Residency · Residency · Infectiousdisease

Prosthetic Joint and Device-Related Infections

Prosthetic Joint Infections (PJI)

Epidemiology

Prosthetic joint infection represents one of the most challenging problems in infectious disease practice, combining complex microbiology, difficult diagnosis, and treatment strategies that require close collaboration between infectious disease specialists, orthopedic surgeons, and other subspecialists. Approximately one million total joint arthroplasties are performed annually in the United States, with PJI complicating 1 to 2 percent of these procedures. The economic burden is substantial, with each PJI episode costing between 50,000 and over 100,000 dollars, and the total annual cost to the United States healthcare system exceeding 1.8 billion dollars. Risk factors for PJI include prior joint surgery, diabetes mellitus, rheumatoid arthritis, immunosuppressive therapy, obesity, malnutrition, smoking, prolonged operative time, and post-operative wound complications.

Classification by Timing

The timing of symptom onset relative to implant placement is a critical determinant of likely microbiology, treatment strategy, and prognosis. | PJI Timing | Onset | Typical Pathogens | Clinical Course | Surgical Approach |

Early infections, occurring within three months of implantation, are typically acquired intraoperatively or through perioperative wound complications. The predominant pathogens are virulent organisms including Staphylococcus aureus, gram-negative bacilli, and polymicrobial flora. Delayed infections, occurring between three and twelve months post-implantation, are caused by low-virulence organisms acquired at the time of surgery that produce a slowly progressive clinical course. Coagulase-negative staphylococci and Cutibacterium acnes are the characteristic pathogens.

Late infections, occurring beyond twelve months after implantation, result from hematogenous seeding of the prosthetic joint during episodes of bacteremia originating from dental procedures, urinary tract infections, skin infections, or other sources. S. aureus, streptococcal species, and gram-negative organisms are the typical pathogens. Acute hematogenous PJI is characterized by the abrupt onset of symptoms in a previously well-functioning joint, with fever, acute joint pain, and swelling developing over fewer than three weeks.

Microbiology

Staphylococcal species collectively account for 50 to 60 percent of prosthetic joint infections, with S. aureus and coagulase-negative staphylococci each responsible for approximately 25 percent. Streptococcal species cause 10 to 15 percent, and gram-negative organisms account for 5 to 10 percent of cases. Cutibacterium acnes is responsible for 10 to 12 percent of PJI, with a particular predilection for shoulder prostheses. Polymicrobial infections account for 10 to 20 percent of cases, especially in early infections. Culture-negative PJI occurs in 5 to 15 percent of cases and may reflect prior antibiotic exposure, fastidious organisms, or biofilm-embedded bacteria that fail to grow in standard culture conditions. Fungal PJI, primarily caused by Candida species, is rare at less than 1 percent but is associated with prolonged antibiotic exposure and immunosuppression.

Biofilm

Biofilm formation is the central pathophysiologic concept underlying the difficulty of treating prosthetic joint infections. Within hours of bacterial adherence to a prosthetic surface, organisms begin to produce an extracellular polysaccharide matrix that provides structural integrity to the developing microbial community. A mature biofilm is established within two to three weeks, creating a highly organized structure in which bacteria exist in a sessile, metabolically quiescent state that is profoundly resistant to both antibiotic therapy and host immune clearance. Minimum inhibitory concentrations within biofilm can be 1,000-fold higher than for planktonic (free-floating) organisms of the same species.

The clinical implication of biofilm biology is unequivocal: antibiotics alone cannot eradicate mature biofilm, and surgical intervention in the form of thorough debridement or implant exchange is essential for cure. Among oral antibiotics, rifampin occupies a unique position as the only agent with proven efficacy against staphylococcal organisms embedded within biofilm, where it can penetrate the extracellular matrix and kill sessile bacteria. This property makes rifampin an indispensable component of antibiotic regimens for staphylococcal PJI when implant retention is attempted.

Diagnosis of PJI

MSIS/EBJIS 2018 Criteria

The 2018 Musculoskeletal Infection Society and European Bone and Joint Infection Society criteria provide a structured, evidence-based framework for the diagnosis of PJI using a combination of major and minor criteria with a scoring system.

Major criteria that are individually diagnostic of PJI include two positive periprosthetic cultures with an identical organism and the presence of a sinus tract communicating with the joint. Either of these findings alone confirms the diagnosis.

