Secondary Logo

Journal Logo

Symposium

Best Practices and Evolving Techniques for Preventing Infection After Fracture Surgery

Joshi, Manjari MBBS

Author Information
doi: 10.1097/BTO.0000000000000416
  • Free

Abstract

Infections are a frequent complication of surgical procedures and are associated with significant morbidity and mortality. There are estimated to be ~80 million surgeries performed in the US per year: 46 million in inpatient settings and 32 million in ambulatory settings. Approximately, 500,000, (1.9%) of these procedures are complicated by surgical site infections (SSIs), as defined by the Centers for Disease Control and Prevention (CDC).1 In the inpatient setting, SSIs are the most common hospital-acquired infection and comprise 30% of all infections. Besides impacting the quality of life, and productivity of the patient, SSIs also contribute to a mortality rate of 3%.2

Incidence of SSI after elective orthopedic surgery is in the range of 1% to 4%. In the trauma setting, the incidence is ~1% in low-energy fractures and >30% in complex high-energy, open fractures.3,4 In this setting, major determinants of infection are the degree of contamination of the wound for open fractures and damage to soft tissue and vasculature for all fractures. Open fractures are classified on the basis of Gustilo-Anderson classification; and the risk of infection increases with a higher gradation of fractures.5 The consequence of such infections can be loss of limb, poor functional status, worse quality of life, and substantial financial burden to society. Osteoaricular infections are also more difficult to treat and are associated with recurrence rates of 10% to 20%. Therefore, focus on the prevention of such infections is of the utmost importance.

The United States Center for Disease Control, Institute for Healthcare Improvement and the Surgical Care Improvement Project have promoted several interventions for reducing the incidence of SSIs. It is estimated, that with the appropriate implementation of evidence-based strategies, 50% of SSIs may be preventable.6 Public reporting of SSIs, outcomes, and quality improvement measures are now a requirement.7

PATHOPHYSIOLOGY OF INFECTIONS IN FRACTURES

Infections are a frequent complication of trauma-induced open fractures. Unique features of SSIs related to orthopedic surgery include pathogenicity of skin commensals, ability of low inoculum of organisms to cause implant-related infections and a prolonged follow-up/surveillance period of ≥1 year to diagnose implant-related infections. Tsukayama in 1999 provided a detailed review of the pathophysiology of infections in traumatic fractures.8 Bacteria enter the wound from the patient’s skin or the environment. Damaged tissue and the presence of foreign body exposes binding sites, which promotes adherence of bacteria. Organisms that are initially in planktonic form, rapidly form biofilms over implants and damaged tissue. Skin commensals such as staphylococci have great propensity to form biofilms and produce glycocalyx. Biofilms have a survival advantage and are more resistant to eradication by antibiotics. In addition, bacteria such as staphylococci, which are the most common bacteria associated with SSIs and osteomyelitis, use specific mechanisms that promote adherence and counteract the host immune system to establish infection. Traumatized tissue has compromised blood supply, which leads to an inability to deliver specific immune substrates to the site of injury and creates more tissue necrosis. The host reaction to trauma and the presence of contaminating bacteria includes an acute complex inflammatory reaction. Trauma has been reported to delay the inflammatory response and impair cell-mediated immunity, which further contributes to infection.

RISK FACTORS FOR INFECTION

Development of an SSI depends on multiple factors including the number and nature of contaminating organisms, antimicrobial prophylaxis, host condition, and surgical technique. In trauma patients, most SSIs are acquired from the patient’s own microbial flora. Less frequently, operating room (OR) staff and environment could also be a source.9

The risk factors for SSIs can be divided into general factors related to host features, which can contribute to impaired wound healing or specific factors related to trauma and surgery.10

General Factors

Smoking, obesity, malnutrition, extremes of age, diabetes mellitus, use of steroids, immunosuppressive drugs, or prolonged prehospital stay can increase the risk of infection.11,12 The presence of other comorbidities or active or remote infection can also increase the risk of infection.

Specific Factors

Injury-related factors including gradation of fractures on the basis of Gustilo-Anderson classification, severity of soft tissue damage, degree of wound contamination, and complexity of fractures play a critical role in the development of infection.5 Surgery-related factors such as emergency procedures, duration of surgery, need for blood transfusion, timing, and appropriateness of prophylactic antibiotic therapy are also important.12

In addition, in general surgery, National Nosocomial Infection Surveillance (NNIS) and SENIC scores have been used as tools to calculate infection rates. However, in fracture surgery, these scores have not been found to be useful. A study conducted by Paryavi et al13 (RIOTS study) reviewed 235 high-energy fractures such as tibial plateau, pilon, and calcaneal fractures. In this study, the risk of infection was on the basis of fracture classification AO type C3 or Sanders type 4 fractures, American Society of Anesthesiology score (ASA) of 3 or higher and body mass index <30 as predictors of infection rather than NNIS or SENIC scores.

