Infection is one of the most serious complications after artificial joint replacement, which not only brings multiple surgical blows to patients, but also consumes huge medical resources. According to previous reports, the incidence of infection after total knee arthroplasty (TKA) is 0.5%-5%; while the incidence of infection after total hip arthroplasty (THA) is 0.6%-16%. In the last 10 years, improvements in the surgical environment and updates in antibiotics have led to a significant decrease in the rate of post-arthroplasty infections. The rate of growth of patients undergoing arthroplasty is now much greater than the rate of decline in infection, so the population of patients with postoperative infections can no longer be ignored. Early and accurate diagnosis of joint infection is particularly important, as it can guide surgeons to deal with the infection in a timely manner, while selecting the appropriate treatment modality, which can effectively increase the eradication rate of the infection.
1. Risk factors
1.1 Surgical environment
The incidence of postoperative infection can be effectively reduced by vertical laminar flow control, leak-proof sheets and gowns in the operating room. Salvati et al. found that the early infection rate was 3.9% when using only horizontal laminar flow operating rooms without vertical laminar flow operating rooms and exhaust suits, while the incidence of infection decreased significantly when using vertical laminar flow operating rooms and exhaust suits. et al. completed a total of 6489 TKA cases using a vertical laminar flow operating room and exhoust suits, and the early postoperative infection rate was only 0.43%.
1.2 Patients with self-conditions
Postoperative infections are likely to occur in the presence of the following comorbidities.
(1) rheumatoid arthritis.
(2) Autoimmune deficiency.
(3) Diabetes mellitus.
(4) Poor nutritional status.
(5) Obesity.
(6) History of previous open surgery.
(7) Foci of infection at other sites.
Some studies have shown that the number of comorbidities is positively correlated with the incidence of infection after revision surgery [17]. Therefore, a detailed preoperative history should be taken to assess the patient’s systemic status, estimate the incidence of postoperative infection, and select a surgical procedure to appropriately eradicate the infection. peersman G reported that 13 of 113 infections (11.5%) were post-revision infections, whereas only 5 of 226 controls (2.12%) in a 1:2 matched group were post-revision infections. hart WJ et al. concluded that joint The greater the number of surgeries experienced prior to the infection, the more difficult the infection is to eradicate.
1.3 Duration of surgery
The duration of surgery is undoubtedly an important factor influencing postoperative infection in any open surgery. The longer the duration of surgery, the longer the contact time between the surgical instruments, prosthesis and wound and airborne microorganisms, the more likely it is to cause infection. Assuming that T is the 75th percentile for a particular type of operative time, a procedure can be considered significantly longer if it takes longer than T hours. the Peerman G study showed that only 5% of 6373 uninfected TKA were >2.5 hours, compared with 25% of 116 infected TKA >2.5 hours; the mean operative time was 120 minutes for infected initial TKA, 93 minutes for uninfected The mean operative time was 120 minutes for infected initial TKA and 93 minutes for uninfected initial TKA, and 160 minutes for infected revision TKA and 96 minutes for uninfected revision TKA.
2. Diagnosis
2.1 Preoperative diagnosis
2.1.1 Hematological examination methods
The main hematological examination methods are white blood cell count plus classification, C-reactive protein (CRP) and sedimentation (ESR). The advantages of these methods are their simplicity, rapid results and low cost. Peripheral blood leukocyte counts are generally in the range of 4-10E9, and if >10E9, an infection is considered to be present. However, the white blood cell count is affected by many factors, such as the patient’s condition, medications taken, and the location and extent of inflammation, and it is often the case that an infection is present and the white blood cell count does not rise. The sensitivity of CRP and ESR for the diagnosis of joint infection is also greatly reduced if the patient has rheumatoid arthritis or other connective tissue disease. By taking a medical history and careful physical examination, it was mostly possible to clarify whether the patient had a past medical history of rheumatoid arthritis or connective tissue disease. After excluding these interfering factors, the sensitivity, specificity, positive predictive value and negative predictive value of leukocytes for the diagnosis of infection were 0.20, 0.96, 0.54 and 0.85, respectively; CRP was 0.96, 0.92, 0.74 and 0.99, respectively; ESR were 0.82, 0.85, 0.58, and 0.95 [25]. The CRP changes faster than the ESR, and generally the CRP reaches its peak on the second day after aseptic surgery, after which if the CRP value does not decrease but increases, the possibility of postoperative infection should be considered after excluding inflammatory diseases such as rheumatoid arthritis.
