Optimizing Antibiotic prophylaxis in Cardiac Surgery: Evidence and Best Practices

Worldwide, thousands of people undergo cardiac surgery every day, most often valve replacements and coronary artery bypass grafting. While the techniques used are similar everywhere, surgical prophylaxis varies quite drastically, both between countries as within (1,2). This is surprising, considering the fact that surgical prophylaxis is well-researched area within infectious diseases, with a multitude of randomized controlled trials available. This blog explores what the optimal antibiotic prophylaxis for cardiac surgery should look like, based on the following questions.

1. When should antibiotic prophylaxis be administered in cardiac surgery?

2. Which antibiotic coverage is required for prophylaxis in cardiac surgery?

1. When should antibiotic prophylaxis be administered in cardiac surgery?

When to start? As in all surgeries, peak antibiotic concentration should be reached at the time of skin incision (3) with dosing adjusted to the body weight. Interestingly, a retrospective analysis of 28,250 cardiac surgical procedures found a U-shaped relationship between timing of antibiotic prophylaxis and risk of infections (4). Optimal administration time was 15 minutes before incision for cephalosporins and 32 minutes for vancomycin.

Re-dosing during operation? Most guidelines recommend repeating the antibiotic dose if the operation exceeds the half-life of the drug (5,6). Moreover, pharmacokinetic models suggest that an additional dose of cephalosporins at the start of cardiopulmonary bypass may be beneficial (7).

When to stop? In most surgeries, continuing antibiotic prophylaxis beyond the end of the operation does not reduce the infection risk (1). However, cardiopulmonary bypass poses some unique challenges:

I. Systemic hypothermia during cardiopulmonary bypass (8).

II. Dysfunctional host defenses due to cardiopulmonary bypass, such as impaired phagocytosis and humoral immunity (8).

III. Bleeding and transfusion due to coagulopathy (8).

Additionally, some randomized controlled trials have compared extended versus solely perioperative antibiotic prophylaxis. The methodologically most robust, randomized trial showed a significant reduction in surgical site infections with a 24-hours prophylaxis although it did not affect mortality or hospital stay (9). Besides, this trial was not blinded, raising concerns about selective reporting (10).

Most guidelines suggest continuing antibiotic prophylaxis for 24 to 48 hours (5,6,11). This recommendation is supported by two meta-analyses, favoring durations longer than 24 hours (1, 12). Moreover, extending antibiotic prophylaxis beyond 48 hours provided no additional benefit (12). However, both meta-analyses also have some important limitations: heterogeneity in antibiotic regimens (1), potential investigator bias (1) and inclusion of mostly older studies that may not reflect the current epidemiology (10).

2. Which antibiotic coverage is required for prophylaxis in cardiac surgery?

 

Despite best precautions, considerable wound contamination is inevitable during every surgical procedure (13). Globally, first-, second-, and third-generation cephalosporins are most commonly used to prevent this contamination becoming surgical site infections. The United Kingdom is a notable exception, actively avoiding cephalosporins due to the risk of C. Difficile infections (2). This risk is particularly associated with cephalosporin use for three or more days (2), but there is currently no strong evidence linking short-term cephalosporin prophylaxis to increased C. Difficile rates (12).

Which microorganisms should be covered?

1) Gram-positive microorganisms

Depending on the study, gram-positive micro-organisms cause 66% (11) to 86% (9) of surgical site infections after cardiac surgery, with S. aureus being the most common pathogen (13). However, polymicrobial infections occur frequently, both as a mix of gram-positive organisms only, as well as a mix of gram-positive and gram-negative bacteria (9,10).

2) Gram-negative microorganisms

Guidelines differ on the need for gram-negative coverage. While European guidelines (EACTS) favor cefazolin/ cefuroxime (or vancomycin/clindamycin in case of penicillin-allergy) as surgical prophylaxis in cardiac surgery (6), American guidelines (Surgical Infection Society) recommend adding gram-negative coverage based on the local epidemiology (11).

Some reflections about these recommendations:

1) Second- and third-generation cephalosporins have broader activity against gram-negative bacilli than the first-generation. However, a meta-analysis of 29 studies found no difference in infection rates between these options for general surgery prophylaxis (14). In contrast, a similar comparison in another meta-analysis - this time specifically for cardiac surgery - showed that second- and third-generation cephalosporins significantly reduced pneumonia and all-cause mortality (12). Nevertheless, the number needed to treat was high (74 in case of pneumonia and 88 in case of mortality) and no differences in surgical site infections was observed.

