Prophylactic Antibiotics in Orthopaedic Surgery

Laura Prokuski, MD

Abstract The use of prophylactic antibiotics in orthopaedic surgery is effective in reducing surgical site infections in hip and knee arthroplasty, spine surgery, and open reduction and internal fixation of fractures. To maximize the beneficial effect of prophylactic antibiotics while minimizing adverse effects, the correct antimicrobial agent must be selected, the drug must be administered just before incision, and the duration of administration should not exceed 24 hours.
pproximately 27 million surgical procedures are performed in the United States each year.1 Surgical site infections (SSIs) are a major source of postoperative illness. The Centers for Disease Control and Prevention (CDC) estimate that nearly 500,000 SSIs occur annually.2 The CDCs National Nosocomial Infections Surveillance System (NNIS), established in 1970, monitors reported trends in nosocomial infections in acute care hospitals in the United States.3 Despite advances in infection control practices, SSIs remain a substantial cause of morbidity and mortality among hospitalized patients. Among surgical patients in one study, SSIs were the most common nosocomial infection. A patient who develops an SSI is five times more likely to be readmitted to the hospital, 60% more likely to spend time in an intensive care unit, and twice as likely to die compared with a patient without an SSI.4 In one study, of the surgical patients with an SSI who died, 89% of the deaths were attributable to the infection.5 Postoperative infections not only produce human suffering but also have a considerable economic impact. In the 1990s, a patient with an SSI averaged 12 days of total excess

hospitalization, and the direct cost attributable to the SSI was $5,038.4

Criteria for Defining Surgical Site Infections

The NNIS has developed standardized surveillance criteria for defining SSIs (Table 1). These definitions have been applied consistently by surveillance personnel and are currently a national standard. SSIs are classified as superficial when they involve only skin and subcutaneous tissue, and deep when the infection is within the fascia or muscle. Organ/space SSIs involve any part of the anatomy, other than incised body wall layers, that were opened or manipulated during an operation. Osteomyelitis, epidural abscess, diskitis, septic bursitis, and septic arthritis are considered organ/ space SSIs.3

Dr. Prokuski is Associate Professor, University of Wisconsin Hospitals, Madison, WI. Neither Dr. Prokuski nor a member of her immediate family has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article. Reprint requests: Dr. Prokuski, University of Wisconsin Hospitals, 600 Highland Avenue, Madison, WI 53792. J Am Acad Orthop Surg 2008;16:283293 Copyright 2008 by the American Academy of Orthopaedic Surgeons.

Pathogenesis
Bacteria contaminate every surgical wound. The most common source is the endogenous flora of the skin, which are usually comprised of aerobic gram-positive cocci. The skin may also harbor fecal organisms, including gram-negative rods and anaerobic bacteria. SSI occurs when the surgical wound bacterial contam283

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Prophylactic Antibiotics in Orthopaedic Surgery

Table 1 National Nosocomial Infections Surveillance System Criteria for Defining a Surgical Site Infection (SSI)3 Supercial incisional SSI Infection occurs within 30 days after the operation and the infection involves only skin or subcutaneous tissue of the incision and at least one of the following: 1) Purulent drainage, with or without laboratory conrmation, from the supercial incision 2) Organisms isolated from an aseptically obtained culture of uid or tissue from the supercial incision 3) At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat and supercial incision is deliberately opened by surgeon, unless the incision is culture-negative 4) Diagnosis of supercial incisional SSI by the surgeon or attending physician Deep incisional SSI Infection occurs within 30 days after the operation when no implant is left in place, or within 1 year when the implant is in place and the infection appears to be related to the operation and infection involves deep soft tissues (eg, fascial and muscle layers) of the incision and at least one of the following: 1) Purulent drainage from the deep incision but not from the organ/space component of the surgical site 2) A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following signs or symptoms: fever (>38 C), localized pain, or tenderness, unless the site is culture-negative 3) An abscess or other evidence of infection involving the deep incision is found on direct examination, during revision, or by histopathologic or radiologic examination 4) Diagnosis of a deep incisional SSI by a surgeon or attending physician Organ/Space SSI Infection occurs within 30 days after the operation if no implant is left in place, or within 1 year if the implant is left in place and the infection appears to be related to the operation and infection involves any part of the anatomy (eg, organs, spaces), other than the incision, that was opened or manipulated during an operation and at least one of the following: 1) Purulent drainage from a drain that is placed through a stab wound into the organ/space 2) Organisms isolated from an aseptically obtained culture of uid or tissue in the organ/space 3) An abscess or other evidence of infection involving the organ/space that is found on direct examination, during revision, or by histopathologic or radiologic examination 4) Diagnosis of an organ/space SSI by a surgeon or attending physician
Reproduced with permission from Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR: Guideline for prevention of surgical site infection, 1999: Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1999;20:250-278.

