JBJS | Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Prevention of Deep Periprosthetic Joint Infection*†

The Journal of Bone & Joint Surgery, Volume 78, Issue 3

Instructional Course Lecture | March 01, 1996

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Prevention of Deep Periprosthetic Joint Infection*†

ARLEN D. HANSSEN, M.D.‡; DOUGLAS R. OSMON, M.D.‡, ROCHESTER, MINNESOTA; CARL L. NELSON, M.D.§, LITTLE ROCK, ARKANSAS

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An Instructional Course Lecture, The American Academy of Orthopaedic Surgeons

The Journal of Bone & Joint Surgery. 1996; 78:458-71

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Introduction

Although the prevalence of postoperative deep wound infection after total joint arthroplasty has decreased over the past few decades, it remains a feared consequence for both surgeons and patients¹⁰⁷. Moynihan stated that "every operation in surgery is an experiment in bacteriology."⁸⁰ This statement provides remarkable insight into the seemingly variable and unpredictable nature of infection. Often, the specific mechanism and timing of bacterial delivery in a given wound is unknown, and it is usually extremely difficult to prove the exact cause of the infection in an individual situation. Despite improved outcomes of treatment for established deep periprosthetic infection, prevention remains a meaningful objective. The estimated cost of treatment⁶⁷ of an infection at the site of a total hip or total knee arthroplasty exceeds $50,000.

A thorough appreciation of and respect for the innumerable factors that may contribute to an infection is essential in the development of an over-all approach to prevention. The concept of an interdependent relationship among the triad of bacteria, host, and wound is helpful when considering prevention Fig. 1. Infection depends on the number and virulence of the bacteria introduced into a wound, the host's ability to eliminate these bacteria, and the status or viability of the wound environment. Within this triad, multiple variables can contribute to the deposition of bacteria into the wound, many conditions may impair the patient's ability to eliminate bacteria, and numerous vagaries of the wound milieu can facilitate the infectious process (Table I). Every variable may be influenced by the other variables within the triad. For example, the effect of a foreign body on the absolute number of bacteria required to facilitate the infectious process is well known²⁹.

When developing an approach toward the prevention of deep periprosthetic infection, the entire healthcare team must integrate its disciplined prevention efforts into the preoperative, operative, and postoperative time-periods and direct them toward all three areas of the triad by optimizing the wound environment, augmenting the host's ability to fight infection, and minimizing the number of bacteria in the wound. Preventive measures include both methodologies that have been proved in a scientific manner and techniques that are considered to be reasonable despite the fact that their effectiveness in the clinical setting probably cannot be proved. It is important to emphasize the need to educate all members of the health-care team and to make them aware of the importance of their participation in the preventive efforts.

*Printed with permission of The American Academy of Orthopaedic Surgeons. This article will appear in Instructional Course Lectures, Volume 46, The American Academy of Orthopaedic Surgeons, Rosemont, Illinois, March 1997.

†No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

‡Department of Orthopedics (A. D. H.) and Division of Infectious Diseases (D. R. O.), Mayo Medical School, Mayo Clinic and Mayo Foundation, 200 First Street, S.W., Rochester, Minnesota 55905. Please address requests for reprints to Dr. Hanssen.

§Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 531, Little Rock, Arkansas 72205.

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Venn diagram demonstrating the dependent nature of bacteria, host factors, and wound environment on the development of infection.

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TABLE I VARIABLES INFLUENCING DEEP PERIPROSTHETIC INFECTION

	Preoperative Period	Operative Period	Postoperative Period
Bacteria	Urinary tract infection, skin ulcers, other remote infections, poor dental hygiene, shaving of operative site, prolonged hospitalization, prophylactic antibiotics	Instrument sterilization; operating-room traffic; personnel; dispersers; face masks or hoods; body-exhaust suits; ultraviolet light; laminar airflow; skin preparation; surgical scrub, gloves, drapes, or gowns; plastic surgical drape; wound irrigation; suction tips; splash basins	Urinary tract management, remote sites of infection, intravenous catheters, invasive procedures, possibly prophylactic antibiotics

Host	Altered immune system, immunosuppressive medications, diabetes mellitus, rheumatoid arthritis, advanced age, malnutrition, anesthetic risk		Rheumatoid arthritis, altered immune system

Wound environment	Extensive scarring, previous operation, previous infection, obesity, vascular disease, anatomical site, local skin conditions, thin atrophic skin	Duration of procedure, operative technique, suture selection, implant selection, antibiotic bone cement, structural bone graft, hemostasis, surgical drains, wound closure	Wound hematoma, wound drainage, skin necrosis, reoperation, loose prostheses, particulate debris

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TABLE I VARIABLES INFLUENCING DEEP PERIPROSTHETIC INFECTION

	Preoperative Period	Operative Period	Postoperative Period
Bacteria	Urinary tract infection, skin ulcers, other remote infections, poor dental hygiene, shaving of operative site, prolonged hospitalization, prophylactic antibiotics	Instrument sterilization; operating-room traffic; personnel; dispersers; face masks or hoods; body-exhaust suits; ultraviolet light; laminar airflow; skin preparation; surgical scrub, gloves, drapes, or gowns; plastic surgical drape; wound irrigation; suction tips; splash basins	Urinary tract management, remote sites of infection, intravenous catheters, invasive procedures, possibly prophylactic antibiotics

Host	Altered immune system, immunosuppressive medications, diabetes mellitus, rheumatoid arthritis, advanced age, malnutrition, anesthetic risk		Rheumatoid arthritis, altered immune system

Wound environment	Extensive scarring, previous operation, previous infection, obesity, vascular disease, anatomical site, local skin conditions, thin atrophic skin	Duration of procedure, operative technique, suture selection, implant selection, antibiotic bone cement, structural bone graft, hemostasis, surgical drains, wound closure	Wound hematoma, wound drainage, skin necrosis, reoperation, loose prostheses, particulate debris

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TABLE II EFFECTS OF CLEAN AIR AND USE OF PROPHYLACTIC ANTIBIOTICS ON THE RATE OF INFECTION AFTER TOTAL HIP AND TOTAL KNEE ARTHROPLASTY*

* Modified from: Lidwell, O. M.: Lowbury, E. J.; Whyte, W.; Blowers, R.; Stanley, S. J.; and Lowe, D.: Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomized study. British Med. J., 285: 12—13, 1982.

