Surgical site infection (SSI) is a serious postoperative complication after cardiac surgery. The objective of this research is to examine the efficacy of administering gentamicin in minimizing the incidence of SSI while closely monitoring the therapeutic level of the drug. Prospective research included 50 Iraqi patients divided into two groups, 25 in each: Group 1 received a combination of flucloxacillin and ceftriaxone, while Group 2 received a combination of flucloxacillin and gentamicin 2 mg/kg of ideal body weight given before surgery, then 80 mg*3 for 48 hours after surgery. A total of five patients had an infection at the surgical site, with four patients in Group 1 and one patient in Group 2. Additionally, two patients in each group exhibited increased renal indices. Among the patients in Group 2, the highest concentration of gentamicin in the blood was ≤ 2.5 µg/ml for eight patients, while for 17 patients, the gentamicin concentration in the blood ranged from 3 to 4.4 µg/ml.

surgical site infection, cardiac surgery, prophylactic antibiotics, gentamicin, survival

Surgical site infections (SSIs) are defined as infections that arise during the first 30 days after a surgical procedure or within 1 year after introducing foreign material into the body (Remschmidt et al. 2023). The incidence of surgical site infection ranges from 0.5% to 3% among people who have surgery. Patients who develop a surgical site infection need a longer hospital stay of around 7 to 11 days compared to those who do not get an infection after surgery (Seidelman et al. 2023). Infections subsequent to cardiac surgery occur in 5% to 21% of cases, and severe infections can increase the risk of death after surgery by more than five times and prolong the recovery process (de Tymowski et al. 2023a). Additionally, 47% of these patients need to stay in the hospital for more than 14 days, compared to only 5.9% of patients without a severe infection (Pérez-Granda et al. 2024). Consequently, infectious complications significantly raise the cost of healthcare. Nevertheless, these complications can be reduced through various straightforward measures, starting with modifying risk factors during the initial preoperative screening and continuing with careful monitoring of risk factors in the intensive care unit (ICU) shortly after surgery (Lepelletier et al. 2013).

The optimum period of antimicrobial prophylaxis after cardiothoracic surgeries is a subject of debate. However, it is generally recommended that prophylaxis be administered during the surgery and for fewer than 24 hours thereafter (Droogh et al. 2023). Moreover, preventive antibiotics have been given for a maximum of 48 hours; however, there is not enough evidence to determine the most effective method (Zhang et al. 2023). Furthermore, researchers have observed that administering antimicrobial prophylaxis for a period of 1 to 4 days does not result in any decrease in SSIs when compared to single-dose prophylaxis or prophylaxis limited to the duration of the operation. Additionally, there is no advantage to prolonging the use of antimicrobial prophylaxis until the removal of indwelling lines, drains, and catheters (Ahmed et al. 2023). The outcomes of surgical site infections are influenced by the presence of antibiotic resistance. Gram-positive bacteria and gram-negative bacteria were isolated from the SSIs of 67% and 23% of the patients in the third-generation group and from 62% and 24% of the patients in the first-generation group, respectively. Staphylococcus aureus and coagulase-negative staphylococci Staphylococci, which are significant organisms causing SSIs in cardiac surgery, sometimes exhibit resistance to β-lactam medicines (Bae et al. 2022).

For the prevention of SSI, it is recommended to provide cephalosporins within 60 minutes after making the surgical incision. The primary objective of the rules about the appropriate timing of antibiotics is to ensure that sufficient levels of the medication are present in the bloodstream and tissues, above the minimum inhibitory concentration required to effectively combat the bacteria, hence reducing the risk of surgical site infections (Albacker et al. 2022). Vancomycin has been shown to be less efficient in preventing SSIs in cardiac surgery trials compared to anti-staphylococcal penicillins or first- or second-generation cephalosporins, particularly in cases where the infections are caused by methicillin-susceptible staphylococci (MSS) (de Tymowski et al. 2023b).

Remarkably, there has been little research that has directly examined the effectiveness of gentamicin and cephalosporins (Lebeaux et al. 2020). A meta-analysis conducted in 2015, which included 14 trials and a total of 22,135 patients, showed a significant decrease in the incidence of sternal wound infection when utilizing implanted local gentamicin-impregnated collagen sponges. However, in comprehensive and extensive research including 1502 patients who had heart surgery at 48 different medical facilities in the United States, the results mentioned before could not be validated (Elgariah and Omran).

Gentamicin is an aminoglycoside antibiotic that exhibits a wide range of antibacterial effects, mostly targeting Gram-negative bacteria, while its effectiveness against Gram-positive organisms is comparatively weaker. Gentamicin has significant efficacy against multidrug-resistant bacteria as well. Gentamicin is often used in conjunction with beta-lactam antibiotics to provide enhanced therapeutic efficacy via a synergistic effect, particularly in cases of gram-positive and multidrug-resistant bacterial infections (Zukowska and Zukowski 2022).