ination cannot be contained by host defenses. The amount of bacteria required to cause infection is variable and depends on the virulence of the organisms, the condition of the wound (eg, quantity of necrotic tissue), the presence of nonbiologic substances (eg, metallic implants), and host immunocompetence. Bacteria also may enter the surgical wound through hematogenous dissemination or from the exogenous environment. Bacteria have adaptive strategies to increase their virulence. Of particular importance to orthopaedic surgeons are the surface compounds that some bacteria produce. These compounds inhibit phagocytosis and facilitate adherence to implants, shielding them from immune defenses.3,6 According to the NNIS, the distribution of pathogens isolated from
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SSIs did not change markedly from 1986 to 1996.7 Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus species, and Escherichia coli were the most frequently isolated pathogens. An increasing proportion of SSIs are caused by antimicrobial-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA).3 The change in proportion of antibiotic-resistant surgical wound pathogens in the subsequent decade will be an important factor in directing future recommendations for surgical antibiotic prophylaxis.

Historical Perspective
Postoperative infection has always been a great concern to surgeons. In the early days of surgery, patients of-

ten developed postoperative irritative fever, followed by purulent drainage from their incisions, and ultimately sepsis and death. It was not until Joseph Lister implemented his principles of antisepsis in the 1860s that the morbidity and mortality of surgery decreased substantially.3 In 1961, Burke8 performed a series of experiments that laid the foundation for current recommendations for using perioperative prophylactic antibiotics. He investigated the effect that antibiotics had on inflammation in surgical incisions contaminated with S aureus in guinea pigs. Antibiotics were administered at different times in relation to the bacterial inoculation of the wound. When antibiotics were given 1 hour before the inoculation, there was no inflammatory response. These wounds did not

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differ either clinically or microscopically from incisions inoculated with dead bacteria. When antibiotics were given 1 hour after inoculation, an inflammatory response was observed. When antibiotics were administered 3 hours or longer after inoculation, the inflammatory response was no different than that observed in animals that had received no antibiotics. Burke8 concluded that the susceptibility of bacteria was greatest when the antimicrobial agent was in the tissue when the bacteria arrived and that the effective period of antibiotic action was restricted to the initial few hours after inoculation. The clinical use of prophylactic antibiotics in orthopaedic surgery was not always supported. Early, poorly designed studies found that perioperative use of antibiotics in clean orthopaedic cases was associated with increased infection rates.9,10 Despite these unfavorable results, investigation continued into the use of prophylactic antibiotics in orthopaedic surgery.11 Subsequent studies demonstrated that antibiotic prophylaxis in general orthopaedic surgery was beneficial in reducing postoperative infections. Fogelberg et al12 prospectively investigated the effects of prophylactic penicillin in preventing wound infection in patients undergoing arthroplasty and spine fusion. These procedures were selected for inclusion in the study because their duration was generally longer than 3 hours, extensive dissection was performed in deep tissue planes, and considerable exposure of bleeding bone surfaces occurred. The infection rates were 1.7% in the penicillin group and 8.9% in the group that received no antibiotics. Pavel et al13 performed a doubleblind prospective study of clean orthopaedic surgical procedures. The group that received cephaloridine had a 2.8% infection rate, compared with a 5% infection rate in the placebo group. Henley et al14 reported on a prospective randomized doubleVolume 16, Number 5, May 2008

Table 2 Recommendations for the Use of Prophylactic Antibiotics in Orthopaedic Surgery Choice of Antimicrobial Agent Cephalosporin (cefazolin, cefuroxime) If -lactam allergy, use clindamycin or vancomycin Consider preoperative screening for MRSA colonization If infected or colonized with MRSA, use vancomycin Timing of Administration Start up to 60 min before incision: cefazolin, cefuroxime, clindamycin Start up to 120 min before incision: vancomycin Infusion completed 10 min before tourniquet ination Dosing Cefazolin, 1-2 g (2 g for patient weighing >86 kg) Cefuroxime, 1.5 g Vancomycin and clindamycin dosing based on patient mass Pediatric dosing based on patient mass Duration of Antimicrobial Use Single preoperative dose Redose antimicrobial intraoperatively for prolonged procedure or signicant blood loss When using postoperative doses, discontinue within 24 h after wound closure
MRSA = methicillin-resistant Staphylococcus aureus

blind study of general orthopaedic procedures. The group that received cefamandole had a 1.6% infection rate, and those who received placebo had a 4.2% infection rate. The authors of these studies concluded that perioperative prophylactic antibiotics were effective in reducing the infection rate after general orthopaedic surgical procedures. Subsequent studies have demonstrated that prophylactic antibiotics reduce the incidence of SSI after a variety of orthopaedic surgical procedures.