Prophylactic Antibiotics	Laminar Airflow
	No	Yes
No	39 of 1161	13 of 1060	(p < 0.01)
	(3.4%)	(91.2%)
Yes	24 of 2968	10 of 2863	(p < 0.1)
	(0.8%)	(0.3%)
	(p < 0.001)	(p < 0.01)

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TABLE II EFFECTS OF CLEAN AIR AND USE OF PROPHYLACTIC ANTIBIOTICS ON THE RATE OF INFECTION AFTER TOTAL HIP AND TOTAL KNEE ARTHROPLASTY*

Prophylactic Antibiotics	Laminar Airflow
	No	Yes
No	39 of 1161	13 of 1060	(p < 0.01)
	(3.4%)	(91.2%)
Yes	24 of 2968	10 of 2863	(p < 0.1)
	(0.8%)	(0.3%)
	(p < 0.001)	(p < 0.01)

Preoperative Period

Efforts during this time-period should concentrate on assessment of patients who have impaired host defenses, evaluation of operative sites that may provide a poor wound environment, and identification of remote sources of infection (Table I). In general, conditions such as impairment of the immune system or malnutrition may not be entirely reversible but need to be decreased as much as possible before the arthroplasty. Some studies have suggested that patients who are managed with immunosuppressive medications⁴³; who have diabetes mellitus^30,35,73,77, rheumatoid arthritis^16,35,96,130, or an advanced age^32,37,82; or who are obese^12,70,115, at high risk for anesthesia-related complications⁴², or malnourished^37,43,55,111 should be considered high-risk hosts. Open reduction and internal fixation of fractures in patients who have acquired immunodeficiency syndrome is associated with an increased risk of infection, but the effect of the syndrome on elective joint replacement has not been established⁵⁴. Prolonged hospitalization just before the operative procedure has been associated with an increased prevalence of infection²⁰. In a study of 23,649 operative wounds by Cruse and Foord²⁰, the prevalence of deep infection was 1.1 per cent for patients who were admitted on the day of the operation or who were hospitalized for only one day preoperatively, 1.6 per cent for patients who were hospitalized for two to six days preoperatively, 2 per cent for patients who were hospitalized for seven to thirteen days preoperatively, and 4.3 per cent for patients who were hospitalized for at least fourteen days preoperatively. Whether this represents a selection bias for high-risk patients with other serious medical illness or is due to skin colonization with nosocomial organisms resistant to antibiotics commonly used for prophylaxis is unknown.

Preoperative laboratory assessment of nutritional status should be individualized and may include appraisal on the basis of anthropometric indicators (circumference of the arm to indicate the muscle mass, thickness of the triceps skin fold, and weight-height ratio), immunological indicators (total lymphocyte count), or biochemical indicators (levels of serum albumin and transferrin, total iron-binding capacity, and nitrogen balance)^25,43,55,111. A preoperative total lymphocyte count of less than 1500 cells per cubic millimeter (1.5 x 10⁹ per liter) and an albumin level of less than thirty-five grams per liter have been associated with an increased prevalence of wound complications⁴³. Serum transferrin levels have been shown to be an even more sensitive indicator of wound complications after hip arthroplasty than lymphocyte counts and serum albumin levels³⁷. Currently, there is no accepted standard of or definition for nutritional depletion in patients who are scheduled to have an elective total joint arthroplasty; however, the nutritional index of Rainey-MacDonald et al. and the total lymphocyte count have been helpful for predicting which patients will not have a postoperative infection and serve as baselines for future studies⁹⁷.

The local wound environment is often suboptimum in patients who have advanced vascular disease, a history of multiple operative procedures, extensive scarring, or a history of wound infection (Table I). Although conditions such as extensive scarring cannot be altered, careful preoperative assessment may allow modification of the operative approach and technique to minimize the risk of infection.

Preoperative shaving of the operative site results in rapid colonization of the small nicks left by the razor and is associated with an increased risk of deep infection^75,109. Shaving should be avoided until immediately before the operative procedure or depilatory agents should be used¹⁰⁹. Psoriatic plaques in the region of the operative site may increase the risk of infection, although reports on the effect of this condition have been conflicting^9,72,116. Preoperative assessment of psoriatic lesions, when classified on the basis of severity and treated accordingly by a dermatologist, will probably minimize the risk of postoperative infection⁹. Certain anatomical sites, such as the elbow and knee, are associated with a higher prevalence of deep infection, and although the exact reasons are unknown it has been suggested that this vulnerability may be due to the relatively subcutaneous position of these joints^40,62,78,96. Cognizance of this anatomical susceptibility suggests the need for meticulous wound closure and attentive wound care in the postoperative period for patients who have a knee or elbow arthroplasty. Likewise, thin atrophic skin at any site should be particularly noted for special wound care both in the operating room and postoperatively.

Remote sites of infection, such as the oral cavity, the genito-urinary tract, the pulmonary system, and skin ulcers, increase the risk of postoperative infection^67,82,130. A disciplined and consistent physical examination preoperatively is advised for every patient who is scheduled to have an arthroplasty. Abrasions or follicular infection at the intended operative site, venous stasis ulcers, skin breaks in the web spaces of the toes, infections under toenails, poor dentition, and infections of the pulmonary system or urinary tract should be identified and eliminated before the operation whenever possible.

Prophylactic Antibiotics

Prophylactic administration of antibiotics is probably the single most effective method for reducing the prevalence of postoperative wound infection^24,51,53,86. Despite limitations in the designs of most published studies, most consensus panels support the routine use of systematic antimicrobial prophylaxis because the consequences of infection about a prosthetic joint are so severe. Most clinicians routinely use systemic antibiotic prophylaxis at the time of total joint arthroplasty^47,131. The current controversies with regard to such prophylaxis include identification of the optimum antibiotic, the appropriate timing and duration of antimicrobial prophylaxis, and whether or not antimicrobial prophylaxis and ultraclean operating rooms used concurrently are additive in their ability to reduce the prevalence of infection.

The ideal prophylactic antimicrobial agent would have excellent in vitro activity against staphylococci and streptococci, penetrate tissue well, have a relatively long serum half-life to provide coverage for the duration of the entire operative procedure, be relatively non-toxic, and be inexpensive^34,47. The penicillinase-resistant penicillins and cephalosporins have been studied most extensively; however, no single agent has been shown to be superior^{12,23,31,70,95,112}. It should be recognized that there is no universal agreement on the optimum antimicrobial agent, and some have advocated the prophylactic use of broad-spectrum antimicrobials such as cefamandole and cefuroxime because of concern regarding organisms resistant to the spectrum of coverage provided by first-generation cephalosporins^12,31,70. To our knowledge, no data have shown the efficacy or cost-effectiveness of this approach. Cefazolin, a first-generation cephalosporin that has been studied extensively, has a long serum half-life, is relatively non-toxic, and is inexpensive compared with other agents; it is thus a prudent choice for antimicrobial prophylaxis^34,47. For patients who have a type-I hypersensitivity reaction to penicillin (an IgE-mediated hypersensitivity reaction manifested by immediate urticaria; laryngeal edema; and bronchospasm, with or without cardiovascular shock), vancomycin is an excellent alternative for antimicrobial prophylaxis.

