Identifying Risk Factors Associated With Postoperative Infection Following Elective Lower-Extremity Total Joint Arthroplasty


Michelle Lespasio DNPJDNP1; Michael Mont MD2; Anthony Guarino PhD3

Perm J 2020;24:20.013 [Full Citation]
E-pub: 12/02/2020


This article addresses the importance of identifying risk factors associated with postoperative infection following elective lower-extremity total joint arthroplasty. Specifically, this review discusses risk factors recognized by the American Academy of Orthopaedic Surgeons that should be carefully considered and assessed by the orthopaedic team in collaboration with the primary care provider before proceeding with surgery.


This review addresses the importance of identifying risk factors associated with postoperative prosthetic joint infection (PJI) following elective lower-extremity total joint arthroplasty (TJA). Addressing associated risk factors before surgery is essential to reducing PJI after surgery. Although the literature differentiates risk factors as modifiable or nonmodifiable, we take the position that all risk factors (to some extent) are modifiable prior to elective TJA surgery. Therefore, this review discusses risk factors recognized by the American Academy of Orthopaedic Surgeons (AAOS)1 that should be carefully considered and assessed by the orthopaedic team in collaboration with the primary care provider (PCP) before proceeding with surgery (see Tables 1, 2, and 3 and Sidebar: Advance Organizer Quiz to Organize the Materials Presented). These associated risk factors include the following: substance abuse, diabetes mellitus (DM), anemia, mental health disorders and neurological disorders, obesity/increased body mass index (BMI), low BMI, malnutrition/hypoalbuminemia, vitamin D deficiency/insufficiency, HIV/AIDS, hepatitis C virus (HCV), liver disease, obstructive sleep apnea (OSA), rheumatoid arthritis, immunocompromised status, cardiovascular disease (eg, congestive heart failure, arrhythmia, atrial fibrillation, postoperative myocardial infarction), hypothyroidism, chronic renal failure/kidney disease, blood clotting disorders, peripheral vascular disease (PVD), homelessness/low socioeconomic status, and special surgical considerations.

Table 1. Careful consideration of risk

1. Active infection of joint, bloodstream, or local tissue
2. Anticoagulation status, active thromboprophylaxis
3. Autoimmune disease
4. HIV status
5. Institutionalized patients
6. Prior bariatric surgery

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

Table 2. Unclear effect on risk of prosthetic joint infection

1. Age (conflicting evidence)
2. Dementia (insufficient evidence)
3. Poor dental status (insufficient evidence)
4. Asymptomatic bacteriuria (conflicting evidence)

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

Table 3. Absolute contraindication to elective TJA

1. Active infection of arthritic joint, presence of septicemia, and/or presence of active local cutaneous, subcutaneous, or deep tissue infection
2. Superobesity, body mass index > 50
3. Active intravenous drug abuse
4. Intra-articular injection within 3 mo of surgery
5. Uncontrolled hyperglycemia with blood glucose > 200 mg/dL
6. Severe malnutrition with serum albumin < 3 g/dL
7. Untreated HIV

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

What Is a TJA?

TJA is a surgical operation performed to provide the most effective relief of pain and is appropriate for patients with advanced, end-stage arthritic disease or inflammatory arthritis of a large joint who nonsurgical treatment modalities have failed.2 For the purposes of this review, TJA includes both total knee arthroplasty (TKA) and total hip arthroplasty (THA).

Prevalence of TJA

The prevalence of TJA procedures is more than 1 million THA and TKA operations performed each year in the United States3,4 and that number is expected to rise steadily over the next 10 years.5 According to the Agency for Healthcare Research and Quality,6 more than 400,000 total hip replacements and more than 600,000 knee replacements are performed each year in the United States.

