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CME: Orthopedic Medicine

Recognizing and managing infections in total joint arthroplasty

Aumiller, Wade D. PhD; Kleuser, Thomas M. MD

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doi: 10.1097/01.JAA.0000465216.73739.f0
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Box 1

Despite advances in sterile procedures, periprosthetic joint infections are rising along with the increasing demand for joint arthroplasty. Several factors predispose a patient to a periprosthetic joint infection, including patient demographics, preexisting conditions such as diabetes, intraoperative processes and interventions, and postoperative complications. Three main issues complicate the ability of healthcare providers to effectively manage periprosthetic joint infections: the lack of a uniform definition, the lack of a reliable gold standard diagnostic test, and increasing antibiotic resistance of microorganisms. To facilitate prompt recognition and appropriate intervention, this article will review epidemiology, risk factors, pathophysiology, diagnosis, and management of periprosthetic joint infections.


The demand for total knee and total hip arthroplasty is expected to increase significantly from 2005 to 2030.1 Primary total hip arthroplasties are projected to increase by 174% to 572,000 procedures per year in 2030.1 Primary total knee arthroplasties are projected to increase by 673% to 3.48 million per year in 2030.1

An estimated 1% to 4% of patients who have total knee arthroplasty develop a periprosthetic joint infection.2 A periprosthetic joint infection (defined as an infection within the joint capsule meeting specific criteria) is the most common indication for total knee revision, and the third most common indication for total hip revision.3,4 One study estimated that in the United States, periprosthetic joint infections cost $250 million annually due to increased hospitalizations, surgeries, complications, inpatient days, and outpatient visits.5 Another study that examined nationwide inpatient data from 2001 to 2009 found the annual cost of revision surgery due to periprosthetic joint infections increased from $320 million to $566 million.6 The study projected that the cost would exceed $1.62 billion by 2020. The cost of revision surgery due to periprosthetic joint infection is higher than aseptic revision averaging between $50,000 to $60,000 per case.7 Periprosthetic joint infection is not only costly but also causes significant physical and psychological morbidity.8

Box 2


Diabetes more than doubles the infection risk for patients undergoing knee or hip replacement; a study of 7,181 patients found the rate of infection was highest in morbidly obese patients with diabetes.9 A trend toward higher infection rates was observed in patients with undiagnosed diabetes and a preoperative glucose level of 124 mg/dL or greater, compared with patients whose glucose levels were below 124 mg/dL.9 The authors note that patients with diabetes diagnosed at the time of surgery had about twice the risk of a periprosthetic joint infection.9

Other risk factors for periprosthetic joint infection include previous joint arthroplasty, simultaneous bilateral arthroplasty, hospital stay of more than 5 days, postoperative atrial fibrillation, postoperative urinary tract infection, postoperative myocardial infarction, surgical site infection not involving the joint prosthesis, a National Nosocomial Infections Surveillance System risk index greater than 1 (indicating an increased risk of surgical site infection), malignancy, allogenic blood transfusion, and an American Society of Anesthesiologists score greater than 2 (indicating increased operative risk).10-12


In the prosthetic joint space, the implant can serve as a growth medium for pathogens introduced from a direct wound to the joint cavity, or an injury elsewhere in the body that introduces bacterial pathogens to systemic circulation.13 Once bacteria attach to the implant surface, they become less metabolically active and form a glycocalyx biofilm that makes them unresponsive to antibiotics at therapeutic levels.14 Because of the significant protective effect of the biofilm, eradicating a periprosthetic joint infection may require antibiotic concentrations 10 to 100 times the normal systemic dose, a potential drug safety issue.14

A periprosthetic joint infection cohort study of 9,245 patients found that the most common infecting organisms were gram-positive cocci: methicillin-resistant S. aureus (19%), methicillin-sensitive S. aureus (19%), methicillin-resistant S. epidermidis (11%), and methicillin-sensitive S. epidermidis (8%).12 Gram-negative microorganisms were found in 11% of the study's patients, with E. coli and K. pneumoniae being the most common infectious agents.12


The American Academy of Orthopaedic Surgeons' (AAOS) guideline for diagnosing periprosthetic joint infection of the hip and knee is shown in Table 1.15

AAOS guideline for diagnosing periprosthetic joint infection15

Patients at higher probability of periprosthetic joint infection have pain or stiffness in the joint implant and at least one of the following:

  • risk factors such as diabetes, immunosuppression, previous knee joint infection, superficial surgical site infection of the hip or knee, or extended operative time (more than 2.5 hours)
  • a physical examination finding: warmth, effusion, redness, and swelling, or a sinus tract associated with the joint (Figure 1)
  • early implant loosening (within 5 years of surgery) or osteolysis as demonstrated on radiograph.15
Periprosthetic joint infection of the knee showing multiple draining sinus tracts

Lower probability is associated with pain or joint stiffness and absence of the criteria listed above.