It is important to note that some deep periprosthetic infections, such as late hematogenous infections, are due to causes that occur after the effective time-period of perioperative antibiotic prophylaxis^{1,2,6,63,67,68,96,107,117,119,120}. These infections should not be included in the intended spectrum of antibiotic coverage for the initial operative procedure. Furthermore, the entire spectrum of nosocomial infections within a given institution should not be considered collectively when the type of antibiotic prophylaxis for a total joint arthroplasty is determined. Rather, the susceptibility patterns of operative wound infections, with special emphasis on the infections that have occurred after implantation of a prosthesis, should be reviewed with the local infection control officer. Decisions should then be individualized and based on the susceptibility patterns demonstrated in that particular institution.

The appropriate time to administer antimicrobials prophylactically is just before the skin is incised¹³. A large prospective clinical trial of 2847 patients who had a variety of clean and clean-contaminated operative procedures revealed the lowest rate of operative wound infection when prophylactic antimicrobials had been administered within two hours before the skin incision was made as compared with administration after or more than two hours before the incision¹⁸. Currently, we recommend that systemic antimicrobial prophylaxis be given within thirty to sixty minutes before the skin incision is made and at least five to ten minutes before inflation of a tourniquet, to allow proper penetration of the tissues by the antibiotic⁴. For prolonged procedures exceeding one to two times the half-life of the antibiotic or for procedures associated with extensive blood loss, an additional intraoperative dose of antibiotic is advised⁴⁷.

The optimum duration of systemic antimicrobial prophylaxis has been addressed in several clinical trials but has not been definitively established^52,70,95. In these studies, a short duration of administration of the prophylactic agent was as efficacious as longer time-periods. In a randomized clinical trial involving 2651 total hip arthroplasties, deep infection developed in eleven (0.8 per cent) of 1327 patients who had received one postoperative dose of cefuroxime, compared with six (0.5 per cent) of 1324 patients who had received three postoperative doses¹³³. Although this difference was not significant, the power to detect meaningful statistical differences between the patient groups was low and therefore it was difficult to provide any definitive conclusions. Because of the extremely low rate of infection after total joint arthroplasty, the calculation of the statistical power of a study and the limitations that it imposes on any conclusions must always be remembered. In fact, this concern applies to many available reports that discuss possible risk factors for deep periprosthetic infection^5,100.

Most authorities recommend a single preoperative dose of antibiotics followed by two or three postoperative doses to reduce the possibility of antimicrobial toxicity, prevent selection of resistant organisms, and minimize the expense associated with antimicrobial prophylaxis^47,51,86. For example, the estimated reduction in annual health-care costs for 100,000 patients would be $7,700,000 if prophylactic antibiotics were administered in only one intraoperative dose rather than for forty-eight hours postoperatively⁸². Furthermore, these costs escalate substantially when a more expensive antibiotic is selected or if the duration of prophylaxis is extended.

The use of antibiotic-impregnated bone cement for prophylaxis in primary total joint arthroplasty has been shown to be effective in experimental models⁹³, and it has been used extensively for antibiotic prophylaxis outside of the United States. However, its use for primary total joint arthroplasty in North America remains controversial^{14,57,65,66,123}. Potential disadvantages of the routine use of antibiotics in bone cement include a possible allergic reaction that may lead to a second operation to remove the implant and all bone cement, emergence of resistant organisms, and weakening of the bone cement. Although it seems reasonable to add antibiotics to cement for high-risk patients, such as those who have a history of infection at the operative site, the proper role of antibiotic-impregnated cement for use as prophylaxis during primary total joint arthroplasty has not been clearly defined and requires additional study.

Operating-Room Environment

Clean-Air Technology

The use of ultraviolet light to sterilize air particles carrying bacteria was initiated in 1936, but the absolute effectiveness of this technology in the clinical setting has not been definitively determined, as studies to date have been retrospective, with comparison of clinical experiences and historical controls^41,50,64. The lack of conclusive clinical studies combined with concern regarding exposure of operating-room personnel to ultraviolet light has led to only tentative acceptance of this methodology. However, recent cost-effectiveness comparisons have created a resurgent interest in ultraviolet-light technology since it is considerably less expensive than laminar airflow systems^8,64.

In 1969, Charnley and Eftekhar reported a dramatic reduction in the prevalence of postoperative infection after total hip arthroplasty, from 9 per cent (seventeen of 190) to 1 per cent (nine of 708), with the implementation of a clean-air operating theater¹⁶. Careful analysis of their data suggested that multiple factors over the course of the study, such as the method of subcutaneous wound closure and the use of antibiotics, may also have contributed to the reduced rate of infection. In a subsequent report that attempted to clarify these other variables, Charnley concluded that clean air was the most important factor but was not the sole reason for this reduction in the prevalence of infection¹⁵. It should be noted that he suggested that clean air is optimally provided by a combination of laminar airflow, with a room-air-exchange turnover rate of more than 300 times an hour; the use of a vertical airflow system; and the use of personnel isolator suits. He also stressed that horizontal laminar airflow systems should be used with body-exhaust systems and impermeable gowns¹⁵. Finally, he stated: "I most certainly do not wish to be reported as advocating clean air as a panacea for all surgeon's problems of sepsis in total hip replacement."¹⁵

