Prevention of Surgical Site Infections in Joint Replacement Surgery

Abstract

Prosthetic joint infections (PJI), although rare, represent a serious complication of total joint arthroplasty as they pose not only a direct financial burden to the patient but also an indirect burden related to psychosocial impact that PJI incur on the patient. Treatment of PJI is complex and requires a combined surgical and medical approach. Patients are often subjected to multiple surgical procedures and prolonged courses of antimicrobial therapy. Therefore, all efforts should be directed toward maximizing the prophylactic measures in the peri-operative and post-operative phases in order to prevent the occurrence of surgical site infections. This article explores primarily the prophylactic measures that target the host and the operative theater environment. Implementation of such preventive measures requires a multi-disciplinary approach and is crucial for a successful outcome of the total joint arthroplasty.

Periprosthetic joint infection (PJI) is a devastating and challenging complication of total joint arthroplasty (TJA). Although PJI rarely occurs following joint replacement, it can pose a substantial burden in terms of cost and the healthcare resource utilization [1].

The relative incidence of PJI ranges between 1% and 2.4% of total hip arthroplasties (HPRO) and total knee arthroplasties (KPRO). The annual cost of infected revisions to US hospitals increased from $320 million to $566 million between 2001–2009 and is projected to exceed $1.62 billion by 2020 [1,2]. At the Mayo Clinic, Rochester, Minnesota, 1.8% of patients developed a PJI over a course of 22 y, with the majority of cases occurring after 2 y following the index arthroplasty [3]. It is estimated that by 2030 the number of patients receiving a total joint arthroplasty will be around four million [2,4]. In addition to the direct financial burden of PJI, there is an indirect burden related to psychosocial impact that PJI incur on the patient and the treating team. Patients with PJI are often subjected to multiple surgical procedures and prolonged courses of antimicrobial therapy [5].

PJI often occurs as a result of contamination of the prosthesis and or surgical incision at the time or immediately following arthroplasty surgery. Periprosthetic joint infection will occur as a result of an imbalance between the burden of contaminating organisms and the surgical incision's and host ability to eradicate or control this contamination. Rarely, post-operative hematogenous seeding of the arthroplasty from a remote source may also occur.

For the purpose of this review, the words organ space surgical site infection (SSI) and PJI will be used interchangeably. Prevention strategies targeting factors related to the host, operating room environment, and surgical parameters will be discussed in this review. Factors related to the prevention of hematogenous seeding of the joints will be briefly discussed in this review [6,7]. These preventive measures implemented by multi-specialty teams pre-operatively at the time of operative procedure and post-operatively may require a change in systems, processes, and behavioral modifications by the patients and the treating team.

The Host

A thorough evaluation of the patient's medical history and laboratory evaluation should be conducted prior to TJR. Special emphasis is placed on comorbidities, social history, nutritional status, dental health and medications.

Nutritional status

Nutritional status is assessed by pre-operative measurement of the serum albumin, prealbumin, transferrin, and absolute lymphocyte concentrations. Suboptimal pre-operative nutrition is associated with an increased risk of SSI following TJR. Conversely, obesity has been linked to an increased risk for SSI mostly because of mechanical issues associated with increased body mass as well as suboptimal pharmacokinetics of prophylactic antimicrobial agents. A recent meta-analysis done by Kerkhoffs et al. found that deep infections following total knee arthroplasty occurred more often in obese patients, with an odds ratio of 2.38 (95% confidence interval [CI], 1.28–4.55) [8]. Paradoxically, obesity can be associated with malnourishment, so called paradoxical malnutrition [9,10]. Optimization of nutritional factors prior to TJR may reduce the risk of SSI following TJR.

Hyperglycemia

Peri-operative hyperglycemia has been linked to an increased risk of SSI following TJR. In a recent study by Mraovic et al., post-operative morning hyperglycemia (BG >200 mg/dL) increased the risk of SSI by more than two-fold. In this study, infected patients had substantially greater perioperative blood glucose (BG) values: Pre-operative BG (112 ± 36 versus 105 ± 31 mg/dL, p = .043) and post-operative day one BG (154 ± 37 versus 138 ± 31 mg/dL, p < .001) [11]. Current recommendations suggest a goal serum glucose less than 180 mg/dL [12]. Elevated glucose concentrations may reveal uncontrolled diabetes mellitus, and these patients should not be operated on at all [5].

