Periprosthetic Infection With A Focus On The Knee: Pathogenesis, Evaluation, And Treatment

Daniel C. Allison MD, MBA, FACS
Cedars-Sinai Medical Center

Infection remains a significant problem affecting joint implants, with a 1.1-2.2 percent incidence in total hip arthroplasty (THA),1,2 0.9-4.0 percent in total knee arthroplasty (TKA)3,4 and 1-7 percent in all joint arthroplasty.5 Furthermore, the incidence and prevalence is increasing, with a two-fold increase in hip and knee periprosthetic infections (PPI) from 1990 to 2004.6,7,8

The clinical impact is significant, with PPI representing a significant cause of mortality (2.7-18 percent)9 and the leading cause of primary knee and revision hip arthroplasty failure.5,4 Infected revisions result in a hospital length of stay 1.7 times longer than their aseptic counterparts.10 The economic costs are also great, with infected joint replacements costing three to four times that of aseptic primary arthroplasty, 7,11,12 at an estimated cost of $50,000 per infection.5

Figure 1A and 1B. After articulating antibiotic spacer placement in treatment of chronic TKA infection.


The pathogenesis of PPI involves introduction of the offending organism and subsequent establishment and development of infection. Introduction of the organism can occur through three means: 1) direct inoculation – which is estimated as the cause of 60 percent of PPI;13 2) hematogenous spread – 34 percent of cases of S. Aureus bacteremia result in PPI;13 3) contiguous spread from adjacent focus (i.e. surgical site infection) – 41 percent of PPI cases in one study resulted from adjacent surgical site infection.14 The establishment and development of infection is related to host factors (local and systemic immunosuppression), pathogen factors (virulence, susceptibility to host and medical defenses, bacterial load), and outside factors (bacterial contamination and environment). A multitude of host factors have a significant impact of the development of PPI, including: obesity, smoking, myocardial infarction, atrial fibrillation, rheumatologic disease, diabetes, public assistance, organ transplantation, coagulopathy, medical comorbidities (Charlson index > 1 and ASA > 2), systemic malignancy, malnutrition (five to seven times increased major wound complications), and anemia.9,15 Biofilm formation remains the key component in the development of infection, and is related to host, pathogen, and environmental factors. Biofilm is defined as the aggregation of microbe colonies enclosed within an extracellular polysaccharide matrix (glycocalyx) that adheres to the surface of implants or devitalized bone. Biofilm protects the organism from antibiotics and host defense mechanisms, such as antibody formation and phagocytosis, allowing infections to exist in a subclinical state and recur. One study indicates that 59 percent of orthopaedic biomaterial-related infections have positive findings of glycocalyx-enclosed organisms on electron microscopy.13

The diagnosis of PPI can be challenging and recent guidelines have significantly helped our ability to diagnose these often elusive condition.16 Musculoskeletal Infection Society (MSIS) criteria for diagnosis includes one of the following:

  • A sinus tract communicating with the prosthesis; or
  • A pathogen is isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint


Or four of the six following:

  • Elevated ESR or CRP
  • Elevated synovial white blood cell (WBC) count (as low as 1,100 – 4,000)
  • Elevated synovial neutrophil percent (as low as 64-69 percent PMN)
  • Presence of purulence in the affected joint • Isolation of a microorganism in one culture of periprosthetic tissue or fluid
  • Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at 400 times magnification.

The prevention of PPI mirrors the same approach we use to treat the condition. The primary goals involve 1) optimizing systemic host immune and healing potential, 2) eradicating potential sources of hemotogenous bacterial innoculation, 3) optimizing the local soft tissue envelope, and 4) minimizing local contamination. In regard to optimizing host immune and healing potential, the surgeon should ensure strict smoking cessation, strict glycemic control, nutritional optimization (even in the morbidly obese), maintenance of total lymphocyte count (ALC >1500) and prealbumin (>3.5 g/ dl) in high risk patients, oral vitamin and mineral supplementation [Zinc (>5 mcg/ml) and Transferrin (>200 ng/ ml)], weight loss, cessation of immunosuppressive medications (especially biologic rheumatologic agents), correction of anemia and coagulopathies, optimization of medical comorbidities (cardiac, pulmonary, etc.), and avoidance of pre-surgical hospital stay.17,18,19,20 The elimination of sources of bacterial seeding includes confirming the absence of active dental, urinary tract, skin, and gastrointestinal tract infections. Optimization of the local soft tissue envelope involves treatment of vascular insufficiencies (arterial & venous), and the careful planning of surgical approaches, avoiding unnecessary and superficial skin flaps, and using local rotational flaps when appropriate. Local contamination can be minimized through meticulous skin care (psoriasis, breakdown, ulcers), MRSA testing in high risk patients (institutionalized), mupirocin x one week in MRSA carriers, chlorhexidene shower starting one to five days prior to surgery, preoperative chlorhexidine wipes on the day of surgery, and shaving the surgical site with clippers.22,23,24

Figure 2A and 2B. Two years after reimplantation, with no evidence of infection.