Subsequently, substantial interest developed in the use of clean-air technology as a method of preventing infection in association with total joint arthroplasty. Many initial studies retrospectively evaluated the efficacy of laminar airflow systems by comparing historical rates of infection, and a thorough review by Nelson et al. detailed many of these studies⁸⁵. A large multicenter prospective randomized clinical trial⁶² evaluating the effect of laminar airflow during 6781 hip arthroplasties and 1274 knee arthroplasties performed between 1974 and 1979 was published in 1982. Infection occurred in sixty-three (1.5 per cent) of 4129 patients in the control group and in only twenty-three (0.6 per cent) of 3923 patients in the ultraclean-air group (p < 0.001)⁶². Although these results seemed to provide irrefutable evidence as to the efficacy of laminar airflow systems, the study design had flaws that included randomization irregularities and lack of patient stratification, and, furthermore, the use of prophylactic antibiotics was not controlled⁵⁹. This study did demonstrate clearly that body-exhaust suits reduced the bacterial counts in the room air and, in general, that vertical airflow systems performed better than horizontal airflow systems. The inconsistency in the use of prophylactic antibiotics in this study⁶² was a major problem because, in the presence of prophylactic antibiotics, the independent effect of laminar airflow was reduction of the prevalence of infection further from twenty-four (0.8 per cent) of 2968 in the control group to ten (0.3 per cent) of 2863 in the ultraclean-air group, which was not significant (p < 0.1) (Table II). However, in the absence of prophylactic antibiotics, the rate of infection was reduced from thirty-nine (3.4 per cent) of 1161 to thirteen (1.2 per cent) of 1060, which was significant (p < 0.01) (Table II). These data suggest that both factors have an independent effect on the reduction of infection but leave open the question of whether laminar airflow is necessary when prophylactic antibiotics are used.

A large retrospective study of 2384 total hip arthroplasties resulted in additional doubt about the absolute efficacy of laminar airflow technology when prophylactic antibiotics are used⁶⁹. Between 1975 and 1978, when none of the patients received prophylactic antibiotics, infection developed after nine (3.1 per cent) of 289 arthroplasties performed in a conventional operating room, compared with nine (2.5 per cent) of 363 arthroplasties performed in a laminar airflow room (p = 0.5). After the use of prophylactic antibiotics was initiated in 1979, infection developed following six (0.9 per cent) of 669 arthroplasties performed in the conventional operating room, compared with three (0.3 per cent) of 1063 arthroplasties performed in a laminar airflow room. Again, these differences were not significant (p = 0.1). The difference in the rates of infection between the two study periods (2.8 per cent without antibiotic prophylaxis, compared with 0.5 per cent with antibiotic prophylaxis) was highly significant (p < 0.00001)⁶⁹. Although retrospective, the study was limited to patients who had had the arthroplasty performed by the same surgeons in one hospital and who had received the same prosthesis, and it was based on excellent documentation of the use of prophylactic antibiotics and consistent use of vertical laminar airflow and body-exhaust suits⁶⁹.

A large retrospective study by Salvati et al. of 3175 total hip and knee replacements, performed with or without a horizontal unidirectional filtered airflow system, demonstrated a detrimental effect of laminar airflow¹⁰⁴. It is extremely important to note that personnel isolator suits were not used in this study. The paradoxical increase in the rate of infection after total knee arthroplasty performed in the laminar airflow rooms was attributed to positioning of the operating team between the patient and the airflow unit, with subsequent entrainment of air containing particulate matter and bacteria from the operating-room personnel into the operative wound¹⁰⁴.

The preliminary results were recently reported for a randomized blinded prospective study of 7305 patients who had a total hip or knee arthroplasty with use of horizontal unidirectional airflow and no personnel isolator suits³³. All of the patients received antibiotic prophylaxis. Although there was no significant difference in the rate of deep periprosthetic infection between the patients who had the procedure in a room with activated laminar airflow and those who had it in the presence of conventional airflow, it should be noted that these preliminary results essentially parallel the results of Salvati et al.¹⁰⁴, in that there was a trend toward a higher rate of infection in some groups with laminar airflow but not in others.

These recent studies emphasize the need for appropriate application of clean-air technology and the paradoxical effects that can occur with the misunderstanding of clean-air concepts. Although there is still considerable controversy regarding the necessity of laminar airflow for the performance of total joint arthroplasty if prophylactic antibiotics are used, the following points can be reasonably drawn from the available literature.

1. Vertical laminar airflow units generally reduce airborne contamination better than horizontal airflow units. This is especially true when personnel isolator suits are not used.

2. Strict attention to laminar airflow protocol is essential, and there can be paradoxical increases in the rates of infection if these concepts are disregarded.

3. During the past few decades, the appropriate use of clean-air technology to reduce airborne contamination has reduced the prevalence of infection after total hip and knee arthroplasty.

4. The current literature has not established that clean-air technology can greatly reduce the prevalence of infection when prophylactic antibiotics are also used. However, if the rate of early postoperative infection following the procedures performed by an individual surgeon or at a specific institution exceeds four or five per 1000 total hip arthroplasties and six, seven, or eight per 1000 total knee arthroplasties, the use of some method of clean-air technology should be considered to reduce further the prevalence of infection^{15,16,33,49,61,62,108}. It is important to remember that, with this low prevalence of infection of less than 1 per cent, analysis of more than 6000 patients is required to achieve the statistical power necessary to determine the effect of any one independent variable, such as airflow, on the rate of infection after total joint replacements.

Other Methods of Reducing Bacterial Contamination

Reduction of bacterial contamination should be a primary focus of the entire operating-room team. Proper sterilization of instruments, careful preparation of the operative site, avoidance of contact with objects outside the sterile field, and maintenance of fundamental aseptic protocols are all essential. When the patient is transported into the operating room, ward bedding should be excluded. Traffic in and out of the operating room should be restricted, and the number of personnel in the operating room should be minimized⁸². In one study, microbiological counts in an unoccupied operating room increased significantly (p < 0.05) when the door was left open to the hallway, and the addition of five operating-room personnel further increased the microbiological counts by more than sixfold¹⁰¹. Although many bacteria are normally shed every minute by all individuals, some individuals, known as dispersers, shed substantially more bacteria, and their presence in the operating room has been associated with an increased prevalence of wound infection^22,126.

There is conflicting evidence regarding the efficacy of face masks since some studies have demonstrated that their use does not make any difference in the number of colony-forming units deposited on culture plates in an operating room or in the prevalence of postoperative wound infection^76,101,124. Conversely, one study demonstrated that the method with which a mask was used when combined with a surgical hood was an important factor in the reduction of airborne contamination⁶⁰. In this study, airborne contamination was most effectively reduced when the surgical mask was donned beneath an overlapping hood rather than over the hood, which allows dispersal of bacteria along the sides of the mask. Minimizing conversation also decreased airborne contamination⁶⁰.

The operative site should be prepared with an antiseptic agent or isopropyl alcohol; however, superiority of an actual agent or the optimum duration of the operative preparation has not been established^39,102. A one-step water-insoluble iodophor-in-alcohol solution effectively reduces bacterial counts on the skin as does the traditional two-step scrub-and-paint skin preparation³⁹. Iodophor sprays have also demonstrated excellent bacteriocidal action and are less time-consuming than the traditional scrub¹⁰². Although antiseptic agents effectively eliminate the immediate bacterial count at the operative site, hair follicles prevent complete sterilization of the skin and, within thirty minutes, the bacteria on the skin begin to recolonize⁵⁶.

