A Clinical Update on the Prevention, Treatment of Periprosthetic Joint Infections

Despite continued advances in orthopedic surgery over past decades, periprosthetic joint infection (PJI) remains a serious threat to successful joint replacement. PJIs can lead to limitations in joint function, the need for revision surgical procedure(s), and prolonged periods of disability.¹ The majority of PJIs occur as a result of microorganism introduction at the time of surgery.² Once introduced, bacteria continue to grow inside the biofilm that forms on the surface of the implant.

In an interview with Rheumatology Advisor, Alberto V. Carli, MD, assistant attending surgeon and Ashley E. Levack, MD, MAS, orthopedic surgery resident at Hospital for Special Surgery in New York, New York, provided an update on preventive and treatment options for PJIs.

Rheumatology Advisor: Can you briefly describe why PJIs develop and which microorganisms are most often implicated?

Alberto V. Carli, MD: The precise pathophysiology of PJI remains poorly understood. Currently, PJI is believed to develop through 2 possible means²: direct contamination into the joint space during the perioperative period or hematogenous spreading to the joint space at some point postoperatively. Perioperatively, bacteria are believed to enter the joint space either due to encroachment from the patient’s skin adjacent to the surgical incision, from shedding from members of the surgical team, or from contaminated surgical instruments. Hematogenous spreading can occur at any point following surgery and has been specifically reported to occur following dental work, systemic bacterial infection, or from infections involving the genitourinary or gastrointestinal tract. Perioperative contamination is currently believed to be the most common cause of PJI, and consequently, gram-positive organisms such as Staphylococcus aureus and Staphylococcus epidermidis are responsible for over half of reported PJIs.¹

Rheumatology Advisor: Which implant-related factors contribute to the development of PJIs?

Ashley E. Levack, MD, MAS: Currently, joint replacement implants are composed of metal alloys (cobalt-chrome-molybdenum, titanium-aluminum-vanadium, stainless steel, oxidized zirconium), ceramic materials, and dense plastics composed of high-molecular weight polyethylene. Bacteria are able to adhere to all of these implant surfaces and form a glycocalyx-based biofilm, which protects them from immune responses.³ No specific implant material has been consistently shown to increase or decrease the rate of PJIs. Implant fixation can be augmented when necessary (often in knee replacement) using polymethylmethacrylate (PMMA) cement, which can also be loaded with antibiotic powder that elutes into the joint space postsurgery. Although use of antibiotic-loaded cement has been extremely popular in Europe, several studies have shown minimal differences in PJI incidence.⁴

Rheumatology Advisor: Which approaches are currently used to prevent PJIs and how effective are they?

Dr Carli: Robust preoperative guidelines are utilized to [ensure optimal] patient [health] prior to joint replacement surgery to reduce the risk for PJI.⁵ Patients should be screened and treated preoperatively for poor dentition, malnutrition, anemia, impaired glycemic control, cutaneous ulcers, and evidence of any active infection. Patients who are underweight or who have a body mass index that exceeds 40 kg/m² should be referred for weight management. [Patients with diabetes] should undergo hemoglobin A1c evaluation, and generally a perioperative level under 7% is required to proceed with surgery. Patients on disease-modifying agents for inflammatory conditions or who are on other immune-modulating agents should have their medications managed in accordance with guidelines⁶ and likely with the assistance of the treating rheumatologist. Patients are often screened for colonization with methicillin-resistant Staphylococcus aureus and complete a presurgical cleanse if colonized.

Within the perioperative period, additional strategies are in place to decrease PJI risk.⁵ Patients are instructed to clean the operative site the night before surgery, they receive prophylactic intravenous antibiotics both before and after surgery, and the surgical site is prepped — usually with chlorhexidine — before surgery. Operating room traffic is kept to a minimum and laminar flow ventilation is employed. Tranexamic acid and tourniquets are used when possible to decrease blood loss and decrease the infection risk associated with allogenic blood transfusion. Antibacterial sterile dressings are commonly used to dress the wound.

Rheumatology Advisor: What is the standard approach to treating PJI?

Dr Levack: The treatment of PJI depends on the duration of symptoms and how much time has passed since the original joint replacement surgery. PJI that develops within the first 6 weeks following surgery is generally considered to be acute⁷ and is consequently treated with an operative irrigation and debridement, exchange of modular components, and postoperative treatment with intravenous antibiotics for at least 4 to 6 weeks.

In the event that PJI develops after the sixth postoperative week, produces symptoms of pain and disability that last for several days or weeks, or is associated with a chronic draining sinus, such a PJI is defined as being chronic and therefore has mature biofilm on the implant surface. Currently, the gold standard treatment for chronic PJI in North America is a 2-stage revision.⁸ The first-stage involves removing the infected implant, performing a thorough irrigation, debridement, and synovectomy of the infected joint, and inserting either a static or articulating antibiotic PMMA cement spacer. The spacer fills the joint space and releases broad-spectrum antibiotics into the local tissue. The patient is also placed on targeted intravenous antibiotics for 6 to 12 weeks. Upon suspected resolution of the infection (using a combination of serum inflammatory markers and joint aspiration), the second-stage is performed whereby the PMMA spacer is removed and a definitive joint replacement is inserted. Although 2-stage procedures have been the standard of care for chronic deep PJI, the revision [results in some morbidity], is costly, and can fail to eradicate PJI in some cases.

Rheumatology Advisor: What are the potential complications of PJIs?

Dr Carli: It is important to stress that the onset of PJI is a life-changing event for patients. The 5-year mortality risk for these patients has been reported to be as high as 25%.⁹ Complications from untreated or recurrent PJI involve wound dehiscence, the possible need for joint fusion or limb amputation, and onset of systemic sepsis leading to death. PJI surgery carries a high risk for morbidity and requires extensive incisions and thorough tissue debridement. Consequently, there are numerous surgical risks,¹⁰ including bleeding, neurovascular injury, deep vein thrombosis, pulmonary embolism, joint instability due to surrounding muscle loss, periprosthetic fracture, and either long-term or permanent need for an assistive walking device. Antibiotic spacers can break or cause fractures due to their less structurally-rigid design. The risk for superinfection with another offending organism also exists during revision surgery. Mitigating these increased perioperative risks is achieved through meticulous preoperative optimization, anesthesia consultation, and efficient surgery performed by an experienced surgical team.

Rheumatology Advisor: Which alternative biomaterials are currently being researched as potential replacements for bone cement (PMMA) and how could they contribute to a lower incidence of PJI?

Dr Levack: Calcium sulfate and calcium phosphate bone graft substitutes are currently under investigation as alternative methods of local antibiotic delivery. These resorbable materials avoid the limitation of the high polymerization temperatures of PMMA, avoid the necessity of a second surgery for removal, and theoretically have more complete antibiotic release due to their absorbable nature. However, they lack the benefit of mechanical support afforded by PMMA. Most novel alternatives for local antibiotic delivery are presently in the preclinical stages of investigation. Cyclodextrin has been successfully coupled with several types of orthopedic implants and other types of surgical grafts in preclinical studies. The on-demand filling capacity of this technology would afford clinicians the opportunity to quickly administer local antibiotics intraarticularly without an additional surgical procedure.¹¹ This has implications for infection prophylaxis as well as during treatment of PJI when re-dosing is necessary. Further research is needed to define the potential uses and limitations of this technology in the setting of PJI.

This interview was lightly edited for clarity.

References

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This article originally appeared on Rheumatology Advisor