A straightforward diagnostic method for infection is the assessment of body temperature. Another easy and cost-effective diagnostic approach is the assessment of the peripheral white blood cell (WBC) count and the differential cell count. There is a suggestion that the WBC and differential counts might be helpful in predicting bacterial infection. In addition, toxic granulations and vacuolization in the peripheral blood smear have been proposed as indicators of bacterial infection (Marik and Stephenson 2020).

This study aims to evaluate the efficacy of administering gentamicin in combination with flucloxacillin as a pre-medication and for 48 hours after surgery in reducing the incidence of surgical site infections in patients undergoing cardiac surgeries, as compared to using a combination of ceftriaxone and flucloxacillin. Additionally, the study aimed to observe the therapeutic level of gentamicin required to achieve an effective concentration of the drug.

The research included a total of 50 patients, with 25 patients in each group. Table 1 presents the demographic data and medical history of the patients under assessment.

Group 1 consisted of 18 male patients (72%) and 7 female patients (28%), whereas Group 2 consisted of 16 male patients (64%) and 9 female patients (36%). In addition, the average age of patients in Group 1 was 47.76 ± 17.34 years, whereas in Group 2, it was 51.60 ± 13.61 years. In addition, 32% of patients in Group 1 were diagnosed with DM, whereas 25% of patients in Group 2 had this metabolic condition (P-value 0.333). Participants from both groups underwent different types of cardiac surgeries including atrial septal defect (ASD) closure, aortic valve replacement (AVR), coronary artery bypass graft surgery (CABG), mitral valve replacement (MVR), cor-triatriatum closure, double valve replacement (DVR), right atrial myxoma (RAM), ventricular septal defect (VSD) closure. Furthermore, it was observed that just one patient in each group had a left ventricular ejection fraction (LVEF) below 40% (P-value = 0.92). In Group 1, the average cardiopulmonary bypass (CPB) duration is 100.52 minutes, whereas in Group 2, it is 109.22 minutes (p-value = 0.154). Additionally, the average aortic cross-clamp (ACC) time is 77.08 minutes in Group 2 and 70.72 minutes in Group 2 (p-value 0.323).

There was no significant difference (P-value 0.349) in the incidence of infection between Group 1 and Group 2. In Group 1, 16% of patients (4 out of 25) had an infection, while in Group 2, 4% of patients (1 out of 25) developed an infection. Additionally, both groups had the same number of patients with increased renal indices (2 patients in each group).

On the fifth day after the operation, there was no significant difference (P > 0.05) in the average white blood cell count between Group 1 (12.56 ± 4.87) and Group 2 (11.32 ± 2.4). Similarly, there was no significant difference (P > 0.05) in the average erythrocyte sedimentation rate between Group 1 (64.9 ± 29) and Group 2 (63.16 ± 18.9). Additionally, there was no significant difference (P > 0.05) in the average of hemoglobin level between Group 1 (10.89 ± 1.26 mg/dl) and Group 2 (11.12 ± 0.71 mg/dl), as indicated in Figs 2–4.

Figure 2. 

Changes in mean WBCs through baseline, day 1, day 3 and day 5 postoperatively in the studied patients’ groups. (G1B = group 1 at baseline, G1D1 = group 1 at day 1, G1D3 = group 1 at day 3, G1D5 = group 1 at day 5, G2B = group 2 at baseline, G2D1 = group 2 at day 1, G2D3 = group 2 at day 3, G2D5 = group 2 at day 5). A T-test was employed in the statistical analysis.

Figure 3. 

Changes in mean ESR through baseline, day 1, day 3 and day 5 postoperatively in the studied patients’ groups. (G1B = group 1 at baseline, G1D1 = group 1 at day 1, G1D3 = group 1 at day 3, G1D5 = group 1 at day 5, G2B = group 2 at baseline, G2D1 = group 2 at day 1, G2D3 = group 2 at day 3, G2D5 = group 2 at day 5). T-test was employed in the statistical analysis.

Figure 4. 

Changes in the mean Hb through baseline, day 1, day 3 and day 5 postoperatively in the studied patients’ groups. (G1B = group 1 at baseline, G1D1 = group 1 at day 1, G1D3 = group 1 at day 3, G1D5 = group 1 at day 5, G2B = group 2 at baseline, G2D1 = group 2 at day 1, G2D3 = group 2 at day 3, G2D5 = group 2 at day 5). A T-test was employed in the statistical analysis.

Group 2 patients were assessed for the peak level of gentamicin concentration. In Table 2, it is seen that among the 25 patients, 7 (32%) had a concentration of less than 3 µg/ml, while 17 (68%) had a value between 3 and less than 4.5 µg/ml. None of the patients had a concentration equal to or more than 4.5 µg/ml.