ORGANISMS

Staphylococci species remain as the leading cause of SSIs in traumatic wounds and fractures and account for almost 50% of all infections.14,15 A study by Montalvo et al15 quantified the bacteriology of infections in fractures over a decade. The proportion of each bacterial type from deep SSI was compared between periods of 2006 to 2010 and 2011 to 2015. In their study, the overall incidence of Staphylococcal infections remained steady, although the incidence of methicillin-resistant Staphylococcus aureus (MRSA) declined. Methicillin-sensitive S. aureus (MSSA) infection rate was unchanged but the isolation of coagulase-negative Staphylococcus was on the rise.15 Other gram-positive cocci, such as streptococci and enterococci, were encountered in 15% to 20% of infections. In recent years, there has been a steady increase in the rates of gram-negative organisms and they may account for nearly 30% of infections.15 Anaerobes and gram-positive rods, such as propionibacterium sp and corynebacterium sp are causative agents in 10% of infections. Polymicrobial infections occur in 25% of patients. Approximately 10% of infections remain culture negative by standard microbiological testing. Furthermore, antimicrobial resistance has been on the rise, complicating the management of these patients. Specific preventive strategies have targeted organisms such as S. aureus.

PREVENTIVE MEASURES

In 2016, the CDC reported a declining incidence of SSIs, which was attributed to heightened awareness and implementation of preventive measures. Evidence-based preventive measures can decrease SSI rates by 50%.6 In one report by Dellinger et al,16 56 hospitals redesigned their systems as part of the National Surgical Infection Prevention Collaborative over 1 year. Forty-four hospitals reported data on 35,543 patients and reported a decrease in infection rate by 27%. Improvement in measures related to normothermia, euglycemia, oxygenation, appropriate hair removal, and antimicrobial selection was noted. This study demonstrates that collaborative efforts and bundling of the preventive measures can lead to quality improvement and decrease in SSIs and such interventions will be important to implement in the future.

In 1999, the CDC published the original guidelines for the prevention of SSIs.17 Several strong recommendations offered then are now considered an accepted practice for the prevention of SSIs. The new guidelines for the prevention of SSIs were published by the CDC in 2017 and focuses on select areas.18 Preventive factors discussed below are inclusive of the CDC recommendations but are more detailed.

Preventive measures can be broken into 4 categories: preoperative, perioperative, postoperative, and evolving techniques (Table 1).

TABLE 1
TABLE 1:
Summary of Measures to Prevent SSIs in Fracture Patients

PREOPERATIVE

Because of the emergent nature of the surgery, several of these preventive measures cannot be applied to an acute trauma patient. However, if surgery is delayed or there is additional surgery, these principles will be applicable.

Timing of Surgery

Emergency procedures are more likely to be associated with higher complication rates and SSIs. A 5-year study evaluated 3096 patients requiring orthopedic procedures. Seventy-nine patients were infected with an SSI incidence of 2.55%.19 Fifty-two patients (65.8%) were infected in the emergency surgery group versus 27 infections (34.2%) in the elective group (P<0.001). Another study compared the performance of 198 hospitals in emergency versus elective general surgery operations and demonstrated that emergency surgery patients are at much higher risk of complications.20 Most trauma patients undergo emergency orthopedic procedures that places them at higher risk of infection. Therefore, future research and quality improvement projects especially focusing on this group could identify processes that can improve SSI outcomes in these patients.

Remote or Active Infection

In 1976, a study reviewed 41,000 operations. Remote infections were identified in 2056 patients.21 Results of the study noted a significant reduction in SSIs through control of remote sites of infection.

Immunosuppressive Therapy

Agents such as glucocorticoids suppress inflammation and could have an impact on wound healing.22 Limited data suggest that acute, high-dose steroid administration for <10 days has no impact on wound healing.22 Patients who require steroid therapy for >30 days, particularly at prednisone doses of ≥40 mg/day, may demonstrate 2 to 5 times higher wound complication rates compared with patients not on steroids.22 Cytotoxic agents and radiation therapy can also affect wound healing. Chemotherapeutic agents affect the vascular endothelial growth factor, which can impair early wound healing and angiogenesis.23 If possible, before surgery, immunosuppressive therapy should be tapered to the lowest dose possible. Radiation therapy can cause apoptosis, tissue necrosis, and hypovascularity. It is recommended to perform surgery 3 to 6 weeks after radiation therapy ends.24 However, in the absence of randomized controlled studies, the impact of immunosuppressive therapy on SSIs remains incompletely answered.

Smoking

Smokers have a higher risk of infection than nonsmokers do. Cessation of smoking 4 to 6 weeks before surgery decreases wound complications such as SSIs.25 Tobacco smoke has several components, which cause vasoconstriction, decreased inflammatory response, and alteration in collagen metabolism leading to impaired wound healing and SSIs.26

Anticoagulation

A retrospective case-control study reviewed primary total hip arthroplasties performed in a single center during a 5-year period and compared outcomes of the patients on warfarin with a double-matched control group of patients not on anticoagulation.27 The warfarin group had a significantly higher risk of deep joint infection (9% vs. 2.2%), hematoma/wound ooze (28% vs. 4%), and superficial infections (13.5% vs. 2.2%). Managing patients undergoing orthopedic surgery with therapeutic anticoagulation is a balance between the risk of thromboembolic disease and bleeding and infection-related complications.

