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Updated: Jan 21 2024

Prosthetic Joint Infection

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  • summary
    • Prosthetic joint infections are serious complications of hip and knee arthroplasty and a common cause for revision arthroplasty
    • Diagnosis is multifaceted and includes elevated inflammatory markers, radiographic changes around the prosthesis, and aspiration results
    • Treatment generally involves prolonged IV antibiotics and two-stage revision arthroplasty
  • Epidemiology
    • Incidence
      • primary joint replacement
        • 1-2% TKA vs. 0.3-1.3% THA
      • revision joint replacement
        • 5-6% TKA vs. 3-4% THA
    • Risk factors
      • preoperative
        • active infection
          • local cutaneous, subcutaneous, deep-tissue, or joint infection
          • systemic septicemia
        • previous local surgery/prior local infection
      • postoperative
        • immune suppression
          • immunosuppressant drugs
            • anti-TNF agents (e.g. infliximab, etanercept, adalimumab, certolizumab, golimumab)
            • antimetabolites (e.g. leflunomide)
            • corticosteroids
          • immunosuppressive conditions (dysplasia or neoplasia)
            • poorly controlled diabetes mellitus (HBA1c >7)
            • chronic renal disease
            • acute liver failure
            • malnutrition (e.g. albumin <3.5; total serum leukocytes <800)
            • HIV (CD4 counts <400)
        • inflammatory arthropathy
          • rheumatoid arthritis
          • psoriasis
          • ankylosis spondylitis
        • lifestyle factors
          • morbid obesity
          • smoking
          • excessive alcohol consumption
          • intravenous drug use
          • poor oral hygiene
  • Etiology
    • Pathophysiology
      • most common bacterial organisms include
        • Staphylococcus aureus
        • Staphylococcus epidermidis
        • Coagulase-negative Staphylococcus (chronic infections)
      • most common fungal pathogen
        • Candida species (e.g. Candida albicans)
    • Prophylaxis
      • screening
        • screen and optimize risk factors
        • nasal mupirocin for decolonization of nasal MSSA/MRSA
        • routine urine cultures NOT warranted preoperatively, unless history or symptoms of UTI
        • stop DMARDs 4-6 weeks prior to surgery
        • revision joint replacement
          • normalized ESR, CRP off antibiotics
        • patients with a reported allergy to cephalosporin or penicillin antibiotics should undergo preoperative allergy screening
      • operatively
        • preoperative skin cleansing with antiseptic wash
        • systemic antibiotics
          • administered within 30 minutes to incision, and >10 minutes prior to tourniquet
          • continued for 24 hours after surgery
            • no benefit to extended (24 to 48 hours) antibiotics in the aseptic revision setting
          • weight-based dosing should be utilized, as patients weighing >120 kg are frequently underdosed
            • For cefazolin: 1 gram for patients <60 kg, 2 grams for patients 60-120 kg, and 3 grams for patients >120 kg
        • operative room
          • vertical laminar airflow systems
          • limit hospital personnel OR traffic in-and-out of room
      • postoperatively
        • antibiotic prophylaxis prior to dental work is dependent on host risk factors
  • Classification
    • Time of onset
      • acute infection
        • infection within 3-6 weeks from surgery
          • CDC definition <90 days from date of joint replacement
        • biology
          • usually confined to joint space
          • no invasion into prosthetic-bone interface
          • no biofilm production
        • S. aureus commonly associated with acute THA PJIs
      • chronic infection
        • infection more than 3-6 weeks from surgery
          • CDC definition >90 days from date of joint replacement
        • biology
          • biofilm created by all bacteria forms on implant within 4 weeks
            • composition
              • 15% cells and 85% polysaccharide layer (glycocalyx)
              • glycocalyx allows biofilm to adhere to prosthesis and seal off infection to protect bacteria from host immune system
            • quorum refers to the concentration of bacteria needed in order to shift the colony's focus away from replication and toward biofilm production
            • consequence
              • no method exists to safety remove biofilm and eradication is difficult
              • prosthetic explant indicated with infection >4 weeks due to biofilm
            • infection has invaded prosthetic-bone interface
          • S. epidermidis most common organism in chronic THA PJIs
    • Source of infection
      • direct invasion
        • sinus tract into joint capsule
        • wound dehiscence
      • hematogenous infection
        • infection in a longstanding infection-free joint secondary to another infection (e.g. dental work, infected gallbladder)
  • Presentation
    • History
      • may have history of the following
        • recent or active bacteremia
