Controversies in Perioperative Antimicrobial Prophylaxis

Brooke K. Decker, M.D.; Alexander Nagrebetsky, M.D.; Pamela A. Lipsett, M.D.; Jeanine P. Wiener-Kronish, M.D.; Naomi P. O'Grady, M.D.


Anesthesiology. 2020;132(3):586-597. 

In This Article

Patient-related Considerations

Obesity, Large-volume Blood Loss, and Fluid Resuscitation

A several-fold increase in the risk of surgical site infections in patients with higher percent of body fat suggests the need for adjusted dosing of antimicrobial agents.[10] Obese patients have increased volumes of distribution, altered protein binding, metabolism, and elimination.[11–13] Vancomycin and gentamicin are commonly used antibiotics given at higher doses when used in obese patients. Limited evidence that suggests larger volumes of distribution in obese patients affect the clearance of gentamicin,[14] while the effects of obesity on the pharmacokinetics of vancomycin remain somewhat unclear.[15]

Current guidelines recommend 3 g of cefazolin dosing in patients with body mass greater than or equal to 120 kg.[8] This is a weak recommendation because of the paucity of data. One study found that in patients with body mass index of 40 or higher, higher body mass index was associated with reduced achievement of target serum cefazolin concentration after a 2-g initial dose and a second dose at 3 h.[16] A more recent study in bariatric surgery patients suggested that a single 2-g dose of cefazolin was sufficient to exceed mean minimum inhibitory concentration for methicillin-sensitive Staphylococcus aureus in adipose tissue samples.[17] Although a separate study did not show a significant difference, there was a trend toward increasing surgical site infections in patients not receiving the increased cefazolin dose.[18]

Guidelines from the United States and Canada recommend redosing prophylactic antibiotics in case of excessive blood loss, defined as more than 1,500 ml.[8,19] These recommendations are consistent with conclusions from two small studies in spinal surgery patients, one of which has demonstrated a correlation between blood loss and reduced tissue cefazolin concentration.[20,21] The volume of intravenously administered fluid has also been shown to correlate with serum and reduced tissue concentrations of antibiotics.[22] Some authors suggest that patients who receive more than 2,000 ml of intravenous fluid may need antibiotic redosing.[23]

Allergic Reactions and Cross-reactivity

Patients with reported penicillin allergy may have a 50% or higher likelihood of developing surgical site infections because of suboptimal performance of second-line agents.[24,25] Although vancomycin provides appropriate antimicrobial coverage for Gram-positive flora (the predominant cause of surgical site infections in clean procedures) from a microbiologic standpoint, the increased administration time of 1 to 2 h and time before incision (within 120 min)[8] has led centers to try to time incision for 60 to 120 min after start of infusion. Utilizing this protocol, Blumenthal et al.[24] found that less than 3% of patients received vancomycin within 60 to 120 min, although Garey et al.[26] actually found that the surgical site infection rate in cardiac surgery was lowest for patients whose infusion started 16 to 60 min before incision. Additional reasons for increased surgical site infections with vancomycin alone could be the underappreciated role of Gram-negative pathogens in these infections[27] and the greater effectiveness of cephalosporins as compared with glycopeptides for methicillin-sensitive S. aureus.[25]

Because 85 to 95% of patients with documented antibiotic allergy have negative skin testing,[28,29] further investigation into the individual reaction would optimize antimicrobial coverage and may decrease the frequency of surgical site infection. Formal allergy testing is feasible in patients with unclear types of reactions to penicillin or cephalosporins who are expected to undergo elective surgery.[30] Evidence of successful and safe penicillin skin testing carried out by intensivists suggests that perioperative physicians may also utilize such a test.[31]

In patients with documented or presumed immunoglobulin E–mediated reaction to penicillin (anaphylaxis, bronchospasm, or urticaria), current guidelines recommend against using cephalosporins or carbapenems for surgical prophylaxis.[8] It should be noted, however, that cefazolin has low cross-reactivity with penicillin because of a unique side chain[32] and carbapenems demonstrate less than 1% cross-reactivity with penicillin.[33] In a single center, not one of 282 patients with reported penicillin allergy suffered adverse consequences when administered cefazolin.[34] Furthermore, the majority of patients with immunoglobulin E–mediated reaction to penicillin can tolerate penicillin within a decade.[35] Thus, even in patients with documented immunoglobulin E–mediated reaction to a first-line antibiotic, formal allergy testing may demonstrate tolerance to penicillin if the reaction occurred in the distant past.[36]

