthesiology 2020;132:586-97; Surg Infect (Larchmt) 2013;14:73-156).

For cardiothoracic procedures, the most common causative organism associated with cardiothoracic surgery is S. aureus and coagulase negative staphylococcus. The gram-negative organisms are occasionally observed with saphenous grafts. Nasal colonization with S. aureus increases the risk of SSI in cardiac surgery patients. SSIs in cardiac surgical patients not only increase patient morbidity but could cause hospitals to be penalized with reductions in reimbursement from Medicaid and Medicare (Ann Thorac Surg 2007;83:1569-76; Eur J Cardiothorac Surg 2019;56:800-6).

Cefazolin is the first-line antibiotic for cardiac surgery. Vancomycin is added for patients who have nasal colonization with MRSA, prosthetic valve/s and aortic grafts, and inpatients. Vancomycin alone is not recommended since it lacks gram-negative coverage (Ann Thorac Surg 2007;83:1569-76).

Although cardiopulmonary bypass is known to alter antibiotic pharmacokinetics by increasing the volume of distribution, sequestering drugs in the circuit, and delaying clearance, the Society of Thoracic Surgeons recommends cefazolin re-administration every four hours regardless of bypass status. If vancomycin and aminoglycosides are used in lieu of cefazolin, redosing is not indicated (Ann Thorac Surg 2007;83:1569-76).

Pacemakers, implanted defibrillators, and other devices placed via cardiac catheterization have a risk of both SSI and endocarditis from contaminated electrical leads. These cases account for 10% of all endocarditis cases (Anesthesiology 2020;132:586-97; Arch Intern Med 2009;169:463-73). A single dose of cefazolin effectively prevents SSIs in these patients (Anesthesiology 2020;132:586-97).

Obese patients are at a higher risk for SSI, and higher doses as listed in the table are suggested (Anesthesiology 2020;132:586-97; Ann Thorac Surg 2007;83:1569-76). Patients who are immunocompromised or on antirejection drugs following transplantation will require clinical evaluation for possible colonization in both the donor and recipients, necessitating additional antibiotic coverage (Anesthesiology 2020;132:586-97).

Women undergoing cesarean delivery are at increased risk of SSI and deserve prophylactic antibiotics. Cefazolin is the drug of choice for non-laboring patients with intact membranes. In women with ruptured membranes, azithromycin 500 mg is added to cover mycoplasma. In case of cefazolin hypersensitivity, the parturient with intact membranes may receive clindamycin with gentamicin (Obstet Gynecol 2018;132:e103-19).

For newborns, the antibiotic of choice remains cefazolin in a dose of 25 mg/kg until <45 weeks post-menstrual age. The cefazolin dosage in infants and children is similar to adults, i.e., 30 mg (A Practice of Anesthesia for Infants and Children. 6th Edition, 2018). In children with documented hypersensitivity, or children colonized with MRSA, vancomycin is (again) the antibiotic of choice. The dosage of vancomycin is 15 mg/kg in neonates, infants, and children (A Practice of Anesthesia for Infants and Children. 6th Edition, 2018).