        • multiple local surgeries
        • skin/epithelial tissue penetration (eg. IV drug use, colonoscopy, dental work, ulceration, wound complication)
    • Symptoms
      • persistent pain and stiffness at site of arthroplasty is associated with infection in >90% of patients
      • acute onset with swelling, tenderness, and drainage
      • chronic infections show pain and more subtle symptoms
        • function deteriorates over time
        • pain worsens over time
    • Physical exam
      • inspection
        • sinus tract to the joint is a definite infection
        • warmth, redness, or swelling
        • low grade fever
      • motion
        • limited by pain and swelling
  • Imaging
    • Radiographs
      • findings
        • periosteal reaction
        • scattered patches of osteolysis
        • generalized bone resorption without implant wear
        • transcortical sinus tracts
        • implant loosening
    • Bone scan
      • modalitity
        • Tc-99m (technetium) detects inflammation and In-111 (indium) detects leukocytes
        • triple scan can differentiate infection from fracture or bone remodeling
      • indications
        • if infection is suspected, but cannot be confirmed by aspiration or blood work
      • sensitivity and specificity
        • 99% sensitivity and 30% to 40% specificity
    • Positron emission tomography (PET)
      • indication
        • may help to identify areas of high metabolic activity using fluorinated glucose
      • sensitivity and specificity
        • 98% sensitivity and 98% specificity
  • diagnostic criteria
    • 2018 criteria for prosthetic joint infections as defined by Parvizi and associates
      • derived from 2011 MSIS; 98% sensitivity and 99.5% specificity for diagnosing PJI
      • major criteria (diagnosis can be made when 1 major criteria exist)
        • sinus tract communicating with prosthesis
        • pathogen isolated by culture from 2 separate tissue/fluid samples from the affected joint
      • minor criteria (preoperative diagnosis)
        • the below scores are added together to determine:
          • ≥6 = infected; 2-5 = inconclusive; 0-1 = not infected
        • serum labs
          • elevated CRP (>10 mg/L) or D-dimer (>860 ng/mL) - 2 points
          • elevated ESR (>30 mm/h) - 1 point
        • synovial fluid analysis
          • elevated synovial WBC (>3,000 cells/µl) or leukocyte esterase - 3 points
          • positive alpha-defensin - 3 points
            • most sensitive and specific marker for PJI
          • elevated synovial PMN (>80%) - 2 points
          • elevated synovial CRP (>6.9 mg/L) - 1 point
      • inconclusive (inconclusive preop score (2-5) or dry aspiration)
        • positive histology (>5 PMN per hpf in 5 hpf at x400 magnification (intraoperative frozen section of periprosthetic tissue) - 3 points
        • purulence in affected joint - 3 points
        • single positive culture - 2 points
        • preoperative score + intraoperative score combined
          • combined score ≥6 = infected; 4-5 = inconclusive; 0-3 = not infected
  • Studies
    • Labs
      • blood panel
        • WBC
          • not specific or sensitive
      • ESR and CRP
        • CRP
          • physiology
            • peaks 2-3 days after surgery
            • returns to normal at 21 days (3 weeks)
          • normal range
            • acute (<6 weeks from surgery) = <100 mg/L
            • chronic (>6 weeks from surgery) = <10 mg/L
        • ESR
          • physiology
            • peaks 5-7 days after surgery
            • returns to normal 90 days (3 months)
          • normal range
            • acute (<6 weeks from surgery) = no consequences
            • chronic (>6 weeks from surgery) = <30 mm/hr
      • serum interleukin-6 (IL-6, normal <10 pg/mL)
        • physiology
          • peaks 8-12 h after surgery
          • returns to normal 48-72 h after surgery (3 days)
          • less commonly followed, but can monitor and follow the progress of infection
        • outcomes
          • has been shown to have the highest correlation with periprosthetic joint infection
          • sensitivity 100%, specificity 95%
          • false positives
            • RA
            • multiple sclerosis
            • AIDS
            • Paget's disease of bone
    • Joint aspiration
      • indications
        • whenever there is a strong suspicion in order to confirm the diagnosis
      • lab order request
        • cell count and differential
        • crystals
        • Gram stain
        • cultures and specificity
      • outcomes
        • cell count and differential
          • lowest serologic values suggestive of infection
            • synovial WBC >3,000 cells/ul and PMN >80% in knees
              • synovial WBC >10,000 cells/ul in the first 6 weeks after TKA suggestive of infection
            • WBC >3,000 cells/ul and PMN >80% for hips
            • WBC >4,350 cells/ul and PMN >85% for MoM hips
            • WBC >1,166 cells/ul and PMN >64% for hip antibiotic spacers
        • Gram stain
          • stain for bacteria in sample
          • specificity > sensitivity
            • positive test would be indicative of infection, however a negative test does not rule out infection