mal prophylaxis ensures that adequate concentrations of an appropriate antibiotic are present in the serum and tissue during the entire time the surgical wound is open and at risk for bacterial contamination. The antibiotic should be active against bacteria that are likely to contaminate the wound as well as be safe and inexpensive. The antibiotic prophylaxis should have the smallest impact possible on the normal bacterial flora of the patient and the BIOGRAM of the community15 (Table 2). Choice of Antimicrobial Agent
Cephalosporins

Antimicrobial Prophylaxis in General Orthopaedic Surgery

Surgical antimicrobial prophylaxis is administered not to sterilize the tissues but as an adjunct to modulate intraoperative contamination of the surgical wound to a level that will not overwhelm the host defenses.3 Opti-

The organisms of concern in clean orthopaedic surgery are bacteria found on the skin, primarily aerobic gram-positive cocci. A firstgeneration cephalosporin, such as cefazolin, provides adequate coverage against most staphylococci
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and other gram-positive bacteria that may contaminate the wound. Second-generation cephalosporins, such as cefuroxime, have a slightly broader spectrum, covering some gram-negative bacteria while remaining effective against grampositive organisms. Cephalosporins also rapidly achieve optimal tissue concentrations in subcutaneous tissue, muscle, and bone. First- and second-generation cephalosporins have a long enough half-life to provide adequate tissue concentrations during the entire time the wound is open in most orthopaedic procedures. The cost of these agents is relatively low. Adverse effects are rare, but include a spectrum of allergic reactions.16
-lactam Allergy

dergoing elective orthopaedic surgery.18

Vancomycin and MRSA

Although many patients have drug allergies documented in their medical records, efforts should be made to determine whether the patient has a true allergy (eg, urticaria, pruritis, bronchospasm, hypotension) or a serious risk for adverse drug reaction (eg, diarrhea). The incidence of adverse reactions to cephalosporins among patients with reported penicillin allergy is rare. A patient with a history of penicillin allergy and a negative penicillin skin test is not at increased risk of an adverse reaction to cephalosporins.16 Alternative antimicrobials should be considered for a patient who, on the basis of history and/or skin testing, has a high likelihood of serious adverse reaction or allergy. Vancomycin or clindamycin may be used for a patient with a true -lactam allergy.3,16,17 Vancomycin should be reserved for the treatment of serious infection with -lactamresistant organisms or for the treatment of infection in a patient with a lifethreatening allergy to -lactam antimicrobials. Consultation with an allergist and penicillin allergy skin testing can decrease prophylactic vancomycin use in patients un286

The routine use of vancomycin for prophylaxis is discouraged because it may promote the emergence of vancomycin-resistant organisms.19 However, current or previous infection with MRSA and known MRSA colonization are indications to use vancomycin for surgical prophylaxis. Sanderson20 states that MRSA infection or colonization should label the patient colonized for life because subsequent negative screening swabs may not be accurate. Rates of MRSA colonization are higher among patients who have previously spent more than 5 days in an institutional setting.21 Patients with prior exposure to an intensive care unit as well as those on hemodialysis or with chronic wounds are at higher risk for MRSA colonization. Preoperative nasal swabbing can detect 80% to 90% of MRSA carriers and may be a helpful screening test for elective surgery.20 Vancomycin may be an appropriate prophylactic agent in facilities with recent MRSA outbreaks. Some argue that vancomycin is the correct prophylactic agent in institutions with a high prevalence of MRSA. Unfortunately, no threshold exists as to what constitutes a high enough prevalence rate to justify using vancomycin for routine surgical prophylaxis. There is no evidence that routine use of vancomycin instead of cephalosporins for prophylaxis in institutions with perceived high rates of MRSA infection will result in fewer SSIs.16 In one such institution, Finkelstein et al22 randomized 885 cardiac surgery patients to prophylaxis with cefazolin or vancomycin. There was no difference in the rate of SSI between the two groups. Patients who received cefazolin and later developed an SSI were more likely to be infected with MRSA, whereas those who developed an SSI

after vancomycin prophylaxis were more likely to be infected with methicillin-sensitive S aureus. The choice of antimicrobial agent used for prophylaxis changed the infecting organism but did not alter the infection rate.
Mupirocin