Possible Complications with TJA

Risks associated with TJA comprise systemic complications, such as those related to anesthesia, including deep vein thrombosis, pulmonary embolism, stroke, heart attack, and pneumonia. In addition, risks associated with TJA include surgical complications such as infection (at the site of incision and in deeper tissues near the affected joint), fracture, dislocation, nerve injury, leg length discrepancy, implant loosening, inflammation and swelling, increased pain, stiffness in the affected joint, allergic reaction to the bone cement, and damage to structures around the joint.

Possible Complications of PJI in TJA

Possible complications related to infection associated with TJA may involve a range from self-limited problems such as superficial skin infections (SSIs) to more detrimental problems seen with deep PJIs, which can lead to loss of limb or amputation. Infections that enter the bloodstream (eg, septicemia) can be fatal and lead to death. These infecting microorganisms may be introduced at the time of surgical intervention, through the bloodstream (hematogenously), by contiguous spread from another site, or from recurrence of a previously infected joint.7

Prevalence of PJI in TJA

The rate of PJI is highest during the first 2 years following surgery,8 with the risk of PJI greater for knee arthroplasty than hip arthroplasty.8,9 The rate of PJI in most medical centers ranges between 0.5% and 2% for knee replacements and 0.5% and 1.0% for hip replacements.5,10,11 The higher rate of PJI in TKAs may be attributed to greater mobility in the joint and soft tissue and less protective soft tissue coverage.5

Diagnosis of PJI in TJA

PJI is among the most serious complications of prosthetic joint implantation. After completing a comprehensive medical history that includes a review of associated TJA risk factors, the clinician should perform a focused clinical examination of the affected hip or knee and compare it to the contralateral side. The examination should include an assessment of the identified signs and symptoms noted above and inspection of the affected joint. Presence of fever (lasting more than 48 hours in the first month after primary surgery) and persistent wound drainage are 2 of the most important aspects of the examination. In addition, it is important to note both the presence or history of chronic pain at the site of the joint prosthesis and a history of superficial or deep infection or prior wound healing problems.

Plain radiographs, laboratory testing for inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), evaluation of synovial fluid, and tissue biopsy are important to establish a diagnosis of PJI. Other scans and imaging studies (eg, leukocyte count, positron emission tomography, computed tomography, bone scan, and magnetic resonance imaging) usually do not provide a definitive diagnosis in PJI and are generally not useful for routine diagnosis of suspected PJI.12

Management of PJI

Once a PJI is clinically established (see Table 4), the goals for management include eradication of the infection, alleviation of symptoms, restoration of function, and minimization of PJI-related morbidity and mortality.13 Management of PJI almost always requires surgical intervention and prolonged courses of intravenous or oral antimicrobial therapy.13 The approach to management of infection depends on the timing (eg, early, delayed onset, or later) and microbiology (eg, virulence) of infection, condition of the joint and implant, quality of the soft tissue envelope, and individual patient circumstances (see Table 5).14

Table 4. Clinical practice guidelines and recommendations for suspicion of prosthetic joint infection

a. Presence of fever
b. Persistent wound drainage (which may reflect sinus tract) at the site of a joint prosthesis
c. Acute onset of pain at the site of a joint prosthesis
d. Chronic pain at the site of a joint prosthesis, particularly in the absence of a pain-free interval following implantation
e. History of superficial or deep infection or prior wound healing problems

Adapted from Osmon et al.12

Table 5. Clinical practice guidelines

a. Not intended to be a fixed protocol
b. Not all patients in any given clinical situation are the same
c. Individual patient’s specific circumstances must always be considered
d. Clinician’s medical judgement always provides basis of patient care and treatment

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

There are 3 categories of onset of PJI infections (see Table 6).15,16 Early onset occurs within 3 months of implantation. Later infections (ie, occurring more than 24 months following implantation) typically originate in the blood. Antimicrobial therapy should be delayed until culture specimens are obtained (by joint aspiration, debridement, and/or removal of hardware). Clinical approaches for surgical management of PJI include 1) debridement and retention of the prosthesis, 2) resection arthroplasty with reimplantation, 3) permanent resection arthroplasty, or 4) amputation (see Table 7).17