Diabetes and Hyperglycemia

Risk of infection is high in patients with diabetes because of underlying vasculopathy, neuropathy, and the presence of numerous cytologic factors.28,29 The peripheral arterial disease causes limb ischemia, which leads to diminished delivery of oxygen and nutrients to tissue, and impairment of the removal of metabolic products and contributes further to impaired wound healing. Neuropathy can affect sensory, motor, and autonomic nerves. Sensory neuropathy diminishes the sensation of pain, which is protective when tissue injury occurs. Motor nerve involvement leads to deformities of the foot, which increases local tissue pressure and resultant skin ulceration. In addition, autonomic neuropathy creates dryness of skin and loss of vascular tone causing breaks in the skin and localized edema. Lastly, impaired wound healing also occurs because of cytologic factors, such as impaired collagen accumulation, altered macrophage function, epidermal barrier dysfunction, altered angiogenic response, and numerous other factors.29

A systematic review and meta-analysis of the literature in 2015 reported diabetes as an independent risk factor for SSIs across multiple surgical procedures.30 In addition to multiple other factors discussed earlier, hyperglycemia has been proposed as a causative factor of infections in patients with and without diabetes in orthopedic trauma patients.31 The use of protocols for perioperative glucose monitoring and control (blood glucose level, <200 mg/dL) are strongly recommended and supported by CDC guidelines for the prevention of SSIs with high to moderate quality of evidence.18

Obesity

The available data suggest that in nonorthopedic surgeries, obese people are more likely than people of normal weight to develop postoperative infections.32 Local factors, such as poor vascularity of adipose tissue, result in poor antibiotic delivery and increased local edema. Systemic factors such as hyperglycemia may be associated with obesity. In fracture surgery, the data in obese patients are mixed. RIOTS study demonstrated that body mass index score of <30 was predictive of infection in lower extremity fractures.13 Another study performed in patients with pelvic fracture was associated with higher infection rates in the obese group.33 It is conjectured that in the obese population, the cushion effect provided by the “insulating” layers of fat may be protective in lower extremity fractures but is not in pelvic fractures.

Patient Decolonization

These measures include S. aureus decolonization, skin antisepsis, and hair removal.

Staphylococcus aureus Decolonization

Approximately 30% of the population is colonized with S. aureus (MSSA or MRSA) with nares being the most frequent site. MRSA colonization in trauma patients is estimated to be anywhere between 5% and 12%. Carriage of S. aureus has been associated with increased risk of SSIs. Routine preoperative screening and decolonization for S. aureus have been shown to be cost-effective and beneficial in elective orthopedic surgery. Decolonization regimens include preoperative bathing with soap and nasal decolonization. A study, which evaluated 709 patients undergoing elective orthopedic procedures and placement of hardware, demonstrated SSI rates of 1.1% in decolonization group and 3.8% in the control group.34 Chen et al35 performed a systematic review of the literature including patients with elective orthopedic (17 studies) and trauma surgery (2 studies). All studies showed a reduction in SSIs or wound complications with S. aureus screening and decolonizing regimens. However, there were several unanswered issues raised by this review. Questions such as, which decolonization regimen to use; which systemic antibiotic prophylaxis to use; should follow-up screening for MRSA be performed; and which screening method should be used for detection of MRSA were raised in this review. They concluded that although preoperative screening and decolonization of S. aureus in orthopedic patients is a cost-effective means to reduce SSI, additional research needs to be performed. At this juncture, for fracture surgery patients, this issue still needs further resolution. If decolonization is performed, antimicrobial prophylaxis guidelines published in 2013, recommends that mupirocin be given intranasally to patients with documented colonization with S. aureus.36

It is important to know that nasal screening may miss 20% of patients with S. aureus colonization, and both mupirocin and chlorhexidine resistance could be associated with failures and persistent carriage of MRSA.37 In addition, there are also no standard guidelines for decolonization regimens, duration of decolonizing therapy, or the best time to initiate therapy. Unfortunately, in an emergency setting with a patient with fractures, there is no time to screen or decolonize the patients.

Hair Removal

Routine hair removal should be avoided because it increases the risk of SSIs. In addition, to reduce the risk of SSIs, if hair removal needs to be performed, it should be done immediately before surgery outside the operating room. Clippers, not razors should be used, because the latter causes gross skin cuts.38

Antimicrobial Prophylaxis

Of all the preventive strategies, antibiotic prophylaxis is possibly one of the most important interventions. Multiple studies have shown that failure of antibiotic administration is associated with a higher risk of SSI and administration of antibiotics reduces the risk of SSIs.

Antimicrobial prophylaxis recommendations are on the basis of the Clinical Practice Guidelines developed jointly by several US societies36 and World Health Organization (WHO) guidelines.39

The key principle of antibiotic prophylaxis is to obtain adequate tissue concentration above the minimum inhibitory concentration of the anticipated organisms at the time of incision. One of the earlier clinical studies was conducted by Classen and colleagues. They evaluated 1708 surgical cases prospectively and found that when antibiotics were administered within 2 hours before surgery the risk of infection was 0.59%, and 3.8% when antibiotics were given 2 to 24 hours before surgical incision.40 Several other studies have been performed in different surgical procedures that are described in detail in the clinical practice guidelines for surgical prophylaxis by Bratzler et al.36 These studies strongly support the recommendation that antibiotic should be administered within 120 minutes before the surgical incision. In trauma patients, often this goal cannot be met as contamination occurs at the scene of the injury and prophylactic antibiotics are administered when the patient reaches the hospital. Some studies recommend that in trauma surgery, it is more optimal to administer antibiotics 15 to 60 minutes before incision.39

Use of an appropriate agent is critical. The recommended regimen in orthopedic procedures involving internal fixation is cefazolin.36 Clindamycin and vancomycin should be reserved as alternative agents because they are less efficacious and more toxic.36 Prophylactic regimens differ for closed fractures versus open fractures.