Compared with a cloth drape, a plastic surgical adhesive drape reduces wound contamination (as measured on culture of deep wound specimens taken just before closure), probably by preventing lateral migration of the skin bacteria³⁶. However, a simple plastic skin drape allows normal recolonization of the skin beneath it within thirty minutes, and microbial counts reach normal levels within three hours⁵⁶. In contrast, a plastic drape impregnated with slow-release iodophor effectively eliminates any skin colonization for as long as three hours; therefore, this drape seems preferable⁵⁶. At the end of long operative procedures, when the edges of the plastic drape are peeled away from the incision, it seems reasonable to swab the exposed skin with a povidone-iodine solution to reduce the bacterial colony count again before wound closure. Finally, plastic adhesive drapes can avulse or harm thin, friable skin, and the use of a one-step water-insoluble iodophor-in-alcohol solution without the use of a drape offers a satisfactory alternative for sterilization of the skin³⁹.

The optimum antiseptic agent and proper duration for the surgical hand scrub has not been established; however, application of a hexachlorophene foam compound provides excellent bacteriocidal action and is also less time-consuming than traditional scrubbing methods²⁸.

The use of double gloves is advisable because of the large number of perforations that routinely occur during an orthopaedic procedure. In one study, use of double latex gloves resulted in a significantly higher rate (p < 0.0001) of puncture of the inner glove during orthopaedic procedures, compared with that incurred when a cloth outer glove was used over an inner latex glove¹⁰⁵. With the use of double latex gloves, the number of punctures correlated directly with the duration of the operation, and all gloves had punctures after procedures that lasted more than 180 minutes¹⁰⁵. It has been reported that the rates of wound contamination are similar with single or double-gloving routines and that contamination is due to sources other than puncture of the glove⁹⁹. Despite this observation, routine changing of the outer gloves during procedures that last more than several hours is probably still advisable to protect both the surgeon and the patient.

Surgical gowns and drapes should prevent the spread of bacteria by airborne dispersion or direct contamination through the gown by capillary action^16,79,128. Some materials are more effective than others; for example, Gore-Tex (W.L. Gore and Associates, Flagstaff, Arizona) prevents the dispersion of bacteria 1000 times more effectively than ordinary cotton¹²⁸. Because bacteria invariably do progress to the surface of the gown, the members of the operating team should avoid repetitive touching of the surgical gown with their gloves.

The suction tip is a recognized source of operative contamination since large volumes of air pass through it, and the airborne bacteria that collect on the suction tip can be transferred to the wound^44,71,118. In one study, after an average of 100 minutes of operative time, twelve (55 per cent) of twenty-two suction tips were contaminated¹¹⁸. In another study, eleven (37 per cent) of thirty were contaminated at the end of a hip arthroplasty, compared with only one (3 per cent) of thirty-one when the tip had been exchanged before preparation of the femoral canal⁴⁴. Placement of the suction tip into the medullary canal for prolonged periods of time effectively draws airborne contaminants into the operative wound, and this common practice should be avoided. Changing the suction tip at thirty-minute intervals, using a clean femoral tip, and turning the suction system on only before its actual use help to minimize this source of bacterial contamination.

Another demonstrated source of bacterial contamination is the splash basin. In one study, fifty-eight (74 per cent) of seventy-eight splash basins were culture-positive at the end of the orthopaedic procedure³. Thirty-four (59 per cent) of the fifty-eight positive cultures yielded multiple organisms, and the most common organism was coagulase-negative Staphylococcus—the organism most frequently associated with deep periprosthetic infection. Contrary to usual practice, instruments that have been placed into the splash basin should not be returned to the operative wound.

Operative sites are invariably contaminated with bacteria to some degree, despite fastidious attempts to minimize the bacteria during the operative procedure. Copious irrigation with a syringe, pulsatile lavage, application of antiseptic agents, and use of antibiotic irrigating solutions are all reasonable methods of wound decontamination. Pulsatile lavage has the potential to remove as many as 99 per cent of wound contaminants, but high-pressure lavage may damage tissue⁴⁸. When applied to the wound, concentrated antiseptic agents may also damage tissue. Furthermore, many of these agents are deactivated by plasma products present in the wound^11,134. Chlorhexidine is not deactivated in the wound, and a 0.05 per cent solution applied with syringe lavage has been shown to remove as many as 99.8 per cent of wound contaminants¹²¹. Antibiotic irrigating solutions have been shown to be effective in the reduction of bacterial contamination of experimental wounds^7,93,103,106. The potential for systemic aminoglycoside toxicity must be remembered, particularly when intraoperative blood transfusion retrieval systems and antibiotic irrigation fluid containing an aminoglycoside are used concomitantly. Repetitive irrigation to prevent tissue desiccation, reduce bacterial colonization, and remove clot or tissue debris should be a part of the overall prevention approach.

Optimization of the Wound Environment

The extensive dissection and long operative time necessary for total joint arthroplasty, combined with the implantation of a large foreign body, create a fertile environment for infection. Quantification of the many variables related to operative technique is difficult and emotionally laden; however, the importance of adept and proficient operative technique cannot be overstated. Prolonged operating time influences the rate of deep periprosthetic infection^35,37. The utilization of existing scars to avoid postoperative skin necrosis is especially essential about the knee joint. If possible, preexisting scars should be excised, unless doing so compromises wound closure. Appropriately placed incisions avoid the need for excessive tissue retraction. Gentle handling of tissue and avoidance of devitalization of tissue are essential. Dissection of subcutaneous tissue from the underlying fascia devitalizes the subcutaneous tissue layer, and awareness of this tissue fragility suggests that retractors should be placed carefully along fascial planes rather than in the subcutaneous tissue plane. Prolonged use of self-retaining retractors may also produce large areas of devitalized tissue.

Inappropriate placement of sutures strangles tissue and facilities infection. Careful suturing of tissue layers to eliminate dead space, attentive hemostasis (while avoiding tissue destruction by excessive diathermy), and the use of surgical drains are generally considered to be effective in minimizing the postoperative wound hematoma. A tense hematoma can compromise the surrounding soft tissues and prevent antibiotic access⁸³. It should be emphasized that, although recent reports have suggested that the routine use of surgical drains is not indicated for total hip and total knee arthroplasty^5,100, the numbers of patients evaluated in these studies were far too small for an assessment of the effect of this practice on the prevalence of infection. Careful epidermal apposition is essential for early wound-sealing, and a hasty wound closure with overlapped skin often leads to prolonged postoperative wound drainage and a potential portal for the retrograde introduction of bacteria into the operative wound.