Table 6. General categorization of prosthetic joint infections

Early onset within 3 mo of implantation
Delayed onset within 3 to 24 mo of implantation
Later onset later than 24 mo following implantation
Considerable overlap between early- and delayed-onset prosthetic joint infections (PJIs), and hip PJIs tend to occur sooner than knee PJIs

Adapted from Brusch et al15 and Lewis et al.16

Table 7. Clinical approaches for surgical management of prosthetic joint infection

Approach Description
Debridement, antibiotics, and retention of prosthesis (DAIR) procedure The DAIR procedure can be a successful treatment option for prosthetic joint infection (PJI) in total joint arthroplasty (TJA). It can effectively eradicate infection, resulting in improved functional outcome and a reduction in the need for more extensive surgery, which may be associated with far greater morbidity.103 The effectiveness of DAIR is still unclear due to a lack of comparative data among the treatment options and limited evidence to suggest superiority of any one treatment. The treatment decision must be made on a case-by-case basis and account for underlying medical conditions, infection history, organism characteristics, and surgical history. DAIR is most appropriate for acute PJI without complicating factors such as extensive and pervasive infection or organism virulence or resistance.104
Resection arthroplasty with reimplantation Reimplantation of a total hip or knee arthroplasty after a previous resection arthroplasty for infection can be performed with a low risk of reinfection. However, the incidence of infection following arthroplasty revision surgery is higher than that following primary implantation arthroplasty in this setting and is especially challenging because of the potential for significant bone and soft tissue deficits. The incidence of infection following arthroplasty revision surgery is higher than that following primary implantation.105-109 Postulated reasons for this include prolonged operating time during the revision surgery or unrecognized infection at the time of revision, with subsequent recrudescence. The abnormal soft tissue envelope may also be a contributing factor.13
Permanent resection arthroplasty Resection arthroplasty is a procedure in which the prosthetic components (implants) are removed as a consequence of failed surgery, in the setting of a periprosthetic infection. This is only performed when no other reconstructive options are possible and is typically reserved as a salvage strategy to avoid amputation after prior failed treatment attempts or for patients who are not candidates for DAIR or 1-stage arthroplasty exchange.5,13
Arthrodesis of amputation of limb This approach is reserved for patients for whom all other treatment options for PJI have failed110 or who have life-threatening infections in which emergent source control is required.111 Failure of the repeat 2-stage exchange arthroplasty appears to be dependent on the host grade and status of the extremity. Surgeons thus should consider the patient’s comorbidities and expectations when deciding whether to undergo repeat 2-stage exchange arthroplasty.112

Organism Profile Causing SSI/PJI in TJA

The published literature depicts Staphylococcus aureus as the leading cause of PJI after TJA,18-20 and there is limited evidence to support a difference in the organism profile causing SSI/PJI between hip and knee arthroplasty. Isolated studies have reported an increased prevalence of streptococcal and culture-negative PJI around the knee, whereas staphylococcal, enterococcal, and pseudomonal PJI may be more prevalent around the hip.21 The incidence of PJI affecting TKA versus THA is estimated at 1% to 3% and 0.3% to 2%, respectively.20 Several studies have examined the organism profile causing PJI after arthroplasty, but few have identified any significant difference in the organism’s profile between hip and knee arthroplasty.21


Prior to referring a patient for evaluation of TJA, we recommend that the PCP assess the following risk factors for PJI and treat and/or refer the patient accordingly.