A single dose of antibiotic is recommended in closed fractures. In a large clinical trial, Boxma et al41 demonstrated that a single dose of antibiotics was effective in reducing the incidence of implant-related infections in closed fractures. These results were also confirmed by a Cochrane analysis.42

In open fractures, the evidence is not as clear. The East Practice Management Guidelines for Prophylactic Antibiotic Use recommends that systemic antibiotic coverage should be directed at gram-positive organisms.43 In addition, gram-negative coverage should be added for type III fractures and antibiotics should be continued for 72 hours after surgery. High-dose penicillin should be added in the presence of potential fecal contamination (eg, farm-related injuries).43 There have been several studies that have not supported the East guidelines recommendations. A retrospective study published by Dunkel and colleagues reviewed 1500 open fractures and showed that infection in open fractures was related to the extent of tissue damage and not to the duration of antibiotics. They stated that for grade III fractures, 1-day duration of prophylactic antibiotics might be sufficient.44 A study by Rodriguez et al45 supported similar results and showed that with shorter courses there was a lower risk of nephrotoxicity and less emergence of resistance because of improved antimicrobial stewardship.

The standard institutional practice, at a large trauma center at the author’s site, has been to use IV cefazolin for a period of 24 hours for grade I and II open fractures, and 48 hours for grade III fractures. Gram negative rods coverage with gentamicin and anaerobic coverage with penicillin is added for severely contaminated injuries. In our experience, longer duration and expanded coverage of antibiotics increase the risk of adverse events and the emergence of resistant bacteria without providing additional benefit.45

MRSA Coverage

Routine use of vancomycin prophylaxis is not recommended for any procedure. In patients colonized with MRSA or at high risk of MRSA, vancomycin should be considered.36 However, vancomycin is less effective than cefazolin for preventing infections with MSSA.46 Therefore, one potential but unproven approach is for combining cefazolin with vancomycin to cover both MSSA and MRSA.36

Gram-negative Coverage

If there are surveillance data showing that gram-negative organisms are a potential cause of SSIs for the procedure, one may consider combining vancomycin with another agent [cefazolin, if the patient does not have a beta-lactam allergy; an aminoglycoside (gentamicin or tobramycin), aztreonam, or single-dose fluoroquinolone, if the patient has a beta-lactam allergy].36 However, there are no solid data supporting routine gram-negative coverage in patients with prior colonization by such organisms in either open or closed fractures at this time.

Redosing of antibiotics is recommended during surgery where there is excessive blood loss or when the duration of surgery exceeds two half-lives of the antibiotic. Clinical studies in cardiac and colorectal surgery patients have demonstrated that low antibiotic levels at the end of surgery are associated with higher SSI rates. Clinical practice guidelines for antimicrobial prophylaxis in surgery by Bratzler et al36 provide details regarding this recommendation. Antibiotics also have to be adapted for allergies, weight, and pertinent medical history.36

Hand Hygiene

Surgical hand preparation is considered to be an important strategy for the prevention of SSIs although its requirement has never been proven by a randomized controlled clinical trial. However, there have been several reports of health care–associated infection outbreaks with hand contamination of the surgical team.47 Therefore, it is recommended that all members of the surgical team should practice hand hygiene. Cleansing with an alcohol-based formulation is considered as effective, as scrubbing with antiseptic soap.48 Removal of false nails and jewelry is recommended because they may be colonized with bacteria. Other factors such as existing skin conditions and technique for rubbing, drying, and gloving may also be important.

Skin Antisepsis

Skin preparation before surgery with an alcohol-based antiseptic agent is important to reduce the burden of skin flora.18 For several decades, either 2% chlorhexidine combined with 70% isopropyl alcohol or 10% povidone-iodine has been used for skin antisepsis. Several studies have been performed, documenting the superiority of one product over the other. Cochrane analysis in 2013 found some evidence that 0.5% chlorhexidine in alcohol base was associated with lower rates of SSIs but the evidence was minimal at best.49 A large multicenter trial, comparing both products is being conducted in orthopedic trauma patients, which should provide results by the year 2021.50 On the basis of current systematic reviews, it is generally accepted that chlorhexidine-based preparation may be superior to iodine, because of rapid action, persistent activity, residual effect, and ability to resist inactivation by blood but ongoing trials should help answer this question definitively.50

PERIOPERATIVE

Surgical Attire

Surgical attire includes scrub suits, gloves, and barrier devices (gowns, masks, caps, and drapes).51 Experimental studies have shown that organisms can be shed from the exposed skin and mucous membranes of the OR personnel, but no randomized clinical studies have been performed to evaluate this relationship.17 Nevertheless, the use of surgical attire is recommended to prevent exposure of patients to the organisms from the OR personnel and also protect the surgical team from exposure to the bloodborne pathogens from the patient.

It is recommended that gowns should be changed if visibly soiled, and surgical masks and gowns should be changed between operations and every 3 to 4 hours even during surgery on the same patient. Surgeon’s hands can also be an ongoing source of contamination for the patient. Gloves are important not only for the prevention of infection in the patient but also for the protection of the surgeon. Especially in trauma patients, perforation rates of gloves can be as high as 4% to 21% and increase with the duration of wear. Routine double gloving is recommended by the American College of Surgeons, primarily to protect the surgeon.51

Hooper et al52 studied the use of spacesuits for the prevention of infection in total hip and knee replacements. An increase in infection rates was noted in procedures performed with the spacesuits. Multiple factors may have contributed to increase in infection rates, such as a false sense of security of the surgeon, need for adjustment of the suit and hood causing contamination of the gloves, and little knowledge regarding the flow of the expelled air from the exhaust system that may have resulted in higher concentration of bacteria at the surgical site. Although in orthopedic surgery, the surgical attire continues to be recommended for the prevention of SSIs, but there is no evidence of a relationship with these measures and the occurrence of SSIs.