Despite our best efforts at prevention, periprosthetic joint infections still occur. The goals of treatment of these infections must include: 1) a thorough and meticulous removal and debridement of all infected and devitalized bone, soft tissue, and foreign material, 2) maintenance of mechanical stability, 3) preservation of the soft tissue envelope, and 4) delivery of appropriate antibiotic, locally and systemically. In my experience, persistent refractory PPI is usually secondary to one or more of these issues not being addressed. The treatment options for periprosthetic infection of the knee include:

  • Chronic antibiotic suppression alone
  • Irrigation & debridement (I&D) and retention of prosthesis with or without modular component exchange
  • Single staged implant removal & immediate reimplantation
  • Two staged implant removal & reimplantation
  • Using a temporary spacer (static antibiotic cement, articulating antibiotic cement, or metal / polyethlene prosthetic secured with antibiotic cement)
  • Implant removal & knee arthrodesis
  • Above knee amputation

With regard to antibiotic suppression alone, success rates are low, and this treatment is usually only considered in the very sick or elderly.25 Surgical I&D with component retention also has variable success rates (18-52 percent), especially in the chronic setting, which may be improved with antibiotic suppression.26,27 Single staged implant removal and reimplantation has recently emerged as a viable option in chronic PPI cases. One study comparing single staged revision to standard two staged revision demonstrated a non-statistical lower infection rate in the single staged group (0 percent vs 7 percent [P = 0.16]) and statistically improved Knee Society Scores in the single staged group (88 vs 76 [P < 0.001]); however, the single staged cohort was carefully selected.28


With regard to end-stage procedures, above knee amputation remains a procedure of last resort, with significant increases in energy expenditure for ambulation (68 percent increase in metabolic demand compared to normal limb), which may be particularly problematic in the elderly or those with medical comorbidities. Knee arthrodesis carries the advantages of a significant cure rate, a longevious and durable construct, and improved ambulatory ability when compared to above knee amputation in elderly,29 with the disadvantages of poor acceptance from the patient and difficulty converting to secondary total knee arthroplasty.

Many argue that two-staged implant removal and reimplantation remains the gold standard treatment of chronic PPI of the knee.25 This method of treatment involves implant removal, meticulous debridement, complete synovectomy, and insertion of a mechanical construct which serves to maintain the space for future reimplantation, a means to deliver antibiotic locally, and means to confer stability to the area. This “spacer” may consist of a static block of antibiotic cement or an articulating construct similar to that of a total knee arthroplasty. After implant removal and antibiotic pacer placement, a prolonged course of tailored intravenous antibiotics is instituted, with planned reimplantation at eight- 24 weeks (if and when clinical, serologic, and aspiration studies show no evidence of infection). The goals of antibiotic spacer use include: 1) maintenance of joint stability, 2) elution of local antibiotic, 3) optimization of patient function and comfort, and 4) increasing the ease of revision surgery by preserving bone stock, maintaining the appropriate space, and preventing soft tissue contracture.

Articulating antibiotic spacers offer potential benefits of improved antibiotic delivery and increased surface area for greater antibiotic elution.


Static block spacers demonstrate 80-90+ percent cure rates, with the downsides of soft tissue contracture, instability / patient discomfort, posterior femoral condyle soft tissue growth, quadriceps scarring to anterior distal femur, and bone loss30. Metal and polyethylene “spacers” have evolved in order to avoid the downsides of static spacers, but serve as persistent source of biofilm establishment; early results demonstrate similar reinfection rates and improved range of motion with articulating metal and polyethylene construct (107.8o vs 93.7o), however, long term results are still pending.31


Articulating antibiotic spacers offer potential benefits of improved antibiotic delivery and increased surface area for greater antibiotic elution. They also optimize revision surgery by potentially preserving motion, prevention of soft tissue contracture, and preservation of the joint space, especially in the area posterior femoral condyles and anterior femur. Many articles have been published comparing static and articulating spacers, and a well-written review summarizes seven of the best studies, noting a similar reinfection rate between both (7 percent articulating vs 12 percent Static [P = 0.2]), similar functional scores between both, and improved range of motion with articulating spacers 101o (articulating) vs 91o (static) (P = 0.0002).32

In summary, periprosthetic joint infections remain a major problem in the arthroplasty world, with increasing incidence and prevalence, high associated morbidity and mortality, and extensive monetary burden. Preoperative prevention involves optimizing medical comorbidities, eradicating potential sources of bacteremia, optimizing the soft tissue envelope, and decreasing local bacterial contamination. Effective treatment requires adequate debridement, ensuring appropriate soft tissue coverage, conference of stability to the area, and delivering appropriate antibiotic therapy. The two-staged procedure remains the gold standard for chronic PPI, and articulating antibiotic spacers optimize the goals of infection treatment as well as joint preparation for implantation. •



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