Substance Use

Substance use includes 1) excessive alcohol use, 2) cigarette smoking, and 3) chronic opioid use, illegal drug use, and/or intravenous drug abuse. Substance use can lead to substance use disorders, which may contribute to medical and related physical health problems such as an increased risk of liver, lung, or cardiovascular disease, infectious diseases such as hepatitis B or C, and HIV/AIDS.22 PCP identification of patients with substance use disorders preoperatively can provide an opportunity to refer these individuals for early intervention and subsequently avoid delay in scheduling TJA.23

Excessive Alcohol Use

Excessive alcohol use increases the risk of PJI. Alcohol use disorder remains the most common form of substance use disorder in the United States and begins as early as age 12 years.22,24,25 The US Centers for Disease Control and Prevention26 defines excessive alcohol consumption as 4 or more drinks on a single occasion or 8 or more drinks per week for women and 5 or more drinks on a single occasion or 15 or more drinks per week for men. Excessive alcohol consumption increases individuals’ risk for cardiopulmonary problems, alcohol withdrawal symptoms/delirium, immune system dysfunction, and metabolic stress responses.27,28

Although the optimal period of alcohol cessation remains unspecified, a period of at least 4 weeks of abstinence is required to reverse certain physiologic abnormalities.29 In some cases, orthopaedic surgeons require a medically documented 6-month period of abstinence before they will perform elective TJA (Eric L Smith, MD, personal communication, October 16, 2017).a

SIDEBAR.Advance Organizer Quiz to Organize the Materials Presented

Please answer true or false to the following items:
1. True/False. Estimates indicate that by 2030, more than 3 million total joint arthroplasties (TJAs) will be performed each year in the United States.
2. True/False. Prosthetic joint infection (PJI) in TJA is associated with an increase in morbidity, implant failures, and financial and emotional costs.
3. True/False. Associated risk factors for PJI in TJA can be modified to reduce the incidence of systemic comorbid systemic complications and implant failure postoperatively.
4. True/False. For patients with a hemoglobin A1C of 8% to 9% or greater or glucose levels between 180 to 200 mg/dL, optimization of the elevated levels is mandated prior to undergoing TJA.
5. True/False. High hemoglobin levels can increase a patient’s risk for perioperative allogenic blood transfusions and PJI after surgery.
6. True/False. Mental health disorders in patients undergoing TJA are relatively easy to detect.
7. True/False. Malnutrition is not a risk factor in patients with an elevated body mass index (greater than 40) undergoing TJA.
8. True/False. Hyperalbuminemia significantly increases the risk of superficial site infections following TJA.
9. True/False. Homelessness is often overlooked as a potential barrier to recovery.
1. True
2. True
3. True
4. True
5. False
6. False
7. False
8. False
9. True

a Chief, Division of Arthroplasty, Associate Professor of Orthopaedic Surgery, New England Baptist Hospital.

Cigarette Smoking

Clinical studies demonstrate that smokers undergoing both THA and TKA are 9 times more likely to experience superficial SSIs, smokers undergoing THA are 6.5 times more likely to have deep SSIs, and smokers undergoing TKA are 2.5 times more likely to develop deep SSIs.30 Bone healing is an essential component of successful TJA, requiring bone to grow into the implant. However, the restricting effect of nicotine on microvascular (small blood vessel) constriction places smokers at an increased risk of TJA infection because there is as much as 25% less blood flow to the wound in smokers compared to nonsmokers with less oxygenation and there are fewer healing nutrients and white blood cells protective to wounds, thereby slowing and potentially interfering with the healing process.31 Smoking cessation is advised at least 6 weeks prior to surgery to at least 6 weeks postoperatively, although permanent cessation of smoking is preferred.32,33

Chronic Opioid Use/Illegal/Intravenous Drug Abuse

Ongoing illegal drug abuse (eg, opioids, barbiturates, or amphetamines) is an absolute contraindication for elective TJA.34 Patients with a history of intravenous drug use are more likely to develop a deep infection compared with other patients undergoing TJA.35 Chronic opioid use in patients often leads to tolerance requiring a higher than usual opioid dose in the intraoperative and postoperative period. Identifying individuals with a chronic opioid addiction or illegal/intravenous drug abuse problem and referring them to inpatient or outpatient rehabilitation programs prior to surgical evaluation provides the best solution for optimal care. Twelve-step programs, psychotherapy or cognitive behavioral therapy, and medication are other recommended options.36-38