Ventilation System

Laminar flow system in the OR produces airflow at positive pressure, which prevents air flowing from less clean areas to the clean areas. The purpose is to decrease the bacterial load in clean areas, hence reducing the incidence of SSIs. Earlier studies supported the use of laminar flow systems, but recent studies have questioned its use in terms of SSI reduction.53 There is an inconsistent relationship between surface and air bacterial counts in laminar airflow units, indicating that increased air contamination may not translate into higher rates of SSIs.

Normothermia

Thermoregulation during surgical procedures has been recommended by the CDC as a measure to prevent SSIs.18 Hypothermia can cause vasoconstriction, decrease subcutaneous oxygen tension, and lead to coagulopathy and hemorrhage. It can also affect glucose metabolism, drug elimination and cause immune dysfunction11 In trauma patients, the effects of hypothermia can be even more pronounced. There are a few studies, which support thermoregulation, and there are other studies, which have countered the hypothesis. Most surgeons and anesthesiologists, however, support the use of normothermia for reducing the risk of SSIs.54

Hyperglycemia

It is important to keep glucose concentrations <200 mg/dL during surgery. Please see details under preoperative section.

Supplemental Oxygen

The CDC recommendation in 2017 supports the administration of increased FiO2 intraoperatively and in the immediate postoperative period after extubation for all patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation.36 Some of the available data do not support the use of a high fraction of inspired oxygen compared with the routine fraction of inspired oxygen during all surgical procedures for prevention of SSIs.55 In 2013, Stall et al56 conducted a study in 222 patients with high-energy lower extremity fracture and demonstrated a trend towards reduction of SSIs in the study group, 12% versus 16% (P=0.31). When the imbalances in the study groups were adjusted for risk factors such as length of stay, the results approached statistical significance (P=0.17). Currently, in patients with fracture, use of supplemental oxygenation for prevention of infection is still unanswered. A large ongoing trial is underway to answer this question.57

Surgical Technique

The good surgical technique can reduce the incidence of SSI by maintaining effective hemostasis, gentle handling of tissue, removal of devitalized tissue, eradication of dead space, avoiding excessive drying, and closure of wound without tension.52 For extensive open fracture injuries, surgical debridements should be repeated until healthy tissue is obtained.

Time from injury to debridement after surgery has also been deemed important in the past; and the “6-hour rule” was the historical standard. Recent studies have not supported this rule even for the most severe wounds and current studies recommend debridement within 24 hours.58 Some surgeons recommend more timely debridement of highly contaminated wounds but data supporting this practice are lacking.59

Irrigation is an important supplement to aggressive debridement and prophylactic antibiotics in open fractures. The specifics of the irrigation fluid and the extent of irrigation remains a topic of debate. Use of wound irrigation has been addressed by the FLOW trial, which assigned 2551 patients with open fracture into 3 irrigation pressure groups: high, low, and very low.60 In addition, each study group received 1 of 2 irrigation solutions, castile soap, or normal saline. In this study, rates of reoperation were similar regardless of the pressure but the rates were higher in the soap group. The study recommended low-cost, low-pressure irrigation with normal saline instead of castile soap.60

Local Antibiotics

Particularly in complex open fractures, but to some extent for all fractures, systemic antibiotics may not be able to reach the damaged and poorly perfused tissue at the fracture site. Both absorbable, acrylic-based polymer cement (eg, PMMA) and nonabsorbable, mineral-based bone cement (eg, calcium sulfate and/or phosphate) can be utilized for antibiotic delivery and dead space management. These materials can deliver very high local concentrations of antimicrobial agents to the surgical site, which otherwise could not be achieved systemically because of toxicity. The principle is that a high concentration of antibiotic locally would kill planktonic bacteria before it can form biofilms. However, the emergence of resistance remains a primary concern. Although studies with these products are sometimes difficult to interpret, the consensus is that antibiotic-loaded acrylic products are useful in the prevention of orthopedic infections.61 A recent meta-analysis including 2738 patients with open limb fractures showed a lower infection rate with the use of the local antibiotic application, 4.6% in the study group and 16.5% in the control group (P<0.001)62

Data from a large prospective, randomized study using the application of intrawound vancomycin powder in patients with tibial plateau and pilon fractures were recently presented. It demonstrated an infection rate of 10.3% in the control group and 6.7% in patients who received intrawound vancomycin powder (P=0.07). The analysis of gram-positive infections showed a drop in the infection rate from 7.8% to 2.7% (P=0.01).63 The study findings provide further support for the use of a local antibiotic application.

