Prosthesis infection

1. High-Yield Summary

Periprosthetic joint infection (PJI) is a catastrophic complication of total joint arthroplasty characterized by microbial colonization of implant surfaces and adjacent periprosthetic tissues. Definitive clinical management and surgical decision-making rely on five core principles:

• Diagnostic Imperative and Workup Sequence: PJI must be actively excluded in any painful, stiff, or mechanically failing total joint replacement. Serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) serve as mandatory first-line screening biomarkers. Empiric antimicrobial therapy must strictly never be initiated prior to diagnostic joint arthrocentesis. Synovial fluid leukocyte count, polymorphonuclear neutrophil percentage (% PMN), leukocyte esterase (LE), and synovial alpha-defensin guide diagnosis according to validated International Consensus Meeting (ICM) 2018 and European Bone and Joint Infection Society (EBJIS) criteria.
• Biofilm Pathobiology: PJI is fundamentally an implant-associated biofilm disease. Planktonic microorganisms adhere to abiotic biomaterial surfaces (cobalt-chromium, titanium, polyethylene, PMMA) and synthesize a protective extracellular polymeric substance (EPS) matrix. Within 3 to 4 weeks of initial inoculation, bacteria transition into a metabolically quiescent, sessile persister phenotype that confers up to a 1,000-fold tolerance to host immune responses and systemic cell-wall active antibiotics.
• Surgical Stratification: Debridement, Antibiotics, and Implant Retention (DAIR) is indicated strictly for acute early post-arthroplasty infections presenting within 3 to 4 weeks of index arthroplasty, or acute hematogenous infections with less than 3 weeks of symptoms, provided implants are well-fixed, soft tissues are healthy, and modular components are exchanged. Chronic mature biofilm infections require complete component explantation via one-stage or two-stage exchange arthroplasty.
• Antimicrobial Synergy and Biofilm Penetration: Eradication requires pathogen-directed bactericidal agents with documented biofilm activity. Staphylococcal infections require rifampin-based combination regimens initiated only after surgical debridement, negative blood cultures, and complete wound healing. Fluoroquinolones provide comparable oral biofilm activity for susceptible Gram-negative organisms. Contemporary evidence confirms that early transition to targeted high-bioavailability oral antimicrobials achieves infection eradication rates equivalent to prolonged intravenous therapy.
• Eradication Benchmarks: Infection-free survivorship reaches 60% to 80% following DAIR in rigorously selected acute presentations, 85% to 90% after one-stage exchange arthroplasty in highly selected patients with identified sensitive pathogens, and 85% to 95% after two-stage exchange arthroplasty, which remains the global benchmark for chronic, polymorphic, resistant, or culture-negative infections.

2. Anatomy

Surgical intervention for periprosthetic joint infection demands precise anatomical knowledge to safely debride infected tissues, retrieve well-fixed hardware, and reconstruct massive osseous defects without injuring adjacent neurovascular structures.

Neurovascular Danger Zones

Revision exposures for infected hip and knee arthroplasties navigate scarred, distorted anatomical beds with elevated risk of neurovascular injury:

• Sciatic Nerve (Hip): Exits the greater sciatic foramen inferior to the piriformis and traverses posterior to the acetabulum over the obturator internus, gemelli, and quadratus femoris. In chronic PJI with extensive posterior scarring, component displacement, or metallosis, the sciatic nerve is frequently tethered directly to the posterior pseudocapsule. Retractors placed over the posterior acetabular rim or aggressive posterior capsulectomy can cause traction neuropraxia, laceration, or thermal injury during cement removal. The nerve is at extreme risk during extended trochanteric osteotomy (ETO) or posterior column screw placement.
• Femoral Neurovascular Bundle (Hip): Courses anterior to the hip joint within the femoral triangle. Anterior capsular debridement, anterior retractor placement over the anterior acetabular wall, or transfixion screws directed into the anterior-superior and anterior-inferior quadrants of the acetabulum place the femoral artery, femoral vein, and femoral nerve at immediate risk of puncture, pseudoaneurysm, or transection.
• Superior Gluteal Nerve (Hip): Exits the greater sciatic notch superior to the piriformis and courses anteriorly between the gluteus medius and gluteus minimus. Proximal dissection or retractor placement exceeding 3 to 5 cm superior to the greater trochanter during transgluteal (Hardinge) or anterolateral approaches causes denervation of the tensor fasciae latae, gluteus medius, and gluteus minimus, precipitating permanent abductor insufficiency and a severe Trendelenburg gait.
• Obturator Neurovascular Bundle (Hip): Traverses the obturator canal along the medial wall of the acetabulum. Deep intrapelvic acetabular reaming, protrusio acetabuli revision, medial cement extrusion, or penetration of screws through the true medial acetabular wall or teardrop risks severe intrapelvic vascular hemorrhage and obturator nerve injury.
• Popliteal Neurovascular Bundle (Knee): Composed of the popliteal artery, popliteal vein, and tibial nerve, situated immediately posterior to the posterior knee capsule and posterior cruciate ligament footprint, separated only by thin retrocondylar fat. Radical posterior synovectomy, posterior capsulotomy, posterior osteophyte resection, or oscillating saw penetration through the posterior femoral cortex exposes the popliteal artery to catastrophic laceration. Maintaining the knee in greater than 90 degrees of flexion allows the neurovascular bundle to fall posteriorly away from the tibial rim, expanding the safe margin of debridement.
• Common Peroneal (Fibular) Nerve (Knee): Winds around the fibular neck lateral to the proximal tibia. Vulnerable during radical posterolateral capsular debridement, release of the lateral collateral ligament, extensive subperiosteal exposure of the proximal lateral tibia, or secondary to acute correction of long-standing severe valgus and flexion contractures during spacer or implant seating.

Internervous and Intermuscular Planes

Safe surgical re-exposure requires disciplined adherence to anatomical planes, particularly when previous surgical scarring obscures normal fascial boundaries:

• Posterior (Moore / Southern) Approach to the Hip: Intermuscular approach splitting the gluteus maximus (inferior gluteal nerve) along its fiber orientation, followed by division of the short external rotators (piriformis, obturator internus, gemelli, quadratus femoris). It protects the abductor mechanism (superior gluteal nerve) and femoral nerve, but requires continuous visual protection and palpation of the sciatic nerve.
• Direct Anterior (Smith-Petersen / Hueter) Approach to the Hip: Employs the true internervous plane between the tensor fasciae latae (superior gluteal nerve) laterally and the sartorius and rectus femoris (femoral nerve) medially. Ascending branches of the lateral circumflex femoral vessels must be coagulated or ligated. The lateral femoral cutaneous nerve courses in close proximity across the anterior fascia and requires deliberate protection.
• Anterolateral (Watson-Jones) Approach to the Hip: Utilizes the plane between the tensor fasciae latae and the anterior border of the gluteus medius. Both muscles are innervated by the superior gluteal nerve, making this an intermuscular interval between distinct nerve branches.
• Medial Parapatellar Approach to the Knee: The standard exposure for septic knee revision. Incises longitudinally through the medial third of the quadriceps tendon, medial patellar retinaculum, and along the medial border of the patellar tendon into the proximal tibia. There is no internervous plane because the quadriceps musculature is innervated exclusively by the femoral nerve; extensive proximal extension requires care to avoid denervating the vastus medialis obliquus.