Smoking

Smoking increases the risk of SSI two-fold. This is likely related to the negative effects on surgical incision healing related to vasoconstriction. Smoking cessation efforts should target patients prior to TJR. Patients are advised to quit smoking at least 4 wks prior to TJR [12,13]. A systematic review found that smoking is associated with substantially greater risk of post-operative complication and death following total knee arthroplasty or total hip arthroplasty [14]. In this study, current smokers were substantially more likely to have any post-operative complication (risk ratio 1.24, 95% CI 1.01–1.54) and death (risk ratio 1.63, 95% CI 1.06–2.51) compared with non-smokers. Former smokers were substantially more likely to have any post-operative complication (risk ratio 1.32, 95% CI 1.05–1.66) and death (risk ratio 1.69, 95% CI) compared with non-smokers [14]. Current smokers undergoing THR/TKR were substantially more likely than never smokers to have surgical site infections (odds ratio 1.41, 95% CI 1.16–1.72) [15].

Further laboratory investigation

Additional blood tests to consider prior to TJR should be done to evaluate for the the presence of anemia, or disorders of coagulation. In a recent study by Greenky et al. on 15,222 patients undergoing TJR, 19.6% had pre-operative anemia. PJI occurred in 4.3% of anemic patients compared with 2% in non-anemic patients [16].

A high international normalized ratio (INR) concentration may lead to a greater risk of intra-operative bleeding and peri-operative hematoma formation. A mean INR of greater than 1.5 was found to be more prevalent in patients who developed post-operative surgical incision complications and subsequent periprosthetic infection. The authors concluded that cautious anticoagulation to prevent surgical incision hematoma formation or drainage may reduce the risk of periprosthetic infection [17].

Distant infection

Screening patients for the presence of an active infection elsewhere, such an urinary tract infection, an active skin infection, abscess, or an infected ulceration prior to TJR is advised. Pre-operative dental clearance, and preopertive dental hygiene to detect an active dental infection is advised [5,7].

Staphylococcus aureus nasal screening

Pre-operative screening for Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA) colonization followed by decolonization prior to surgery has been proven to be successful in reducing SSI rates in orthopedic surgery [18]. A study done by Kalmeijer et al. showed that decolonization with mupirocin ointment beginning 5 d before surgery decreased endogenous S. aureus infection five-fold compared with those receiving placebo, although the difference in results did not reach statistical significance [19]. A study done by Perl et al. concluded that prophylactic intra–nasal application of mupirocin did not substantially reduce the rate of S. aureus SSIs overall, but it did substantially decrease the rate of all nosocomial S. aureus infections among the patients who were S. aureus carriers. In this study, among the patients with nasal carriage of S. aureus, 4.0% of those who received mupirocin had nosocomial S. aureus infections, as compared with 7.7% of those who received placebo (odds ratio for infection, 0.49; 95% CI, 0.25–0.92; P = 0.02) [20].

Most recently Bode et al. found that pre-operative screening for S. aureus and then cleansing with CHG and intra-nasal mupirocin were effective in preventing SSI. This study did include patients undergoing orthopedic procedures [21].

Nasal S. aureus colonization has also been associated with colonization at other body sites and thus it is recommended to use pre-operative body chlorhexidine (CHG) bathing [12]. In patients colonized with S. aureus, chlorhexidine baths have been recommended for the last 5 d before the surgery in an attempt to decrease SSIs caused by S. aureus. The emergence of mupirocin resistant S. aureus strains in addition to the potential patient non-compliance with mupirocin because of out-of-pocket expense has led to the introduction of a nasal use of povidone-iodine (PI) antiseptic. Preliminary analysis of a randomized open label, non-inferiority trial revealed that nasal mupirocin vs nasal PI, both coupled with topical CHG, were equivalent in preventing S. aureus SSI following arthroplasty and spine fusion surgery [22].