The increased susceptibility of the wound to infection in the presence of a foreign body is well known²⁹. Initial studies, with the use of silk suture as the foreign body, revealed that 2 x 10² staphylococci were required to create an abscess in the presence of a silk suture; however, 2 to 8 x 10⁶ staphylococci were required to create a subcutaneous abscess in its absence²⁹. Subsequently, it was demonstrated that the chemical composition of the suture is an important determinant of infection in the contaminated wound²⁷. Monofilament absorbable synthetic suture is associated with a lower rate of infection than braided absorbable synthetic suture, which is, in turn, better than non-absorbable braided suture or non-synthetic natural suture, such as catgut or silk^17,58,110. Therefore, careful choice of suture, particularly for a high-risk wound, seems advisable.

As the surgeon selects from a large array of implant alternatives for total joint arthroplasty, the effect of the specific physical and chemical properties of many of these foreign materials on the development of infection has been investigated extensively^{19,45,46,58,81,87,88,92,94}. Although the exact role of most of these variables in the genesis of deep periprosthetic infection in the clinical setting is unknown, it is helpful to review some of these investigative efforts. For example, the physical and chemical characteristics of a specific biomaterial affect the efficiency of bacterial adhesion to the surface, so the coagulase-negative staphylococci exhibit preferential adhesion to polymers whereas coagulase-positive staphylococci adhere more readily to metals⁴⁵. The metabolic characteristics of bacteria can also be altered when they adhere to a biomaterial, changing the susceptibility of the bacteria to antibiotics⁸¹. This metabolic effect appears to be independent of the presence of a glycocalyx, or slime covering; instead, it is dependent on the properties of the biomaterial, as bacteria that are adherent to methylmethacrylate demonstrate a remarkably higher resistance to antibiotics than do bacteria that are adherent to metals⁸¹.

In experimental models, it has been demonstrated that the prevalence of infection is increased in the presence of various foreign implants commonly used in total joint arthroplasty^89,94. Polymethylmethacrylate promoted infection with coagulase-negative Staphylococcus at a rate that was four times higher than the rate associated with high-density polyethylene and fifteen times higher than that associated with stainless steel or aluminum⁸⁹. Furthermore, the rate of infection associated with polymethylmethacrylate cured in vivo was higher than that associated with polymethylmethacrylate that had been first cured and then placed into the experimental model⁹⁴. Polymethylmethacrylate has been shown to impair the chemotactic and phagocytic functions of human leukocytes⁹².

On the basis of these observations, it has been postulated that infection might occur less often with implants that rely on tissue integration for fixation than with those that are fixed with bone cement. A large clinical series revealed a significant difference (p < 0.01) between the rates of infection associated with total hip and knee arthroplasties, with deep periprosthetic infection developing after twenty-one of 2575 knee arthroplasties and after only six of 2392 hip arthroplasties⁴⁹. However, comparison of the rate for implants inserted with cement with that for porous-coated implants revealed no significant differences in either the hip or knee groups: deep infection developed after two of 958 hip arthroplasties with a porous implant and after four of 1434 hip arthroplasties with cement (p = 0.19), while deep infection developed after three of 201 knee arthroplasties with a porous implant and after eighteen of 2374 knee arthroplasties with cement (p = 0.71)⁴⁹. One possible explanation for this finding was provided by a recent experimental rabbit model¹⁹. The bacterial concentrations of Staphylococcus aureus required to cause infection were similar for hips with a polished titanium implant and those with a cobalt-chromium implant, but the concentration was reduced by a factor of 2.5 for hips with a porous-coated Titanium and by a factor of forty for those with a porous-coated cobalt-chromium implant¹⁹. The increased susceptibility to infection is probably due to the marked increase in the surface area of porous-coated implants, as described by Gristina⁴⁵.

In another in vitro study, adherence of coagulase-negative staphylococci to stainless-steel, titanium alloy, hydroxyapatite-coated titanium, and sintered hydroxy-apatite implants was evaluated⁸⁸. Assays revealed that the sintered hydroxyapatite had a higher level of bacterial adherence than the other three materials. This increased adherence may reduce the susceptibility of bacteria to antibiotics or to the host's bacterial clearance mechanisms. Another study revealed that the ability of bacteria to adhere to polymethylmethacrylate is inhibited by the presence of antibiotics within the bone cement⁸⁷. As previously mentioned, the clinical importance of these experimental findings is not yet known; however, discoveries like these may be used to support the use of certain methods under the surgeon's control or they may affect the decision about the type of implants used in high-risk individuals.

Postoperative Period

In the postoperative period, one must be vigilant for the development of infection and address the many factors that may contribute to it. Careful positioning of the patient any padding of osseous prominences should be undertaken to prevent the development of skin ulcerations. Hematomas are commonly identified as important factors in the development of postoperative infection^35,40,82. A rapidly expanding hematoma necessitates formal evacuation and débridement in the operating room since the pressure from it can devitalize adjacent tissues and prevent the influx of antibiotic into the operative site⁸³. Benign neglect of superficial skin necrosis all too commonly allows it to progress to a deep periprosthetic wound infection. Therefore, superficial skin necrosis should also be treated intensively with formal excision and débridement in the operating room. Serous wound drainage may be treated initially with compressive dressings and antimicrobial coverage to prevent retrograde introduction of bacteria into the wound; however, continued drainage mandates a return of the patient to the operating room for formal débridement^35,127. Persistent wound drainage portends a 3.2 times higher risk of eventual deep infection¹²¹. Operative intervention itself for a complication in the immediate postoperative period, such as evacuation of a hematoma or open reduction of a dislocated hip, increases the risk of infection by a factor of more than four¹²¹.

Hematogenous Infection

Although the true prevalence of early or late hematogenous seeding of the sites of total joint prostheses is unknown, there is no question that this phenomenon occurs^{1,2,6,63,67,68,96,107,117,119,120}. In the early postoperative period, the operative hematoma at the site of a total joint arthroplasty is susceptible to hematogenous seeding; therefore, when possible, conditions that may create an episode of bacteremia should be avoided during this period¹⁰. For instance, as it has been suggested that peripheral intravenous catheters made of Teflon (polytetrafluoroethylene) may be a distant source of bacterial contamination of the operative site, these catheters should be removed as soon as feasible¹²⁹.