Periprosthetic Pseudocapsule and Osseous Dead Space

Chronic periprosthetic infection induces massive biological transformation of the surrounding joint envelope. The physiological synovium is replaced by a thickened, avascular pseudocapsule composed of dense fibrous connective tissue, granulation tissue, inflammatory neointima, and necrotic debris. This pseudocapsule acts as a physical shield harboring microscopic bacterial colonies and preventing adequate penetration of circulating systemic antimicrobials. Radical capsulectomy and synovectomy are obligatory steps during revision surgery to eradicate this biological reservoir.

Implant loosening, osteolysis, and aggressive debridement create critical periprosthetic osseous dead spaces. When bone stock is lost from the acetabulum, proximal femur, distal femur, or proximal tibia, dead space fills with hematoma and serous fluid, creating an ideal low-oxygen environment for persistent bacterial proliferation. Surgical reconstruction must eliminate dead space through the strategic use of antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers, bioactive absorbable carriers, or modular porous metal reconstruction.

3. Pathogenesis

The pathogenesis of periprosthetic joint infection represents a dynamic battle between host immune defenses and microbial adaptation, centered entirely upon the lifecycle of implant-adherent biofilms.

The Biofilm Lifecycle

A biofilm is an organized bacterial consortium enclosed within a self-produced extracellular polymeric substance (EPS) matrix irreversibly attached to an abiotic or biotic surface. The developmental progression follows five defined phases:

• Phase 1: Reversible Planktonic Attachment (Seconds to Minutes): Immediately upon implantation, prosthetic hardware is coated by host plasma and extracellular matrix proteins, including fibronectin, fibrinogen, vitronectin, and type I collagen. Circulating planktonic bacteria encounter this conditioned surface via passive hydrodynamic transport, Brownian motion, and electrostatic interactions. Bacterial surface adhesins, notably Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs), bind specific host ligands. At this earliest juncture, bacterial attachment remains weak and physically reversible.
• Phase 2: Irreversible Sessile Adhesion and Phenotypic Transition (Hours): Stable anchorage occurs as bacteria engage surface structures through hydrophobic interactions, pili, and fimbriae. This mechanical contact triggers immediate mechanosensitive signal transduction cascades, downregulating flagellar and motility genes while upregulating genes responsible for EPS synthesis and quorum-sensing communications. Attachment becomes irreversible.
• Phase 3: Extracellular Polymeric Substance (EPS) Matrix Synthesis and Maturation (Days to Weeks): Microcolonies proliferate and secrete large quantities of EPS, composed of hydrated polysaccharides (such as staphylococcal polysaccharide intercellular adhesin [PIA]), extracellular DNA (eDNA), structural proteins, and amyloid fibers. The EPS forms a hydrated three-dimensional scaffold accounting for greater than 90% of total biofilm biomass. Interspersed interstitial fluid channels deliver nutrients and evacuate metabolic byproducts throughout the colony.
• Phase 4: Sessile Phenotype and Metabolic Dormancy (Persister Cells): Within the deep hypoxic and nutrient-deprived core of the mature biofilm, bacterial cells undergo severe metabolic downshifts. Cellular respiration decelerates, cell wall turnover halts, and bacteria transition into dormant “persister cells.” Because beta-lactams and aminoglycosides target actively replicating bacteria and cell wall synthesis, persister cells demonstrate profound phenotypic antibiotic tolerance. The minimum biofilm eradication concentration (MBEC) can exceed the minimum inhibitory concentration (MIC) of planktonic bacteria by 100 to 1,000 times.
• Phase 5: Detachment, Dispersal, and Metastatic Seeding: Under the control of quorum-sensing gene systems (such as the staphylococcal accessory gene regulator [agr] system) and targeted enzymatic digestion (proteases, nucleases, and surfactant phenol-soluble modulins), clusters of sessile bacteria detach from the mature biofilm. These released planktonic organisms colonize adjacent periprosthetic bone, enter the synovial fluid to cause acute septic arthritis, or enter the systemic circulation to generate bacteremia.

Microbial Spectrum

The microbial etiology of PJI spans high-virulence pyogenic organisms, indolent commensal skin flora, and complex polymicrobial communities:

• Staphylococcus aureus (20% to 30%): Includes methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains. Manifests with acute, highly destructive presentations mediated by powerful virulence factors, including alpha-hemolysin, coagulase, protein A, Panton-Valentine leukocidin, and enterotoxins that trigger rapid tissue necrosis and bone destruction.
• Coagulase-Negative Staphylococci (CoNS) (20% to 30%): Primarily Staphylococcus epidermidis, followed by Staphylococcus lugdunensis, Staphylococcus capitis, and Staphylococcus hominis. These ubiquitous skin commensals are the quintessential biofilm producers on arthroplasty hardware, typically presenting as delayed, low-grade, or subacute infections characterized by progressive loosening and mild joint pain. Note that S. lugdunensis possesses unique virulence traits and behaves clinically with the aggressive destruction of S. aureus.
• Streptococcal and Enterococcal Species (8% to 12%): Includes beta-hemolytic streptococci (Groups A, B, C, G), Streptococcus viridans, and Enterococcus faecalis / Enterococcus faecium. Streptococci frequently present as acute hematogenous seeding from pharyngeal or skin infections. Enterococci produce recalcitrant biofilm, demonstrate intrinsic resistance to cephalosporins, and show high clinical failure rates requiring dual-agent synergistic bactericidal therapy (such as ampicillin plus ceftriaxone).
• Cutibacterium acnes (5% to 10% overall; 30% to 40% in shoulder arthroplasties): An anaerobic, slow-growing Gram-positive bacillus inhabiting sebaceous glands. Highly prevalent in periprosthetic shoulder infections due to the high density of pilosebaceous units around the shoulder girdle. Causes insidious, indolent osteolysis, component loosening, and persistent discomfort without classic signs of inflammation, fever, or elevated serum CRP/ESR. Requires extended anaerobic culture incubation (14 to 21 days) for detection.
• Gram-Negative Bacilli (5% to 10%): Includes Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis. Often originating from urinary, gastrointestinal, or decubitus ulcer sources, or following prior surgical interventions. Frequently multidrug-resistant (ESBL or carbapenemase producers) and associated with lower salvage rates following DAIR.
• Polymicrobial and Culture-Negative PJI (10% to 15% and 5% to 12%): Polymicrobial infections typically occur following sinus tract fistulization, extensive surgical wound dehiscence, or contaminated trauma arthroplasties. Culture-negative PJI is most commonly driven by recent empiric antibiotic suppression prior to joint aspiration, fastidious or nutritionally deficient pathogens, fungal organisms (such as Candida albicans or Candida parapsilosis), or atypical mycobacteria.

