Peri-articular prosthetic infections are one of the most serious challenges facing joint surgeons. Despite concerted efforts by physicians and scientists to reduce the incidence of periprosthetic infections, the percentage of patients who develop infections after initial total knee arthroplasty is still 0.4 to 2 percent. Medical data show that the incidence of periprosthetic infections is 1.55% in the first 2 years after knee arthroplasty and increases by 0.46% in the following 2 to 10 years.
Kurtz et al. predicted that the number of cases requiring primary total knee replacement would increase from 450,000 in 2005 to 3.48 million in 2030, an increase of 673%. If 2% of the 3.48 million patients develop an infection in the first year after knee replacement, approximately 69,000 patients per year will be treated for periprosthetic knee infections.
These do not include patients who develop infections after 1 year postoperatively or after revision knee surgery. The burden on the patient and the complexity of the disease increases because of the development of drug-resistant bacteria.
Staphylococcus aureus infections account for the majority of peri-articular prosthetic infections. In particular, methicillin-resistant Staphylococcus aureus (MRSA) infections are more difficult to treat. Staphylococcal infections may be medically acquired, but some patients are carriers of S. aureus and are self-infected. Carriers of pathogenic bacteria can be screened and treated preoperatively, which can reduce the risk of periprosthetic infection.
Prevention
There are multiple interventions that can reduce the incidence of infection. Preoperatively, the surgeon should identify and address the major risk factors that increase infection, and antibiotics should be used for antimicrobial therapy when the patient is a carrier of pathogenic bacteria. Prophylactic antibiotics are effective in preventing surgical site infections and are usually given 1 hour prior to the start of surgery. rosenberg et al. reported that only 26 of 40 patients (65%) were given prophylactic antibiotics 1 hour prior to surgery during the 3 months prior to the implementation of this regimen to confirm consistency with the antibiotic dose.
Once the regimen was initiated, implementation improved, with 180 of 186 patients (97%) receiving preoperative prophylactic antibiotics (p < 0.0001). The American Academy of Orthopaedic Surgeons (AAOS) has published guidelines for the use of the most appropriate antibiotics, with cefazolin and cefuroxime preferred and clindamycin or vancomycin for those allergic to beta-lactams. Vancomycin may also be used in patients undergoing surgery at institutions with >25% incidence of MRSA or MRSE in orthopedic patients.
Patients infected with MRSA or so-called drug-resistant carriers are also candidates for treatment with vancomycin, and these patients should also receive adjunctive therapy such as chlorhexidine scrubs and nasal mupirocin sprays. Treatment regimens that remove pathogenic bacteria have been shown to reduce the incidence of staphylococcal infections. Studies have also shown that this treatment regimen is effective in eradicating MRSA from patients.
Major risk factors
Peri-articular prosthetic infections are associated with the following major factors: malnutrition, smoking, alcohol abuse, urinary tract infections, and obesity (Table 1). 6,108 patients underwent a total of 8,494 hip or knee replacements between 1991 and 2004, which were reviewed by Malinzak et al. and studied in a controlled study of deeply infected and uninfected individuals. The results found 43 cases of deep infection (30 associated with total knee replacement and 13 with total hip replacement), with a prevalence of 0.51%. Obesity, younger age and diabetes mellitus were identified as high-risk factors for susceptibility to infection. Patients who were morbidly obese (body mass index [BMI] >50 kg/m2) were significantly more likely to develop infection (probability 21.3). In the group undergoing total knee replacement, 40 kg/ m2
In a comparison of morbidly obese patients with a total of 50 total knee replacements and non-morbidly obese patients with a total of 1768 total knee replacements, Winiarsky et al. showed a wound infection rate of approximately 22% (11/50) in the morbidly obese group, with 5 cases of deep infection.
In the control group, the incidence of wound infection was 2% and the incidence of deep infection was 0.6%. The nutritional status of obese patients was assessed by measuring serum protein, transferrin levels, and total lymphocyte count. If the nutritional status was poor (transferrin <200 mg/dL, serum protein <3.5 g/dL, or lymphocyte count <1500 cells/mm3), basic nutritional support should be administered prior to total knee arthroplasty.
Patients who are at increased risk of infection due to obesity should be informed of their risk and some methods of risk reduction should be recommended. If the morbidly obese patient is in good nutritional status, bariatric surgery is recommended prior to total knee arthroplasty.
Complications during postoperative wound drainage and wound healing are associated with an increased incidence of infection. A comparative study of 78 patients who developed periprosthetic infections and control patients without infections showed that hematoma formation, wound drainage, and mean INR >1.5 were more common in the periprosthetic infection group.Galat et al. reviewed 42 patients who developed a hematoma and underwent hematoma debridement within 30 days after initial total knee arthroplasty, with an additional 42 patients as controls. The aim was to determine the lifting factors for the occurrence of hematoma.