Urinary tract management is a frequent problem in the postoperative period, and there is no universal agreement on the proper postoperative protocol. If possible, patients who have difficulties related to the urinary tract should be identified and managed before the total joint arthroplasty¹³². The short-term use of an indwelling urinary catheter, placed while the patient is in the operating room, reduces the prevalence of urinary retention and prevents overdistention of the bladder⁷⁴. There does not appear to be an increased risk of urinary tract infection if the indwelling catheter is used for only a short time in the immediate postoperative period^74,98. Although no data are available, it seems reasonable to maintain antimicrobial coverage for manipulation of the genito-urinary tract in the early postoperative period.

In most of the reported cases of periprosthetic joint infection attributed to hematogenous seeding, it has been difficult to document the bacteremia preceding the infection^{1,2,6,63,67,68,96,107,117,119,120}. It seems prudent to diagnose and to treat intensively remote infections of the urinary tract, respiratory tract, and skin as well as overt dental infection in order to prevent hematogenous seeding. Effective selection of the antimicrobial agent in these situations depends on the site of infection, the in vitro susceptibility of the microorganism causing the infection, and the patient's history of intolerance to antibiotics.

Many reports of hematogenous infection have detailed the importance of the host's ability to resist infection. Patients who have rheumatoid arthritis are frequently cited as being susceptible to hematogenous infections^{1,2,6,15,40,67,117}. There are many other predisposing factors as well. The presence of structural bone graft, the use of metal-metal prostheses, and the use of constrained prostheses have all been cited as additional risk factors^6,96,108,130. These additional risk factors are actually variables related to the wound environment that impair the host's ability to clear bacteria seeded in the wound. It has been demonstrated that total joint implants are surrounded by an immunoincompetent, fibroinflammatory zone⁴⁶. Within this zone, there is an increased susceptibility to infection because of repeated macrophage stimulation by particulate debris, which leads to the formation of superoxide radicals and cytokine-mediated tissue damage. A self-perpetuating cytokine cascade is initiated, leading to progressive enlargement of the immunoincompetent fibroinflammatory zone surrounding the implant. In advanced stages, this zone is recognized on radiographs as osteolysis. The production of reactive oxygen intermediates, macrophage exhaustion, and continual tissue damage around these implants may result in aseptic loosening, but hematogenous seeding of the immunoincompetent zone may lead to periprosthetic infection. Progressive osteolysis caused by polyethylene, polymethylmethacrylate, or metallic particulate debris, or a combination of these, is therefore an additional factor that may predispose the patient to hematogenous infection. We have observed this phenomenon in patients with asymptomatic loosening of a prosthesis whom we were following closely to monitor the progress of periprosthetic osteolysis. There is an acute onset of pain and the patients are diagnosed with a deep periprosthetic infection, presumably from a hematogenous source. To our knowledge, there are currently no data available to quantify the risk for these patients, and substantial investigative efforts are necessary to identify the various risk factors associated with the host and wound environment for late hematogenous infection as well as the appropriate antibiotic prophylaxis.

Antimicrobial prophylaxis for patients with a prosthetic joint who have a dental procedure or an invasive procedure, such as endoscopy of the gastrointestinal tract or cystoscopy of the genito-urinary tract, is extremely controversial^{2,38,63,67,68,84,86,115,125}. The rate of bacteremia after dental and certain diagnostic or therapeutic procedures has been well documented²⁶, and the frequency and intensity of bacteremia is generally high in association with oral procedures, lower in association with genito-urinary manipulation, and lowest in association with diagnostic procedures of the gastrointestinal tract²⁶. Since it is possible that bacteremia can lead to hematogenous deposition of bacteria around the total joint prosthesis, the questions that remain unanswered are (1) what types of procedures or conditions result in bacteremia that can lead to hematogenous infection around a prosthetic joint, (2) which prostheses put the hip at risk for infection when there is bacteremia, and (3) what type of interventions can prevent infection?

Reports of periprosthetic infection caused by flora indigenous to the body and temporally related to these invasive procedures have documented that late hematogenous infection can occur^63,119,120. The difficult issue is whether the prevalence of hematogenous infection caused by these procedures is sufficiently high to outweigh the risks and cost of antimicrobial prophylaxis. Currently, the answer to this question is unknown^38,86. Furthermore, the efficacy of antibiotic prophylaxis for these procedures in patients with a prosthetic joint has not been studied.

The controversial issues of antibiotic prophylaxis for patients who have a prosthetic joint parallel the controversy surrounding the use of antibiotic prophylaxis to prevent infective endocarditis^21,26,114. The compliance with recommended guidelines for the prevention of infective endocarditis has continued to improve with time, primarily because of the continued education of healthcare providers and ongoing investigations of this disease²⁶. It must be noted that the information obtained from investigations into the prevention of infective endocarditis has been much more extensive than that for patients who have a prosthetic joint^21,26,114. Although it is helpful to review the current treatment guidelines for antibiotic prophylaxis to prevent infective endocarditis, direct extrapolation of study results and recommendations to a patient who has a prosthetic joint is probably not appropriate. Despite the large amount of knowledge that has been assimilated regarding infective endocarditis, the following issues have not been resolved. No prospective studies have definitively proved the efficacy of antibiotic prophylaxis for the prevention of infective endocarditis; many cases of apparent failure of antibiotic prophylaxis have been reported; and routine antibiotic prophylaxis cannot be justified on the basis of cost-effectiveness studies, and prophylaxis should be reserved only for patients who have a high-risk cardiac disorder²⁶.

With these considerations in mind, Osmon et al.^90,91 as well as Steckelberg and Osmon¹¹³ identified the rates of periprosthetic infection of the hip and knee that could be epidemiologically linked to an oral source. They demonstrated that the presence of teeth was a risk factor for infections caused by Streptococcus viridans after total hip and knee arthroplasty (odds ratio = 6.4; 95 per cent confidence interval, 2.2 to 18.0; p = 0.001) but not for infection due to Staphylococcus aureus or peptostreptococci⁹⁰. It must be emphasized that the infections with Streptococcus viridans were due to all oral sources and not just clean dental procedures. The rate of deep periprosthetic infection was highest in the first two years after an arthroplasty, occurring at a frequency of 0.14 cases per 1000 joint-years (confidence interval; 0.07 to 0.25), whereas the annual rate after the first two years was only 0.03 cases per 1000 joint-years (confidence interval, 0.01 to 0.07)⁹¹. The rate after the first two years is similar to that for infective endocarditis due to Streptococcus viridans among patients in the general population who do not have a heart murmur or endocarditis, patient groups for which the American Heart Association currently recommends no antimicrobial prophylaxis because the toxicity outweighs the potential benefit.^21,114.