DM Control

Patients with a sole diagnosis of well-controlled DM control do not confer a clinically significant risk for PJI.37 DM, preoperative hyperglycemia, and elevated hemoglobin A1C are generally not independent risk factors for PJI, but they are considered to be indirect markers of and associated with an increased risk of more serious systemic comorbid conditions (eg, chronic kidney disease, stroke, urinary tract infection, ileus, postoperative hemorrhage, transfusion) and surgical complications (eg, wound infection, PJI), higher mortality, and increased length of hospital stay.37,38 Conversely, others report that without a diagnosis of DM, perioperative hyperglycemia at the time of primary knee or hip arthroplasty has been associated with an increased risk of subsequent PJI.39 Severely uncontrolled DM (eg, serum glucose of 200 mg/day or higher) is an absolute contraindication for TJA. For those with hemoglobin A1C of 8% to 9% or greater or glucose levels between 180 and 200 mg/dL, optimization of the elevated levels is mandated in the preoperative period.

PCP evaluation and optimization of a patient’s DM with an elevated hemoglobin A1C greater than 8 and possible referral for an endocrine consultation is the mainstay of treatment prior to referring the patient for TJA evaluation. Several months or more of ongoing care and management can be expected prior to achieving optimization of DM in TJA.


Anemia is common in patients undergoing TJA and is linked to more PJI in patients undergoing TJA than those without anemia, affecting 4.3% and 2% of anemic and nonanemic patients, respectively.40,41 Preoperative anemia, as defined by a hemoglobin level of less than 13.0 g/dL in men and 12.0 g/dL in women, is an independent risk factor for postoperative SSI/PJI following TJA.42 Low hemoglobin levels can increase a patient’s risk for perioperative allogenic blood transfusions and PJI after surgery.43

Mental Health and Neurological Disorders

Patients with mental health disorders and psychiatric diagnoses (eg, depression psychosis, schizophrenia) are demonstrated to have increased complication rates after primary TJA.44-46 The most common etiologies of mental health disorders and neurological disorders include acute changes due to 1) delirium, stroke, and Alzheimer dementia; 2) movement disorders (eg, Parkinson disease, multiple sclerosis, epilepsy, and tardive dyskinesia); and 3) mood/behavior disorders (eg, major depressive disorder, anxiety, bipolar disorder, schizophrenia).47 Patients who have a history of delirium, stroke, and Alzheimer disease are shown to be at greater risk of unfavorable outcomes (in particular, higher mortality and longer lengths of hospital stay leading to greater chances of infection) and may acquire greater levels of dependence. Patients undergoing TJA who have movement disorders are known to have longer postoperative hospitalizations and higher rates of perioperative complications.48 Patients undergoing TJA who have mood/behavior disorders, such as major depressive disorders, may have perceptions of pain and disability that encourage a greater need to consume more opioids during the immediate postoperative period compared to similar patients without major depressive disorders.49 Patients with moderate anxiety or depression also appear to have an increased risk of wound complications (eg, infection) after THA.50

Obesity/Increased BMI

Obesity is associated with a higher risk for PJI following THA among elderly individuals (defined as older than 75 years), but no such association was found for patients undergoing TKA.51 It is not yet known whether PJI correlates with higher BMI (above 30 kg/m2) in patients undergoing TKA.

