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Interact CardioVasc Thorac Surg 2007;6:442-446. doi:10.1510/icvts.2006.147769 © 2007 European Association of Cardio-Thoracic Surgery
Cefuroxime as antibiotic prophylaxis in coronary artery bypass grafting surgeryDepartment of Surgical Intensive Care Unit, Onassis Cardiac Surgery Center, Athens, Greece Received 1 November 2006; received in revised form 22 March 2007; accepted 23 March 2007
*Corresponding author: Tel.: +30-210-66616760.
Nosocomial-acquired infections remain a serious problem in patients undergoing coronary artery bypass grafting (CABG) surgery. The objective of this retrospective study was to compare the incidence of nosocomial infections in patients undergoing CABG surgery within two periods (1994 and 2003). A single dose of a second generation cephalosporin (cefuroxime) was administered as antibiotic prophylaxis in all patients. There was no statistical significant difference regards to the incidence of hospital-acquired infections between these two periods (4.9% in 1994 and 5.6% in 2003, P=0.62). The most frequent types of postoperative infections were the respiratory tract infection (2.3%) in the first period and the superficial surgical site infection (3.1%) in the second period. The majority of isolated pathogens were Gram-positive cocci (68%) in both periods. The majority of incisional surgical site infections and of central venous catheter-related infections were attributed to Staphylococcus coagulase negative strains. Only one episode of hospital-acquired infection due to a resistant Gram-negative bacterium was recorded during the second period. A single-dose of cefuroxime remains the antibiotic prophylaxis of choice in adult patients submitted to CABG surgery. It is still associated with a low incidence of postoperative infections mainly due to sensitive pathogens.
Key Words: CABG surgery; Postoperative infections; Antibiotic prophylaxis; Cefuroxime; Cephalosporins
Patients who have undergone coronary artery bypass grafting (CABG) surgery are at risk for serious postoperative infections [1]. These nosocomial infections lead to increased morbidity and mortality, prolonged hospital stay and raised hospital costs [2]. Thus, antibiotic prophylaxis is widely used in this type of surgery. A relatively large number of comparative trials of antibiotic prophylaxis in cardiac surgery have been published [3, 4]. Each of them examined the use of one or more antibiotics trying to reduce serious postoperative infections. The objective of this retrospective study was to compare the early postoperative infection rate in adult patients undergoing isolated CABG surgery in the years 1994 and 2003 at the same institution where, within the last 12 years, a single dose of a second generation cephalosporin (cefuroxime) was administered as antibiotic prophylaxis.
2.1. Study design-setting This is a retrospective case–control study conducted at the Onassis Cardiac Surgery Center, Athens, Greece which is a referral center for patients undergoing open heart surgery. Approval was obtained from the Ethics and Research Committee of the center. The primary end-point of the study was the comparison of incidence of postoperative infectious complications in both groups of enrolled patients. The study enrolled 1232 adult patients (age >16 years) who underwent isolated CABG surgery with the use of extracorporeal circulation within two periods. Patients were divided into two groups. The first group (Group A) consisted of 429 patients who underwent CABG surgery in 1994. Group B consisted of 803 patients who were submitted to CABG surgery nine years later (2003). In both groups, cefuroxime was given intravenously as antibiotic prophylaxis (3 g single doses) at the induction of general anesthesia. The study was designed according to a database program including demographics, preoperative left ventricular ejection fraction, NYHA class, preoperative infection and use of antibiotics. Patients with pre-existing infection or receipt of antibiotics during the last two days before surgery, with hypersensitivity to beta-lactams, pre-existing intra-aortic balloon pump (IABP) or with left ventricular assist device (LVAD), as well as the patients who died in the operating room and in the cardiothoracic ICU during the first postoperative day, were excluded from this study. We recorded all postoperative infectious complications that occurred within a period of 30 days regardless of the length of stay in the ICU and in the hospital generally. All data referring to the site of infection, positive cultures, antibiotic susceptibilities, and administered antibiotics were also prospectively collected. All these surgical procedures were performed by the same three surgical teams. General anesthesia was provided by the same three teams according to a set protocol. The same myocardial protection protocol was used in all patients. Antibiotic prophylaxis was given in all patients undergoing CABG surgery based on a standard protocol (as described above). All patients were admitted to the cardiothoracic ICU immediately after surgery and subsequently transferred to the ward according to the improvement of their medical condition. If bacteremia was suspected, 2 blood samples for culture were obtained from separate sites before the initiation of antibiotic therapy.