Disease modifying and biologic therapies

An increasing number of patients with rheumatoid arthritis and other inflammatory or autoimmune diseases are currently undergoing TJR. Patients with rheumatoid arthritis are at a greater risk for developing PJI and surgical incision healing complications following TJR in part related to the use of immunosuppressive or immunomodulating agents [23,24]. There is a continuous debate over whether such therapies should be continued throughout the pre-operative and post-operative period. Studies looking at methotrexate use perioperatively and its risk for post-operative infections have led to conflicting results [23 –25]. Recent multinational recommendations pertaining to the use of methotrexate have been developed. The authors of this study concluded that methotrexate can be safely continued in the post-operative period in rheumatoid arthritis patients undergoing elective orthopedic surgery [26]. The authors believe that until further data is made available that discontinuation of immunosuppressive agent prior to TJR be done on a case by case basis. The potential increased risk of PJI that might be associated with continuation of such therapy should be weighed against the possibly of the exacerbation of the autoimmune and inflammatory process. For instance, in elderly frail patients with comorbidities and a degree of renal impairment, it may be prudent to withhold methotrexate the week prior to surgery [25]. Standard practice at the Mayo Clinic is to stop methotrexate for 1 wk pre-operatively and 2 wks post-operatively in order to enhance surgical incision healing.

Other immunomodulating agents such as sulphasalazine, leflunomide, and hydrochloroquine are routinely prescribed in patients with autoimmune inflammatory arthritis. One study on leflunomide use found that the incidence rate of SSI was 6.1% in 41 study patients who continued leflunomide compared with 6.3% in the 41 study patients who discontinued leflunomide during the perioperative period. The study concluded that there was no increased risk of post-operative infectious complications in patients with rheumatoid arthritis who continued leflunomide in the perioperative period [27]. In contrast, a subsequent study found that in comparison with patients receiving methotrexate, there was an increased risk of post-operative surgical incision-healing complications in patients receiving leflunomide (13.6% vs 40.6%) [28]. No comparison was made between a group continuing leflunomide and a group discontinuing leflunomide in this study. The authors concluded that leflunomide increased the risk of surgical incision healing complications in patients with rheumatoid arthritis undergoing elective orthopedic surgery [28]. The increased risk of serious infections in patients treated with anti-tumor necrosis factor (TNF) agents continues to be a concern. Recent studies by Giles et al. detected an increased risk of SSIs with the use of perioperative anti TNF agents [29]. Another retrospective cohort study done by den Broeder et al. on 1219 patients with RA who underwent elective surgery showed a 50% increase in SSI (odds ratio 1.5) [30]. Considering the morbidity and cost associated with orthopedic SSIs withholding anti-TNF agents for at least 2–8 wks pre-operatively depending on the half-life of the drug appears to be a prudent approach [23,25]. These drugs should not be re-instituted until the surgical incision has healed (usually 2–4 wks post-operatively).

The Operating Room

It is postulated that most SSIs following TJR are acquired in the operating room. Risk mitigation and interventions to reduce SSI in the operating room (OR) may have a favorable impact on SSI reduction. Studies have shown that surgical incision contamination often occurs during surgery, by either contaminated gloves or instruments.

Personnel

Traffic in the OR is associated with an increased bacterial air counts and may lead to increased risk of SSI. In rooms equipped with laminar flow, the opening and closing of the OR doors has been shown to disrupt the airflow in close proximity to the patient. This disruption of the flow might allow the microorganisms to enter the airspace around the surgical site [31]. A recent paper by Panahi et al. concluded that there were 60 door openings in primary total joint arthroplasty cases and 135 in revisions, yielding per minute rates of 0.65 and 0.84, respectively [31]. Efforts aimed at minimizing the number of authorized personnel allowed in the OR are warranted in an effort to decrease the risk for perioperative SSI.

Hand hygiene and gloving

Preventive strategies utilized by the healthcare personnel must begin with proper hand-washing; some authors advocate the use of three sets of gloves, where the outer set is changed following draping [5]. In addition, double gloving should be used during TJA to reduce the perforation of the inner gloves [32]. Another strategy is to change gloves at regular intervals during TJR surgery at crucial points (i.e., after draping, permanent prosthesis handling). This strategy becomes particularly important especially if the surgical time extends beyond 3 h or if an obvious puncture in the gloves is observed [33,34].