On the basis of these data, a blanket recommendation for antimicrobial prophylaxis for routine, clean dental procedures in all patients who have had an arthroplasty of a large joint does not appear warranted for the rest of the patient's life. These preliminary data suggest that in the first postoperative year, during which soft-tissue healing occurs and inflammation subsides, prophylactic antibiotics may be appropriate in an effort to prevent deep periprosthetic infection with Streptococcus viridans. It is important to note, however, that Streptococcus viridans causes only a small proportion of deep periprosthetic infections. Furthermore, data are currently inadequate to formulate recommendations regarding prophylaxis for genito-urinary or gastrointestinal procedures in the absence of infection.

Medicolegal considerations cloud this issue further. The decision to provide antibiotic prophylaxis for invasive procedures in patients who have a prosthetic joint is more complex than that associated with infective endocarditis because of the paucity of information available for patients who have a prosthetic joint compared with for those who have infective endocarditis. Since the patients who are at risk for a deep periprosthetic infection after an invasive procedure have not yet been clearly identified, it is difficult to make any definitive recommendations. The following statement, as applied to infective endocarditis, is worthy of review. "A reasonable standard of care requires that a physician or dentist know the connection between procedure-induced bacteremia and endocarditis; ask whether the patient has a predisposing heart disorder; inform patients of the small risk; and decide whether to advise prophylaxis according to the perceived risks and benefits. If these steps are taken and documented, claims based on the later development of endocarditis should not succeed."²⁶

As is the current practice with regard to infective endocarditis, rational recommendations regarding antimicrobial prophylaxis for clean dental procedures, genito-urinary procedures, or gastrointestinal procedures in patients who have a large orthopaedic implant depend on the identification of groups of patients who are at substantially increased risk for infection after these procedures. If a physician elects to recommend antimicrobial prophylaxis for the prevention of hematogenous infection, the antibiotic should be chosen on the basis of the flora expected at the site of the procedure, and potentially rare but life-threatening adverse reactions as well as the more common drug toxicities should be considered by both physician and patient.

Overview

In conclusion, few areas in orthopaedic surgery are the subject of as much controversy, myth, and dismay as deep periprosthetic infection. Prevention of such an infection is complex, with many unresolved issues that require considerable investigation. The attentive application of reasonable principles of infection control with the goals of optimization of the wound environment, augmentation of the host response, and minimization of bacterial contamination in the preoperative, operative, and postoperative time-periods is essential to the over-all reduction of the prevalence of infection.

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Venn diagram demonstrating the dependent nature of bacteria, host factors, and wound environment on the development of infection.

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TABLE I VARIABLES INFLUENCING DEEP PERIPROSTHETIC INFECTION

	Preoperative Period	Operative Period	Postoperative Period
Bacteria	Urinary tract infection, skin ulcers, other remote infections, poor dental hygiene, shaving of operative site, prolonged hospitalization, prophylactic antibiotics	Instrument sterilization; operating-room traffic; personnel; dispersers; face masks or hoods; body-exhaust suits; ultraviolet light; laminar airflow; skin preparation; surgical scrub, gloves, drapes, or gowns; plastic surgical drape; wound irrigation; suction tips; splash basins	Urinary tract management, remote sites of infection, intravenous catheters, invasive procedures, possibly prophylactic antibiotics

Host	Altered immune system, immunosuppressive medications, diabetes mellitus, rheumatoid arthritis, advanced age, malnutrition, anesthetic risk		Rheumatoid arthritis, altered immune system

Wound environment	Extensive scarring, previous operation, previous infection, obesity, vascular disease, anatomical site, local skin conditions, thin atrophic skin	Duration of procedure, operative technique, suture selection, implant selection, antibiotic bone cement, structural bone graft, hemostasis, surgical drains, wound closure	Wound hematoma, wound drainage, skin necrosis, reoperation, loose prostheses, particulate debris

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TABLE I VARIABLES INFLUENCING DEEP PERIPROSTHETIC INFECTION

	Preoperative Period	Operative Period	Postoperative Period
Bacteria	Urinary tract infection, skin ulcers, other remote infections, poor dental hygiene, shaving of operative site, prolonged hospitalization, prophylactic antibiotics	Instrument sterilization; operating-room traffic; personnel; dispersers; face masks or hoods; body-exhaust suits; ultraviolet light; laminar airflow; skin preparation; surgical scrub, gloves, drapes, or gowns; plastic surgical drape; wound irrigation; suction tips; splash basins	Urinary tract management, remote sites of infection, intravenous catheters, invasive procedures, possibly prophylactic antibiotics

Host	Altered immune system, immunosuppressive medications, diabetes mellitus, rheumatoid arthritis, advanced age, malnutrition, anesthetic risk		Rheumatoid arthritis, altered immune system

Wound environment	Extensive scarring, previous operation, previous infection, obesity, vascular disease, anatomical site, local skin conditions, thin atrophic skin	Duration of procedure, operative technique, suture selection, implant selection, antibiotic bone cement, structural bone graft, hemostasis, surgical drains, wound closure	Wound hematoma, wound drainage, skin necrosis, reoperation, loose prostheses, particulate debris

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TABLE II EFFECTS OF CLEAN AIR AND USE OF PROPHYLACTIC ANTIBIOTICS ON THE RATE OF INFECTION AFTER TOTAL HIP AND TOTAL KNEE ARTHROPLASTY*

Prophylactic Antibiotics	Laminar Airflow
	No	Yes
No	39 of 1161	13 of 1060	(p < 0.01)
	(3.4%)	(91.2%)
Yes	24 of 2968	10 of 2863	(p < 0.1)
	(0.8%)	(0.3%)
	(p < 0.001)	(p < 0.01)

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TABLE II EFFECTS OF CLEAN AIR AND USE OF PROPHYLACTIC ANTIBIOTICS ON THE RATE OF INFECTION AFTER TOTAL HIP AND TOTAL KNEE ARTHROPLASTY*

Prophylactic Antibiotics	Laminar Airflow
	No	Yes
No	39 of 1161	13 of 1060	(p < 0.01)
	(3.4%)	(91.2%)
Yes	24 of 2968	10 of 2863	(p < 0.1)
	(0.8%)	(0.3%)
	(p < 0.001)	(p < 0.01)