Host Immune Evasion and Septic Osteolysis

Biofilms confer profound immune evasion capabilities. The EPS matrix acts as a physical barrier preventing host immunoglobulins (IgG) and complement factors (C3b) from opsonizing bacterial cell walls, thereby blocking neutrophil and macrophage phagocytosis. Furthermore, neutrophils encountering mature biofilms become exhausted and release reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) into the local microenvironment, causing collateral destruction of surrounding host periprosthetic tissue without killing the embedded bacteria. Additionally, S. aureus can invade host osteoblasts and osteocytes via alpha5-beta1 integrin-mediated endocytosis, establishing an intracellular sanctuary within the bone canalicular network.

Septic osteolysis results from an uncoupling of normal bone remodeling driven by pathogen-associated molecular patterns (PAMPs). Bacterial lipoteichoic acid (LTA), peptidoglycan, and lipopolysaccharide (LPS) bind to Toll-like receptors (TLR-2 and TLR-4) on resident macrophages, dendritic cells, and osteoblasts. This signaling activates nuclear factor kappa B (NF-kB), unleashing a surge of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and receptor activator of nuclear factor kappa B ligand (RANKL). Massive upregulation of RANKL relative to osteoprotegerin (OPG) drives osteoclastogenesis and pathologic osteoclastic bone resorption, while bacterial toxins simultaneously induce osteoblast apoptosis. The consequence is progressive periprosthetic cavitation, endosteal scalloping, loss of mechanical fixation, and component loosening.

4. Natural History

Without timely and definitive surgical and antimicrobial intervention, periprosthetic joint infection is a progressive, debilitating, and potentially lethal condition.

Epidemiology and Risk Stratification

The baseline incidence of PJI following elective primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) ranges from 0.5% to 2.0%. Following revision arthroplasty, the incidence increases to 3.0% to 5.0%, and can exceed 10% to 15% following complex oncologic reconstructions or revisions performed for prior septic failures. In total shoulder arthroplasty, the incidence is approximately 1.0% to 1.5%, rising to 2.0% to 4.0% in reverse shoulder arthroplasty. Total elbow arthroplasty carries the highest baseline risk among joint replacements, with infection rates of 3.0% to 8.0% due to the thin surrounding soft-tissue envelope.

Patient-specific and surgical risk factors dramatically amplify this risk:

• Host Factors: Uncontrolled diabetes mellitus (HbA1c > 7.5% to 8.0%), morbid obesity (BMI > 40 kg/m²), active tobacco smoking, chronic kidney disease on hemodialysis, liver cirrhosis, severe rheumatoid arthritis, active immunosuppressive therapy (particularly biologic TNF-alpha antagonists), severe malnutrition (serum albumin < 3.5 g/dL, total lymphocyte count < 1,500 cells/µL), and active bacteremia or distant chronic foci of infection.
• Surgical and Perioperative Factors: Operative duration exceeding 120 minutes, bilateral simultaneous procedures, allogeneic blood transfusion, postoperative hematoma formation, prolonged wound drainage (>48 to 72 hours), early wound dehiscence, and lack of weight-adjusted, appropriately timed perioperative prophylactic antibiotics.

Temporal Windows of Presentation

PJI presents along a temporal continuum dictated by the mode of inoculation and microbial virulence:

• Early Postoperative Infections (<4 Weeks from Surgery): Direct intraoperative inoculation or immediate postoperative contamination by virulent pathogens (S. aureus, Gram-negative bacilli). Manifests acutely with severe incisional pain, persistent wound drainage, spreading periprosthetic erythema, local warmth, joint effusion, and systemic fevers.
• Delayed / Subacute Infections (3 Months to 2 Years): Direct intraoperative inoculation by low-virulence organisms (CoNS, C. acnes). Characterized by an insidious, indolent clinical course. Patients report progressive, unremitting joint ache, joint stiffness, and gradual loosening. Systemic signs and laboratory inflammatory markers are often normal or only mildly elevated, leading to frequent misdiagnosis as aseptic loosening.
• Late Hematogenous Infections (>2 Years): Secondary bacteremic seeding of a previously well-functioning, pain-free prosthetic joint from a distant source (urosepsis, bacteremic dental manipulation, pneumonia, indwelling vascular catheters, skin cellulitis). Characterized by sudden, explosive onset of severe joint pain, massive effusion, inability to bear weight, and high fevers in a patient with a previously asymptomatic arthroplasty.

Progression of Untreated Infection

Untreated PJI invariably culminates in structural and systemic destruction. Locally, ongoing osteoclast activation produces catastrophic periprosthetic bone loss, leading to component subsidence, gross hardware migration, periprosthetic fracture, and complete joint destabilization. The expanding purulent effusion tracks along paths of least resistance, eroding the joint capsule and deep fascia to form a cutaneous sinus tract. Spontaneous fistulization may provide temporary decompression of joint pressure, converting an acute toxic presentation into a chronic, foul-smelling draining sinus with secondary polymicrobial superinfection.

Systemically, chronic infection drives persistent catabolism, secondary amyloidosis, recurrent bacteremia, metastatic seeding to native heart valves (endocarditis), severe sepsis, and death. Epidemiological registry analyses demonstrate that the 5-year mortality rate following periprosthetic joint infection exceeds 20%, a mortality burden surpassing that of common malignancies, including breast cancer and prostate carcinoma.

5. Clinical Presentation

The clinical evaluation of suspected PJI requires a comprehensive history paired with a rigorous physical examination designed to distinguish infection from mechanical arthroplasty failure.