Minor criteria are assigned point values and summed to reach a diagnostic threshold. Elevated serum CRP above 1 milligram per deciliter scores 2 points, elevated serum D-dimer above 860 nanograms per milliliter scores 2 points, elevated ESR above 30 scores 1 point, elevated synovial white blood cell count above 3,000 per cubic millimeter scores 3 points, elevated synovial polymorphonuclear percentage above 80 percent scores 2 points, positive alpha-defensin in synovial fluid scores 3 points, a single positive periprosthetic culture scores 2 points, and positive histopathology with more than 5 polymorphonuclear cells per high-power field scores 3 points. A combined score of 6 or more confirms PJI, while a score of 3 to 5 represents possible PJI warranting further evaluation.

Preoperative Workup

The preoperative diagnostic evaluation begins with serum inflammatory markers, specifically CRP and ESR, as screening tests. Joint aspiration is the cornerstone of preoperative diagnosis and should include synovial fluid white blood cell count and differential, aerobic and anaerobic cultures with a hold time of 14 days to detect Cutibacterium, and crystal analysis to evaluate for coexisting gout.

Synovial fluid alpha-defensin has emerged as the most accurate single biomarker for PJI, with both sensitivity and specificity of approximately 97 percent. Notably, alpha-defensin levels are not affected by prior antibiotic use, making it valuable in patients who have already received antibiotics. When clinically feasible, antibiotics should be held for at least two weeks before aspiration to improve culture sensitivity.

Imaging studies contribute to the diagnostic evaluation but have limitations. Plain radiographs may reveal prosthetic loosening or periosteal reaction. CT and MRI are limited by metal artifact but can identify periprosthetic fluid collections. Nuclear medicine studies, including white blood cell-labeled scans and FDG-PET, are useful for equivocal cases.

Intraoperative Diagnosis

Intraoperative diagnosis requires a systematic approach to tissue sampling. A minimum of five tissue samples should be obtained from different periprosthetic locations and submitted for aerobic, anaerobic, and fungal culture with a 14-day hold time. Frozen section histopathology demonstrating more than 5 PMN per high-power field across at least 5 fields supports the diagnosis, though the specific threshold varies by published criteria.

Sonication of the explanted prosthesis represents a significant advance in diagnostic sensitivity. The technique uses ultrasound energy to dislodge bacteria from the biofilm on the prosthetic surface, and the resulting sonication fluid is cultured. Sonication increases culture sensitivity by 20 to 30 percent over tissue cultures alone, with reported sensitivity of 79 percent compared to 61 percent for tissue cultures in the landmark study by Trampuz and colleagues. Sonication should be requested routinely when available.

<image>A diagnostic workup algorithm for suspected prosthetic joint infection. Start with "Clinical suspicion of PJI (pain, swelling, wound drainage, sinus tract, fever)." Step 1: "Serum markers: CRP (>1 mg/dL suspicious), ESR (>30 suspicious), D-dimer." If elevated: "Proceed to joint aspiration (hold antibiotics ≥2 weeks if possible)." Aspirate analysis: "Synovial WBC count (>3000 = suspicious), PMN% (>80%), alpha-defensin, aerobic + anaerobic culture (hold 14 days)." Decision based on results: "Definitive PJI (sinus tract or ≥2 positive cultures with same organism)" → "Surgical planning + ID consultation." "Possible PJI (equivocal results)" → "Consider repeat aspiration, nuclear imaging (WBC scan or FDG-PET), or proceed to operative exploration with intraoperative cultures (5 tissue samples + sonication of explant)." Include the MSIS scoring system in a sidebar. Use a clinical decision pathway format with diagnostic thresholds clearly labeled.</image>

Treatment Strategies

DAIR (Debridement, Antibiotics, and Implant Retention)

Debridement, antibiotics, and implant retention, known as DAIR, is appropriate for a specific subset of PJI patients. The indications include early post-operative infection occurring within three months of implantation or acute hematogenous infection with fewer than three weeks of symptom duration. The implant must be stable and well-fixed with no radiographic evidence of loosening. Soft tissues must be intact or exchangeable, and the infecting organism should be susceptible to biofilm-active therapy, ideally a rifampin-susceptible staphylococcal species.

The surgical procedure involves open arthrotomy, thorough debridement of all infected and necrotic tissue, exchange of the polyethylene liner and modular femoral head, copious irrigation, and collection of at least five tissue cultures. Overall success rates for DAIR range from 50 to 70 percent, with higher success rates of 70 to 80 percent achieved when strict selection criteria are met. Success rates are lower for MRSA infections and in immunocompromised patients.

Two-Stage Exchange Arthroplasty

Two-stage exchange arthroplasty is considered the gold standard for chronic PJI occurring more than three months after implantation or for cases in which DAIR has failed. The first stage involves complete removal of all prosthetic components and cement, thorough debridement of infected tissue, and placement of an antibiotic-laden spacer, typically containing tobramycin and vancomycin in polymethylmethacrylate cement. Intraoperative cultures guide definitive antibiotic therapy.

