Antibiotic prophylaxis in cardiac surgery: challenges and future perspectives

Postoperative surgical site infections (SSIs) subsequent to cardiac surgery persist as a noteworthy source of both morbidity and mortality due to the devastating nature of procedures associated with cardiac surgery1. The administration of antibiotic prophylactics is a crucial element among various measures implemented to prevent postoperative SSI in cardiac surgery, however, their use is often hindered by challenges such as inadequate dosing, inappropriate timing, and inadequate duration of therapy. Furthermore, the use of antibiotic prophylactics is associated with the risk of adverse events, such as allergic reactions and Clostridium difficile infections. This manuscript aims to highlight challenges associated with antibiotic prophylaxis in cardiac surgery along with future perspectives. Insufficient administration of antibiotics presents a prevalent obstacle in the context of cardiac surgery. This is especially true for medications with narrow therapeutic windows, such as aminoglycosides and vancomycin2. Insufficient doses may result in inadequate antibiotic concentrations at the surgical site and the growth of antibiotic-resistant bacteria, which raises the risk of SSIs. According to studies, individuals who have heart surgery and receive a low dose of vancomycin have a higher chance of developing SSIs3,4. Moreover, the use of weight-based dosage is not always suitable in cardiac surgery, as the alterations in body mass and hydration levels that occur during surgical procedures can have an impact on the metabolism and excretion of antibiotics, resulting in inadequate concentrations5. Hence, it may be imperative to employ alternative dosing strategies, such as continuous infusion or pharmacokinetic-guided dosing6, to attain the most favorable antibiotic concentrations in the surgical site. Furthermore, Therapeutic drug monitoring (TDM) has been suggested as a means of enhancing antibiotic dosing in cardiac surgery. TDM entails the quantification of drug levels in blood specimens to calibrate the dosage and attain desired concentrations7. Despite its potential benefits, TDM has not been extensively employed in the realm of clinical practice. Another important element in the prevention of SSIs is the timing of antibiotic medication. The objective of administering antibiotic prophylaxis is to attain satisfactory levels of the medication in the tissue during the incision period8. Hence, the timing of the initial administration of antibiotics holds paramount importance. According to the guidelines of the American College of Surgeons and the Surgical Infection Society, it is recommended that the initial administration of antibiotics be administered within a 60-minute timeframe following surgical incision9. Nevertheless, complying with this recommendation can present difficulties in practical application. The delayed administration of antibiotics may result from various factors, including but not limited to surgical scheduling delays, patient preparation, and anesthesia induction10. Research has indicated that postponing the administration of antibiotics is linked to a heightened likelihood of SSIs11. Premature administration of antibiotics can lead to suboptimal drug concentrations during surgery11. It is therefore imperative to optimize the timing of antibiotic therapy and minimize any potential delays in its administration. The duration of antibiotic prophylaxis in cardiac surgery is a topic of debate. The patient’s unique SSI risk factors, the kind of surgery, and the microbiological profile of any positive cultures may all influence how long the patient receives antibiotic treatment12. The duration of prophylaxis recommended by different guidelines may vary and can range from a solitary administration to a period of 48 hours or more13. However, a study indicates that extended prophylaxis exceeding 24 hours has no advantageous effects in mitigating SSIs14. Extended use of antibiotic prophylaxis may result in the emergence of antibiotic resistance and heighten the likelihood of unfavorable outcomes, such as the contraction of C. difficile infection15. Conversely, premature cessation of antibiotic prophylaxis could potentially elevate the likelihood of SSIs14. Hence, the determination of whether to persist or terminate antibiotic prophylaxis must be personalized, taking into account the patient’s risk factors, surgical factors, and the existence of SSIs. Frequent occurrences of antibiotic allergies and adverse reactions have been observed among patients undergoing cardiac surgery16. These occurrences may result in the cessation of antibiotic prophylaxis or necessitate the administration of alternative antibiotics. Nonetheless, the utilization of substitute antibiotics may augment the likelihood of antibiotic resistance and SSIs. For example, according to the recommendations of the Society of Thoracic Surgeons, the administration of antibiotics in the context of penicillin allergy should follow a specific protocol. Specifically, patients who have experienced an immunoglobulin-E (IgE)-mediated reaction to penicillin or cephalosporin, such as anaphylaxis, hives, or angioedema, should be prescribed vancomycin before surgery. It is recommended that