History

Specific historical inquiry must identify key diagnostic flags:

• Pain Characteristics: Clinicians must distinguish septic pain from mechanical loosening. PJI typically causes continuous, unremitting pain present at rest and at night, superimposed on weight-bearing discomfort. In contrast, aseptic mechanical loosening produces strictly mechanical, start-up pain that resolves completely with recumbency and joint unloading.
• Index Surgical History and Wound Complications: Inquire about prolonged wound drainage beyond postoperative day 3, hematoma formation requiring re-aspiration or surgical evacuation, delayed incision healing, superficial dressing soaked with serosanguinous fluid, or manipulation under anesthesia (MUA) for unexplained stiffness. A history of an “unremarkable” surgery followed by never achieving a pain-free interval strongly suggests indolent infection.
• Antimicrobial History (“Antibiotic Holidays”): Document any recent courses of oral or intravenous antibiotics prescribed by primary care physicians, emergency departments, or dentists for vague joint pain or presumed cellulitis. Prior antibiotic therapy suppresses microbial proliferation in synovial fluid, causing false-negative joint aspirates. Whenever clinically safe, all antimicrobials must be withheld for at least 2 weeks prior to diagnostic arthrocentesis.
• Extrarticular Infectious Sources: Screen for recent invasive dental procedures, recurrent urinary tract infections, chronic decubitus ulcers, diabetic foot infections, indwelling catheters, recent colonoscopy, or intercurrent bacteremic illnesses.

Physical Examination

The physical examination must systematically evaluate the local soft-tissue envelope, joint biomechanics, and limb neurovascular status:

• Sinus Tract Inspection: Direct visualization of a cutaneous sinus tract or fistulous communication extending to the prosthetic hardware or joint cavity. Finding: Purulent or serosanguinous drainage tracking from deep fascia -> Pathognomonic for PJI [Sensitivity 20% to 30%, Specificity 100%].
• Cutaneous Temperature and Erythema Assessment: Palpation of local skin temperature compared to the contralateral unoperated joint using the dorsal aspect of the examiner’s hand, accompanied by mapping the borders of erythema and cutaneous induration. Finding: Palpable local calor and non-blanching erythema -> Highly suspicious for active soft-tissue inflammation or superficial cellulitis [Sensitivity 60% to 70%, Specificity 75% to 80%].
• Effusion and Fluctuance Ballottement: Compression of the suprapatellar pouch and lateral gutters in the knee, or deep palpation of the anterior groin and greater trochanteric bursa in the hip. Finding: Tense, warm, fluctuant periprosthetic joint effusion with patellar ballottement or tender anterior hip fullness -> Strongly predictive of intra-articular infection [Sensitivity 75% to 85%, Specificity 70% to 80%].
• Active and Passive Range of Motion Testing: Careful measurement of joint arc of motion and pain provocation. Finding: Severe guarded global restriction of motion with pain elicited throughout the entire passive arc, rather than isolated pain at terminal extension or flexion -> Indicates diffuse synovitis and joint distension characteristic of PJI [Sensitivity 80%, Specificity 50%].
• Neurovascular and Compartment Examination: Meticulous assessment of peripheral pulses (dorsalis pedis, posterior tibial), capillary refill, and motor/sensory distribution of the femoral, sciatic, common peroneal, and tibial nerves to exclude compartment syndrome, deep vein thrombosis, or compressive hematoma.

6. Imaging and Diagnostic Studies

The diagnostic workup of PJI follows an evidence-based hierarchy combining plain radiography, targeted advanced imaging, serum biomarkers, and rigorous synovial fluid analysis.

Plain Radiographs

High-quality plain radiographs remain the baseline diagnostic modality. Required views include weight-bearing anteroposterior (AP) and lateral projections of the affected joint, full-length femur/tibia views, and an AP pelvis view. Serial comparison against early postoperative baseline films is critical. Characteristic radiographic hallmarks of PJI include:

• Progressive Periprosthetic Radiolucency: Development of circumferential radiolucent lines exceeding 2 mm at the bone-implant or bone-cement interface within the first year postoperatively.
• Rapidly Evolving Osteolysis: Focal, aggressive endosteal scalloping, cortical bone cavitation, and patchy osteopenia occurring without a history of extensive wear particle generation.
• Periosteal Bone Formation: Laminated (onion-skin) or solid periosteal reaction along the femoral or tibial diaphysis, indicative of subacute cortical irritation and subperiosteal inflammatory extension.
• Component Migration and Subsidence: Rapid tilt, subsidence (>3 to 5 mm), or angular change of components, representing gross mechanical failure and bone destruction.
• Soft-Tissue Gas: The presence of periprosthetic radiolucent gas pockets in the absence of recent arthrocentesis or surgery, indicative of gas-producing organisms (e.g., Clostridium species or fermenting Gram-negative bacilli).

Advanced Imaging

Advanced imaging plays an adjunctive role when clinical, radiographic, and laboratory assessments are inconclusive:

• Computed Tomography (CT) with Metal Artifact Reduction (MARS): Accurately delineates osteolytic bone loss, cortical breaches, component rotational alignment, and tracks the exact course of cutaneous sinus tracts. CT is invaluable for preoperative bone graft and augment planning prior to revision.
• Technetium-99m (Tc-99m) Bone Scintigraphy: Demonstrates high sensitivity for altered osseous remodeling around implants. However, its specificity is poor because physiologic bone remodeling normally causes elevated tracer uptake for 12 to 24 months after uncomplicated primary arthroplasty. A completely negative bone scan strongly excludes loosening or infection (negative predictive value >95%).
• Combined Indium-111 Labeled Leukocyte and Tc-99m Sulfur Colloid Marrow Scintigraphy: The gold standard nuclear medicine examination for PJI. Labeled leukocytes accumulate in areas of active infection and active hematopoietic bone marrow. In contrast, sulfur colloid concentrates strictly within functional bone marrow. Spatial discordance—demonstrated by marked leukocyte accumulation without corresponding sulfur colloid activity—confirms periprosthetic infection with 85% to 90% sensitivity and 90% to 95% specificity.
• 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET/CT): Quantifies hypermetabolic leukocyte activity around components. While sensitive, distinguishing infectious biofilm from particle-induced aseptic granulomatous wear remains challenging.

Serum Biomarkers

Serum biomarkers are mandatory screening tests for all patients undergoing evaluation for painful or dysfunctional arthroplasty:

• Erythrocyte Sedimentation Rate (ESR): Normalizes slowly after uncomplicated arthroplasty, peaking around postoperative day 5 and taking 3 to 12 months to return to baseline. In chronic PJI, an ESR threshold >30 mm/h demonstrates approximately 85% sensitivity.
• C-Reactive Protein (CRP): An acute-phase reactant synthesized by hepatocytes. Rises rapidly within 6 to 12 hours of surgical trauma, peaks on postoperative day 2 to 3, and normalizes rapidly within 3 to 6 weeks. A serum CRP >10 mg/L in chronic presentations demonstrates >90% sensitivity and specificity. In the acute postoperative period (100 mg/L.
• Serum D-dimer: Reflects systemic fibrinolysis triggered by periprosthetic inflammation. Validated in the ICM 2018 criteria at a cutoff of >860 ng/mL, showing high diagnostic sensitivity. However, D-dimer is easily confounded by systemic venous thromboembolism, hematoma, recent surgery, or underlying rheumatologic disease.
• Serum Interleukin-6 (IL-6): Demonstrates an acute postoperative spike that returns to baseline within 48 to 72 hours, far faster than CRP. Useful for ruling out infection in the early postoperative window (<4 to 6 weeks), although limited by higher commercial assay cost and variable availability.