In orthopedic trauma surgery, staples or sutures obtain wound closure. No difference between materials has been noted. Antibiotic-coated sutures such as triclosan-coated sutures may reduce the risk of SSIs, but the data are limited.36 Wound dressings were analyzed in a Cochrane review in nontrauma patients.64 There was insufficient evidence that covering the wound with a specific kind of dressing or applying antibiotics over incision reduces the incidence of SSIs. In patients with open fractures associated with extensive soft tissue damage, negative pressure wound therapy has been used to lower the rates of SSIs.65 A recent randomized trial of standard wound management therapy versus negative pressure wound therapy in 460 patients with open fractures of lower limbs showed no difference in the infection rates between the 2 groups: 8.1% in the standard therapy group and 7.1% in the study group (P=0.64).66

POSTOPERATIVE

Wound Care

Compliance with standard hand hygiene and infection control procedures should be maintained throughout the hospital stay. There was no difference in infection rate noted in early dressing removal (up to 48 h postsurgery) versus delayed removal (beyond 48 h) after wound closure.11

Antimicrobial prophylaxis for dental, urologic, or gastrointestinal procedures is currently not recommended in patients with orthopedic implants. A panel convened by the America dental association council on scientific affairs judged that the current evidence does not demonstrate an association between dental procedures and prosthetic joint infections.67

OTHER MEASURES

Bundles or Checklists

Several risk factors and/or interventions are bundled and implemented as safety checklists. A study by De Lucas-Villarubia et al68 demonstrated that by implementing a group of measures such as MRSA screening, preoperative decolonization, improved antibiotic prophylaxis, postdischarge surveillance, and heightened awareness of infections, the SSIs rates decreased from 12% to almost zero over 12 months.

Behavioral Changes

This concept is an emerging field in surgical practice. It evaluates the impact of changes of behaviors and routines in the OR on the incidence of SSIs. This area needs further research and evaluation.

Evolving Concepts

Several new strategies for the prevention of infection are in evolution.69,70

Antibacterial Coatings

Coating device surfaces with compounds in an attempt to reduce the ability of microbes to bind to the surface of prosthetics.

  • Biosurfactants: positively charged biomaterial surfaces were successful in slowing the adherence of bacteria. Macromolecules (ie, heparin and heparin and polypeptides) formed a hydrated layer on the artificial surface and also showed promise.
  • Antimicrobial metal and metal oxide nanoparticles: silver has antibacterial activity against both planktonic and sessile organism and has been incorporated in bone cement and into hydroxyapatite. There has been some success with silver-coated external pins and mega prosthesis.71 However major concern remains for the potential emergence of resistance, toxicity, and lack of kinetic data.
  • Antibiotic-coated metals: direct tethering of antibiotics to metal orthopedic implants has promised to kill bacteria when they first come into contact with a prosthesis and hence halt the progression of biofilm formation. Although coatings offer the advantage of protecting a particular component, there are still issues regarding the longevity of the coating or possible reactions with the underlying material.

Nonantibiotic Biofilm Target

These strategies are targeted against biofilms.69,70

  • Vaccination is one of the most effective approaches for prevention of infection. Unfortunately, several biofilm-specific vaccines against S. aureus have failed for different reasons. There are no current vaccines available.
  • Using agents such as eDNA-digesting enzyme, the DNase I, that disrupts the extracellular polymeric slime and eDNA, which holds biofilm bacteria together and attaches them to a surface. These products are still under development.
  • Quorum-sensing inhibitors and biofilm-degrading enzymes: quorum-sensing is a mechanism that many microorganisms use to coordinate gene expression in populations in response to local conditions, including cell density. These products are still under investigation.
  • Antibiofilm and antimicrobial peptides (AMPS): AMPs are innate defense molecules existing in animals with a broad spectrum of antimicrobial activity and low risk of resistance development. Several AMPs also have the capacity to prevent biofilm formation and some molecules are in development. In addition, an AMP could be potentially tethered and immobilized on an orthopedic device to provide antimicrobial activity.
  • Attacking the persister/dormant state: dormant or persister population of bacteria within biofilms, are thought to be responsible for high levels of antibiotic tolerance. It is a useful concept but is still in the development phase.

CONCLUSIONS

Infections related to fractures remain a challenging problem and can result in lifelong functional impairment. Therefore, the prevention of such infections is of utmost importance. Guidelines for prevention of SSIs published by CDC and WHO, provide the general concepts of prevention that are also applicable to musculoskeletal trauma patients. However, there are unique differences in fracture surgery patients that need to be addressed. Patients with fracures usually present as emergent care and may have other associated injuries that may impact on the care of the fractures. They often have associated soft tissue damage and compromised vascular supply that hinders access to host defenses and antibiotic delivery. Open fractures are also contaminated with bacteria that are implanted into the bone and soft tissue upon initial injury. Furthermore, patients with fractures may need frequent trips to OR, and for bone stability, often require insertion of foreign body implants in a contaminated field. These unique features require that research protocols need to be developed, which address the specific needs of musculoskeletal trauma patients and create best practices for the future.

