Perioperative Antimicrobial Prophylaxis and Treatment of Surgical Infection
Joseph Solomkin
Introduction
The prevention of surgical site infection (SSI)1 remains a focus of attention because wound infections continue to be a major source of expense, morbidity, and even mortality. Surgical site infections complicate an estimated 780,000 operations in the United States each year, and are the second most common hospital-associated infection. A patient who develops a wound infection while still hospitalized has an approximately 60% greater risk of being admitted to the intensive care unit, and an attributable extra hospital stay of 6.5 days, at an extra direct cost of $3,000. Risk of readmission within 30 days is five times more likely for infected patients, at a cost of more than $5,000. Three quarters of deaths of surgical patients with SSIs are attributed to nosocomial infection, nearly all of which are organ/space infections.
Since these definitions of SSIs were first developed, however, things have changed, but not for the better. These frightening numbers come primarily from infections presenting while patients are still in hospital. And therein lies the rub for putting this information in perspective.
The CDC definition for SSI encompasses three specific subtypes of infection: superficial incisional, deep incisional, and organ space. Collectively, deep incisional and organ space infections can be termed “complex” SSIs, and in most series represent about a third of infections seen, the others being superficial. Complex SSIs are serious infections that typically require rehospitalization, return to the operating room, and intravenous antibiotic therapy. Such infections are difficult to ignore or miss when they do occur, and they are of undoubted significance to patients and their surgeons. These are the infections with cost and morbidity information, as stated above.
In contrast, superficial incisional SSIs often do not require rehospitalization and are inconsistently diagnosed in outpatients by postdischarge surveillance. Many surgeons believe that such infections are more often a nuisance than a real problem, and believe that such infections should not be given equal weight with complex infections. Because of the preceding issues, some have recommended that external (public) reporting of rates of SSI exclude superficial incisional SSIs and include only complex SSIs. (Modified From Kaye: Infect Control Hosp Epidemiol 2008, 29:941–6).
The public reporting of hospital-acquired infections, including SSIs, is obviously a subject of great discussion. The interested reader is referred to a statement by the Society for Healthcare Epidemiology of America (http://www.shea-online.org/Assets/files/Essentials_of_Public_Reporting_Tool_Kit.pdf, accessed August 29, 2010).
This is a view that I share, and the CDC is considering this reporting change. However, much of the trials looking at benefits from various interventions to prevent infection have primarily focused on superficial incisional infections, since deeper SSIs are only a third of the total and statistical significance is more difficult to identify. Indeed, many interventions may be highly effective at preventing superficial infection and of little value for organ space infection (e.g., skin preparation where the major risk for organ space infection is from enteric flora).
Considerable effort has been expended to identify potentially controllable variables that influence infection rates. A major review of this subject and an extensive list of recommendations for preoperative patient preparation and operating room environment have recently been published by the Hospital Infection Control Practices Advisory Committee of the CDC.
Recently, new organisms have appeared as pathogens in SSIs in the United States. Perhaps, most important is community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). This organism is genetically different than the staphylococci previously seen in surgical infections. In particular, it carries an array of virulence factors that allow it to more easily colonize and invade cutaneous wounds—including surgical incisions. It has become the most common form of S. aureus found in SSIs, and may be responsible for a recent increase in SSIs. How to reduce the risk of infection from this organism is becoming a focus point.
USA300, the primary strain of CA-MRSA in the United States, is now the predominant hospital-acquired MRSA strain in particular hospitals in the United States (Deurenberg and Stobberingh: Infect Genet Evol 2008, 8:747). This attests to the abilities of this organism to colonize patients. In parallel findings, an analysis of SSIs caused by S. aureus showed that most of the SSIs occurring in hospitalized patients were due to CA-MRSA, but not those following outpatient procedures.
It is important to note that administration of systemic anti-infectives is only part of a broad program of infection control involving adequate operating room ventilation, sterilization, barrier usage, and delicate surgical technique. Furthermore, the importance of the process used to provide therapies that reduce SSIs is now recognized, and much of the discussion on prophylaxis centers on process. One of the key conclusions of the Institute of Medicine’s “Crossing the Quality Chasm” is that poorly designed delivery systems, rather than cognitive deficits or negligence on the part of individuals, account for many of infections seen.
We have now moved into an era with zero tolerance for hospital-acquired infection. This philosophical stance may be argued with but is the direction of Center for Medicare and Medicaid Services (CMS) in regards pay for hospital-acquired infections. This, in addition to public reporting of individual hospital compliance, has recalibrated the equation of a risk/benefit in favor of providing antimicrobial prophylaxis to nearly all patients undergoing clean or clean contaminated surgical procedures.