A BMI threshold of 35 kg/m2 is most commonly used to define obesity, but a BMI of 40 kg/m2 or greater (severely obese) is the threshold in some medical centers. Under no circumstance should elective surgery be performed on patients diagnosed as superobese (ie, BMI greater than 50). Patients who have an increased BMI are more likely to experience PJI, deep vein thrombosis, and pulmonary embolism. Possible reasons for the increased risk associated with obesity are postulated to be prolonged operative duration, vascular insufficiency leading to decreased capacity to fight infection and decreased ability to support the healing process.52,53

Current management guidelines indicate that weight loss is helpful in reducing PJIs in this patient population. Weight loss prior to surgery will help to reduce the risk of PJIs and other perioperative complications, including anesthesia-related complications, and reduce the risk of surgical revision.54 However, the current approach to weight loss protocols remains controversial, with no absolute guidelines for which methodology (eg, diet/exercise versus medically prescribed very low-calorie diets versus bariatric surgery) is best. It is suspected that in patients undergoing bariatric surgery prior to TJA, the risks for PJIs are reduced due to decreasing BMIs but this is offset by the increased risk for malnutrition.54


Underweight and low BMI are associated with suppressed immune systems in some patients, possibly reflecting an altered physiological state55 and higher morbidity and mortality rates.56 A low BMI is typically defined as less than 18.5 kg/m2,57-60 and these patients comprise approximately 2.3% of the US population.61 A low BMI is hypothesized to be an indirect measure of nutritional status, as patients with a lower BMI are shown to have lower levels of albumin, prealbumin, and/or protein.62 Patients with a low BMI who have decreased nutritional reserves and reduced ability to accurately react to stress because of a suppressed immune system are at increased risk of PJI and should be referred for a nutritional consultation before undergoing TJA.56


Malnutrition and hypoalbuminemia are known to increase the risk of postoperative wound complications, SSIs, and PJIs in patients undergoing TJA.63-67 Patients diagnosed with malnutrition are 2 times more likely to have postoperative wound complications compared to those with adequate nutritional stores.68,69 While the mechanism of how malnutrition leads to postoperative wound complications is not entirely clear, malnutrition is believed to impair wound healing, cause persistent wound drainage, and prolong inflammation by reducing collagen synthesis and fibroblast proliferation.63 In addition, malnutrition may impair the ability of the immune system to fight infection through lymphocytopenia and cause PJI.63 In the event of an SSI or deeper wound infection, malnourished patients demonstrate low success rates of initial irrigation and debridement procedures.70,71 Thus, evaluation is essential for patients who have malnutrition to determine whether the cause is due to not eating enough key nutrients or if an underlying medical condition such as liver failure may be causing malabsorption of key nutrients into the body.

Vitamin D Deficiency/Insufficiency

Risk factors associated with vitamin D deficiency (25-hydroxy vitamin D of 20 ng/mL or lower) or insufficiency (25-hydroxy vitamin D less than 30 ng/mL) and PJI remain controversial and undefined.72 Some research has reported a higher prevalence of vitamin D deficiency in patients with PJI compared to patients without infection, thereby suggesting an association between low vitamin D levels and possible suboptimal postsurgical outcomes.73 Most research, however, demonstrates little evidence to support hypovitaminosis D as a risk factor linked to reduced postoperative functional recovery or increased risk of PJIs.74,75 Some orthopedists nevertheless recommend screening and treating hypovitaminosis D prior to undergoing orthopaedic surgery.74 When recommended, a standard vitamin D regimen consists of 50,000 units of vitamin D3 weekly for 6 to 8 weeks to increase low levels to an optimal level of 30 to 60 ng/mL. Maintenance doses of 2,000 units of vitamin D3 daily or 5,000 units 3 times a week are recommended thereafter. Fifteen minutes of exposure to sunlight daily if possible is also recommended.74


Patients who have HIV with a CD4 level below 200/mm3 are known to have a 10-fold increase in infection.76 Research demonstrates that patients with well-controlled HIV who receive highly active antiretroviral therapy with undetectable viral loads and have a CD4 level above 200/mm3 are at similar risk of PJI as the average population.77 Thus, for patients with HIV who are medically optimized with highly active antiretroviral therapy, the risk is small and comparable to patients who are HIV negative in conjunction with optimization of underlying associated conditions such as malnutrition, renal disease, and liver disease.1