        • repeat aspiration
          • indicated in cases of inconclusive aspirate and peripheral lab data
          • waiting 2 weeks for a repeat aspiration off antibiotics
      • other tests
        • alpha-defensin immunoassay test
          • peptide released by neutrophils
          • 100% sensitivity and 98% specificity for diagnosis of PJI
          • sensitivity not affected by previous antibiotic administration
        • leukocyte esterase colorimetric strip test
    • Perioperative analysis
      • microbiology
        • definitive diagnosis can be made if the same organism is obtained by repeat aspirations or at least 3 of 5 periprosthetic specimens obtained at surgery
          • complications
            • false-positive rate is 8%
            • tissue samples are better than swabs
      • histology
        • intraoperative frozen section
          • indications
            • equivocal cases with elevated ESR and CRP or suspicion for infection
            • sensitivity 85% and specificity 90-95%
            • >5 PMNs/hpf x 5 hpf is probable for infection
  • Treatment
    • Nonoperative
      • chronic suppressive antibiotic therapy
        • indications
          • unfit for surgery
          • refuse surgery
          • systemic spread and maintain joint motion with symptomatic relief
        • outcomes
          • 10-25% eradication success rate
          • 8-21% complication rate
    • Operative
      • Debridement, Antibiotics, and Implant Retention (DAIR)  
        • indications
          • acute infection (<3-4 weeks after initial TKA/THA)
          • acute hematogenous infection (ideally <48-72 h from symptom onset)
        • techniques
          • modular component exchange (i.e. polyethylene, femoral head), tissue debridement with synovectomy, and 6-9 L irrigation
        • outcomes
          • 50-55% success rate
          • implants must be removed if reinfection documented
          • dependent on bacteria speciation
      • one-stage replacement arthroplasty
        • indications
          • used more commonly in Europe for infected THA
          • no sinus tract, healthy patient and soft tissue, no prolonged antibiotic use, no bone graft
          • low-virulence organism with good antibiotic sensitivity
        • technique
          • use antibiotic-impregnated cement
        • advantages
          • lower cost and convenience with single procedure
          • earlier mobility
        • disadvantages
          • higher risk of continued infection from residual microorganisms
        • outcomes
          • variable success of 75-100%
      • two-stage replacement arthroplasty
        • indications
          • gold standard for an infected joint >4 weeks after arthroplasty
          • must be medically fit for multiple surgeries
          • requires adequate bone stock
          • requires confirmation of microbial eradication
            • benign clinical exam
            • normal labs (WBC, ESR, and CRP)
            • negative aspiration cultures
              • obtain repeat cultures at least 2 weeks after planned antibiotic course has been completed
        • techniques (see section below)
          • prosthesis removal, antibiotic spacer, IV antibiotics for 4-6 weeks, and delayed reconstruction
        • outcomes
          • bilateral TKA resection arthroplasty followed by 6 weeks of antibiotics and bilateral reimplantation has excellent results at 2-year follow-up
          • early reimplantation within 2 weeks has 35% success rate
          • delayed reimplantation >6 weeks has a 70-90% success rate
          • cementless reimplantation in the hip has better outcomes than cemented
      • resection arthroplasty
        • indications
          • poor bone and soft tissue quality
          • recurrent infections with multi-drug resistant organisms
          • medically unfit for multiple surgeries
          • failure of multiple previous reimplantations
          • elderly nonambulatory patients
        • disadvantages
          • short limb, poor function, and patient dissatisfaction
        • technique
          • remove all infected tissue and components with no subsequent reimplantation
        • outcomes
          • total knee success rate is 50-89%
          • total hip success rate is 60-100%
      • arthrodesis
        • indications
          • reimplantation is not feasible due to poor bone stock
          • recurrent infections with virulent organisms
        • outcomes
          • 71-95% success rate with bony fusion and infection eradication
      • amputation
        • indications
          • total knee infections recalcitrant to other options
          • severe pain, soft tissue compromise, severe bone loss, or vascular damage
        • technique
          • AKA
  • Techniques
    • Surgical debridement and polyethylene exchange
      • debridement
        • modular parts should be removed to remove fibrin layer between plastic and metal parts (acts as a nidus of infection)
      • polyethylene exchange
        • be sure component available
    • Two-stage replacement arthroplasty
      • prosthetic explant