REFERENCES

1. Mu Y, Edwards JR, Horan TC, et al. Improving risk-adjusted measures of surgical site infection for the national healthcare safety network. Infect Control Hosp Epidemiol. 2011;32:970–986.
2. Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198–1208.
3. Patzakis MJ, Wilkins J. Factors influencing rate in open fracture wounds. Clin Orthop Related Res. 1989;243:36–40.
4. Metsemakers WJ, Kuehl R, Moriarty TF, et al. Infection after fracture fixation: current surgical and microbiological concepts. Injury. 2018;49:511–522.
5. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty five open fractures of long bones: retrospective and prospective analysis. J Bone Joint Surg Am. 1976;58:453–458.
6. Umshceid CA, Mitchell MD, Doshi JA, et al. Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs. Infect Control Hosp Epidemiol. 2011;32:101–114.
7. US Department of Health and Human services. National action plan to prevent health care-associated infections: road map to elimination. 2013. Available at: https://health.gov/hcq/prevent-hai-action-plan.asp. Accessed January 18, 2019.
8. Tsukayama DT. Pathophysiology of posttraumatic osteomyelitis. Clin Orthop Relat Res. 1999;360:22–29.
9. Ayliffe GA. Role of the operating suite in surgical wound infection. Rev Infect Dis. 1991;13:S800–S880.
10. Armstrong DG, Meyr AJ. Risk factors for impaired wound healing and wound complications. UpToDate; May 16, 2018.
11. Metsemakers WJ, Onsea J, Neutjens E, et al. Prevention of fracture-related infection: a multidisciplinary care package. Int Orthop. 2017;41:2457–2469.
12. Jorge LS, Fucuta PS, Oliveira MGL, et al. Outcomes and risk factors for polymicrobial posttraumatic osteomyelitis. J Bone Joint Infect. 2018;3:20–26.
13. Paryavi E, Stall A, Gupta R, et al. Predictive model for surgical site infection risk after surgery for high energy lower extremity fractures: development of the risk of infection in orthopedic trauma surgery score. J Trauma Acute Care Surg. 2013;74:1521–1527.
14. Torbert J, Joshi M, Moraff A, et al. Current bacterial speciation and antibiotic resistance in deep infections after operative fixation of fractures. J Orthop Trauma. 2015;29:7–17.
15. Montalvo RN, Natoli RM, O’Hara NN, et al. Variations in the organisms causing deep surgical site infections in fracture patients at a Level I Trauma Center (2006-2015). J Orthop Trauma. 2018;32:e475–e481.
16. Dellinger EP, Hausmann SM, Bratzler DW, et al. Hospitals collaborate to decrease surgical site infections. Am J Surg. 2005;190:9–15.
17. Mangram AJ, Horan TC, Pearson ML, et al. Guidelines for Prevention of Surgical Site Infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Contol Hosp Epidemiol. 1999;20:250–278.
18. Berrios-Torres SI, Umscheid CA, Bratzier DW, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection. JAMA Surg. 2017;152:784–791.
19. Al-Mulhim FA, Baragbah MA, Sadat-Ali M, et al. Prevalance of surgical site infection in orthopedic surgery: a 5-year analysis. Int Surg. 2014;99:264–268.
20. Ingraham AM, Cohen ME, Raval MV, et al. Comparison of hospital performance in emergency versus elective general surgery operations at 198 hospitals. J Am Coll Surg. 2011;212:20–28.
21. Edwards LD. The epidemiology of 2056 remote site infections and 1966 surgical wound infections occurring in 1865 patients. Ann Surg. 1976;184:758–766.
22. Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg. 2013;206:410–417.
23. Erinjeri JP, Fong AJ, Kemeny NE, et al. Timing of administration of bevacizumab chemotherapy affects wound healing after chest wall port placement. Cancer. 2011;117:1296–1301.
24. Wang J, Boerma M, Fu Q, et al. Radiation responses in skin and connective tissues: effect on wound healing and surgical outcome. Hernia. 2006;10:502–506.
25. Nasell H, Adami J, Samnegard E, et al. Effect of smoking cessation intervention on results of acute fracture surgery: a randomized controlled trial. J Bone Joint Surg. 2010;92:1335–1342.
26. Sorensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy. Ann Surg. 2012;255:1069–1079.
27. McDougall CJ, Gray HS, Simpson PM, et al. Complications related to therapeutic anticoagulation in total hip arthroplasty. J Arthroplasty. 2013;28:187–192.
28. Armstrong DG, Boulton AJM, Bus SA, et al. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376:2367–2375.
29. Brem H, Tomic–Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117:1219–1222.
30. Martin ET, Kaye KS, Knott C, et al. Diabetes and risk of surgical site infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;37:88–99.
31. Richards JE, Kauffmann RM, Zuckerman SL, et al. Relationship of hyperglycemia and surgical site infection in orthopaedic surgery. J Bone Joint Surg. 2012;94:1181–1186.
32. Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006;6:438–446.
33. Porter SE, Graves ML, Zhen Q. Operative experience of pelvic fractures in the obese. Obese Surg. 2008;18:702–708.
34. Bebko SP, Green DM, Awad SS. Effect of preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation. JAMA Surg. 2015;150:390–395.
35. Chen AF, Wessel CB, Rao N. Staphylococcus aureus screening and decolonization in orthopaedic surgery and reduction of surgical site infections. Clin Orthop Relat Res. 2013;471:2383–2399.
36. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health-Syst Pharm. 2013;70:195–283.
37. Lee AS, Macedo-Vinas M, Francois P, et al. Impact of combined low-level mupirocin and genotypic chlorhexidine resistance on persistent methicillin resistant Staphylococcus aureus carriage after decolonization therapy: a case-control study. Clin Infect Dis. 2011;52:1422–1430.
38. Lefebvre A, Saliou P, Lucet JC, et al. Peroperative hair removal and surgical site infections: network meta-analysis of randomized controlled trials. J Hosp Infec. 2015;91:100–108.