Other risk factors (supported by consensus) for periprosthetic joint infection include bacteremia or candidemia within 1 year of joint surgery; metachronous (previous) periprosthetic joint infection; disorders such as psoriasis, chronic cellulitis, lymphedema, chronic venous stasis, and ulcers; IV drug use; MRSA infection or colonization within 3 years of surgery; and active infection at another site.15

According to the AAOS, testing strategies should be based on the patient's probability of a periprosthetic joint infection (Table 2).15 Joint appearance, serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, synovial fluid culture, white blood cell (WBC) count and WBC differential, histological tissue analysis, and intraoperative tissue sample cultures are the primary diagnostic tools.13 Serum ESR and CRP are first-line tests when a periprosthetic joint infection is suspected. Both tests have good sensitivity to periprosthetic joint infection (96%), but poor specificity (59%) because peripheral inflammations can also raise the level of these markers.13,16 With limited specificity, the guideline suggests confirmatory synovial fluid aspirate testing of suspect serological results.

AAOS testing recommendations for periprosthetic joint infection15

Recommended synovial fluid testing is culture, WBC count, and differential.8 The fluid culture test aims to identify the pathogen and guide treatment of the infection.13 However, false-positive culture results may occur. PAs need to be aware of the parameters used to distinguish between expected postoperative elevations in synovial fluid results and those that represent pathology. The range of values for synovial WBC and polymorphonuclear neutrophil (PMN) percentage that are diagnostic for periprosthetic joint infection vary, and these values are normally elevated postoperatively because of the resulting inflammatory response. A recent study by Bedair and colleagues defines threshold values of 10,700 cells/mcL for synovial WBC count and 89% for PMN percentage for diagnosis of periprosthetic joint infection in the early postoperative period.8

Infection is highly probable in a patient who presents with one or more symptoms, risk factors, physical examination findings, or radiograph findings suggestive of periprosthetic joint infection.15 If further diagnostic confirmation is needed, the AAOS guideline recommends noninterventional imaging, including F-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET), labeled leukocyte imaging, and gallium imaging.15 FDG-PET has shown high diagnostic value for periprosthetic joint infection (85% sensitivity and 93% specificity) and has a limited recommendation from the AAOS as a diagnostic method for periprosthetic joint infection.16,17 Labeled leukocyte imaging and gallium imaging modalities have shown low diagnostic value.18

Recent research on alternate biomarkers for diagnosis of periprosthetic joint infection has shown good potential. An investigational study of 37 patients found that PCR analysis of aseptic fluid extract from surgically removed joint prostheses could detect infection with 100% sensitivity, even in patients who had preoperative antibiotics.17

A study of 87 revision arthroplasty procedures concluded that a biosensor system was effective in detecting known pathogens in synovial fluid both in suspected cases of periprosthetic joint infection, culture-negative cases, and cases undertaken for proposed aseptic loosening.19

Leukocyte esterase is an additional biomarker for periprosthetic joint infection with exceptional clinical practicality. Parvizi and colleagues reported results indicating 80.6% sensitivity, 100% specificity, 100% predictive value, and 93.3% negative predictive value for colorimetric strip testing of intraoperative knee synovial fluid.20 However, more studies are needed to build confidence in this test method.


The AAOS guideline provides a structured framework for diagnosing a suspected periprosthetic joint infection. However, the ability to diagnose these infections accurately and promptly has been compromised by the lack of a uniform definition that takes into account synovial aspirate analysis.13 Parvizi and colleagues propose using the definition in Table 1, which in a comparison analysis with other definitions showed 53% to 100% accuracy leading to definitive diagnosis.13

Periprosthetic joint infections can be classified into four types:

  • Type I, identified from routine cultures at the time of arthroplasty revision when infection is not expected
  • Type II, an infection discovered within the first month after surgery
  • Type III, an infection that occurs years after arthroplasty, and as an acute hematogenous event from a known source
  • Type IV, an infection present for 1 month or longer.21


Nonsurgical treatment options for periprosthetic joint infections are limited and often case-dependent. For example, antimicrobial therapy alone may be appropriate for a patient whose infection has low virulence and antibiotic susceptibility, and for whom surgical revision would present an exceedingly high risk.13 Antibiotic therapy also can be used after surgical debridement for infection control if the patient is unable to tolerate additional surgeries.13


The type of infection typically guides the degree and approach of surgical intervention.

