Periprosthetic joint infection remains a challenge to the orthopaedic community

Although the incidence of periprosthetic joint infection is low — around 1% to 2% — the consequences for patients can be devastating and lead to reduced function, increased morbidity and multiple surgeries. While the medical community has adopted protocols to prevent and treat these infections, in many cases there is little scientific evidence to support those practices and the procedures used vary significantly throughout the world.

In August 2013, 400 delegates from nearly 60 countries met to evaluate the existing evidence for the treatment of periprosthetic joint infection (PJI) from more than 3,500 relevant publications. The resultant document — International Consensus on Periprosthetic Joint Infection — provides orthopaedic surgeons worldwide with guidance on PJI prevention, diagnosis and treatment.

Because there has been no standard definition to date of PJI, according to the consensus statement, PJI should be defined as follows:

• Two periprosthetic cultures positive for the same organism;
• A sinus tract communicating with the joint; or
• Having three of the five following minor criteria:
• Elevated serum C-reactive protein (CRP) and erythrocyte sedimentation (ESR); or
• Elevated synovial fluid white blood cell count or a positive change on a leukocyte esterase test strip; or
• Elevated synovial fluid polymorphonuclear percentage; or
• Positive histological analysis of periprosthetic tissue; or
• One positive culture.

Risk factors

Orthopaedists agree there are several risk factors for PJI, including active infection of the arthritic joint, septicemia, active local cutaneous or subcutaneous or deep tissue infection. All of these are contraindications for performing elective total joint arthroplasty.

In terms of patient-related risk factors, the most important are the patient’s age and general condition and the severity of the underlying illness, Olivier Borens, MD, chief of the septic surgery unit and chief of the orthopaedic trauma unit at Centre Hospitalier Universitaire Vaudois, in Lausanne, Switzerland, told Orthopaedics Today Europe.

“These are non-modifiable risk factors,” Borens said.

The patient-related modifiable risk factors include uncontrolled diabetes, obesity, malnutrition, smoking, excessive alcohol consumption, intravenous drug use and immunodeficiency.

Concerning surgery-related risk factors, Borens, who participated in the consensus meeting, said, “We can have problems, for instance, in preparing the patient for the operation. We can have problems in the preparation of the surgeon for the operation, the way that he is scrubbing in, the way that he is attired, and problems related to what is going on in the OR itself.”

Categories of infection

PJIs fall into three categories: early, chronic and hematogenous, with the latter two types of late or delayed infection labeled as such according to the classification by Gustilo, Anderson and colleagues. Early infection is detected in the first 4 weeks to 6 weeks after the primary operation, according to Ole Ovesen, MD, an orthopaedic surgeon at Odense University Hospital, in Odense, Denmark.

Early infections are easy to diagnose because the patient has clear infection signs: usually a red, oozing wound and a fever, he said.

“In these cases, we would always try to preserve the prosthesis by doing a soft tissue revision but leave the prosthetic in place,” Ovesen told Orthopaedics Today Europe. “If it is an uncemented hip, we change the liner, and we will change the femoral head. [We] do a thorough soft tissue revision and put [the patient] on antibiotics for at least 6 weeks.”

This treatment course yields a 70% success rate, he said.

Delayed or hematogenous infection generally develops 3 months to 24 months postoperatively.

“Delayed infections are normally caused by germs that are not aggressive and do not reproduce themselves quickly and do not provoke heavy signs of infection,” Borens said.

Staphylococcus epidermidis and Propionibacterium acnes are typical bacteria associated with delayed infection, he said.

“These are [found in] patients who have had a total knee or total hip arthroplasty, who are never doing well and are feeling some persistent pain,” Borens said.

In these cases, some lysis can be visible on a radiograph.

Late infections occur 2 years postoperatively, he said.

“The cases that have the most impact are the chronic infections,” according to Ovesen. “In chronic infection, we will always treat [it] with a two-stage procedure. In the first stage, we will take out the prosthesis and do debridement of the soft tissue and bone. Then we treat the patient with relevant antibiotics for at least 6 weeks,” he said.

Blood analysis, ESR

“[Diagnosis of PJI] is largely based on clinical suspicion,” Mike R. Reed, MD, FRCS, consultant trauma and orthopaedic surgeon at Northumbria Healthcare NHS Foundation Trust in the United Kingdom, said.

After the clinical exam, the next step is a blood analysis to identify any parameters that indicate a possible infection, such as an elevated CRP level, according to Borens.

Measuring ESR and lymphocytes also has some value, he said. “But probably the best and cheapest one right now is CRP, which is going to give you a good exam.”

Plain radiographs are necessary in all cases of suspected PJI, according to the consensus document.

Radiographs will most often be normal with acute infection, Borens noted.