39. WHO. Global Guidelines for the Prevention of Surgical Site Infection. Geneva: World Health Organization; 2016.
40. Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326:281–286.
41. Boxma H, Broekhuizen T, Patka P, et al. Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: the Dutch Trauma Trial. Lancet. 1996;347:1133–1137.
42. Gillespie WJ, Walenkamp G. Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures. Cochrane Database Syst Rev. 2001;1:CD000244.
43. Hoff WS, Bonadies JA, Cachecho R, et al. East Practice Management Guidelines Work Group: update to practice management guidelines for prophylactic antibiotic use in open fractures. J Trauma. 2011;70:751–754.
44. Dunkel N, Pittet D, Tovmirzaeva L, et al. Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection. Bone Joint J. 2013;95-B:831–837.
45. Rodriguez L, Jung HS, Goulet JA, et al. Evidence based protocol for prophylactic antibiotics in open fractures: improved antibiotic stewardship with no increase in infection rates. J Trauma Acute Care Surg. 2014;77:400–407.
46. Finkelstein R, Rabino G, Mashiah T, et al. Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a high prevalence of methicillin-resistant staphylococcal infections. J Thorac Cardiovasc Surg. 2002;123:326–332.
47. Widmer AF, Rotter MA, Voss A, et al. Surgical hand preparation: state of the art. J Hosp Infect. 2010;74:112–122.
48. Boyce JM, Pittet D. Guideline for Hand Hygiene in Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Infect Control Hosp Epidemiol. 2002;23(suppl 12):S3–S40.
49. Dumville JC, McFarlane E, Edwards P, et al. Preoperative skin antiseptics for preventing surgical wound infections after clean surgery. Cochrane Database Sys Rev. 2015:CD003949.
50. Principal Investigator. Pre-operative Aqueous Antiseptic Skin Solutions in Fractures (Aqueous-PREP). Clinical trials Gov Identifier. NCT03385304. Accessed December 28, 2017.
51. Ban KA, Minei JP, Laronga C, et al. American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. 2017;224:59–74.
52. Hooper GJ, Rothwell SG, Frampton C, et al. Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement. J Bone Joint Surg Br. 2011;93-B:85–90.
53. Brandt C, Hott U, Sohr D, et al. Operating room ventilation with laminary airflow shows no protective effect on the surgical site infection rate in orthopedic and abdominal surgery. Ann Surg. 2008;248:695–700.
54. Anderson DJ, Podgorny K, Berrios-Torres SI, et al. Strategies to prevent surgical site infections in actue care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:605–627.
55. Wetterslev J, Meyhoff CS, Jorgensen LN, et al. The effects of high perioperative inspiratory oxygen fraction for adult surgical patients. Cochrane Database Syst Rev. 2015;25:CD008884.
56. Stall A, Paryavi E, Gupta R, et al. Perioperative supplemental oxygen to reduce surgical site infection after open fixation of high-risk fractures: a randomized controlled pilot trial. J Trauma Acute Care Surg. 2013;75:657–663.
57. O’Toole RV, Joshi M, Carlini A, et al. Supplemental perioperative oxygen to reduce surgical site infection after high energy fracture surgery (Oxygen study). J Orthop Trauma. 2017;31 (suppl 4):S25–S31.
58. Pollak AN, Jones AL, Castillo RC, et al. LEAP Study Group. The relationship between time to surgical debridement and incidence of infection after high energy lower extremity trauma. J Bone Joint Surg Am. 2010;1:7–15.
59. Prodromidis AD, Charalambos CP. The 6-hour rule for surgical debridement of open tibial fractures: a systematic review and meta-analysis of infection and nonunion rates. J Ortho Trauma. 2016;30:397–402.
60. The FLOW Investigators. A trial of wound irrigation in the initial management of open fracture wounds. N Engl J Med. 2015;373:2629–2641.
61. Metsemakers WJ, Moriarty TF, Nijs S, et al. Influence of implant properties and local delivery systems on the outcome in operative fracture care. Injury. 2016;47:595–604.
62. Morgenstern M, Vallejo A, Mcnally MA, et al. The effect of local antibiotic prophylaxis when treating open limb fractures. A systematic review and meta-analysis. Bone Joint Res. 2018;7:447–456.
63. O’Toole RV, Joshi M, Carlini A, et al. Paper 71. Presented at Orthopaedic Trauma Association Annual Meeting; October 18-20, 2018; Orlando, FL.
64. Dumville JC, Gray TA, Walter CJ, et al. Dressings for the prevention of surgical site infection. Cochrane Database Syst Rev. 2016;12:CD003091.
65. Schlatterer DR, Hirschfeld AG, Webb LX. Negative pressure wound therapy in grade IIIB tibial fractures: fewer infections and fewer flap procedures. Clin Ortho Relat Res. 2015;473:1802–1811.
66. Costa ML, Achten J, Bruce J, et al. Effect of negative pressure wound therapy versus standard management on 12 month disability among adults with open fractures of the lower limbs. The WOLFF randomized clinical trial. JAMA. 2018;319:2280–2288.
67. Sollecito TP, Abt E, Lockhart PB, et al. The use of prophylactic antibiotics prior to dental procedures in patients with prosthetic joints. JADA. 2015;146:11–16.
68. De Lucas-Villarrubia JC, Lopez-Franco M, Granizo JJ, et al. Strategy to control methicillin-resistant Staphylococcus aureus post-operative infection in orthopaedic surgery. Int Orthop. 2004;28:16–20.
69. Moriarty TF, Kuehl R, Coenye T, et al. Orthopedic device-related infection: current and future interventions for improved prevention and treatment. EFORT Open Rev. 2016;1:89–99.
70. McConoughey SJ, Howlin R, Granger JF, et al. Biofilms in periprosthetic orthopedic infections. Future Microbiol. 2014;9:987–1107.
71. Romano CL, Scarponi S, Gallazzi E, et al. Antibacteeial coating of implants in orthopedics and trauma: a classification proposal in evolving panorama. J Orthop Surg Res. 2015;10:157–168.
Keywords:

prevention; fracture; skin and soft tissue infections; guidelines

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.