Research indicates that patients with HCV are at increased risk of both acute and long-term medical and surgical complications.78 Treatment for HCV prior to THA appears to be associated with fewer postoperative complications, primarily periprosthetic joint infection.78 For patients with known HCV, many orthopaedic surgeons require that patients complete HCV treatment in entirety prior to elective TJA (Eric L Smith, MD, personal communication, October 16, 2017).a

Patients with liver disease (eg, hepatitis and/or cirrhosis) are at increased risk for SSI/PJI and intraoperative and postoperative bleeding.79 Patients with cirrhosis are found to have longer lengths of hospital stay, increased costs, and higher rates of mortality, readmission, and reoperation.80 Although currently there are no universal treatment guidelines for managing liver disease prior to elective TJA, referring patients with known liver disease to a liver disease specialist for preoperative optimization of care is recommended.


The American Society of Anesthesiologists recommends screening patients for OSA before they undergo elective TJA.81 While there is no apparent association between OSA and PJI reported in the literature, there may be some indirect links. As previously noted, patients with alterations in mental status (eg, delirium) and neurological disorders (eg, stroke) may have prolonged postoperative lengths of hospital stay and higher rates of perioperative complications, which can increase their risk for PJI.

Clinical studies demonstrate that patients undergoing primary TJA who have OSA are at greater risk of postoperative cardiovascular and pulmonary complications, and death.82,83 In elderly patients without a history of dementia who elect to undergo elective TJA, there is an association between preexisting OSA and postoperative dementia, which can lead to longer lengths of hospital stay and perioperative complications.84

Rheumatoid Arthritis

It is postulated that immunosuppressive therapies collectively contribute to increased PJI susceptibility for patients who have rheumatoid arthritis and associated comorbidities.13 Immunosuppressive therapies involving corticosteroids (eg, prednisone) and disease-modifying antirheumatic drugs (eg, methotrexate) place patients with rheumatoid arthritis undergoing TJA at greater risk of infection.85 Some studies report no increase in the incidence of PJI, regardless of whether these treatments are discontinued perioperatively.86,87 The American College of Rheumatology and the British Society for Rheumatology88-90 both recommend withholding tumor necrosis factor-α inhibitors perioperatively to TJA. Likewise, the International Consensus Group on Periprosthetic Joint Infection91 recommends stopping disease-modifying antirheumatic drugs within the clinical judgement of the medical team for at least 14 days prior to elective TJA.

Immunocompromised Status

Patients who are concurrently undergoing immunosuppressive therapies involving corticosteroids and disease-modifying antirheumatic drugs are at greater risk of PJI due to their compromised ability to heal, fight infections, and maintain homeostasis.1 Therefore, a risk-benefit analysis is recommended for these types of patients.

Cardiovascular Disease

Specific cardiovascular diseases are shown to significantly predispose patients to PJI. Congestive heart failure, PVD, valvular heart disease, atrial fibrillation, and myocardial infarction are independent comorbid factors associated with a higher risk of PJI.20 It is postulated that the increased risk of infection associated with these conditions could be related to more aggressive treatment with anticoagulation.20


There is some evidence of an association between hypothyroidism and PJI.92 In one clinical study, patients who developed PJI demonstrated a statistically significant, 2.46 times greater thyroid-stimulating hormone than those without PJI.92 Buller et al93 reported that hypothyroidism was associated with greater risk of postoperative complications compared to matched controls. Evaluation and proper management of thyroid function in patients with thyroid disease is important prior to elective TJA.