At the moment, MRI, CT and nuclear imaging do not have a direct role in PJI diagnosis; however, they may help identify other causes of joint pain or failure. According to Borens, all these testing methods have excellent sensitivity, but it still takes a long time to get the results and specificity is not sufficient.

“We are trying to work on speeding up the different methods to be quicker in diagnosing the germ,” he said.

Fast identification of the bacteria is important because delayed diagnosis can make the infection more difficult to treat. Bacteria live in either planktonic or biofilm mode, according to Borens. Once they reach the implant, they start producing slime or a biofilm, he said.

“Once they are living as a mature biofilm, we can no longer get rid of them with only antibiotics,” Borens said.

“If we know what germ it is and we have an early infection, we know that we can choose a combined therapy consisting of surgical debridement and exchange of the mobile parts and biofilm active antibiotic treatment. With this we have a greater than 90% chance to successfully preserve the implant,” Borens said. “If we know that it is a resistant germ where we cannot do any antibiofilm treatment...our chances of eradicating the infection are [less].”

Treatment options

“If we are more or less convinced that there is an infection, we are going to take the patient to the operating room,” Borens said. “We are going to do a number of microbiological and histological exams. Besides standard microbiological testing, where it is important to take at least five tissue cultures, we will check if there are any leukocytes growing on our microscopic control. We can do fresh frozen sections to see whether there is an infection.”

One reason PJIs are challenging to diagnose is the biofilm, where bacteria live in a state where they reproduce little or not at all. Standard microbiological methods help identify planktonic bacteria and this lessens the chances of finding an infection. To overcome that problem, Ovesen’s group uses sonication whereby they explant the prosthesis and expose it to sonication.

“You have to shake off the biofilm with the bacteria,” Ovesen said.

In a recent study, researchers found that 48 of 200 revisions had deep infection as determined by clinical and paraclinical diagnosis. Of the 48 revisions, 77% of diagnoses were positive using conventional methods. With sonication, 85% were positive, Ovesen noted.

“[Sonication] can improve your diagnostic precision,” he said.

The consensus group does not recommend routine sonication, however. They suggest its use should be limited to cases when preoperative aspiration does not yield positive culture and antibiotics have been administered within the previous 2 weeks.

Delivery of antibiotics

Traditionally, intravenous (IV) antibiotics have been used to treat patients with PJI, but to do that requires either a hospital stay or stringent at-home care, said José Cordero-Ampuero, MD, PhD, of the department of orthopaedic surgery at Hospital Universitario La Princesa in Madrid.

“About 15 to 20 years ago in Europe, we began using oral antibiotics,” he told Orthopaedics Today Europe. “European surgeons think it is a more modern, more effective and easier protocol.”

Traditional protocols will halt the infection in about 90% of patients, Cordero-Ampuero said. But, with oral antibiotics, that rate increases to between 95% and 98%.

The consensus group agreed there is evidence to support pathogen-specific, highly bioavailable oral antibiotic use to treat PJI. They also noted that oral antibiotics are acceptable after an initial IV antibiotic course. Furthermore, delegates at the consensus meeting agreed that antibiotic therapy should last for 2 weeks to 6 weeks.

One-stage vs. two-stage revision

The big debate in this area that is ongoing is whether to do a one- or a two-stage revision for patients who are diagnosed with PJI.

“One-stage is favored more in Europe and two-stage more in the United States,” Reed said. “And, the United Kingdom is currently somewhere in between the two.”

Although there are no randomized controlled trials on this subject, the consensus at the 2013 meeting was that one-stage revision can be a viable surgical option except in patients with sepsis who may require resection arthroplasty and reduction of bioburden. Relative contraindications for one-stage revision include an infectious organism not identified preoperatively, the presence of a sinus tract and severe soft tissue involvement that may require flap coverage.

Two-stage revision may be preferred over one-stage revision in patients with sepsis, in obviously infected patients with no identified organism, when preoperative cultures identify antibiotic-resistant organisms, when there is a sinus tract and when soft tissue coverage is inadequate or non-viable.

Prevention methods

Prevention of PJI is a priority for orthopaedic surgeons, and there are several actions that may help with the efforts. At Ovesen’s institution, surgeons administer antibiotic prophylaxis for the first 24 hours after surgery with narrow-spectrum antibiotics.

“We are very conservative,” he said.

It was once thought that laminar air flow in the operating room helps prevent these infections, but some reports now question its value.

“The consensus felt that laminar flow was not compulsory,” Reed said.

The consensus group felt strongly that limiting personnel and activity in the operating room was critical for infection prevention. The sources who spoke with Orthopaedics Today Europe for this article agreed that antibiotic-laden cement prevents these infections.

“The use of cement with antibiotic is very effective for prevention,” Cordero-Ampuero said. Results from researchers in Scandinavia show that infection rates decreased from 0.8% to 0.3% with antibiotic cement, he said.