Between stages, an antibiotic holiday of two to six weeks off systemic antibiotics is typically observed to assess for eradication. Some protocols use normalization of serum CRP and repeat aspiration to confirm infection clearance before proceeding to reimplantation. The second stage, reimplantation of a new prosthesis, is performed after infection clearance has been confirmed, typically 8 to 12 weeks after the first stage. Success rates for two-stage exchange are 85 to 95 percent.

One-Stage Exchange

One-stage exchange, in which implant removal and reimplantation of a new prosthesis are performed in a single surgical session, has historically been less common in the United States but is increasingly adopted and is the standard approach in many European centers. Patient selection criteria include the absence of a sinus tract, a known organism with available susceptibility data, adequate soft tissue coverage, and an immunocompetent host. Success rates of 85 to 95 percent in well-selected patients are comparable to two-stage exchange, with the advantages of a single surgery, faster functional recovery, and lower overall cost.

Chronic Suppressive Therapy

Chronic suppressive therapy is reserved for patients who are not surgical candidates or who decline surgery. The goal is suppression rather than cure of the infection, with long-term oral antibiotics administered indefinitely to maintain a stable, functional joint. Prerequisites include a well-fixed prosthesis, an infecting organism susceptible to a tolerable oral agent, and patient ability to adhere to lifelong therapy. Typical agents include trimethoprim-sulfamethoxazole, doxycycline, cephalexin, or a fluoroquinolone, selected based on susceptibility data. Infection will invariably recur if antibiotics are discontinued.

Antibiotic Therapy for PJI

Staphylococcal PJI (MSSA)

For methicillin-susceptible S. aureus PJI managed with DAIR or one-stage exchange, the antibiotic regimen consists of initial intravenous therapy with nafcillin or cefazolin for two to six weeks, followed by transition to an oral regimen of rifampin plus a companion agent for a total treatment duration of three months for hip PJI or six months for knee PJI. Rifampin is administered at 300 to 450 milligrams orally twice daily and must always be used in combination with a second agent, as monotherapy leads to rapid emergence of resistance. Some protocols delay initiation of rifampin by three to five days after debridement until surgical drains have been removed, to reduce the theoretical risk of resistance development during the period of highest bacterial burden. Preferred oral companion agents include levofloxacin 500 milligrams daily, trimethoprim-sulfamethoxazole, or dicloxacillin.

The DATIPO trial, published in 2023, evaluated 6 weeks versus 12 weeks of total antibiotic duration after DAIR for PJI and demonstrated non-inferiority of the shorter course for hip PJI, suggesting that 6 weeks may be sufficient for well-selected cases involving the hip.

Staphylococcal PJI (MRSA)

MRSA PJI is treated with intravenous vancomycin, guided by AUC-based dosing, for two to six weeks, followed by an oral regimen of trimethoprim-sulfamethoxazole or doxycycline plus rifampin for a total duration of three to six months. Daptomycin at 6 to 8 milligrams per kilogram intravenously is an alternative to vancomycin. MRSA PJI treated with DAIR has lower success rates, in the range of 50 to 60 percent, compared to MSSA PJI.

Cutibacterium acnes PJI

Cutibacterium acnes is a particularly important pathogen in shoulder arthroplasty, where it may present with chronic pain and loosening without the typical signs of infection such as erythema, warmth, or purulent drainage. The organism is highly susceptible to penicillin G and amoxicillin, which are the agents of choice. Treatment duration is six to twelve weeks. A critical laboratory consideration is that C. acnes requires prolonged culture incubation of 14 days, and it is frequently missed when standard 5-day culture protocols are used.

Gram-Negative PJI

Gram-negative PJI is treated with an initial intravenous phase using a beta-lactam (ceftriaxone, cefepime) or intravenous ciprofloxacin for two to six weeks, followed by an oral fluoroquinolone, with ciprofloxacin preferred due to its biofilm activity, for a total duration of three to six months. Fluoroquinolones possess biofilm activity against gram-negative organisms that is analogous to the biofilm activity of rifampin against staphylococci, making them the preferred oral agents for this indication.

Fungal PJI

Candida PJI is uncommon but requires aggressive management. Two-stage exchange is the recommended surgical approach, as one-stage exchange is not recommended for fungal PJI. Antibiotic-loaded spacers should contain amphotericin B in the PMMA cement. Systemic antifungal therapy consists of fluconazole 400 milligrams daily for a minimum of six weeks between stages, with some specialists initiating therapy with an echinocandin before transitioning to fluconazole.