this medication be administered for a maximum of 48 hours. In these patients, skin testing may be conducted as an alternative approach. If the test yields negative results, a cephalosporin regimen may be prescribed. This is classified as Class I with a Level of Evidence A. For patients who have previously experienced a non–IgE-mediated reaction to penicillin, such as a simple rash, or have an unclear medical history, it is advisable to use vancomycin or a cephalosporin for prophylaxis. It should be noted that the incidence of significant allergic reactions to cephalosporins in such patients is low (Class I, Level of Evidence B). In addition, the concomitant utilization of antiseptic agents, such as chlorhexidine and antibiotic prophylaxis, may also be effective in addressing these concerns17. Immunocompromised people who have HIV, cancer, or autoimmune diseases are more prone to have postoperative infections following surgery because of their weakened immune systems18. Due to diseases processes or treatments, immunocompromised patients who are critically ill may have altered antibiotic pharmacokinetics and pharmacodynamics19. For instance HIV patients may develop liver dysfunction that affects antibiotic metabolism and clearance. Furthermore, surgical procedures such as cardiopulmonary bypass (CPB) may trigger an inflammatory response and further weaken immune function due to elevated activity of arginase-1 and depletion of L-arginine20, putting immunocompromised heart surgery patients at risk of infection. This complicates antibiotic administration since these individuals may need a greater dosage or longer treatment to reach therapeutic levels. Administration of Immunomodulators like G-CSF may boost the patient’s immune response and lower infection risk21. In addition, the administration of L-arginine during the preoperative nutrition period could potentially improve the immunosuppressive state and cardiac outcomes post cardiac surgery with CPB. However, further research is required to determine the causality between L-arginine and immunosuppression postsurgery20. Due to increased tissue tension, decreased tissue perfusion, and slowed wound healing, obesity is a substantial risk factor for SSIs22, especially in cardiac surgery. The existence of more adipose tissue in obese patients can act as a potential source of microorganisms, rendering them more vulnerable to infections23. Furthermore, the administration of antibiotics to obese patients poses a challenge due to the potential inadequacy of conventional dosing strategies in achieving sufficient tissue concentrations. Patients with obesity exhibit an increased body mass, potentially necessitating elevated antibiotic dosages to attain therapeutic concentrations24. The presence of augmented adipose tissue may result in modified pharmacokinetics of antibiotics, thereby impacting the distribution and elimination of drugs24. Several studies have reported that Cefazolin’s pharmacokinetics can be considerably changed by obesity, changing the drug’s body concentrations25–27. Ryu and colleagues conducted a retrospective study in patients to evaluate the results and side effects between 2 groups of patients: those who received a high dosage of cefazolin that was dose-adjusted for body weight and those who received a conventional dose that was not weight-adjusted. In patients with high body weight, high-dose cefazolin was shown to be generally well tolerated, with no appreciable increase in side effects compared with the standard-dose group28. Salm and colleagues study’s conclusions showed that bodyweight-adjusted antimicrobial prophylaxis reduced the incidence of SSIs. Compared with the group getting the normal fixed-dose prophylaxis, the group receiving body weight-adjusted dosages saw considerably reduced incidence of SSIs29. This study shows that prophylaxis can be made more successful in preventing SSIs by adjusting the antibiotic dosage based on body weight. However, further research may be needed to confirm these findings and establish definitive dosing guidelines for cefazolin in patients with high body weight. Comorbidities including diabetes, hypertension, respiratory diseases, and renal insufficiency may weaken the immune system and slow wound healing, allowing organisms to infect heart surgery patients. These conditions may modify medication metabolism and excretion, affecting pharmacokinetics and pharmacodynamics, making it difficult to achieve therapeutic doses30. Comorbid patients may also be taking drugs that interact with antibiotics, reducing their effectiveness or worsening their side effects. Anticoagulants and some antibiotics may increase bleeding risk31. Antibiotic selection and dose must be customized to each patient’s comorbidities for optimum prophylaxis. Adjunctive therapies, such as topical antibiotics and antiseptics, have been proposed as a means to mitigate the incidence of SSIs among patients32. Notwithstanding, the effectiveness and safety of said therapies remain a topic of debate, and additional investigation is required to ascertain their most advantageous application. The implementation of antibiotic stewardship programs has the potential to mitigate the issue of excessive and inappropriate utilization of antibiotics in the context of cardiac