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 ankylosing 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 (24-48 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 of 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 (e.g. 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 have 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 modality 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 30-40% 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 scores below 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 preoperative score (2-5) or dry aspiration) positive histology (>5 PMN/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% and specificity 95% false positives RA multiple sclerosis AIDS Paget's disease of bone Joint aspiration indications whenever there is a strong suspicion, diagnostic confirmation 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 is 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 wait 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 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 refuses surgery systemic spread and maintenance of 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 poor prognosis: high antibiotic resistance (MRSA, VRE, Pseudomonas), biofilm formation (S. epidermidis), fungi, mycobacterium 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 4-6 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 use antibiotic-impregnated cement when using 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 two-stage revision for methicillin-resistant organisms