Prolonged Antibiotic Prophylaxis After Cardiovascular Surgery and Its Effect on Surgical Site Infections and Antimicrobial Resistance

Methods

This observational cohort study was conducted at the West Campus of Beth Israel Deaconess Medical Center (Boston, Mass), a 320-bed teaching hospital with ≈600 cardiovascular operations per year. Patients were included if they had been operated on for CABG or CABG/valve procedure between September 1, 1993, and August 31, 1997. Each patient was included only once.

An experienced infection-control nurse (D.L.) monitored patients who underwent cardiac operations and reviewed microbiology logs and medical reports to detect SSI. These data were prospectively reviewed and validated by the hospital epidemiologist (M.H.S.). SSIs were defined on the basis of National Nosocomial Infection Surveillance (NNIS) System criteria.¹⁷ All patients were followed up for at least 3 months after hospital discharge to detect late-appearing infections.

Additional demographic and microbiological data were collected from administrative, pharmacy, and laboratory computerized databases by use of a relational database management system (Access, Microsoft Corp). The databases and related methods of data collection were described before.¹⁸

Before surgery, patients took a chlorhexidine shower, and chest hair was clipped without shaving either the night before or on the morning of the operation. Immediately before surgical incision, povidone-iodine was applied for cutaneous disinfection of the operative site. In the operating room, beginning shortly before the first incision, prophylactic intravenous antibiotics (principally cefazolin 1 g; in some cases vancomycin 1 g, ceftriaxone 1 g, or a combination of these agents) were administered to each patient. In case of a prolonged intervention (≥5 hours), the second dose of cefazolin was administered after completion of cardiopulmonary bypass before closure of the sternal wound to ensure an adequate serum level of the antibiotic agent. After surgery, ABP was encouraged to be given for no more than 48 hours, but it could be continued at the surgeon’s discretion.

The main exposure was duration of ABP (<48 hours versus >48 hours). The outcomes of interest were the occurrence of SSIs and isolation of a pathogen with acquired antibiotic resistance from a clinical specimen. For the purpose of the logistic regression analysis, patients with both chest and leg infections were classified as chest infections. In addition, first- and third-generation cephalosporin resistance in enterobacteriaceae (eg, Escherichia coli, Klebsiella spp, Proteus mirabilis) and vancomycin resistance in enterococci were considered to be acquired resistance and were the pathogens further examined.

Results

Discussion

Antimicrobial prophylaxis complements meticulous technique in reducing the incidence of SSI after cardiovascular surgery. Although the principles of surgical prophylaxis have been outlined on numerous occasions, there is still misuse of antimicrobials for this purpose.^{16 19} Our results demonstrate that prolonging ABP beyond 48 hours after CABG surgery is still frequently practiced but does not decrease the risk of SSI. Moreover, it results in an increased risk of acquired antibiotic resistance and should therefore be avoided.

Some researchers have suggested that extended prophylactic use of antibiotics is appropriate when drains or catheters remain in situ for several days after cardiac surgery.²⁰ The antibiotics would presumably protect the wound from a secondary infection that originated in the foreign body and reached the wound by a hematogenous route. Therefore, surgeons tend to continue antibiotics as long as perioperatively placed transthoracic devices are left in place. For instance, in a survey among 43 pediatric cardiovascular surgery centers in the United States, up to 76% continued antibiotics while chest tubes were in place.¹³ A questionnaire sent to 120 UK cardiac surgeons showed that 28% continued antibiotic use until the removal of all chest drains.¹² In a French survey among 1473 anesthetists, 23% prescribed >48 hours of antibiotics after cardiovascular surgery.

However, results from our study and other reports appear to invalidate this practice. Already 20 years ago, in a double-blind, randomized clinical trial comparing a 6-day with a 2-day regimen of cephalothin prophylaxis, Goldmann et al⁵ showed that a 6-day course of prophylactic antibiotics after cardiac surgery is not justified. The only published study comparing single-dose prophylaxis versus extended prophylaxis after thoracostomy in chest trauma patients showed no need for use of prophylaxis for as long as the chest tube was in place.²¹ These findings are also in line with a recent meta-analysis of single- versus multiple-dose prophylaxis for major surgery that indicated no benefit for multiple-dose regimens in preventing SSI in various surgical interventions requiring postoperative drainage.²² In contrast, prolonged antibiotic use after surgery induces antimicrobial resistance and may facilitate the colonization of foreign devices with antimicrobial-resistant organisms.^{23 24 25} Therefore, in place of extended ABP, meticulous handling of catheters, strict compliance with hand disinfection, maintenance of closed drainage systems, and early catheter removal are the preferred means to avoid infections related to foreign devices.²⁶

Observational cohort studies should complement controlled clinical trials dealing with ABP, because the latter have a limited ability to detect adverse effects such as acquisition of resistant microorganisms, provide information only about patients who satisfy the criteria for study entry, and often concentrate on the efficacy of specific agents rather than evaluate variations in the duration of prophylaxis.²⁷ In addition, randomized trials do not provide data on the effect of therapeutic interventions in actual clinical practice. In contrast to many previously reported clinical trials, the present study focused on the duration of prophylaxis rather than on antibiotic choice. All patients undergoing coronary bypass surgery were included in the analysis, thereby increasing the generalizability of the study results. However, as in all observational studies, there may have been unknown or unmeasured confounding factors for which adjustment was not possible. For instance, despite adjustment for important covariates such as age, number of comorbidities, length of ICU stay, and postoperative antibiotic therapy, it is difficult to completely exclude the possibility of residual confounding among subjects with acquired resistance.

The inappropriate prophylactic antibiotic administration in our cardiovascular surgery unit may have arisen primarily from misconceptions regarding the optimal use of prophylaxis. In some cases, ceftriaxone was chosen as prophylactic agent because of its pharmacokinetic profile, including high serum levels, high tissue penetration, and long elimination half-life, which makes it potentially suitable for prophylaxis in prolonged surgery.²⁸ However, shortly before the end of the study period, we introduced strict antibiotic guidelines and stopped this practice because of antibiotic resistance concerns and cost implications.

The findings should be interpreted in the context of the study design. First, because routine surveillance cultures were not obtained from study patients, one may raise questions about the possible underestimation of the frequency of acquired antibiotic resistance. However, by matching for antibiotic agent, adjusting for calendar time, and including only patients with positive cultures, we minimized the possibility of significant detection bias. Second, an explanation for the association of combined CABG/valve surgery with increased antibiotic resistance is not directly apparent from our study results. We hypothesize that these patients are more likely to have received previous courses of antibiotics for prophylaxis or treatment of endocarditis due to underlying valve abnormalities, thus increasing the risk of acquiring antibiotic resistance. Third, the patient population reported in this study is notable for a high frequency of diabetes and referral from other institutions. These characteristics may have increased the SSI rate (but not the rate of mediastinitis, which was similar to that reported elsewhere), although the observed overall infection rate also probably reflected the intensive nature of the surveillance program. However, we do not believe that these surveillance methods and patient characteristics distorted the generalizability of our study findings.

In conclusion, our study confirms that ABP for CABG surgery is frequently extended beyond 48 hours. It shows that prolonged prophylaxis does not reduce the rate of SSI and is associated with an increased risk of acquired antibiotic resistance. We urge surgeons and all concerned physicians not to ignore the potentially harmful and costly effect of prolonged ABP after CABG surgery.