Reed’s group recently completed a large, randomized controlled trial of 848 patients with a hip fracture. “We found a significantly lower infection rate using high dose antibiotic cement (1.7%) versus normal antibiotic cement (5.1%),” he said.

Research on PJI will continue. The consensus group identified many areas that require more study. They include the use of dual antibiotics for prevention, the best method of operating room decontamination and risk factors for failure of irrigation and debridement. – by Colleen Owens

• References:
• Gustilo RB. J Bone Joint Surg Am. 1976;58:453-458.
• Parvizi J. Bone Joint J. 2013; doi:10.1302/0301-620X.95B11.33135.
• For more information:
• Olivier Borens, MD, can be reached at Rue du Bugnon 46, 1011, Lausanne, Switzerland; email: olivier.borens@chuv.ch.
• José Cordero-Ampuero, MD, PhD, can be reached at Océano Antártico 41, Tres Cantos, 28760 Madrid, Spain; email: jcordera@telefonica.net.
• Ole Ovesen, MD, can be reached at the Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark; email: ole_ovesen@hotmail.com.
• Mike R. Reed, MD, FRCS, can be reached at Wansbeck General Hospital, Northumberland, United Kingdom; email: mike.reed@nhs.net.

Disclosures: Borens is a consultant to Heraeus and Zimmer. Cordero-Ampuero is an invited speaker for Stryker, MBA, Pfizer and Merck Sharp & Dohme, but has no relevant financial disclosures related to those companies. Ovesen has no relevant financial disclosures. Reed is an invited speaker for Biomet. His research group has received funding from Heraeus Medical, Johnson & Johnson, Convatec and medical charities.

What practices do you use that most effectively reduce the risk of periprosthetic joint infection?

Gentle tissue handling

Prevention of this devastating complication is one of the primary issues in every surgical procedure, moreover when we are going to use implants. Preoperative screening is followed by optimization of the general health status of the patient and elimination of (all possible) risk factors for surgical site infection and periprosthetic joint infection (PJI), such as an active systemic or local infection, uncontrolled hyperglycemia, malnutrition, active renal disease, intravenous drug use, and excessive alcohol or tobacco consumption. Particular care is taken to decolonize elderly patients who are from a health care facility. Immunosuppressant medication and disease modifying agents are discontinued, when necessary, under the direction of the patient’s treating physician.

Whole-body skin cleansing done early in the morning prior to elective arthroplasty and use of clean garments are also done as standards of care.

When patients have active ulcerations at the site of the skin incision, surgery is delayed until they are healed. Intravenous antibiotic prophylaxis with a weight-adjusted second-generation cephalosporin combined with an aminoglycoside is administered during the hour prior to skin incision and for 24 hours after surgery.

The operative field is prepared with chlorhexidine gluconate scrub and rinsed with same solution prior to drying and a sterile adhesive drape is applied.

All of the above precautions are essentials for the prevention of PJI, but of equal importance is the gentle handling of the tissues, in due time, and avoiding prolonged exposure of the implants and the operative field to harmful contaminants.

Konstantinos N. Malizos, MD, PhD, is 2013 President of the Hellenic Association of Orthopaedic Surgery & Traumatology, International Deputy Editor Journal of Bone & Joint Surgery, and chair of the Department of Orthopaedics & Trauma and member of the University Council Medical School at University of Thessalia, Larissa, Greece.
Disclosure: Malizos has no relevant financial disclosures.

Steps to prevent, manage PJI

We follow several steps to prevent periprosthetic joint infection (PJI). Preoperative screening is first, along with ensuring that diabetes is under control in patients with the disease. Patients should stop smoking before surgery.

In high-risk patients, especially those who are immunocompromised, local anesthetic injection, a minimally invasive approach and hypothermia should be avoided. Thromboprophylaxis should be restricted to postoperative administration.

When the local knee skin perfusion is in doubt, the surgeon should always carefully close the incision his or herself. The patient should avoid early aggressive flexion training.

Following these steps will reduce the risk of disturbing the healing and thereby reduce the risk for a subsequent deep infection.

To maintain aseptic principles and reduce the risk of bacterial contamination of the wound, preoperatively the patient should shower with chlorhexidine sponges. The patient should be admitted to a clean, fenced ward in the hospital as close to their surgery date as possible. The operating room should be totally restricted and the door kept closed during joint implant procedures.

Systemic preoperative antibiotic prophylaxis with correct dosing and timing is a critical step in PJI prevention. Antibiotics should be given via a local carrier for synergistic infection prophylaxis. These steps will kill any bacteria that have contaminated the wound.

Lars Lidgren, MD, PhD, is a member of the Orthopaedics Today Europe Editorial Board. He is professor, head Department of Orthopedics at University of Lund, in Lund, Sweden.
Disclosure: Lidgren is member of the board of Bone Support Sweden and Orthocell Australia.