2.1.2 Arthrocentesis
Arthrocentesis has been described as the standard test for definitive joint infection. The sensitivity for diagnosing joint infections is 45%-100%. In a study by Barrack et al, the overall sensitivity, specificity, positive predictive value and negative predictive value of arthrocentesis in 69 patients with symptomatic TKA were 0.55, 0.959, 0.846 and 0.839, respectively; if two patients (67) who had been off antibiotics for less than 2 weeks were excluded, the statistic was 0.5. If the initial puncture results were inconsistent with the clinical presentation, the puncture could be repeated, and Barrack repeated the puncture in 8 suspected patients, and the diagnostic The sensitivity, specificity, positive predictive value and negative predictive value of Barrack’s repeat puncture in eight suspected patients were increased to 0.833, 0.959, 0.882 and 0.94. The sensitivity, specificity, positive predictive value and negative predictive value of Spangehl et al. were 0.86, 0.94, 0.67 and 0.98 for the initial puncture in 180 patients, respectively; after repeat puncture, they were 0.81, 0.97, 0.77 and 0.97. In Spangehl’s study, the sensitivity of repeat puncture was lower than that of initial puncture because antibiotic interference was not excluded from the sample. In patients with a history of antibiotic administration prior to puncture, repeat puncture still did not reflect the true situation, but increased the number of punctures, so sensitivity was reduced.
2.2 Intraoperative diagnosis
2.2.1 Synovial fluid leukocytes
After surgical exposure of the synovial bursa by counting, the synovial fluid is punctured by needle aspiration and a sufficient amount of synovial fluid is taken and sent for leukocyte counting and classification. Spangehl’s sensitivity, specificity, positive predictive value and negative predictive value for leukocyte count after 183 synovial bursa punctures were 0.36, 0.99, 0.91 and 0.90, respectively; and neutrophil classification was 0.89, 0.85, 0.52 and 0.98. However For patients with low joint fluid or high wound drainage, it will not be possible to collect enough synovial fluid for this examination. 2.2.2 Intraoperative frozen sectioning is a rapid pathologic diagnosis. Intraoperatively, tissue resembling an infection is taken and sent for frozen pathology, and bacterial infection is considered when there are >=5 neutrophils per high-powered field of view. Hart et al. followed up 48 cases of TKA and found that the infection recurred in 4 of 33 patients with negative intraoperative freezing (12.12%) and in 2 of 14 patients with suspicious positive freezing (14.29%), with a positive predictive value of only 0.38 and Spangehl et al. performed intraoperative frozen pathology in 202 cases of TKA and found that the sensitivity, specificity, positive predictive value and negative predictive value of the test for infection were 0.80, 0.94, 0.74 and 0.96, respectively.
2.2.3 Glenn stain
Gram’s stain is a bacterial identification stain created by Danish bacteriologist Christian Gram in 1884 and is the most basic method for identifying bacteria. It helps to identify the infection and the judgment of the infected bacteria. Intraoperative manipulation is performed by taking as much tissue as possible that resembles the appearance of the infection and sending it for Gram staining. However, previous studies have shown that the sensitivity of independent use of this method to determine joint infection is extremely low, averaging about 0.1.
2.2.4 Intraoperative culture
How to take the material directly affects the culture results. Powles et al. in five cases of THA revision with gentamicin-containing bone cement, intraoperative material was taken before and after cement breaking and sent for culture, and the results showed that the local gentamicin concentration increased abruptly after cement breaking, which could kill bacteria rapidly. Neut performed intraoperative sampling in 22 patients with joint infection undergoing revision surgery and found that the positive rate was 41% for normal soft tissue culture, 64% for extended culture time, and up to 86% for scrapings from old prostheses, which led him to introduce a new device (Confocal Laser Scanning Microscopy). This device was able to scan colonies on the patient’s prosthesis preoperatively and see the bacterial film (Biofilm), thus providing a new way to confirm the infection. However, the device is expensive (approximately $350,000) and clinical dissemination will take some time.
2.3 Criteria
2.3.1 Infection diagnosis
Hematologic tests are susceptible to many other factors in the body; arthrocentesis requires strict control of antibiotics, and sometimes blindly obtaining objective results may spread the infection; laboratory tests with synovial fluid are not suitable for patients with little joint fluid or much wound drainage; the positive predictive value of frozen sections does not reach the index of infection; Glenn stain is not enough to diagnose infection independently due to its very low sensitivity Intraoperative cultures are subject to the constraints of the patient, the time and location of the collection and contamination. Spangehl et al. proposed diagnostic criteria by combining the above tests, counting the likelihood of infection, and combining them with the patient’s history and physical examination.