surgery33. The programs in question adopt a multidisciplinary methodology to enhance the efficacy of antibiotic utilization, encompassing the selection, dosage, duration, and timing of antibiotics33. Antibiotic stewardship programs have the potential to mitigate the emergence and dissemination of antibiotic-resistant bacteria within hospital settings by advocating for judicious antibiotic utilization33. Future perspectives Modern medicine’s use of antibiotics to prevent and cure heart surgery infections has revolutionized clinical practice. Due to antibiotic-resistant organisms and the need for customized and effective treatments, it is imperative to explore the future perspective of cardiac surgery. One such potential solutions is personalized antibiotic therapy. The emerging concept of personalized antibiotic therapy involves the customization of antibiotic treatment to cater to the specific requirements of an individual34. The implementation of this particular approach has the potential to enhance the utilization of antibiotics by carefully choosing the most efficacious agent while also preventing unwarranted exposure to broad-spectrum antibiotics34. This is crucial as the latter can facilitate the emergence of antibiotic resistance. This approach takes into account the patient’s age, comorbidities, and microbiome to choose the best antibiotic regimen34. Antibiotics may be prescribed specifically for a patient to maximize therapeutic efficacy while lowering the chance of side effects and the development of antibiotic resistance. The implementation of rapid diagnostic tests to detect bacterial infections and determine the most suitable antibiotic therapy could be employed35. Molecular-based methodologies, including polymerase chain reaction, next-generation sequencing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also have the potential to swiftly detect pathogens and their resistance genes35. This further eases informed decision-making by clinicians regarding the choice of antibiotic treatment. The development of novel antimicrobial agents also presents a promising solution. Beta-lactam antibiotics, which have been utilized for several decades, are currently encountering increasing resistance36. In contemporary times, a number of novel antibiotics including ceftazidime-avibactam and dalbavancin have been authorized for administration in clinical settings37,38. The antibiotics in question have exhibited effectiveness against bacteria that are resistant to multiple drugs, and possess the capability to improve the outcome of cardiac surgery patients37,38. Besides novel antimicrobial agents, inventive drug delivery systems could potentially mitigate the challenges associated with antibiotic utilization39 in the context of cardiac surgery. The administration of antibiotics to the surgical site in a localized manner has the potential to decrease systemic exposure, mitigate the likelihood of unfavorable outcomes, and enhance the effectiveness of antimicrobial agents. The utilization of nanotechnology-based drug delivery systems presents a promising opportunity for the administration of local antibiotics39. They offer potential advantages such as targeted delivery, and enhanced pharmacokinetics. A multidisciplinary team of cardiothoracic surgeons, anesthesiologists, medical microbiologists, pharmacists, and nurses is also important to establish evidence-based protocols for antibiotic prophylaxis in the context of cardiac surgery40. The guidelines can incorporate regional bacterial resistance patterns and customize prophylactic measures accordingly. The guidelines can be periodically reviewed and revised by the team to incorporate alterations in bacterial resistance trends and the accessibility of novel antibiotics40. The hospital can engage in monitoring antibiotic resistance patterns and formulating preventive strategies to curb the emergence and transmission of antibiotic-resistant bacteria. Conclusion The use of antibiotic prophylaxis is essential in preventing SSIs following cardiac surgery. We highlighted various challenges, including inadequate dosing, inappropriate timing, and inadequate duration of therapy, that affect the administration of antibiotic prophylactics. We also discussed the potential risk of adverse events associated with the use of antibiotic prophylactics, such as allergic reactions and C. difficile infections. The emergence of antibiotic-resistant bacteria presents a significant threat to patients undergoing cardiac surgery. Ongoing research and progress in the utilization of antibiotics are crucial in tackling antibiotic-resistant bacteria in the context of cardiac surgery. Finally, there is an urgent need for the development of novel antibiotics with distinct modes of action to combat bacterial infections that have acquired resistance. Ethical approval Ethical approval was not required for this study. Sources funding Authors received no external funding for this project. Author contribution T.A.-R.: conceptualization of ideas. T.A.-R.: data curation. O.E., L.L., A.C., D.E.-I., and M.S.A.: writing of initial draft. T.A.-R.. and W.A.A.: review and editing. Conflict of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor Toufik Abdul-Rahman. Data availability statement No new data was generated.