Synovial Fluid Analysis and Diagnostic Arthrocentesis

Diagnostic arthrocentesis represents the single most crucial step in confirming or excluding PJI. Arthrocentesis must be performed under strict aseptic conditions. Whenever feasible, patients must be free of antibiotics for at least 14 days prior to aspiration.

• Synovial White Blood Cell (WBC) Count and Differential (% PMN):
  • Chronic PJI (Knee): Synovial WBC >3,000 cells/µL; Polymorphonuclear neutrophils (% PMN) >70% to 80%.
  • Acute PJI (<6 Weeks, Knee): Synovial WBC >10,000 cells/µL; % PMN >90%.
  • Chronic PJI (Hip): Synovial WBC >3,000 to 4,200 cells/µL; % PMN >70% to 80%.
  • Acute PJI (<6 Weeks, Hip): Synovial WBC >10,000 to 12,800 cells/µL; % PMN >89% to 90%.
• Leukocyte Esterase (LE) Strip Test: A rapid, inexpensive enzymatic reagent strip test detecting neutrophil esterase activity in synovial fluid. Read visually as negative, trace (+), or positive (++). A positive test indicates elevated leukocyte activation with sensitivity of 85% to 95% and specificity of 90% to 95%. Blood-tinged fluid can obscure visual colorimetric reading; centrifuging the specimen clears cellular debris and restores colorimetric accuracy.
• Synovial Alpha-Defensin: An antimicrobial peptide released by neutrophils into synovial fluid in response to pathogens. Available as a laboratory-based enzyme-linked immunosorbent assay (ELISA) or a point-of-care lateral flow strip. Demonstrates exceptional diagnostic performance, with sensitivity of 95% to 97% and specificity of 96% to 98%. Unlike cellular counts, alpha-defensin results are not invalidated by prior antibiotic administration or underlying systemic inflammatory arthropathies.
• Synovial C-Reactive Protein and D-Lactate: Synovial CRP (>6.9 to 9.5 mg/L) and synovial D-lactate (a byproduct of bacterial fermentation, >1.2 to 1.3 mmol/L) serve as highly sensitive secondary synovial markers of bacterial presence.
• Molecular Diagnostics (mNGS and Multiplex PCR): Metagenomic Next-Generation Sequencing (mNGS) extracts and sequences all microbial cell-free DNA fragments within synovial fluid. Invaluable for diagnosing culture-negative PJI, detecting fastidious or unculturable organisms, and identifying genetic antibiotic resistance determinants.
• Microbiological Culture Protocols: Synovial fluid should be directly inoculated into pediatric blood culture bottles (aerobic and anaerobic) at the bedside to maximize microbial yield. Intraoperative tissue biopsies must be harvested using pristine scalpel blades and forceps for each sample. A minimum of 5 to 6 distinct tissue specimens should be obtained from the pseudocapsule, bone-implant interface, and necrotic fluid. All periprosthetic cultures must be incubated for a minimum of 14 days (aerobically and anaerobically) to isolate slow-growing organisms such as Cutibacterium acnes. Explanted components should undergo ultrasonic sonication to disrupt biofilms prior to culture.

7. Classification

Validated classification and diagnostic staging systems provide standardized clinical definitions that dictate appropriate surgical pathways.

The International Consensus Meeting (ICM) 2018 standardized definition utilizes a validated scoring system incorporating major and minor criteria:

8. Treatment

Eradicating periprosthetic joint infection demands a coordinated multidisciplinary approach integrating aggressive operative intervention with pathogen-directed antimicrobial therapy.

Medical / Antimicrobial Therapy

Antimicrobial management must be tailored to the specific pathogen, its phenotypic resistance profile, and its biofilm-forming capacity:

• Empiric Antimicrobial Therapy: Broad-spectrum parenteral therapy—typically intravenous vancomycin (15 to 20 mg/kg q8-12h targeting a trough of 15 to 20 mcg/mL or AUC/MIC of 400 to 600) combined with an antipseudomonal beta-lactam (cefepime 2 g IV q8h or piperacillin-tazobactam 4.5 g IV q6-8h)—is initiated immediately after intraoperative tissue cultures have been secured. Empiric therapy covers MRSA, enterococci, and Gram-negative bacilli until definitive culture and susceptibility profiles are finalized.
• Targeted Therapy for Staphylococcal Biofilms (Rifampin Principles): Rifampin exhibits outstanding bactericidal activity against slow-growing, surface-adherent staphylococci within biofilms. However, rifampin must never be administered as monotherapy due to rapid, one-step selection of high-level rpoB gene resistance mutations. Furthermore, rifampin must never be started immediately perioperatively. Clinical pearl: Withhold rifampin until surgical debridement is completed, bacteremia has cleared, deep surgical drains are removed, and the surgical wound is clean, dry, and fully closed (typically postoperative day 3 to 7). Recommended dosage: 300 to 450 mg PO twice daily, or 600 mg PO once daily, combined with a primary companion antibiotic (e.g., cefazolin, vancomycin, daptomycin, or a fluoroquinolone).
• Gram-Negative Biofilm Regimens: Oral fluoroquinolones (ciprofloxacin 500 to 750 mg PO BID, or levofloxacin 500 to 750 mg PO daily) display exceptional bactericidal activity and biofilm penetration against susceptible Gram-negative organisms, including P. aeruginosa and Enterobacteriaceae.
• Route and Duration of Antimicrobial Delivery: Groundbreaking randomized clinical trials (the OVIVA trial) have confirmed that transitioning to targeted oral antimicrobial regimens with high oral bioavailability achieves infection eradication rates equivalent to prolonged 6-week intravenous catheter courses, while eliminating PICC-line complications (catheter sepsis, thrombosis). Standard total antimicrobial duration is 6 weeks following DAIR or two-stage spacer exchange, and 6 to 12 weeks for complex single-stage revisions. Chronic oral antibiotic suppression is strictly reserved for patients with unremovable infected hardware who cannot undergo curative revision surgery.