The probability of needing reoperation and deep infection 2 years after surgery was 12.3% and 10.5%, respectively, in the hematoma-removing patients, while the probability of the same complication was 0.6% and 0.8%, respectively, in the control group. A history of bleeding disorders was significantly associated with the development of postoperative hematoma and the need for surgical debridement (p = 0.046). Matar et al. reported a number of other factors associated with periprosthetic infections before, during, and after surgery, and these authors recommended that risk factors that may cause or increase infection should be addressed.
Diagnosis
The evaluation of patients with suspected periprosthetic infections should follow a logical approach, and the AAOS has proposed “clinical practice guidelines” to standardize the evaluation process. Based on the patient’s history and physical examination, questions about the presence of infection should be raised first. In particular, most patients with periprosthetic infections present with persistent knee pain, often with joint stiffness or limited motion. Fever or general malaise strongly suggests infection, but is not typical. If venous collapse is present, joint infection can be considered only if otherwise confirmed.
Another way to assess for suspected infection is laboratory testing, and sedimentation (ESR) and C-reactive protein (CRP) levels should be measured in any patient suspected of having an infection at the site of total knee replacement surgery. In a preoperative study of 145 patients who had undergone knee revision for a total of 151 subacromial knees, criteria for normal and abnormal values of inflammatory markers were evaluated. The study noted that for ESR >22.5 mm/hr and CRP >13.5 mg/L, the presence of infection around the joint prosthesis was clearly indicated.
In a prospective study of 58 patients with periprosthetic infections, the authors evaluated the diagnostic accuracy of serum IL-6 levels, which are produced by stimulated macrophages but have normal values 48-72 hours postoperatively. The authors concluded that IL-6 level values are a more accurate indicator than ESR or CRP in detecting periprosthetic infections. A meta-analysis of the literature related to the diagnosis of periprosthetic infection included 30 eligible studies with a total of 3909 hip and knee replacements.
The incidence of periprosthetic joint infections was 32.5%, and the most accurate diagnostic condition was IL-6 levels, followed by CRP levels, ESR, and WBC in that order. one of the drawbacks of the meta-analysis was that only one large sample and two small sample studies addressed the role of IL-6 levels, 25 studies evaluated the role of ESR, 23 studies evaluated the role of CRP, and 15 studies assessing the role of WBC. The cost of none of these tests was evaluated.
When infection is suspected, another approach is to perform a puncture aspiration around the joint prosthesis and analyze the fluid around the prosthesis. Analysis of the puncture fluid should include a cell count to determine the absolute number of white blood cells and the percentage of neutrophils. If the white blood cell count at a site is between 1100 and 3000 cells/mL, infection is indicated.
A percentage of neutrophils to leukocytes of at least 60% is considered a joint infection. Finally, a culture of the puncture fluid sample should be performed to determine the type of bacteria and susceptibility to antibiotics. Gram staining of the puncture fluid sample is less sensitive and has less predictive value, and the results usually do not change the patient’s treatment plan.
In the early postoperative period, inflammatory marker levels and WBC counts in the synovial fluid may also be elevated despite the absence of infection in the joint.Bedair et al. analyzed and evaluated the results of puncture of the knee 6 weeks after initial total knee arthroplasty and compared ESR, CRP, and WBC counts and their differences between postoperatively infected and uninfected patients.
CRP level, WBC count in synovial fluid and percentage of polymorphonuclear cells in different white blood cell counts were higher in the infected group, but the best value of WBC count in synovial fluid as a reliable indicator of infection was more reliable than all the values given above. In this study, it was shown that a WBC count of 27,800 cells/mL in the synovial fluid of total knee replacement site puncture was then the best predictor of acute postoperative infection. Using this value, it had a positive prediction rate of 94% and a negative prediction rate of 98%.
Aerobic, anaerobic and fungal cultures are routinely performed, but molecular testing, which is still in the developmental stage, may also become routine. Challenges for orthopedic surgeons include false-positive and false-negative culture results, and unfortunately, false-positive fluid and tissue cultures are more common. If the history, physical examination, level values of inflammatory indicators and cell counts in the puncture fluid are normal, then a positive culture result is likely to be a false positive.