Kalmeijer et al23 studied patients undergoing orthopaedic surgery with prosthetic implants. They found that nasal carriage of S aureus was the most important independent risk factor for developing an SSI. Thus, the elimination of nasal carriage of S aureus would be thought to decrease SSI rates. Mupirocin is a topical antimicrobial that is effective against S aureus, and it can be used in the perioperative period to reduce nasal colonization. It is applied inside the nose and has few side effects. Gernaat-van der Sluis et al24 compared wound infection rates in two groups of patients undergoing either arthroplasty or internal fixation of fracture. One group of 1,044 patients received perioperative nasal mupirocin ointment. The other group consisted of 1,260 historical controls. A random sample of 50 patients was taken from each group. The overall rate of SSI and the rate of S aureus SSI were significantly lower in the group that received mupirocin. The authors acknowledge the weakness of a historical control but state that prophylactic treatment with mupirocin can reduce SSI rates. Kalmeijer et al25 randomized patients to receive either placebo or mupirocin nasal ointment before knee arthroplasty, hip arthroplasty, and spine surgery. Perioperative cefamandole was also administered for 24 hours as routine prophylaxis. Eradication of S aureus nasal carriage was significantly more effective in patients who received mupirocin (83.5%) than in those who received placebo (27.8%). However, the overall rate of SSI was comparable between the two groups.

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The effect of prophylactic mupirocin specifically on MRSA SSIs in orthopaedic surgery has also been examined. Wilcox et al26 reported on a consecutive series of patients undergoing orthopaedic surgery for either insertion of metal prostheses or internal fracture fixation. These patients received perioperative prophylaxis with nasal mupirocin for 5 days and a bath or shower with 2% triclosan the day before surgery. The control group consisted of patients undergoing similar procedures in the 6 months before the mupirocin/ triclosan regimen was started. Both groups received intravenous cephradine for 24 hours perioperatively. There was a marked decrease in the incidence of MRSA nasal carriage in the group treated with mupirocin and triclosan. After introduction of the mupirocin/triclosan protocol, MRSA SSIs decreased from 23 per 1,000 to 3.3 to 4 per 1,000. Of the 11 MRSA SSIs that occurred in the mupirocin/triclosan group, only one patient received the intervention correctly. The number of SSIs caused by other pathogens was not affected by the intervention. The relative contributions of mupirocin and triclosan could not be determined. Nevertheless, the authors stated that their results justify empirical, as opposed to targeted, usage of mupirocin prophylaxis because current health care practice makes it almost impossible to preoperatively assess for MRSA carriage and subsequently treat all patients undergoing orthopaedic surgery. It is of concern that Rotger et al27 found that 27% of MRSA isolates causing hip or knee prosthetic joint infection were resistant to mupirocin. Timing of Administration The lowest rate of SSI has been observed with antibiotics given shortly before incision. Classen et al28 prospectively studied patients undergoing a variety of clean or cleancontaminated surgical procedures. The patients who received antibiotic
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prophylaxis during the 2 hours prior to incision had the lowest rates of SSI. Relative risk for SSI increased with antibiotic administration during the 3 hours after incision (2.4), 3 to 24 hours after incision (5.8), and 2 to 24 hours before incision (6.7). Infusion of cephalosporins and clindamycin should begin within 60 minutes of incision and should be completed at the time of incision. Administration of vancomycin should begin 2 hours before incision to accommodate the extended infusion time. Administration of the antimicrobial at the time of anesthesia induction is safe and results in adequate tissue drug levels at the time of incision.16,29 Schurman et al30 measured the concentration of cephalosporins in serum, bone, synovial fluid, and wound drainage during knee and hip arthroplasty. The antibiotics were administered with the induction of anesthesia, and high concentrations of antibiotics were found in all samples. Cefazolin administered immediately preoperatively has resulted in bone cefazolin concentration of 60 times the minimum inhibitory concentration for penicillin-resistant S aureus.29 Tourniquet use is a specific consideration when determining the timing of prophylactic antibiotic administration in extremity surgery. The concentrations of cephalosporin in serum and bone are high immediately after administration; Schurman et al30 found them to be adequate even with the use of a tourniquet. Johnson31 investigated the concentration of cefuroxime in bone and subcutaneous fat during knee arthroplasty. Patients were randomized to receive 1.5 g cefuroxime at 5, 10, 15, and 20 minutes before tourniquet inflation. All patient groups had antibiotic levels greater than the minimal bactericidal concentration for S aureus in bone. In the subcutaneous fat, 86% of the group treated at 5 minutes had antibiotic concentrations lower than the minimal bactericidal concentration