Body exhaust suit

The use of body exhaust systems (BES) can minimize the risk of post-operative PJI [35]. By operating in a clean-air enclosure, and by wearing a body-exhaust suit, Charnley was able to reduce the risk of PJI from 10% to less than 0.5% [36]. In a recent randomized study comparing the use of body-exhaust suits vs, Rotecno occlusive clothing concluded that there was equal contamination of the surgical incisions in spite of a greater air contamination with Rotecno. The study was not powered to detect a difference in the rate of SSI. Other studies have suggested that Rotecno is as good as BES, but more comfortable and economic [37].

Operating-room trays

A recent study by Dalstrom et al., looking at the bacterial contamination rate of open sterile surgical trays, found that contamination rates of open trays increased with time from 4% after 30 min to 30% after 4 h. The study concluded that sterile trays should not be opened until they are specifically needed during the procedure [38]. Other potential reported sources of contamination are suction tips and splash basins [32]. Frequent exchange of the suction tip, and use of a clean suction tip at the time of preparation of the femoral canal, is recommended to minimize bacterial contamination [32]. A study done by Davis et al. on 100 elective primary hip and knee arthroplasties showed rates of contamination of 11.4% for the sucker tips, 14.5% for light handles, 9.4% for skin blades, and 3.2% for the inside blades used during surgery [39].

Maintenance of body temperature

Perioperative hypothermia is a frequent occurrence and can lead to several complications, which adversely affect the patient's outcome, including an increased cardiovascular and hemorrhagic risk for total hip replacement patients and an increased risk for SSIs. Hypothermia facilitates SSIs by inducing a peripheral vasoconstriction with a substantial reduction of subcutaneous oxygen tension and directly inhibiting T-cell mediated antibody production and the nonspecific oxidative bacterial killing of neutrophils [40,41]. It has been demonstrated that pre-warming patients with active forced-air warming systems before they arrive in the operating room can prevent or at least minimize re-distributive hypothermia during both general and regional anesthesia. Therefore, physicians should emphasize the maintenance of core temperature and actively prevent or minimize its reduction using a multimodal approach, which can include active pre-warming before surgery, passive insulation, fluid warming, and forced-air skin warming during the surgery [42].

Skin preparation

Skin preparation is an important step in SSI reduction efforts and should begin at the patient's home with the use of pre-operative chlorhexidine showers [5]. In the operating room, the use of an alcohol-based antiseptic combined with either povidone iodine or chlorhexidine is the preferred agents at the authors' institutions [43]. Skin draping is advocated as a measure to minimize the recolonization of peri incisional skin with microorganisms following skin preparation [44,45].

Hair clipping

Clipping hair immediately before an operation is associated with a lower risk of surgical site infections than shaving or clipping the night before an operation [46].

Blood transfusion

Avoidance of allogeneic blood transfusions has been recommended in order to minimize the risk for PJIs. Efforts to minimize the need for allogeneic transfusion focus on three areas: 1) increase the starting hemoglobin, 2) minimize intra-operative blood loss, and 3) lower the hemoglobin concentration (“transfusion trigger”) for which patients would be considered for transfusion. Patients identified as anemic in the pre-operative period may be evaluated and treated in order to increase the starting hemoglobin. Patients with anemia of chronic disease may benefit from preoperative administration of erythropoietin alpha [47,48]. In addition to expedient surgery, other modalities are available to minimize intra-operative blood loss. Anti-fibrinolytic medications, such as tranexamic acid, have been well-studied and proven to be quite effective at reducing both measured blood loss and the need for transfusion [49]. Intra-operative red cell salvage has mixed results and is best used when substantial blood loss is expected (i.e., bilateral procedures, major revisions). Finally, the vast majority of patients with “symptomatic anemia” are in fact simply volume depleted. Patients must always be treated in an individualized manner, but most patients safely tolerate hemoglobin concentrations down to 8 mg/dL without needing transfusion as long as intra-vascular volume status is maintained.