When the patient’s history, physical examination findings, level values of inflammatory markers and cell counts in the puncture fluid are elevated but the culture result is negative, then it is difficult to draw conclusions. False-negative culture results are also relatively common, occurring in 5-10% of cases. in a study of 897 patients with periprosthetic infections over a 10-year period, Berbari et al. found negative culture results in 60 (7%) patients, 32 (53%) of whom had been treated with antibiotics. of the 60 infected patients, 34 (57%) had stage II endosseous replacement and Of the 60 infected patients, 34 (57%) underwent second-stage endograft replacement, 12 (20%) underwent debridement with partial retention of the endograft, 8 (13%) underwent prosthetic joint removal, 5 (8%) underwent first-stage resurfacing, and 1 (2%) underwent amputation. Patients were treated with intravenous antibiotics for an average of 28 days, and 49 (82%) were treated with cephalosporins.
The 5-year survival rate for those who underwent first-stage replacement without infection was 94%, while the 5-year survival rate for patients who underwent debridement and retained components was 71%. This study highlights the importance of treating patients with positive bacterial cultures. A treatment regimen of parenteral administration of antibiotics and second-stage endograft replacement has a higher success rate for patients with periprosthetic infections and negative bacterial cultures.
Segawa et al. suggested a clinical classification of deep periprosthetic infections, with type I infections being those in which no infection was previously identified but routine culture of the specimen at the time of revision determined that infection was present. Revision surgery is used to treat this type of infection and includes appropriate debridement, replacement of part of the device, and is therefore comparable to one-stage reimplantation of the internal fixation, with complete treatment requiring intravenous antibiotics for 4-6 weeks. Oral antibiotic therapy following intravenous antibiotic therapy is helpful.
Type II infections are early postoperative infections, i.e., those that occur within 1 month of surgery. treatment of type II infections includes surgical debridement, retention of the prosthesis, intravenous antibiotics for 4-6 weeks and possibly oral antibiotics for a limited period of time. If the surgeon has already treated a patient who has undergone revision surgery at an outside institution and notes that the intraoperative specimen has a positive bacterial culture, another debridement may still be necessary. Several factors should be considered: bacterial species, antibiotic sensitivity, complexity of the anticipated future resection and reimplantation of the prosthesis, and the patient’s systemic status and immune status.
Type III infections are those that occur several years after surgery as well as acute hematogenous infections of distant origin. If the duration of infection is 2-3 weeks or less, the internal fixation remains strong, and the patient’s immune status is good, surgical debridement, retention of the prosthesis, and intravenous antibiotics can save the replaced joint. The success rate of this treatment is 30-90%.
Recently, Azzam et al. successfully treated 104 patients with type II and type III periprosthetic infections in a single center using a debridement approach with irrigation and retention of the prosthesis with a mean follow-up of 5.7 years. The success rate was 44% using partial excision or microbiologically proven infection as the endpoint. The authors noted that treatment failure rates were higher for patients with staphylococcal infections, those with high ASA scores, and those with periprosthetic sepsis. Patients treated when symptoms were present within two weeks had the best treatment outcome (treatment success rate of 60%).
Finally, type IV infection is an infection that is more than one month old and is chronic and painless. Stage I or II resurfacing is recommended, including removal of the implant, thorough joint debridement, and 4-6 weeks of intravenous antibiotic therapy. When a phase II procedure is performed, antibiotic polymethylmethacrylate is added in the form of a static spacer or a spacer to replace the removed implant, and a new implant is inserted when the original implant is removed for more than 6 weeks.
First, small doses of antibiotics were added to the polymethylmethacrylate, but large doses have been shown to be safe and effective.Springer et al. used 10.5 g of vancomycin and 12.5 g of gentamicin in 34 patients, 17 of whom had high risk factors for infection. Only one patient developed a transient elevation in serum creatine levels (1.7 mg/dL; normal 0.6 to 1.3 mg/dL), and none developed renal insufficiency, renal failure, or other adverse effects. Other authors have reported complications associated with high local antibiotic concentrations; therefore, patients should be closely followed and observed, and intervals should be removed as soon as adverse reactions associated with antibiotics are confirmed.
J¨amsen et al. reported success rates of 73%-100% for phase I repairs and 82%-100% for phase II repairs, and Haleem et al. reported 5-year survival rates of 93.5% and 10-year survival rates of 85% after phase II repairs with eventual removal of the endosseous implant due to infection.
Fortunately, infections after total knee arthroplasty are rare; however, this complication is unlikely to be completely eliminated. Surgeons and patients alike should strive to focus on preventing infections, optimizing the hospital environment and improving surgeons’ aseptic skills, and addressing high-risk factors in particular patients. Peri-articular prosthetic infections are a major complication after total knee arthroplasty with an incidence of 2%.
Once infection is clinically suspected, prompt diagnosis and treatment is very important. Infection should be suspected in any patient presenting with knee pain or stiffness after total knee arthroplasty with no other definitive cause. Once confirmed, appropriate surgical treatment, usually staged reimplantation of the prosthesis in conjunction with antibiotics, should be undertaken, which has a higher success rate and a better prognosis.