for S aureus; however, the levels were adequate in the other groups. The authors concluded that 10 minutes is an appropriate amount of time between administration and tourniquet inflation to achieve adequate levels of cefuroxime in the tissues. Deacon et al32 demonstrated that adequate tissue concentrations of cephalosporins can be achieved in the foot after tourniquet inflation. Cefazolin concentrations in the medial eminence of the first metatarsal reached adequate levels when the drug was administered 30 to 60 minutes preoperatively and a pneumatic ankle tourniquet was used for hemostasis during bunionectomy. Dosing Cefazolin 1 to 2 g is administered, with 2 g recommended for a patient weighing more than 80 kg.3,16 The dose of cefuroxime is 1.5 g. The optimal dose of vancomycin and clindamycin is related to the patients mass. Pediatric dosing also is based on the patients mass. The optimal dose may change with specific conditions or diseases that affect the metabolism of the drug. When a question on appropriate dose is encountered, consultation with a pharmacist may be helpful. Additional doses of antibiotic are warranted when the duration of the procedure exceeds 1 to 2 times the half life of the antibiotic22,33,34 or when there is significant blood loss intraoperatively.19,32,35 In a study of 40 patients undergoing major surgery with significant blood loss and intraoperative blood salvage, the minimal inhibitory concentration for several cephalosporins in tissue was barely adequate after 4 hours, which indicates that redosing at this time may be beneficial.36 Published redosing intervals are listed in Table 3.16,33 Duration The shortest effective duration of antimicrobial administration for preventing postoperative infection is not known.16,18 Most published
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Table 3 AAOS Recommendations for the Use of Intravenous Antibiotic Prophylaxis in Primary Total Joint Arthroplasty33 Recommendation 1: The antibiotic used for prophylaxis should be carefully selected, consistent with current recommendations in the literature, taking into account the issues of resistance and patient allergies. Currently, cefazolin, and cefuroxime are the preferred antibiotics for patients undergoing orthopaedic procedures. Clindamycin or vancomycin may be used for patients with a conrmed -lactam allergy. Vancomycin may be used in patients with known colonization with methicillin-resistant Staphylococcus aureus (MRSA) or in facilities with recent MRSA outbreaks. In multiple studies, exposure to vancomycin is reported as a risk factor in the development of vancomycin-resistant enterococcus (VRE) colonization and infection. Therefore, vancomycin should be reserved for the treatment of serious infection with -lactamresistant organisms or for the treatment of infection in patients with life-threatening allergy to -lactam antimicrobials. Recommendation 2: Timing and dosage of antibiotic administration should optimize the efficacy of the therapy. Prophylactic antibiotics should be administered within 1 h before skin incision. Due to an extended infusion time, vancomycin should be started within 2 h before incision. When a proximal tourniquet is used, the antibiotic must be completely infused before ination of the tourniquet. Dose amount should be proportional to patient weight; for patients >80 kg, the doses of cefazolin should be doubled. Additional intraoperative doses of antibiotic are advised when the duration of the procedure exceeds one to two times the antibiotics half-life or when there is signicant blood loss during the procedure. The general guidelines for frequency of intraoperative antibiotic administration are as follows: cefazolin every 2-5 h, cefuroxime every 3-4 h, clindamycin every 3-6 h, vancomycin every 6-12 h. Recommendation 3: Duration of prophylactic antibiotic administration should not exceed the 24-hour postoperative period. Prophylactic antibiotics should be discontinued within 24 h of the end of surgery. The medical literature does not support the continuation of antibiotics until all drains or catheters are removed and provides no evidence of benet when they are continued past 24 h.

evidence demonstrates that antimicrobial prophylaxis after wound closure does not provide additional protection against SSI. Studies comparing single-dose prophylaxis with multiple-dose prophylaxis have shown no reduction in SSI rate with the additional doses.16,34 Continuing antibiotic prophylaxis longer than 24 hours after wound closure has not proved to be beneficial; indeed, it may contribute to the development of antimicrobial resistance.16,18 Continuing prophylactic antibiotics for the duration that drains and catheters are in place has not been shown to reduce SSI rates.11,16

seeks to reduce the morbidity and mortality related to postoperative infections in the Medicare population.33 Preliminary data indicate that antibiotic prophylaxis is not always administered in a manner that is supported by scientific evidence.37 Inappropriate use of antibiotics does not prevent postoperative infections; rather, it contributes to antibiotic resistance, increases the risk of adverse reactions, and increases health care costs.