Surgical technique

Meticulous surgical technique is essential in reducing SSI rates following TJR. This begins with appropriate skin preparation and draping. The procedure should be carried out in as expedient a manner as possible while ensuring the long-term success of the reconstruction. The tissues must be handled carefully, and meticulous hemostasis should be ensured prior to surgical incision closure. The use of drains as it relates to SSI is unclear in the literature.

Antimicrobial prophylaxis

One of the most effective agents in the prevention of PJI and SSI is administration of appropriate and timely perioperative antibiotics. Current guidelines for antimicrobial prophylaxis for surgery recommend cefazolin or cefuroxime for patients undergoing total hip arthroplasty [50]. Vancomycin and clindamycin are recommended as alternative agents for patients who have a true type I b-lactam allergy [50] manifested by immediate urticaria, laryngeal edema, or bronchospasm [51]. Addition of vancomycin to the b-lactam regimen has been recommended for methicillin-resistant S. aureus and coagulase-negative staphylococci coverage in procedures associated with a high prevalence of SSI because of these organisms [12]. Despite vancomycin's broader staphylococcal covergage, its inferior antistaphylococcal activity and prolonged infusion time makes it a less attractive prophylactic agent when compared with cephalosporins [52,53]. Routine use of vancomycin for elective orthopedic procedures is generally discouraged and should be reserved to patients with known MRSA colonization or documented Type I allergic reaction to beta-lactams. The U.S. Centers for Disease Control and Prevention (CDC) recommends that prophylactic intravenous antibiotics be administered 1 h prior to the surgical incision, and the dose needs to be repeated if the surgical time extends beyond 2 or 3 h or when substantial blood loss occurs [46,54,55].

Antibiotic-impregnated cement

The use of antibiotic-impregnated cement for primary and revision joint arthroplasty is becoming the standard of practice in Europe and Scandinavia [56]. A recent meta-analysis showed that the use of antibiotic-impregnated cement lowered PJI rate by approximately 50% in primary hip arthroplasty, whereas for revisions of previously infected hips, antimicrobial combinations or antimicrobial agents selected based on culture results culture-dependent lowered infection rates by approximately 40% [57]. The typical dose of antibiotic is one gram of vancomycin, or 1.2 grams of an aminoglycoside antibiotic (gentamicin or tobramycin) per 40 gram batch of cement.

Antibiotic irrigation solutions

The routine use of antibiotic in irrigation solution remains controversial. Most studies have shown no superiority of antibiotic solutions when compared with saline solution in decreasing rates of PJI [58].

Antimicrobial laden implants

More recently, Binoy et al. have proposed and designed a covalent modification to titanium implant surfaces to render them bactericidal. Vancomycin covalently attached to titanium reduced S. aureus colony-forming units by 88% ± 16% over 2 h [59]. Similarly, in another study, Daptomycin bonded titanium foils killed 53 (5% of a high challenge dose of 3 × 10⁵ cfu S. aureus [60]. Another study showed that the stable, tethered vancomycin allograft prevented bacterial infection while not modifying bone cell function [61]. These novel surface treatments are not yet in use but may hold promise for future clinical applications.

Hematogenous seeding

In the post-operative period, antibiotic prophylaxis also aims to protect the prosthetic joint against hematogenous seeding from oral, urologic, skin, or gastrointestinal sources. Identification of a distant infection should prompt immediate therapy. Routine use of antimicrobial prophylaxis prior to dental, gastrointestinal (GI), or GI procedures is currently a subject of a hot debate and is not routinely advised [7,62].

Conclusion

In summary, given the high morbidity and cost associated with SSIs following TJR increasing emphasis on prevention is placed. Public national reporting and reduced reimbursement associated with SSI are driving innovation in this field. Preventive measures encompass a large number of factors related to host response, surgical incision environment, and microorganisms. Prophylaxis should address these areas in the pre-operative, intra-operative, and post-operative periods. Reduction of PJIs require a team effort, which involves the orthopedic surgeons, anesthesiologists, OR personnel, and Infectious Disease and Infection Control specialists.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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