Given the move to wider application of antibiotic prophylaxis, it is important to ask at the outset whether surgical prophylaxis has any substantial impact on bacterial resistance patterns. The answer is that it is unknown but unlikely. In comparison to the raw tonnage of antibiotics prescribed in the community for upper respiratory infections, the amount provided to surgical patients for prophylaxis is quite small, particularly if guidelines for restricting antimicrobial prophylaxis to <24 hours (or 48 h for cardiac procedures) are adhered to. Indeed, it is
extraordinary that for the millions of doses of cefazolin resistance to streptococci and community gram-negatives are uncommon. For vancomycin, there are now a total of 12 isolates identified in the United States as resistant. There has been considerable discussion about increases in MICs for S. aureus, but the data for this are from highly selected observational studies that have important problems in design.
extraordinary that for the millions of doses of cefazolin resistance to streptococci and community gram-negatives are uncommon. For vancomycin, there are now a total of 12 isolates identified in the United States as resistant. There has been considerable discussion about increases in MICs for S. aureus, but the data for this are from highly selected observational studies that have important problems in design.
Furthermore, within the hospital, antimicrobial resistance is principally engendered in the intensive care units. The intensive care unit is a home to patients at great risk for infection by virtue of acute and chronic disease and by the insertion of a range of transepithelial drainage, monitoring, and infusion catheters. These elements lower the inoculum needed to initiate infection and provide portals of entry. Furthermore, the intensive care unit is more likely to be contaminated with highly transmissible and antibiotic-resistant organisms than other units.
This chapter will describe current notions of risk factors for SSIs and discuss problems relating to knowing what infection rates really are. The chapter will then provide recommendations for practices and describe the data supporting those practices. Guidelines published by several expert groups have created a near uniform approach to antibiotic usage for prophylaxis.
Historical Aspects
Administration of antibiotics to decrease the incidence of postoperative wound infection is a surprisingly recent strategy. In fact, early studies of anti-infective prophylaxis, performed in the 1950s, reported either no decrease in infection rates or even higher rates than control. These results are explained by the fact that anti-infectives were begun only in the postoperative period. During the late 1950s and 1960s, important developments were made to rationalize antimicrobial prophylaxis. The most fundamental was definition of the decisive period, the time following wound contamination that antibiotics would still reduce the incidence infection.
Identifying Risk of Surgical Site Infection
It is assumed that at least three categories of variables serve as predictors of SSI risk: Those that estimate the intrinsic degree of microbial contamination of the surgical site; those that measure the duration of the operation and other less easily quantifiable elements of the procedure; and those that serve as markers for host susceptibility.
In 1964, the National Research Council sponsored an examination of the efficacy of ultraviolet irradiation, and provided the data to validate a wound classification scheme describing risk of infection in relation to the extent of wound contamination. That document is a landmark in this area, and the classification scheme has remained useful to the present day. This classification is presented in Table 1. A clear connection between the contaminating flora at various surgical sites and subsequent infecting pathogens was established. This microbiologic correlation included recognition of the role of anaerobes in postoperative wound infection and abscess formation.
Subsequent CDC efforts, the SENIC project (Study of the Efficacy of Nosocomial Infection Control) and NNIS (National Nosocomial Infection Surveillance, since renamed NHSN, the National Hospital Surveillance Network) sought to examine these other variables as predictors of infection.
Table 1 Wound Classification | ||||||||||||||||||
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Table 2 Elements in the American Society of Anesthesia Scoring System | |||||||||||||||||||||
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A risk index was developed to predict a surgical patient’s risk of acquiring a surgical wound infection. The risk index score, ranging from 0 to 3, is the number of risk factors present among the following: (a) a patient with an American Society of Anesthesiologists preoperative assessment score of 3, 4, or 5 (see Table 2); (b) an operation classified as contaminated or dirty/infected; and (c) an operation lasting over T hours, where T depends on the operative procedure being performed. This is typically the 75th percentile. Definitions for wound classes are provided in Table 1. Elements in an American Society of Anesthesiologists preoperative assessment score are in Table 2.
The surgical wound infection rates for patients with scores of 0, 1, 2, and 3 were 1.5, 2.9, 6.8, and 13.0, respectively. The risk index is a significantly better predictor of surgical wound infection risk than the traditional wound classification system and performs well across a broad range of operative procedures.
Table 3 Recommended Antibiotics | ||||||||||||||||||||||||||||||||||||
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It is important to note that this system provides little insight into risk of infection in clean or clean-contaminated wounds, other than identifying a correlation with length of operation. It is specifically worth noting that morbid obesity places a patient into American Society of Anesthesiologists 3 but the relative weight of this and other variables is not more precisely addressed by this shorthand. The problem is that a morbidly obese patient undergoing a procedure, such as a caesarean section, is at a higher intrinsic risk of SSI than predicted by the risk system described. A hospital with a large number of such patients will therefore fall out in public reporting as a hospital with problems.
Accepted Indications for Anti-Infective Prophylaxis and Recommended Agents
There is a wide consensus on specific procedures that warrant antimicrobial prophylaxis. Consensus statements by the Surgical Infection Society of North America, the Infectious Diseases Society of America, the American Society of Hospital Pharmacists, the Canadian Infectious Diseases Society, and the French Society of Anesthesia and Intensive Care all agree on a number of indications. The areas of consensus and recommendations for antimicrobial therapy are provided in Table 3.