The diagnostic criteria for post-arthroplasty infection in adults were defined as one of the following: (1) an open wound or sinus tract communicating with the joint; (2) systemic infection combined with hip pain and purulent joint fluid; (3) at least three of five ancillary findings [25] (i) ESR > 30 mm/Hour; (ii) CRP > 10 mg/L; (iii) positive preoperative (iii) at least one positive preoperative arthrocentesis; (iv) ice-cold result >5 multinucleated leukocytes/high magnification field; (v) positive intraoperative culture >1/3 of the culture results.
2.3.2 Infection staging
The diagnosis of infection should be followed by further staging of the infection, which helps to select the appropriate treatment strategy to eradicate the infection and regain a painless, stable, and functional artificial joint. Currently, Segawa infection staging is the most authoritative.
3.Treatment methods
3.1 Antibiotic treatment
Because of the low success rate of antibiotics alone in treating joint infections, they are only indicated for three conditions.
(1) Those with very poor general condition insufficient to tolerate surgery.
(2) Superficial wound infections, where the infection has not accumulated in the joint.
(3) PIOC.
Surgical intervention is required to treat patients with other infection types. The recommended course of sensitive antibiotics after joint spacer (Spacer) placement is 6 weeks. The most common pathogen of joint infections is Staphylococcus aureus, the most common Gram-stain-positive staphylococcus. Once a diagnosis of S. aureus infection is confirmed, the next thing that needs to be clarified is the susceptibility to methicillin. Methicillin-sensitive can choose anti-coccus penicillin or a generation of cephalosporins, while methicillin-resistant Staphylococcus aureus (MRSA) is mostly resistant to antibiotics containing β-lactam ring, but sensitive to vancomycin, so vancomycin becomes the treatment of MRSA The first-line drug. In type 3 joint infections, the type of bacteria is determined by the location and extent of the primary focus, and therefore multiple bacterial infections are often combined with a wider range of species [75]. This includes Staphylococcus aureus, β-hemolytic streptococci, enterococci and some other Gram-negative bacteria. Multiple cultures must be performed preoperatively, and drugs must be combined for different classes of bacteria.
3.2 Surgical treatment
3.2.1 Preservation of the prosthesis
Surgical treatment for prosthesis preservation includes open debridement and arthroscopic debridement. Debridement has the advantages of less trauma, shorter hospital stay and lower medical costs. This method is mainly used for the treatment of EPOI and acute hematogenous infections. Bengtson performed debridement in 154 infected TKA and was successful in 30 cases (19%); Hanssen debridement in 445 patients with joint infections was successful in 140 cases (31.5%). The success rate was low because most of their samples contained type 4 infections. In addition, different pathogenic species affect the eradication rate of the infection. 31 cases of type 3 infections TKA were selected by Deirmengian et al. 9 were post-revision infections, 2 of which were in hinged knees. Two groups were studied, Staphylococcus aureus infection and other Gram-positive infections, and found that the success rate of retained prosthetic debridement in the former group of infected individuals was only 8%, while the latter group had a power of 56%, envisaging that if the study excluded 9 cases of infected revision TKA with risk factors, that would further improve the success rate of debridement for the treatment of infection. kilgus et al. studied 35 cases of infected THA and 35 cases of infected TKA were studied pathogenetically and THA and TKA were subdivided into methicillin-sensitive and methicillin-resistant subgroups and postoperative outcomes were counted. Since arthrodesis, joint fusion and amputation were defined by Kilgus as successful procedures due to loss of joint function by preserving the prosthesis and replacing the prosthesis. A total of 35 cases were methicillin-resistant with a success rate of 34%, while 34 cases in the methicillin-sensitive group had a success rate of 85%; the other TKA case was a fungal infection and underwent amputation. dixon et al. retrospectively studied 15 cases of infected TKA with a 60% success rate of arthroscopic debridement for infection and suggested that arthroscopic debridement is more suitable for cemented prostheses. Therefore, in today’s world of widespread use of second-stage replacement surgery for joint infections, the use of prosthesis-preserving debridement is not without merit, and surgeons should carefully consider the patient’s indications to take advantage of the unique benefits of this procedure. The following aspects should be considered: (1) age, (2) risk factors, (3) type of infection, (4) type of pathogen, and (5) prosthesis status.