Operative Management

The primary goals of surgery are complete elimination of the bacterial biofilm, restoration of a pain-free stable articulation, and preservation of host bone stock. Four primary surgical pathways exist:

Debridement, Antibiotics, and Implant Retention (DAIR)

DAIR aims to sterilize the joint while preserving well-fixed components:

• Surgical Technique: The previous incision is utilized with full excision of any scarred sinus tract. Arthrotomy is performed, followed by radical synovectomy and complete debridement of the anterior, medial, lateral, and posterior compartments. All necrotic soft tissue, fibrinous exudate, and pseudocapsule are excised back to healthy bleeding margins. Pulsatile lavage irrigation is delivered with a minimum of 6 to 9 liters of normal saline or diluted antiseptic solutions (povidone-iodine 0.35% or chlorhexidine gluconate 0.05%).
• Mandatory Modular Component Exchange: Modular components (polyethylene tibial insert, femoral head, dual-mobility liner) must be removed and discarded. Modular exchange is non-negotiable: it mechanically eliminates the heavily colonized polyethylene surface, exposes the concealed posterior and inferior hardware surfaces for circumferential debridement, and confirms absolute stability of retained components. Retaining modular liners drops DAIR success rates by 20% to 30%.

One-Stage (Single-Stage) Exchange Arthroplasty

One-stage exchange achieves complete biofilm eradication and definitive reconstruction in a single surgical setting:

• Surgical Technique: Complete explantation of all prosthetic components, cement mantles, plugs, and anchors. An aggressive, radical oncologic-style debridement is performed, excising all pseudocapsule, synovium, and avascular cortical/cancellous bone back to punctate bleeding bone (“the paprika sign”). The surgical team then discards all contaminated instruments, re-washes, re-drapes the patient, and dons fresh sterile gowns and gloves. New revision components are implanted, secured with high-dose antibiotic-loaded acrylic bone cement (ALBC) tailored to preoperative sensitivities.
• Strict Patient Selection Criteria: The pathogen must be precisely identified preoperatively with established sensitivity to oral bioavailable antibiotics; intact soft-tissue envelope capable of tension-free primary closure without flap reconstruction; absence of active cutaneous sinus tracts; and adequate bone stock not requiring massive uncontained structural allografts.

Two-Stage Exchange Arthroplasty

Two-stage exchange remains the international gold standard for chronic, resistant, or polymicrobial PJI:

• Stage 1 (Explantation, Radical Debridement, and Spacer Implantation): All prosthetic hardware, polymethylmethacrylate cement, restrictive scar tissue, and necrotic bone are completely removed. A temporary antibiotic-loaded PMMA spacer is inserted.
  • Articulating (Mobile) vs Static Spacers: Articulating spacers (commercially molded cement-on-cement, pre-fabricated implants, or autoclaved explanted femoral components re-cemented with antibiotic PMMA) preserve joint range of motion, prevent collateral ligament and quadriceps contracture, facilitate easier stage-2 exposure, and improve post-revision functional scores. Static block spacers are indicated in the setting of severe ligamentous instability, massive bone loss, compromised extensor mechanism, or severe soft-tissue compromise.
  • Antibiotic Cement Elution Mechanics: High-dose therapeutic antibiotic bone cement is hand-mixed using 2 to 4 g of vancomycin plus 2.4 to 4.8 g of an aminoglycoside (tobramycin or gentamicin) per 40 g batch of PMMA cement. Hand-mixing increases cement porosity, dramatically enhancing passive surface elution. This generates local antibiotic concentrations at the tissue-spacer interface exceeding the MIC by 100 to 1,000 times, while systemic serum absorption remains low, avoiding nephrotoxicity.
• Interim Period: Patients receive 6 weeks of pathogen-directed systemic antimicrobial therapy, followed by a 2- to 4-week antibiotic holiday. Joint wound healing, clinical resolution of pain, and serological normalization of CRP and ESR are monitored prior to reimplantation.
• Stage 2 (Spacer Explantation and Definitive Reimplantation): The joint is re-entered, the temporary cement spacer is carefully removed, and thorough repeat debridement is performed. Frozen section histology is obtained (<5 PMNs per high-power field across multiple fields confirms control of infection). Multiple permanent periprosthetic tissue cultures are obtained. Definitive reconstruction is performed using revision components, modular porous titanium sleeves/cones, structural augments, and prophylactic low-dose antibiotic cement.

Salvage Procedures

Reserved for recalcitrant infections, multiple failed reconstructions, or catastrophic bone/soft-tissue loss:

• Resection Arthroplasty (Girdlestone for Hip; Resection for Knee): Permanent removal of all components without reimplantation. Indicated in non-ambulatory patients, severe systemic medical comorbidities precluding major reconstruction, or refractory polymicrobial/fungal infections. Provides infection eradication at the expense of marked limb shortening (3 to 7 cm), profound instability, and obligatory external walking aids.
• Knee Arthrodesis: Fusion of the knee joint utilizing a long intramedullary modular nail or external fixator. Indicated in active, ambulatory patients with deficient extensor mechanisms, severe bone loss, or refractory PJI following multiple failed revision attempts. Provides a stable, painless, infection-free extremity capable of full weight-bearing.
• Amputation (Above-Knee Amputation / Hip Disarticulation): The ultimate salvage procedure for life-threatening necrotizing soft-tissue infection, persistent overwhelming sepsis, catastrophic vascular injury, or intractable pain with severe loss of limb function.

Indications and Contraindications

Explicit numerical thresholds and objective criteria govern surgical selection:

• DAIR Indications: Acute early postoperative infection (<4 weeks from index surgery) OR acute hematogenous infection (<3 weeks of symptoms); well-fixed components; intact soft tissues; known, susceptible pathogen. Contraindications: Symptom duration >4 weeks; loose or broken components; presence of a sinus tract; fungal or multidrug-resistant pathogens.
• One-Stage Exchange Indications: Known organism with confirmed sensitivities; absence of sinus tract; healthy soft-tissue envelope; uncompromised extensor mechanism; minimal bone loss not requiring structural allografts. Contraindications: Unknown or culture-negative organism; multidrug-resistant pathogens (MRSA, vancomycin-resistant enterococci, carbapenem-resistant Gram-negatives); active sinus tract; extensive uncontained bone defects requiring bulk allografts.
• Two-Stage Exchange Indications: Chronic PJI (>4 weeks duration); unknown or culture-negative infection; resistant, polymicrobial, or fungal organisms; presence of a cutaneous sinus tract; compromised soft tissues; loose hardware; prior failed DAIR. Contraindications: Medically unstable patients unable to tolerate two extensive surgical procedures (consider permanent spacer, resection arthroplasty, or chronic suppression).