These guidelines have needed updating, and this task was undertaken by the American Society of Health System Pharmacists, in collaboration with the Surgical Infection Society, the Infectious Diseases Society of America, and the Society of Health Care Epidemiology. These guidelines are available in draft form (http://www.ashp.org/prophylaxis, accessed August 29, 2010).
Controlled trials of antimicrobial prophylaxis in minimally invasive procedures have recently been reported. In low-risk laparoscopic cholecystectomy and arthroscopic surgery, routine prophylaxis is not indicated. In contaminated laparoscopic procedures, such as high-risk cholecystectomy
and bowel surgery, it is best to apply the standards for similar open procedures.
and bowel surgery, it is best to apply the standards for similar open procedures.
Gastroduodenal
Prophylaxis is recommended for most gastrointestinal procedures. The density of organisms and proportion of anaerobic organisms progressively increase along the gastrointestinal tract, so the recommendation depends on the segment of gastrointestinal tract entered during the procedure. The density of microorganisms contaminating the surgical wound with procedures entering the stomach, duodenum, and proximal small bowel is quite low and consists primarily of gram-positive organisms. However, any disease or therapeutic intervention that decreases gastric acidity causes a marked increase in the number of bacteria and the risk of wound infection. Therefore, previous use of antacids, histamine blockers, or a proton pump inhibitor qualifies the patient for prophylaxis. Prophylaxis is also indicated for procedures treating upper gastrointestinal bleeding. Stasis also leads to an increase in bacterial counts, so prophylaxis is warranted in procedures to correct obstruction. In addition, the intrinsic risk of infection in patients with morbid obesity and malignancy is sufficiently high to warrant prophylaxis in these cases. Although the local flora is altered in these patients, cefazolin provides adequate prophylaxis and is the recommended agent.
Generally, elective surgery on the stomach or duodenum for ulcer disease is now included in those procedures requiring prophylaxis.
Small Bowel and Colorectal Procedures
The flora of the small bowel changes from small numbers of gram-positive organisms proximally to heavier growth of gram-negatives more distally. In the distal ileum, anaerobes emerge and become important in SSIs. Therefore, the recommendation is that proximal small bowel procedures receive prophylaxis with a first-generation cephalosporin; more distally, prophylaxis as for colorectal procedures is recommended.
Colorectal procedures have a very high intrinsic risk of infection and warrant a strong recommendation for prophylaxis. In patients undergoing colorectal surgery, the incidence of wound infection ranges from 9% to 27%. Several studies have demonstrated efficacy with rates of infection decreasing from >50% to <9%. Antibiotics are directed at gram-negative aerobes and anaerobic bacteria.
The use of oral, nonabsorbable agents is no longer recommended. Antibiotics selected for prophylaxis in colorectal surgery should be active against both aerobic and anaerobic bacteria. Certain regimens were found to be inadequate. Inadequate regimens included metronidazole alone (which lacks activity against facultative and aerobic gram-negative organisms), doxycycline alone, piperacillin alone (which lacks activity against anaerobes), and oral neomycin plus erythromycin on the day before operation. The addition of an effective parenteral agent reduced infection rates seen with neomycin/erythromycin to the same level as that seen with the parenteral agent alone.
This study also found no evidence to suggest that the new-generation cephalosporins are more effective than the first-generation cephalosporins combined with metronidazole. Surveys of resistance among anaerobic organisms, specifically the recognized pathogen Bacteroides fragilis, have documented a substantial increase in resistance to cefotetan and, to a lesser extent, cefoxitin. For this reason, cefotetan can no longer be recommended for prophylactic usage. Ampicillin-sulbactam should not be used routinely for prophylaxis because many, if not most, Escherichia coli have become resistant to it.
A major study was recently completed comparing ertapenem, a carbapenem class of antibiotic typically reserved for cephalosporin-resistant gram-negatives, to cefotetan. Cefotetan is no longer available for use in the United States and has only modest B. fragilis activity. Predictably, ertapenem, with excellent activity against E. coli and B. fragilis, was superior to cefotetan.
The American Society of Health System Pharmacists, in draft guidelines, recommends against use of ertapenem because of concerns for the effects of additional carbapenem usage on resistance to these critical agents. I agree with this and, despite FDA labeling that ertapenem is effective in preventing SSIs following colorectal surgery, I find no reason to recommend it against cefazolin/metronidazole.
Topical application of antibiotics in addition to the parenteral administration of appropriate anti-infectives has not been found effective in controlled trials. No additional benefit was observed in six trials that compared parenteral anti-infectives alone with parenteral plus topical antibiotics. There is certainly anecdotal testimony to their efficacy and I doubt this “controversy” will ever go away.
Prophylaxis is also recommended for appendectomy. Although the intrinsic risk of infection is low for uncomplicated appendicitis, the preoperative status of the patient’s appendix may not be known. Metronidazole combined with a first-generation cephalosporin is an acceptable regimen. For uncomplicated appendicitis, coverage need not be extended to the postoperative period. Complicated appendicitis (e.g., with accompanying perforation or abscess) is an indication for antibiotic therapy, thereby rendering any consideration of prophylaxis irrelevant.
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