National Surgical Infection Prevention Project

The National Surgical Infection Prevention Project (SIPP) was initiated in August 2002 as a joint venture between the Centers for Medicare & Medicaid Services and the CDC. By promoting the appropriate selection, timing, and duration of administration of prophylactic antibiotics, SIPP
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Antibiotic Prophylaxis for Orthopaedic Subspecialties and Specific Orthopaedic Procedures

Spine Surgery Early retrospective studies generally supported the use of prophylactic antibiotics for spine surgery.12,38-40 Later randomized underpowered trials did not overwhelmingly prove the efficacy of prophylactic antimicrobials in reducing SSIs in spine surgery.41-45 Barker46 performed a

meta-analysis of antibiotic prophylaxis in spine surgery, including 843 patients from six randomized controlled trials. The meta-analysis provided statistically significant (P < 0.01) evidence that prophylactic antibiotic use for spine operations is effective in reducing SSI rates. The timing of administration of prophylactic antimicrobials has been shown to be critical in reducing SSIs in spine surgery. Antibiotics administered more than 2 hours before incision47 or after completion of the procedure40 produced higher rates of SSI. Redosing antimicrobials intraoperatively to maintain adequate tissue levels has been found to be important in spine surgery. Swoboda et al35 examined patients undergoing elective spinal instrumentation. Blood loss correlated with the change in tissue antibiotic concentrations for cefazolin. Based on measured pharmacokinetic values, the authors recommended additional doses of cefazolin when the operation approaches 4 hours or blood loss exceeds 1,500 mL.

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Arthroscopy The incidence of infection after arthroscopic surgery has been reported to be extremely low, approximately 0.2%.48,49 DAngelo and Ogilvie-Harris49 retrospectively reviewed patients with infection following knee and shoulder arthroscopic procedures performed without prophylactic antibiotics. They found a septic arthritis rate of 0.23%. After comparing the cost of treating the infections and the cost of administering prophylactic antibiotics universally, the authors concluded that it may be cost-effective to use antibiotic prophylaxis to reduce hospital costs and patient morbidity when performing arthroscopic surgery. However, this must be proved in a betterdesigned study. Wieck et al48 performed a prospective randomized double-blind study of 437 patients undergoing arthroscopic procedures on the knee, shoulder, ankle, elbow, and wrist. Procedures included subacromial decompression, lateral release, meniscal repair, and synovectomy. No implants or grafts were inserted. Patients received either cefazolin or placebo preoperatively. No deep infections occurred in either group. One superficial infection occurred in a patient who received placebo. The authors concluded that the routine use of prophylactic antibiotics is not indicated for patients undergoing arthroscopic surgery. Kurzweil50 expressed concern regarding antibiotic prophylaxis in contemporary arthroscopic procedures. Many procedures are not performed exclusively arthroscopically and involve surgical incisions. Other procedures may require prolonged surgical times. More complex arthroscopic procedures may involve the use of implants. All of these conditions present additional risk factors for developing an SSI. No study has truly examined the effect of prophylactic antibiotics along the spectrum of contemporary arthroscopic procedures. Kurzweil50 recommended that routine antibiotic prophylaxVolume 16, Number 5, May 2008

is be provided for patients undergoing arthroscopic surgery. Pediatric Orthopaedics Pediatric patients are subject to many of the same procedures that are performed on adults, but pediatric-specific antibiotic prophylaxis data are sparse. A case-control study designed to identify risk factors for SSIs after spinal fusion in children found that antibiotic prophylaxis was more frequently suboptimal in patients who developed an SSI.51 Of the 13 cases of infection, one patient did not receive antibiotic prophylaxis. Ten of the remaining 12 cases received appropriate doses of cefazolin, but timing was optimal in only 3 cases. No well-controlled studies have evaluated the efficacy of antimicrobial prophylaxis in pediatric patients undergoing clean orthopaedic procedures. In most instances, the recommendations for pediatric patients have been extrapolated from studies performed on adults.18 Foot and Ankle Few studies have examined the effect of prophylactic antibiotics on SSI rates exclusively in foot and ankle surgery. Zgonis et al52 performed a retrospective review of 555 patients who underwent elective foot and ankle surgery. Patients were treated for nontraumatic conditions, and no revision procedures were included. The wound infection rate was 1.6% with prophylactic antibiotics and 1.4% without. The authors concluded that prophylactic antibiotic use in routine elective foot and ankle surgery is not warranted. Paiement et al53 performed a doubleblind randomized prospective study in 122 patients undergoing open reduction and internal fixation of isolated closed ankle fractures. No statistical difference was found in the rates of infection with or without prophylactic antibiotics. However, the authors recognized that the study may be underpowered.