      • surgical debridement
        • must debride bone implant interface and soft tissues
      • antibiotic spacer and IV antibiotics
        • advantages of spacers
          • reduce joint dead space, provide stability, and deliver high dose antibiotics
        • disadvantages of spacers
          • potential local or systemic allergic reactions
          • increased chance of developing antibiotic-resistant organisms
          • only heat-stable antibiotics can be added to cement
        • static or dynamic (articulating) spacers can be used
        • advantages of static spacers
          • allow delivery of higher doses of antibiotics (not premade)
          • better wound healing (no joint motion)
          • indicated when there is flap coverage, extensive bone loss, or ligamentous deficiency 
        • advantages of articulating spacers
          • decreased reimplantation exposure time
          • better maintenance of joint space and motion
          • decreased quad shortening
          • better patient satisfaction
          • both spacer types have equivalent functional outcomes and rate of infection recurrence
        • spacer antibiotics
          • each 40 g bag of cement should have 3 g of vancomycin and 4 g of tobramycin added
            • gentamycin may be substituted for tobramycin
          • elution of antibiotics depends on cement porosity, surface area (beads increase area), and antibiotic concentration
          • must use heat stable antibiotics (vancomycin, tobramycin, gentamicin)
        • IV antibiotics
          • wait to administer intraoperatively until aspiration and cultures taken
          • must be administered for 4 to 6 weeks after explant
          • initial empiric regimen
            • first-generation cephalosporin
            • vancomycin (if any of the following are true)
              • true allergic sensitivity to penicillin
              • prior history of or documented exposure to MRSA
              • unidentified organism
            • fluconazole
              • preferred for antifungal infections
                • similar efficacy with IV and oral formulations
          • tailor the regimen based on microorganism and susceptibility testing
      • reimplantation
        • send tissue specimens for culture and frozen section pathology
        • implant only if all preoperative and intraoperative measures are acceptable
        • if intraoperative frozen section demonstrates acute inflammation, debride the wound, reapply cement spacer, and return later
        • when using cement, use antibiotic-impregnated cement
  • Local Antibiotics
    • Properties
      • active against the organism
      • can be incorporated into delivery vehicle (PMMA)
      • thermo stable (will not denature during exothermic polymerization reaction)
    • Choices
      • aminoglycosides (gentamicin, tobramycin)
        • effective against gram-negative bacilli
        • synergistic against gram-positive cocci (Staphylococcus, Enterococcus)
        • low risk of systemic toxicity
      • Vancomycin
        • effective against gram-positive cocci
        • excellent elution properties
    • Doses
      • low dose = 2 g antibiotics:40 g of cement
        • commercial antibiotic cement is low dose
          • Cobalt G-HV (Biomet)
          • Palacos R+G (Zimmer)
          • Simplex P (Stryker)
          • Cemex Genta (Exactech)
          • SmartSet GMV (Depuy)
          • VersaBone AB (Smith & Nephew)
        • associated with lower infection rate
      • high dose ≥ 3.6 g antibiotics:40 g of cement
        • highest doses without systemic toxicity
          • 12.5 g tobramycin:40 g cement
          • 10.5 g vancomycin:40 g cement
      • practical dose
        • vancomycin is 1 g per vial, tobramycin is 1.2 g per vial
        • use 3 g vancomycin and/or 3.6 g tobramycin in 40 g cement
          • use extra liquid monomer (1.5-2 ampoules monomer:1 bag cement)
    • Elution properties
      • rapid release in initial 24 h
      • followed by rapid decline in release rate
        • combination dosing (both tobramycin + vancomycin) increases release rate of antibiotics (more than if each were used alone)
      • low levels at 5 weeks
      • experimental models do NOT show difference in elution/concentrations in conventional wound closure vs negative-pressure wound therapy (NPWT)
    • Mixing
      • vacuum mixing
        • removes air bubbles
        • enhances mechanical properties
        • may increase/decrease antibiotic elution rates
      • hand mixing
        • may lead to uneven distribution of antibiotics within cement and inconsistent release
      • sequence of ingredients
        • adding vancomycin powder after cement powder + liquid monomer mixed for 30 s results in greater elution
    • Newer techniques
      • vancomycin powder directly into wounds (mostly in spine literature)
      • antibiotic cement coated IM nails
      • local antibiotics bonded to implant surface
  • Complications
    • Failure to eradicate infection
      • poorer prognosis for 2-stage revision for methicillin-resistant organisms
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