9. Outcome

Long-term clinical success after periprosthetic joint infection is measured by infection-free survivorship, patient-reported outcome measures (PROMs), and mechanical durability of revision reconstruction.

Infection Eradication Rates

• Debridement, Antibiotics, and Implant Retention (DAIR): Overall infection eradication success averages 60% to 80% in strictly selected acute cohorts. Procedural success relies on modular component exchange; retaining original modular components reduces eradication to 45% to 55%. Eradication rates drop below 40% when DAIR is attempted in MRSA infections without rifampin, when symptom duration exceeds 4 weeks, or in the presence of compromised host immunology.
• One-Stage Exchange Arthroplasty: Eradication rates range from 85% to 90% in rigorously selected candidates with identifiable, sensitive Gram-positive organisms, intact soft-tissue envelopes, and high-dose antibiotic cement fixation. In specialized international centers with strict protocols, one-stage exchange achieves reinfection-free survival comparable to two-stage revision while eliminating the morbidity of a temporary spacer interval.
• Two-Stage Exchange Arthroplasty: Achieves an 85% to 95% infection eradication rate, maintaining its position as the most dependable and reproducible surgical intervention for heterogeneous, chronic, resistant, and polymicrobial PJI cohorts. Treatment failure occurs in 5% to 15% of patients, frequently manifesting as superinfection with a new, different organism rather than recrudescence of the original pathogen.

Patient-Reported Outcome Measures (PROMs)

Functional outcomes following revision for PJI are substantially lower than those achieved following primary or aseptic revision arthroplasty:

• Total Knee Arthroplasty Functional Metrics: Mean postoperative range of motion following two-stage revision averages 95 to 105 degrees with articulating spacers, compared to 80 to 85 degrees with static spacers. Knee Society Scores (KSS) and Oxford Knee Scores (OKS) improve significantly from spacer placement to final reimplantation, yet long-term scores remain 15% to 20% lower than primary TKA benchmarks, with residual extensor lag occurring in up to 10% of patients.
• Total Hip Arthroplasty Functional Metrics: Harris Hip Scores (HHS) typically range from 75 to 85 points following successful two-stage revision, reflecting persistent mild-to-moderate limp, abductor weakness, and reduced walking tolerance. Girdlestone resection arthroplasty yields poor functional scores (HHS 45 to 60), with patients requiring walking aids and experiencing substantial satisfaction deficits despite successful eradication of sepsis.

Component Survivorship and Long-Term Mechanical Durability

Ten-year mechanical survivorship following septic revision arthroplasty ranges from 70% to 80%. Aseptic loosening, reinfection, and periprosthetic fractures represent the leading mechanisms of secondary failure. Porous titanium metaphyseal cones and sleeves have transformed reconstructive survivorship in knees, achieving over 90% osseous integration rates at 5 to 10 years by providing stable metaphyseal fixation independent of compromised diaphyseal or epiphyseal bone stock.

10. Complications

Management of periprosthetic joint infection carries substantial surgical, mechanical, and systemic complication risks that must be proactively mitigated throughout the treatment course.

11. Pearls and Pitfalls

Expert surgical management requires strict adherence to technical pearls and avoidance of common clinical pitfalls:

Technical Pearls

• Withhold Antibiotics Prior to Joint Aspiration: Strictly withhold all systemic antimicrobial therapy for a minimum of 14 days prior to diagnostic arthrocentesis unless the patient manifests overt clinical sepsis or hemodynamic instability. Even single doses of oral antibiotics clear planktonic organisms from the synovial fluid, precipitating false-negative cultures and rendering subsequent targeted medical therapy extraordinarily challenging.
• The Five-Specimen Protocol: Obtain 5 to 6 distinct periprosthetic tissue biopsy specimens during revision surgery using a fresh, sterile scalpel blade and forceps for each individual sample. Tissue should be harvested from the capsule, pseudocapsule, bone-implant interface, and fluid collection. Discard superficial swabs entirely; superficial swabs capture colonizing dermal flora rather than true infecting pathogens. True infection requires two or more concordant tissue cultures yielding phenotypically identical organisms.
• Mandatory Radical Modular Exchange in DAIR: During DAIR, never retain the existing polyethylene tibial insert, acetabular liner, or modular femoral head. Removing modular components eliminates the massive bacterial load embedded within the microtextured polymer, exposes the hidden retro-acetabular and retro-tibial spaces for debridement, and allows direct mechanical testing of implant fixation. Retaining modular liners is the single greatest risk factor for DAIR failure.
• The Paprika Sign for Bone Debridement: Debridement of periprosthetic bone must continue until healthy, bleeding osseous margins are visualized (the “paprika sign”). Avascular, necrotic cortical bone cannot be sterilized by circulating or local antibiotics and serves as a permanent foreign body harboring dormant persister organisms.
• Delayed Rifampin Initiation: In staphylococcal PJI, delay rifampin administration until the surgical wound is completely dry, surgical drains have been pulled, and blood cultures have confirmed resolution of bacteremia (typically postoperative day 3 to 7). Introducing rifampin in the presence of an active draining wound or high bacterial burden drives rapid selection of rifampin-resistant staphylococcal mutants.
• Dowel-Reinforced Articulating Spacers: When fashioning articulating hip or knee cement spacers, reinforce the cement construct with an internal endoskeleton, such as a commercially designed pre-formed spacer or an autoclaved rush pin/Steinmann pin wrapped in antibiotic cement, to prevent catastrophic spacer fracture and soft-tissue displacement.

Pitfalls to Avoid

• Confusing Low-Grade Infection with Aseptic Loosening: Never assume early radiolucent lines or component loosening represents pure mechanical wear or aseptic failure. Indolent pathogens (C. acnes, CoNS) frequently present with painless loosening and normal serum CRP and ESR. Joint aspiration is mandatory prior to revision arthroplasty for presumed aseptic loosening.
• Operating Through Active Sinus Tracts Without Excision: Incising directly through or adjacent to an active cutaneous sinus tract without complete elliptical excision contaminates the deep joint bed with superficial skin flora. Elliptical excision of the entire sinus tract down to the level of the pseudocapsule must be performed before the arthrotomy is entered.
• Overfilling Cement Spacers into Femoral Canal Defects: Pressurizing high-viscosity cement into cortical perforations or deep femoral canal defects creates mechanical interlocks that make stage-2 spacer extraction exceedingly difficult. Cement spacers should be smooth and shaped to allow effortless extraction without requiring massive osteotomies during the reimplantation stage.
• Under-dosing Antibiotics in Bone Cement Spacers: Using low-dose commercial prophylactic antibiotic cement (0.5 to 1 g antibiotic per batch) for revision spacers is completely inadequate to achieve bactericidal biofilm concentrations. Spacers require hand-mixed, high-dose dual antimicrobials (e.g., 2 to 4 g vancomycin and 2.4 to 4.8 g tobramycin per 40 g batch).