2) Gram-negative surgical site infections are prevalent in some regions. For instance, British data from 2023/24 show that coagulase-negative staphylococci were responsible for most superficial surgical site infections, followed by Enterobacterales, S. Aureus and Pseudomonas (15). Moreover, polymicrobial infections were common (36.2%), with gram-negative organisms involved in over half of these cases.

3) MRSA Coverage

 Most guidelines recommend vancomycin in case of MRSA colonization (6, 11), with or without gram-negative coverage. Australian guidelines, however, recommend combining vancomycin with cefazolin (16). Some studies, after all, have shown that prophylaxis with vancomycin leads to more infections with MSSA although overall surgical site infection rates remain unchanged (13,17). Conversely, a meta-analysis of 10 trials found that glycopeptides were superior to beta-lactams in preventing surgical site infections, provided the duration of prophylaxis was similar (12).

My view: Monitoring the local epidemiology of surgical site infections should be an integral part to every cardiac surgery program, including the prevalence and resistance of surgical site pathogens. I prefer cefazolin as the standard prophylaxis and I would let the local circumstances determine if extra gram-negative coverage is required (and what that should be). For MRSA, I do not find the evidence for double gram-positive coverage compelling, as long as vancomycin is administered in the right dose and for an appropriate duration.

References:

1. Hamouda K, Oezkur M, Sinha B, et al. Different duration strategies of perioperative antibiotic prophylaxis in adult patients undergoing cardiac surgery: an observational study. J Cardiothorac Surg. 2015 Feb 26;10:25.

 2. Ackah JK, Neal L, Marshall NR, et al. Antimicrobial prophylaxis in adult cardiac surgery in the United Kingdom and Republic of Ireland. J Infect Prev. 2021 Mar;22(2):83-90.

 3. Cove ME, Spelman DW, MacLaren G. Infectious complications of cardiac surgery: a clinical review. J Cardiothorac Vasc Anesth. 2012 Dec;26(6):1094-100.

 4. Koch CG, Nowicki ER, Rajeswaran J, et al. When the timing is right: Antibiotic timing and infection after cardiac surgery. J Thorac Cardiovasc Surg. 2012 Oct;144(4):931-937.e4.

 5. Surgical site infections: prevention and treatment. London: National Institute for Health and Care Excellence (NICE); 2020 Aug 19.

 6. Sousa-Uva M, Head SJ, Milojevic M, et al. 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg. 2018 Jan 1;53(1):5-33.

 7. Asada M, Nagata M, Mizuno T, et al. Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass in adult patients undergoing cardiac surgery. Eur J Clin Pharmacol. 2021 May;77(5):735-745.

 8. White RW, West R, Howard P, et al. Antimicrobial regime for cardiac surgery: the safety and effectiveness of short-course flucloxacillin (or teicoplanin) and gentamicin-based prophylaxis. J Card Surg. 2013 Sep;28(5):512-6.

 9. Tamayo E, Gualis J, Flórez S, et al. Comparative study of single-dose and 24-hour multiple-dose antibiotic prophylaxis for cardiac surgery. J Thorac Cardiovasc Surg. 2008 Dec;136(6):1522-7.

 10. Rogers LJ, Vaja R, Bleetman D, et al. Interventions to prevent surgical site infection in adults undergoing cardiac surgery. Cochrane Database Syst Rev. 2024 Dec 2;12(12):CD013332.

 11. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013 Feb 1;70(3):195-283.

 12. Lador A, Nasir H, Mansur N, et al. Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis. J Antimicrob Chemother. 2012 Mar;67(3):541-50.

 13. Bryan CS, Yarbrough WM. Preventing deep wound infection after coronary artery bypass grafting: a review. Tex Heart Inst J. 2013;40(2):125-39.

 14. Ahmed NJ, Haseeb A, Alamer A, et al. Meta-Analysis of Clinical Trials Comparing Cefazolin to Cefuroxime, Ceftriaxone, and Cefamandole for Surgical Site Infection Prevention. Antibiotics (Basel). 2022 Nov 3;11(11):1543.

 15. UK Health Security Agency. Surveillance of surgical site infections in NHS hospitals in England. https://www.gov.uk/government/publications/surgical-site-infections-ssi-surveillance-nhs-hospitals-in-england (accessed on 12th of October 2025).

 16. Therapeutic guidelines. Surgical antibiotic prophylaxis: cardiac surgery. Published in Therapeutic Guidelines, August 2022.

 17. Finkelstein R, Rabino G, Mashiah T, et al. Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a high prevalence of methicillin-resistant staphylococcal infections. J Thorac Cardiovasc Surg. 2002 Feb;123(2):326-32.