Chronic Renal Failure/Kidney Disease

Reports suggest that patients who have chronic renal failure are at greater risk of developing PJI after TJA. One study demonstrated that hemodialysis patients had approximately twice the rate of infection than patients who had undergone a renal transplant.94 The reason for this is thought to be multifactorial, including the immunosuppressive nature of therapies associated with chronic kidney disease, which may increase susceptibility to infection.94,95

Blood Clotting Disorders

Blood clotting disorders (eg, hemophilia and von Willebrand disease) are associated with significantly higher rates of infection, transfusions of blood products, medical complications, and revision surgery after TKA.1 Patients with blood clotting disorders require referral to a hematologist or vascular surgeon for risk assessment and perioperative recommendations, followed by close monitoring by the surgical team after TJA. Intraoperative use of tranexamic acid, an antifibrinolytic agent, promotes blood clotting and reduces bleeding in the surgical wound.96,97 Utilizing tranexamic acid during surgery in patients with hemophilia has demonstrated 1) lower perioperative blood loss, 2) lower hidden blood loss, 3) a lower transfusion rate, 4) lower postoperative joint swelling and pain, and 5) lower levels of inflammatory biomarkers resulting in enhanced overall joint function.98


PVD is an identifiable risk factor for arterial insufficiency that can lead to wound complications and PJI.99 Defined as decreased arterial perfusion to the lower extremities, PVD can be clinically identified by intermittent claudication or the absence of arterial pulses in the lower extremities.99 Patients who have known or suspected PVD should be referred to a vascular specialist for evaluation of arterial perfusion and potential for postoperative blood clots.

Homelessness/Low Socioeconomic Status

Patients who are homeless have potential barriers to recovery because of these common health issues. These barriers include the following: 1) mental illness, 2) drug and alcohol dependence, 3) risk of violence, 4) HIV, 5) hepatitis B and C, 6) neurological disorders, 7) anemia, 8) cardiac disease, 9) tuberculosis and other respiratory infections, and 10) increased mortality rates.100 These potential recovery barriers often lead to longer lengths of hospital stay, reduce the likelihood of attending follow-up clinic appointments, increase the likelihood of returning to the emergency department, and have higher readmission rates for infections. Interventions such as providing stable housing are essential to improve the health outcomes of people who are homeless and to reduce the associated costs to the health care system.101

Special Surgical Considerations

Special surgical considerations to optimize postoperative outcomes include 1) appropriate patient selection, 2) infection control practices, and 3) attentive postoperative management protocols.102 Additionally, other surgical factors that appear to reduce the rate of PJI include shorter duration of surgery, prophylactic antibiotics given within 60 minutes of the surgical incision, S. aureus decolonization with mupirocin ointment, and preoperative chlorhexidine wash.54


It is apparent that when addressing the challenge of PJI, orthopaedic surgeons play an important role in limiting the impact of associated risk factors in the preoperative, intraoperative, and postoperative phases of TJA. Reducing emotional and economic burdens associated with PJI is a primary objective undertaken by orthopaedic surgeons when considering surgical candidates for elective TJA. Although in most cases, orthopaedic surgeons and their teams perform the essential role of identifying and addressing associated risk factors that affect perioperative morbidity and mortality, the role of identifying and addressing these associated risk factors should start with patients’ PCPs. Therefore, it is incumbent on the PCP to ensure patient optimization prior to undergoing TJA and referring patients for surgical evaluation. Through preoperative identification and modification of patient-associated risk factors, along with patient compliance to related medical recommendations, improved overall postoperative clinical outcomes are achievable.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.


The authors wish to graciously acknowledge the editors of this article whose contributions were invaluable to the clarity of explaining this condition.

Author Affiliations

1Department of Orthopaedic Surgery, Boston Medical Center, Boston, MA

2Northwell Health Physician Partners Orthopaedic Institute at Lenox Hill, Lenox Hill Hospital, New York, NY

3Fulbright Association, Washington, DC

Corresponding Author

Michelle Lespasio ()

How to Cite this Article

Lespasio M, Mont M, Guarino A. Identifying risk factors associated with postoperative infection following elective lower-extremity total joint arthroplasty. Perm J 2020;24:20.013. DOI: 10.7812/TPP/20.013


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Keywords: AAOS, American Academy of Orthopaedic Surgeons, associated risk factors, infection, optimized clinical outcomes, prosthetic joint, total joint arthroplasty


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