12. Controversy

Several fundamental controversies remain actively debated in the management of periprosthetic joint infection:

One-Stage vs. Two-Stage Exchange Arthroplasty

The philosophical division between one-stage and two-stage exchange represents the most prominent debate in revision arthroplasty. Proponents of one-stage exchange emphasize substantial clinical advantages: avoidance of a second major operation, elimination of the morbidity and functional limitation associated with an interim cement spacer, preserved joint mechanics, reduced cumulative hospital stay, and dramatically lower healthcare costs. Long-term European data from specialized centers demonstrate infection eradication rates exceeding 85% to 90%, comparable to two-stage revisions.

Conversely, advocates of two-stage exchange assert that it provides a safer, more reproducible platform across diverse patient populations. Two-stage exchange allows delivery of massive local antibiotic concentrations via high-dose PMMA spacers, provides a 6- to 12-week observational window to confirm systemic and local infection clearance, and permits histologic and microbiologic reassessment at the second stage before permanent implants are committed. While one-stage exchange is increasingly accepted for selected patients with identifiable, sensitive pathogens and healthy soft tissues, two-stage revision remains the dominant paradigm for culture-negative, resistant, polymicrobial, and compromised host scenarios.

Oral vs. Intravenous Antimicrobial Delivery (The OVIVA Paradigm)

For decades, standard infectious disease practice mandated 6 weeks of continuous intravenous antibiotic therapy via peripherally inserted central catheters (PICC lines). However, the landmark multicenter OVIVA (Oral Versus Intravenous Antibiotics for Bone and Joint Infection) trial demonstrated that transitioning to oral antibiotics with high oral bioavailability within the first 7 days following surgery yielded infection eradication rates entirely non-inferior to prolonged intravenous therapy. Furthermore, oral therapy eliminated central catheter-related complications, such as line-associated bacteremia, local insertion site infection, and deep venous thrombosis. While the surgical community has widely embraced this shift, debate continues regarding the optimal timing of oral transition in the presence of virulent MRSA or difficult-to-treat Gram-negative pathogens.

Novel Synovial Biomarkers vs. Conventional Analysis

The introduction of synovial alpha-defensin and next-generation sequencing has sparked controversy regarding cost-effectiveness and clinical necessity. While alpha-defensin testing provides near-perfect diagnostic specificity and sensitivity that resists prior antibiotic suppression, critics note its substantial financial cost compared to traditional, inexpensive synovial WBC counts and automated leukocyte esterase reagent strips. Many institutions reserve alpha-defensin testing for diagnostic dilemmas where synovial fluid cell counts are borderline or inconclusive according to ICM criteria.

Bioabsorbable Antibiotic Carriers vs. PMMA Spacers

The role of bioabsorbable calcium sulfate and bioactive glass beads impregnated with high-dose antibiotics is intensely debated. These carriers release 100% of their antibiotic payload through complete dissolution, achieving supreme local antibiotic elution without requiring secondary surgical retrieval. However, critics point to significant complications, including prolonged sterile serous wound drainage, wound breakdown, and transient systemic hypercalcemia, particularly when placed in superficial subcutaneous layers without robust muscular coverage.

13. Evidence-Based Synthesis

Modern clinical decision-making is grounded in high-quality randomized controlled trials and prospective registry analyses, corroborated by seminal biomechanical and anatomical descriptions.

14. References

• Parvizi J, Tan TL, Goswami K et al. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J Arthroplasty. 2018. doi:10.1016/j.arth.2018.02.078 [Level IV (Diagnostic / Consensus): Diagnostic Validation Study / Consensus]
• Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004. doi:10.1056/NEJMra040181 [Level IV (Conceptual Landmark Review): Seminal Conceptual / Clinical Framework]
• Osmon DR, Berbari EF, Berendt AR et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013. doi:10.1093/cid/cis803 [Level V (Expert Practice Guidelines): Clinical Practice Guideline]
• Longo UG, De Salvatore S, Bandini B et al. Debridement, antibiotics, and implant retention (DAIR) for the early prosthetic joint infection of total knee and hip arthroplasties: a systematic review. J ISAKOS. 2024. doi:10.1016/j.jisako.2023.09.003 [Level I (Therapeutic): Systematic Review / Meta-Analysis]
• Fehring TK, Otero JE, Fehring KA et al. One-Stage Versus Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection: A Prospective Randomized Trial. J Bone Joint Surg Am. 2026. doi:10.2106/JBJS.25.00713 [Level I (Therapeutic): Randomized Controlled Trial]

15. Master Class Pro-Tip

Master Class Surgical Pearl: Hardware Extraction, Canal Debridement, and Dowel-Reinforced Spacers in Two-Stage Revision
During hardware explantation in two-stage exchange for chronic PJI, preserving host periprosthetic bone stock while achieving complete removal of foreign material dictates ultimate reconstructive success. When dealing with well-fixed, well-integrated femoral stems, resist the temptation to forcibly drive osteotomes down the endosteal canal; this invariably precipitates catastrophic cortical perforations or spiral femur fractures. Instead, perform an early, controlled extended trochanteric osteotomy (ETO) measuring one-third of the femoral circumference and extending 2 cm distal to the stem tip. An ETO directly exposes the entire bone-implant interface, allows precise circumferential division of porous ingrowth with flexible osteotomes, and provides direct, unhindered visualization for radical curettage of the distal intramedullary pseudomembrane and endosteal biofilm.

When constructing the interim articulating antibiotic PMMA spacer, hand-mix high-dose dual antibiotics (3 g of vancomycin plus 3.6 g of tobramycin per 40 g batch) in a dry bowl to maximize porosity and surface area elution before adding the liquid monomer. Never insert a bare cement construct into the femoral shaft; mechanical fatigue and torsional shear cause unreinforced spacers to fracture at the neck-shaft junction, resulting in painful dislocation and profound soft-tissue shortening. Fashion a central structural endoskeleton by passing a threaded Steinmann pin or rush pin through the core of the femoral cement mantle, extending from the femoral head down into the distal intramedullary canal. Prior to cement polymerization, wrap the proximal femoral neck and head tightly in high-dose cement, cycle the construct in the acetabulum to mold congruency, and maintain the limb in 15 degrees of abduction and neutral rotation until full curing. This simple endoskeleton construct preserves soft-tissue tension, eliminates spacer fractures, maintains patient mobility, and dramatically simplifies exposure during the stage-two reimplantation.

Master Class Surgical Pearl: Periprosthetic Joint Infection