No recommendations exist for the use of prophylactic antibiotics in patients with diabetes mellitus who are undergoing clean elective foot surgery. Patients with diabetes are at a higher risk for postoperative infection, and their infections are typically polymicrobial. Extrapolation of recommendations from other studies may not be accurate.18 Hand Surgery Few studies address the use of antibiotic prophylaxis in patients undergoing clean elective hand surgery. Kleinert et al54 prospectively studied patients undergoing elective upper extremity surgery. Perioperative antibiotics were given unpredictably, and never before incision. Infection developed in 2.6% of patients who received systemic antibiotics and in 1.2% who did not. Statistical analysis demonstrated that systematic administration of antibiotics was not a predictor of infection. Hanssen et al55 reported a retrospective 0.47% infection rate after carpal tunnel release; most patients did not receive perioperative antibiotics. Risk factors for SSI were injection of steroid into the carpal tunnel, flexor tenosynovectomy, prolonged surgical time, and use of a surgical drain. Patients with this combination of perioperative factors had a higher surgical infection rate than did patients who underwent simple carpal tunnel release alone. When patients who received antibiotic prophylaxis were omitted from statistical comparison, the risk factors for SSI remained at the same level of statistical significance. Platt and Page56 prospectively analyzed 112 patients undergoing elective hand surgery. The decision to use antibiotics was made by the operating surgeon, and several different antibiotic regimens were used. No difference was noted in the postoperative infection rate between the 48 patients who received antibiotics and the 64 patients who did not. The study was limited by failure to ran289

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domize the patients and the small number of patients. No randomized controlled studies exist on the efficacy of prophylactic antibiotics in metacarpophalangeal, wrist, and elbow arthroplasty. Many authors recommend prophylactic antibiotics in upper extremity arthroplasty, extrapolating from studies of hip and knee arthroplasty, or justifying their use by emphasizing the seriousness of an arthroplasty infection.56,57 Prophylactic antibiotics have not been proved to be efficacious in clean, elective hand procedures. Properly designed and powered studies do not exist to definitively answer this question. In a review article, Hoffman and Adams57 state that it would be reasonable to use prophylactic antibiotics in reconstructive procedures involving large flaps and procedures of prolonged duration, as well as for arthroplasty. Fracture Fixation Preoperative prophylactic antibiotics are beneficial in reducing SSIs after surgical treatment of hip fractures. In 1973, Boyd et al58 randomized 280 patients with hip fractures to receive either nafcillin or a placebo. The infection rate in the nafcillin group was 0.8%, compared with 4.8% in the placebo group. Others have demonstrated similar benefits with prophylactic antibiotics.59,60 A meta-analysis demonstrated that, compared with placebo, antibiotic prophylaxis significantly reduced the rate of wound infections after hip fracture surgery.61 One preoperative dose of intravenous antibiotics was as effective as multiple doses. Prophylactic antibiotics have also been shown to be effective in reducing SSIs associated with internal fixation of other closed fractures.62 The Dutch Trauma Trial was a prospective randomized double-blind placebo-controlled study of antibiotic prophylaxis administered in the primary surgical treatment of 2,195 closed fractures.63 Fractures of the hip, femur, patella, tibia, fibula, an290

kle, foot, humerus, forearm, and hand were included. Patients received either preoperative ceftriaxone or placebo. The infection rate was 3.6% in the ceftriaxone group and 8.3% in the placebo group. Gillespie and Walenkamp64 performed a meta-analysis examining the effect of preoperative antibiotics on 8,307 patients undergoing fracture surgery in 22 studies. In patients undergoing closed fracture fixation, single-dose antibiotic prophylaxis significantly reduced the number of deep wound, superficial wound, urinary tract, and respiratory tract infections. Multiple-dose prophylaxis was not superior to single-dose prophylaxis in reducing the rate of SSI. Hip and Knee Arthroplasty Although the infection rate is fairly low following hip and knee arthroplasty, the consequences of a prosthetic infection are severe. Prophylactic antibiotics have been shown to reduce the incidence of infection after primary joint arthroplasty. Early studies demonstrated that antibiotic prophylaxis was more effective than placebo in the prevention of postoperative wound infection in patients undergoing total joint arthroplasty.12 In 1973, Ericson et al65 compared infection rates in patients receiving either placebo or cloxacillin before major surgery of the hip. In the first 6 months after the procedure, 12 of 88 patients in the placebo group had infection, versus none of 83 in the cloxacillin group. Carlsson et al66 followed this group for 7 years and found a 15.4% rate of infection without prophylaxis, versus 2% with prophylaxis. Subsequent investigations demonstrate the efficacy of prophylactic antibiotics in reducing SSI after hip and knee arthroplasty.28,67 Cefazolin and cefuroxime are the preferred antimicrobials for prophylaxis in patients undergoing hip and knee arthroplasty.16,17,19,33,34,37,68,69 The rise in the incidence of MRSA infections