An infection was considered as nosocomial when developed 48 h after hospital admission during the first 30 postoperative days [5]. Pneumonia, bacteremia, surgical wound infection, urinary tract infection or nosocomial infections of other body sites or fluids were defined based on the guidelines published from the Centers for Disease Control and Prevention [6].
Analyses were performed with SPSS 10.0 (SPSS, Chicago, IL). Tests on categorical variables were based on Pearson  2 statistics in the case of 2 by 2 tables. The comparison between the isolated microorganisms was determined using independent-samples t-test analysis. A P<0.05 was considered statistically significant.
In 1994, a total of 21 patients (4.9%) developed a postoperative infection, while in 2003 the corresponding number was 46 (5.6%) (P=0.62). The sites of all infections in both groups are presented in Table 1. The most frequent site of postoperative infection in group A was the respiratory tract (2.3% vs. 0.6% in group B). On the contrary, the most frequent kind of infection in group B was the superficial surgical site infection (3.1% vs. 0.5% of group A). However, there was no difference between the development of deep surgical site infection and of postoperative infective endocarditis where only one patient of each group presented with these types of infection. There was also no statistical significant difference between the two groups in regard to catheter-related infections, urinary tract infections, and bacteremia/candidemia.
Isolated pathogens are presented in Table 2. In 1994, a total of 21 micro-organisms were isolated in all patients, while in 2003, the corresponding number was 46. Gram-positive cocci were isolated in 14 patients of group A (14/21, 66.6%) and in 25 patients of group B (25/46, 54.3%). Staphylococcus coagulase negative strains were the predominant isolates among gram-positive cocci in both studied periods [23 of 39 (58.9%)]. None of Staphylococcus aureus strains isolated in both periods was methicillin-resistant (MRSA). Gram-negative bacteria were isolated in seven patients in group A (33.3%) and in 16 patients of group B (34.7%). Of these, only one strain of Klebsiella pneumoniae was resistant to three antimicrobial agents (3rd generation cephalosporins, antipseudomonal penicillins and quinolones). No patient developed an infection due to fungi in group A; in contrast, Candida was isolated in 4 of 46 patients (8.7%) of group B, without reaching statistical significance (P=0.24).
Table 3 presents the association of isolated pathogens and the site of infection. The majority of incisional surgical site infections (10 out of 27, 37%) and of central venous catheter-related infections (9 out of 11, 81.8%) were attributed to Staphylococcus coagulase negative strains.
Clinical response of the infection was observed in all patients of group A (21/21) and in 42 out of 46 patients of group B (91.3%). Unresponsiveness was observed in 4/46 (14.7%) episodes of infection during the second period. Cefuroxime, in the dose of 3 g intravenously, did not cause any registered side-effect. Infections were not responsible for any death in 1994 but in 2003, 5 out of 46 (10.8%) CABG patients with postoperative infection died because of septic shock/multiple organ failure (n=4) and cardiogenic shock/multiple organ failure (n=1).
The main finding of this study is the same incidence of nosocomial infections (approx. 5%) in adult patients undergoing CABG surgery with the use of cardiopulmonary bypass between these two studied periods (1994 and 2003) where the same antibiotic prophylaxis (a single dose of a second generation cephalosporin) was used in all patients. Another interesting finding of the study is the very low incidence of nosocomial-acquired infections due to resistant pathogens, such as methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), and multi-drug resistant Gram-negative bacteria (e.g. Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii) in both studied periods. There are several reasons which could explain this fact. Our Center is not a general hospital, but a tertiary Center specializing exclusively in heart diseases. In addition, the majority of operations are undergone electively while the patients are usually admitted to our Center directly from their home. A strict policy has also been followed since the beginning of the Center's function regarding the prevention of hospital-acquired infections (control for hand washing of personnel, routine examination for nosocomial-acquired infection, and isolation of postoperative patients with nosocomial infection, as well as recording/surveillance of all episodes of infection). All patients transferred to our Center from other hospitals are isolated and all their foreign bodies are removed immediately; bacteriological examinations of blood, urine, and central venous catheter tips are performed just after their admission. In addition, the majority of candidates for elective cardiac surgery are examined preoperatively by the doctors of our Cardiac Center in order to exclude any infectious disease, while all patients with a history of chronic obstructive pulmonary disease (COPD) undergo heart surgery without signs or symptoms of respiratory tract infection or bronchospasm. Although the interval period was 9 years between the two examined periods and the conditions of care have been ameliorated, more high-risk patients have been involved. For example, in our Center the mean age of patients submitted to cardiac surgery has increased from 60–69 