Clinically Relevant Drug Interactions

A number of antibiotics used for surgical prophylaxis manifest significant interactions with other perioperative medications. The frequency of clinically significant interactions has not been adequately studied, but severe complications have been reported. For example, clindamycin, a commonly used second line agent for surgical site infection prophylaxis, may potentiate the effects of neuromuscular blocking agents and, if overdosed, can be fatal in the perioperative setting.[37,38] Experimental studies also suggest that both clindamycin and gentamicin act synergistically with rocuronium.[39] Other consistently reported interactions include profound sedative and cardiovascular effects of ciprofloxacin in patients taking methadone.[40,41]

Immunosuppressed Population

Antimicrobial prophylaxis may be warranted in any procedure performed in an immunocompromised host,[8] including patients receiving glucocorticoids, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents for chronic inflammatory diseases. Increased frequency of surgical site infection with perioperative glucocorticoid use is biologically plausible and has been reported.[42] One subgroup analysis of 364 patients in a trial using steroids in cardiac surgery did not demonstrate increased frequency of surgical site infection in the steroid group,[43] whereas another study of patients on chronic steroids having lumbar fusion showed an association between steroid use and surgical site infection.[42] Surgical site infection may be impacted by the dose of steroid and the chronicity of its use. Studies of perioperative discontinuation of disease-modifying antirheumatic drugs also produced inconsistent results with respect to surgical site infection.[44] It is likely that ongoing treatment of inflammatory bowel disease with anti–tumor necrosis factor agents does not increase the frequency of surgical site infection after abdominal or large joint surgery.[45,46] However, one large study did demonstrate a 50% increase in organ space infections and anastomotic leaks in immunosuppressed Crohn's disease patients after elective colectomy.[47] In this study the immunosuppressive regimen included corticosteroids, which confounds the result. Acknowledging the low quality of available evidence that originates from studies of low-risk patients, the World Health Organization Global Guidelines for the Prevention of Surgical Site Infection suggest not discontinuing immunosuppressive medication before surgery for the purpose of preventing surgical site infection.[9,48]

Transplant Recipients

Antimicrobial prophylaxis and treatment in transplant recipients should be individualized and depend on the procedure performed, geographic epidemiology, and net state of immunosuppression.[8,49–51] Solid organ transplantations are clean-contaminated procedures in which skin flora, Gram-negative rods, and enterococci are the predominant surgical site infection pathogens.[8] Most opportunistic infections occur several weeks after the initiation of immunosuppression rather than in the immediate posttransplantation period.[52] Thus, the recommended antimicrobial prophylaxis regimen for heart, lung, heart–lung, kidney, and pancreas transplantation procedures is a single dose of cefazolin.[8,51] Note that there is significant controversy regarding the duration of antibiotic prophylaxis, with many centers providing 48 to 72 h despite no evidence of improved outcomes and the potential for increased selection of resistant organisms.[53]

Known recipient or graft colonization, surgical technique, or complexity may justify escalation of the prophylactic regimen. For example, in patients with enteric drainage of the pancreas who are at high risk of fungal infections, fluconazole may be considered.[8] Surgical complexity, duration of surgery, and high surgical site infection rates also may necessitate broader antimicrobial prophylaxis in liver transplantation, although a Cochrane meta-analysis suggested the lack of evidence to support any one specific prophylactic regimen.[54,55]

Solid organ transplant patients presenting for nontransplant surgery are likely at increased risk of surgical site infection because of their immunosuppression. Evidence is accumulating on the outcomes of major surgeries in posttransplantation patients. However, no formal recommendations for antimicrobial prophylaxis in this patient population have been identified.[56,57]

Presence of Prosthetic Joints and Prosthetic Material

Prosthetic joints and cardiac devices are commonly encountered in patients having dental procedures. Current dental guidelines recommend against providing patients with prosthetic joints antimicrobial prophylaxis before dental procedures.[58] For patients with prosthetic cardiac valves or those who underwent valve or congenital heart disease repair with prosthetic material, recommendations from the American Heart Association (Dallas, Texas) suggest that antibiotic prophylaxis of infective endocarditis is reasonable during the following procedures: (1) dental procedures with manipulation of gingival tissue or periapical region of teeth or perforation of oral mucosa; (2) respiratory tract procedures; and (3) procedures on infected skin or musculoskeletal tissue. The American Heart Association does not recommend antimicrobial endocarditis prophylaxis in patients undergoing genitourinary or gastrointestinal tract procedures.[59]