prompted Ritter et al70 to examine an alternative prophylactic antibiotic regimen. A series of 201 consecutive patients undergoing total joint arthroplasty received a single dose of 1 g vancomycin and 80 g gentamycin. Trough levels of vancomycin up to 24 hours later exceeded the minimum inhibitory concentration for all sensitive organisms. No postoperative infections were reported. The authors concluded that this is a safe and effective method of prophylaxis for joint arthroplasty. Gram-negative organisms account for 20% to 30% of SSIs reported to the NNIS for cardiac surgery and total joint arthroplasty.71 Antibiotic prophylaxis for joint arthroplasty may soon evolve to include antimicrobials active against gram-negative organisms. The optimal duration of antimicrobial prophylaxis is not known. No further benefit has been demonstrated with antibiotic prophylaxis beyond 24 hours in arthroplasty patients.72-75 Nor has it been proved that continuing antibiotic prophylaxis until removal of drains and catheters reduces the incidence of SSIs.17 The data supporting prophylactic antibiotics in hip and knee arthroplasty are sufficiently strong that national organizations have published recommendations for their use. The Surgical Care Improvement Project has issued recommendations on the use of intravenous antibiotic prophylaxis in primary total joint arthroplasty that are similar to those listed above.16 The American Academy of Orthopaedic Surgeons (AAOS) has issued to its fellows an advisory statement on the use of prophylactic antibiotics in hip and knee arthroplasty33 (Table 3).

Prophylactic Antibiotics in Irrigation Solution

The use of prophylactic intravenous antibiotics has been shown to reduce the infection rate in elective clean orthopaedic cases and open fractures. The addition of antibiotics to the ir-

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rigation solution has become common in an attempt to further decrease the rate of postoperative infection. However, the efficacy of using antibiotics in irrigation fluid has not been proved. Two early clinical studies examined the efficacy of antibiotic irrigation in orthopaedic surgery. One found that topical antibiotics reduced the subsequent rate of infection,76 and the other found that they did not.77 Information on antibiotic irrigation during spine surgery exists in the neurosurgical literature. Savitz et al78 examined the use of antibiotic irrigation in elective clean spine surgery cases. Intravenous antibiotic prophylaxis was also used. No wound infections occurred. The authors stated that the lack of laboratory methodology and statistical analysis precluded an exact explanation for the success in eliminating postoperative sepsis. Haines79 concluded that the existing published evidence did not support the use of antibiotic irrigation for clean neurosurgical procedures for which postoperative infection rates were <5%. Brown et al80 discouraged the inclusion of antibiotics in the irrigation fluid on the grounds that their antibacterial actions are unpredictable and the effectiveness of this practice is unproved. In their study of postoperative infection after elective outpatient procedures on the upper extremity, Kleinert et al54 reported variable use of parenteral antibiotics and antibiotics in irrigation fluid. The wound infection rate was 2.2% in 179 wounds irrigated with antibiotic solution and 1.2% in 1,385 wounds irrigated with a solution that did not contain antibiotics; this was not a significant difference. Anglen81 studied open fracture wounds of the lower extremity, randomizing patients to receive either bacitracin or castile soap added to irrigation fluid. No significant difference was found in infection rate between the two groups. Wound healing problems occurred in 9.5% of the bacitracin irrigation group and in 4%
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of the castile soap irrigation group. The author concluded that irrigation of open fracture wounds with antibiotic solution offered no advantage over the soap solution; in fact, use of the antibiotic may increase the risk of wound healing problems. Several concerns exist with regard to antibiotic irrigation.82 Adverse reactions to topically applied antibiotics occur. Anaphylaxis after irrigation with bacitracin solution has been reported.83,84 Neomycin has prominent neuromuscular blocking actions and may contribute to prolonged unconsciousness and respiratory depression/apnea, bradycardia, and hypotension. Neomycin has caused postoperative deafness and renal failure.84,85 The cost of using antibiotics in irrigation adds to the total cost of patient care. Finally, routine use of antibiotic irrigation may contribute to the development of antibiotic resistance.82

Cochrane Analyses, are presented (references 24, 25, 41-45, 53, 54, 58, 59, 61, 63, 64, 67, 75, and 81). Citation numbers printed in bold type indicate references published within the past 5 years.
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Summary
The use of prophylactic antibiotics in orthopaedic surgery is effective in reducing SSI rates in studies of hip and knee arthroplasty, spine surgery, and open reduction and internal fixation of fractures. To maximize the beneficial effect of prophylactic antibiotics while minimizing adverse effects, the correct antimicrobial must be selected, the drug must be administered just before incision, and duration of administration should not exceed 24 hours.
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Acknowledgment
Dr. Prokuski is a member of the AAOS Patient Safety Committee, which absorbed the AAOS Infections Committee. The author would like to thank the committee members for their knowledge and support.
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References
Evidence-based Medicine: A number of evidence-based studies, including
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