The combination of systemic hypothermia, coagulopathy accompanied by bleeding and the need for transfusions can make patients performing cardiac surgery more susceptible to infection (Banasiewicz et al. 2023). This can result in the need for additional extensive surgery, longer hospital stays, increased costs, higher mortality rates, and reduced long-term survival (Erdoes et al. 2023). Prophylactic therapy for cardiac surgery has been indicated by recent recommendations from the Scottish Intercollegiate Network, the National Institute for Health and Clinical Excellence, and the American College of Cardiology/American Heart Association Task Force (Ackah et al. 2021; Boriani et al. 2021; Dehmer et al. 2020; Wang and Fosbøl 2022). These guidelines do not provide clear suggestions about specified antibacterials. In the surgical ward of the Iraqi Center for Heart Disease, the standard practice is to administer amoxicillin, flucloxacillin, and ceftriaxone as preventive antibiotics before surgery. After the operation, the patient is then given vancomycin and ceftriaxone until they are discharged. The present investigation used flucloxacillin and gentamicin antibiotics before the operation and maintained their use for 48 hours after the operation (Group 2). A comparison was made between the efficacy of this treatment regimen and the regimen of flucloxacillin and ceftriaxone (Group 1). This study found that the incidence of SSI in Group 1 was 16%, while the incidence of SSI in Group 2 was 4%. However, there were no significant differences in the rate of SSI between the two groups. This study aligns with a prior analysis conducted by White et al., which aimed to assess the safety and effectiveness of short-course gentamicin-based prophylaxis. The study suggests that a dosage of 2 mg/kg of ideal body weight, combined with a glycopeptide or flucloxacillin, was equally effective compared to a cephalosporin regimen (White et al. 2013).

The incidence of increased renal indices was comparable in both groups 1 and 2. The findings indicated that the flucloxacillin-gentamicin regimen (Group 2) resulted in a reduced rate of surgical site infections without any increase in the occurrence of renal damage. The decreased likelihood of acute renal impairment in a gentamicin-based treatment regimen may be attributed to enhanced defense against perioperative infection, a well-documented factor in the development of acute kidney damage. While our research did not demonstrate statistical significance, it is conceivable that it has clinical significance. The Scottish government set a goal in 2009 to decrease the incidence of Clostridium difficile infection by 30% over a period of 2 years. As a result, Scottish hospitals switched from using cephalosporins to gentamicin for surgical antibiotic prophylaxis. They investigated the incidence of postoperative acute renal damage before and after implementing this policy modification. The research sample consisted of 12,482 adult individuals who underwent surgical procedures. The modification in antibiotic policy did not result in a substantial rise in acute renal damage among the studied groups (Bell et al. 2014).

The number of white blood cells increased in all patients in groups 1 and 2 starting from the first day after the operations. The count reached its highest level on the third day and then decreased on the fifth day. This increase and subsequent decrease are a characteristic feature of the initial systemic inflammatory and stress response that occurs following heart surgery (Bain et al. 2023). The rise in white blood cell count shown here aligns with the findings of research conducted by Sotir Lako et al. In their study, the average levels of leukocytes and neutrophils showed a quick increase, reaching their peak on the second day after surgery and thereafter returning to normal levels within a period of 21 days (Lako et al. 2015). In this research, there were no significant differences in the ESR level. However, the ESR level continued to increase from day 1 after the operations and reached its peak on day 5 in both Group 1 and Group 2. The mean ESR at day 5 postoperatively was (64.9 ± 29) in Group 1 and (63.16 ± 18.9) in Group 2. This phenomenon may be attributed to the systemic inflammatory response that occurs after heart surgery. This finding is in line with the research conducted by Eissa Bilehjani et al., which demonstrated an elevation in the erythrocyte sedimentation rate after cardiac surgery (Bilehjani et al. 2017). The hemoglobin level experienced a significant decrease on the first day after surgery in both group 1 and group 2. Subsequently, there was a slight increase in Hb levels by day 5. This observed pattern could be attributed to blood loss during and after the surgery. These findings align with previous studies that have reported mild to moderate fluctuations in Hb levels following coronary artery bypass grafting (CABG) surgery. Typically, Hb levels return to normal and preoperative values within 1–3 months post-surgery (Senage et al. 2021; Khalaji et al. 2023; Rogova et al. 2023).

In the present study, peak gentamicin levels were measured for all patients in group 2. Among these patients, 38.5% had concentrations below 3 µg/ml, 61.5% had concentrations ranging from 3 µg/ml to less than 4.5 µg/ml, and none of the patients had concentrations equal to or more than 4.5 µg/ml. Another study has demonstrated that the highest level of gentamicin in the bloodstream is between 3 and 4 µg/ml. This concentration is sufficient when combined with penicillins to effectively treat infective endocarditis. These findings emphasize the importance of therapeutic drug monitoring to ensure that gentamicin reaches the necessary therapeutic concentration, particularly in cases of severe infection (Bauer 2008; Hodiamont et al. 2022).

A short course of flucloxacillin in combination with gentamicin as antibiotic prophylaxis was shown to be as effective as a cephalosporin regimen in avoiding infection after heart surgery. The regular administration of a small dose of gentamicin did not result in a higher occurrence of acute kidney impairment.

The authors have declared that no competing interests exist.

The authors have no funding to report.

The scientific and ethical committees of Iraqi Board of Medical Specializations officially accepted the study protocol on 8/9/2019 with approval number 1420.

Before recruiting each individual, the researcher explained the study’s goal and got written consent.

Further data is available from the authors upon reasonable request. Trial registration: NCT06454643 at https://clinicaltrials.gov/.