years. However, surgeons, anesthesiologists and intensivists have stayed more or less the same. The most serious difference in the number of infections between the two groups (as it is shown in Table 1) has to do with the increase of the incisional surgical site infections during the second period. This observation can be explained by a more meticulous surveillance of postoperative infections during the last years. Intensivists and surgeons were more careful with the observation leading to a pronounced bacteriological examination of the wound. As the number of cultures has been raised, the positive results are more frequent than in the past. In most of them, only one pathogen was isolated without serious complications. Staphylococcus epidermidis was the most frequent isolated pathogen followed by Pseudomonas aeruginosa and Staphylococcus aureus (none of them was methicillin-resistant Staphylococcus aureus). This finding is in agreement with previous studies [7]. The comparison of respiratory tract infections between the two groups shows a significant decrease during 2003. This could be explained by the amelioration of patients' care during mechanical ventilatory support. Cardiac surgery enters mainly into the class I of Altemeier's (‘clean surgery’) and need no antibiotic prophylaxis as documented by Lehot, in 1994 [8]. However, postoperative infections are serious and often life-threatening complications in this group of patients. The incidence of postoperative infections in patients submitted to open heart surgery is approximately 5–6% [9, 10]. Many risk factors may predispose to postoperative infections. These are older age, female gender, low preoperative left ventricular ejection fraction, history of pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and immunosuppression. In addition, perioperative factors such as prolonged bypass time, excessive blood transfusion, low cardiac output syndrome, development of acute renal failure and the use of intra-aortic balloon pump were found to be predictors of development of postoperative infections after cardiac surgery [10]. These infectious complications are associated with substantial morbidity and mortality, prolonged hospital stay, and increased hospitalization costs [11]. Cefuroxime is a second generation cephalosporin with documented low toxicity. It has increased stability to ß-lactamase enzymes, broad antibacterial spectrum and good tissue penetration. Cefuroxime has the highest bactericidal effect at concentrations four- to eight-fold above the minimum concentration (MIC). The time during which the concentration remains above the MIC is the most important factor related to the bactericidal activity of this antimicrobial agent. The maintenance of elevated plasma concentrations for a short period of time does not increase antimicrobial action against most bacteria [12]. This is the reason why a single dose of cefuroxime (3 g) administered intravenously just prior to the induction of anesthesia is still effective in case of prolonged cardiopulmonary bypass time. The recommended antimicrobials for cardiac operations include cefazoline or cefuroxime administered for <24 h or maximum up to 72 h in high risk patients [13]. The combination of cefuroxime with an aminoglycoside may be necessary when infection prevalence due to Gram-negative (–) bacilli is high in a specific hospital environment or with vancomycin if methicillin-resistant Staphylococcus aureus or epidermidis are endemic. A review sponsored by the American Society of Infectious Diseases and endorsed by both it and the Surgical Infection Society recommends that vancomycin can be given instead of cephalosporin to patients who are allergic to cephalosporins or in settings where infections with methicillin-resistant Staphylococcus aureus (MRSA) are prevalent or MRSA strains are frequently isolated pathogens in postoperative wound infections [13]. Although several reports suggest that the carriage of methicillin-resistant Staphylococcus aureus (MRSA) among persons without health care-associated risks has recently increased, a meta-analysis of studies dealing with community-acquired MRSA colonization among community members showed a very low prevalence [14]. Broad-spectrum antibiotics should be avoided as antimicrobial prophylaxis because they promote the development of antimicrobial resistance and may have a considerable effect on the isolation of microorganisms from various specimens increasing the probability for false negative cultures [15]. They should be administered as prophylaxis only in patients previously colonized from multi-resistant pathogens and mainly for the treatment of documented nosocomial infections due to resistant pathogens when sensitivity exists. In conclusion, comparing the rate of postoperative infections in adult patients undergoing isolated CABG surgery between 1994 and 2003, we conclude that a single-dose of cefuroxime (3 g administered intravenously just before the induction of general anesthesia) remains effective and safe throughout the years, despite its continuous use. The administration of cefuroxime as antibiotic prophylaxis in this group of patients, presents certain advantages, such as easier handling, lower cost and minimum side-effects. For this reason, cefuroxime continues to remain the antibiotic prophylaxis of choice in adult patients submitted to coronary artery bypass grafting surgery.
We thank Ekaterini Mastoraki, MD for her contribution in collecting data for this study.
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Abstract
1. Introduction