<image>A treatment strategy comparison for prosthetic joint infection. Create three columns for the three surgical approaches: "DAIR," "Two-Stage Exchange," and "One-Stage Exchange." For each, show: patient selection criteria, surgical procedure steps (with small surgical illustrations), antibiotic regimen timeline (show IV phase and oral phase with specific durations for hip vs. knee), success rates, advantages, and disadvantages. Include a fourth column for "Chronic Suppression" as a non-surgical option. Below the comparison, show an antibiotic regimen detail box for staphylococcal PJI: "IV nafcillin/cefazolin (MSSA) or vancomycin (MRSA) x 2-6 weeks → rifampin + oral companion x total 3 months (hip) or 6 months (knee)." Highlight rifampin's role with a note: "NEVER use rifampin monotherapy -- rapid resistance." Use a professional surgical/medical comparison format.</image>

Other Device-Related Infections

Vascular Graft Infections

Vascular graft infections occur in 1 to 6 percent of aortic grafts, with higher rates in groin grafts. S. aureus is the most common causative organism, followed by coagulase-negative staphylococci, gram-negative bacilli, and Candida species. Clinical presentations include fever, the dreaded graft-enteric fistula (which may manifest initially as herald bleeding followed by massive gastrointestinal hemorrhage), perigraft fluid on imaging, and false aneurysm formation.

Treatment of vascular graft infections typically requires graft excision with extra-anatomic bypass or in-situ replacement using an antibiotic-soaked graft or cryopreserved allograft. Prolonged intravenous antibiotic therapy is followed by lifelong oral suppressive therapy if the infected graft is retained. PET/CT has emerged as a valuable diagnostic tool for occult vascular graft infections.

Cardiac Implantable Electronic Device (CIED) Infections

CIED infections, covered in detail in the endocarditis lecture, require complete device extraction as a mandatory component of treatment. Generator pocket infections without bacteremia necessitate complete extraction followed by 10 to 14 days of antibiotic therapy. Lead-associated endocarditis requires complete extraction followed by intravenous antibiotics for four to six weeks.

Spinal Hardware Infections

Spinal hardware infections are a post-surgical complication, with S. aureus, coagulase-negative staphylococci, gram-negative organisms, and Cutibacterium being the predominant pathogens. Early infections occurring within 30 days of surgery can often be managed with debridement and hardware retention if the spinal construct remains stable. Late infections may require hardware removal after solid bony fusion has been achieved. Antibiotic regimens follow the same principles as PJI, with rifampin included for staphylococcal infections involving retained hardware.

Peritoneal Dialysis Catheter Infections

Peritoneal dialysis-related peritonitis presents with cloudy dialysate containing more than 100 white blood cells per cubic millimeter with more than 50 percent polymorphonuclear cells, accompanied by abdominal pain. Empiric therapy consists of intraperitoneal vancomycin plus ceftazidime or gentamicin, covering both gram-positive and gram-negative organisms. Catheter removal is indicated for fungal peritonitis, mycobacterial peritonitis, refractory peritonitis persisting beyond five days of appropriate therapy, relapsing peritonitis, or exit-site and tunnel infection occurring concurrently with peritonitis.

Key Clinical Pearls

• Biofilm is the fundamental barrier to PJI treatment -- antibiotics alone cannot eradicate mature biofilm without surgery
• Rifampin is the single most important adjunctive antibiotic for staphylococcal PJI -- it penetrates biofilm and kills sessile organisms; NEVER use it as monotherapy
• Sonication of explanted prostheses increases culture sensitivity by 20-30% -- always request this when available
• Hold antibiotics for ≥2 weeks before diagnostic aspiration to maximize culture yield (when clinically safe to do so)
• Synovial fluid alpha-defensin is the most accurate single biomarker for PJI (sensitivity and specificity both ~97%)
• DAIR is appropriate ONLY for early (<3 months) or acute hematogenous (<3 weeks symptoms) PJI with a well-fixed implant -- chronic PJI requires exchange
• Cutibacterium acnes is the "silent" pathogen of shoulder arthroplasty -- cultures must be held for 14 days to detect it
• Fluoroquinolones have biofilm activity against gram-negatives analogous to rifampin's activity against staphylococci

References

1. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the IDSA. Clin Infect Dis. 2013;56(1):e1-e25.
2. Parvizi J, Tan TL, Goswami K, et al. The 2018 definition of periprosthetic joint infection: an evidence-based and validated criteria. J Arthroplasty. 2018;33(5):1309-1314.
3. Lora-Tamayo J, Euba G, Ribera A, et al. Dalbavancin plus rifampicin combination for prosthetic joint infections (DATIPO). Lancet Infect Dis. 2023;23(6):719-730.
4. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004;351(16):1645-1654.
5. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007;357(7):654-663.

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