When a type I (unsuspected) infection is detected intraoperatively, debridement and implant component exchange are appropriate.22 Treatment for type II infections depends on patient, timing, and pathogen variables: If the patient and the implant are stable and if the infecting pathogen is antibiotic-susceptible, then debridement, component retention, and parenteral antibiotic therapy may be appropriate in an attempt to salvage the implant.22,23

Good outcomes and implant retention are possible for type III infections if they are diagnosed in less than 2 to 3 weeks and if the implant and patient immunocompetence are intact. Treatment consists of debridement and IV antibiotics as determined by culture and sensitivity.22

Type IV infections caused by an antibiotic-susceptible pathogen and of less than 1 month duration may benefit from a one-stage exchange: removal of the prosthesis, extensive tissue irrigation and debridement, and placement of a definitive revision prosthesis.22 A two-stage exchange may be appropriate if the infection duration is longer than 1 month and if the pathogen is a more virulent type, such as MRSA. The two-stage exchange involves removing the implant, placing an antibiotic spacer block, and delaying placement of new prosthetic components until the infection resolves (Figure 2).

Anteroposterior and lateral radiographs of a semiconstrained total knee arthroplasty implanted as part of a two-stage procedure to treat an infected primary total knee arthroplasty

Persistent infection may be treatable with successive revisions and antibiotic therapy. Some patients may need multiple two-stage exchange therapy.13 Whiteside and colleagues provided preliminary data supporting the use of direct intra-articular catheters for the delivery of antibiotics to infected prosthetic joints.24

Salvage is considered in patients when the infection cannot be resolved, if treatment occurred too late or if the patient cannot tolerate multiple procedures.13 Salvage procedures for chronically infected knees include above-the-knee amputation and joint arthrodesis. When joint arthrodesis is used to treat periprosthetic joint infections, internal plating is used to set the arthrodesis and has a high probability of biofilm formation. Patients may need long-term antibiotic suppression for an effective treatment outcome.9,13


Preventive treatment for periprosthetic joint infection is divided into three periods with specific risk reduction measures.10

Preoperative period

Early steps involve optimizing blood glucose control and nutritional status, insuring that any perioperative site wounds are healed, addressing vascular insufficiency, smoking cessation, and MRSA decolonization. The day before surgery, the patient may be asked to perform skin decontamination with home shower scrub agents such as chlorhexidine and povidone-iodine.10

Intraoperative period

Sterile field preparation includes preparing the patient's skin (chlorhexidine-alcohol scrub regimens have been shown to be superior to povidone-iodine), sterile draping, and administering prophylactic antibiotics (typically cefazolin, or vancomycin if the patient is allergic to beta-lactams).25 Antibiotics are administered IV within 30 to 60 minutes before skin incision and at least 5 to 10 minutes before tourniquet inflation.14 Frequent glove and scalpel blade changes also can help reduce infection risk, as can reducing time to skin closure, applying a sterile dressing, and using an appropriate irrigation solution. Although antibiotic-containing irrigating solutions are common, evidence does not support these solutions for infection control.26 Wound irrigation with dilute povidone-iodine before wound closure has been demonstrated effective for infection control.27 For patients undergoing total knee arthroplasty, implant cement that elutes antibiotic for weeks after joint arthroplasty is another method of infection control.14,28

Postoperative period

During recovery, patients are continued on antibiotics for 24 to 48 hours, usually until the urinary catheter is removed. Patients should be taught home care for their surgical incision, and to report any signs and symptoms of infection to their healthcare provider. Tell patients to take prophylactic antibiotics before any dental, gastrointestinal, or genitourinary procedure. In addition, explain the infection risk presented by skin lacerations and puncture wounds. Patients are at highest risk for hematologic seeding in the 2 years after joint arthroplasty.14


With the large projected increase in patients seeking joint arthroplasty, primary care providers will need to know how to recognize and manage periprosthetic joint infections. The cost of periprosthetic joint infections is substantial, in terms of longer and more complex medical treatment, effect on patient quality of life and psychologic well being, and possible loss of the joint or limb. Nonsurgical treatment options are suitable only when infections are detected early and when pathogens are antibiotic-susceptible. Surgical treatment options depend on the duration of infection and virulence of the pathogen. Longer duration infections and more virulent pathogens are associated with higher consequences and cost of treatment that may lead to salvage procedures. Education and increased awareness can help increase preventive measures and early diagnosis, improving patient outcomes.


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    periprosthetic joint infection; knee; hip; arthroplasty; implant; orthopedics

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