3.2.2 Replacement of prosthesis
The treatment methods for replacing the prosthesis are direct replacement and second-stage replacement. This type of surgery is mainly aimed at treating type 4 joint infections.
3.2.2.1 Direct replacement
Direct replacement has the advantage of fewer surgeries and shorter hospital stays than second-stage replacement, but if the indications are not strictly controlled, the success rate of this procedure is only 58%. The following principles should be followed before and after performing the procedure: (1) antibiotic-sensitive Gram-positive bacterial infection; (2) no sinus tract formation; (3) debridement of all infected tissues; (4) fixation with antibiotic-containing bone cement; and (5) long-term postoperative antibiotic application. 37 patients were investigated by Silva et al. for direct replacement for joint infection, and 33 cases were successful (89%); 3 of 33 cases (9%) were not Jackson performed direct replacement of 1299 infected THA, 99% used antibiotic-containing bone cement, and 1077 (83%) successfully cured the infection. Due to the narrow indications for direct replacement and the fact that only a few studies have reported success with it, a large number of patients with joint infections still need to undergo second-stage replacement.
3.2.2.2 Second-stage replacement
Second-stage replacements have been favored by surgeons for the past 20 years because of their wide range of indications (adequate bone volume, abundant periarticular soft tissue) and high cure rate compared to other surgical options for treating joint infections. In order to overcome these complications and to improve the function of the joint after surgery, Borden and Gearen first introduced the use of a fixed joint spacer (Gearen, 1987) in the second-stage arthroplasty. Booth, Wilde, and Whiteside subsequently applied the Block Spacer with a success rate of approximately 90% or more. However, the use of Block Spacer still did not solve the problems of joint stiffness, poor Range Of Motion (ROM), difficulty of surgical exposure in Stage II, and decreased patient satisfaction due to Phase I-II joint braking, and Block Spacer was prone to dislocation leading to severe bone defects. Meek et al. used the Prostalac Spacer (Mobile Spacer) in 47 cases of infected TKA with stage II replacement. Emerson et al. compared 26 Block Spacer and 22 Articulating Spacer cases with a follow-up of 36 months, and the reinfection rates were 9% and 7.6%, respectively, with no significant difference; and in terms of improving postoperative mobility, Articulating had 14° more than Block Hofmann also concluded that there was no significant difference between Articulating and Block Spacer in terms of eradication of infection and 16° more than Block Spacer in terms of improved mobility. Regardless of the Spacer technique used, antibiotic-containing bone cement (ALBC) fixation is applied, which greatly increases the intra-articular antibiotic concentration and increases the eradication rate of infection. Commonly used antibiotics are tobramycin, gentamicin, and vancomycin; common types of bone cements are Palacos, Simplex-P, CMW, and Sulfix acrylic, with Palacos releasing antibiotics in higher concentrations and for longer periods than the other three cements . The ability of bone cement to release antibiotics is largely determined by the microporosity of the bone cement, the more and larger the microporosity the greater the ability to release antibiotics, and mixing powdered antibiotics facilitates the creation of bone cement microporosity, which increases release [62]. However, too large a ratio of antibiotics to bone cement can lead to a decrease in the mechanical tolerance of the bone cement. A report from the 71st AAOS Annual Meeting showed that 34 consecutive patients with second-stage replacements were observed with an average of 3.4 cartridges (136 g) of Simplex bone cement containing a total of 10.5 g vancomycin and 12.5 g g gentamicin, and no cases of renal impairment were detected by monitoring serum creatinine concentrations. In another study by Hofmann, tobramycin was found to have potent and broad-spectrum antimicrobial properties, and when added to bone cement, blood levels measured on the first postoperative day were therapeutic, while blood levels on the third postoperative day were barely measurable, and no patients experienced nephrotoxicity. The following are the current recommended doses of antibiotics added to bone cement: (1) bone cement Spacer: 1 g vancomycin + 3.6 g tobramycin; (2) fixation of new prosthesis: 1 g vancomycin + 1.2 g tobramycin.
3.2.3 Removal of prosthesis
Surgery for removal of prosthesis includes arthrodesis, joint fusion and amputation. The common denominator of this type of surgery is that although the joint infection can be effectively eradicated, some or all of the joint function is sacrificed. Falahee et al. performed arthrodesis in 26 patients, 11 of whom had rheumatoid arthritis, with a success rate of 89% in eradicating the infection, but only 15 were able to walk independently, and only 5 of them (19%) had a stable knee joint that did not require any assistance in walking. Joint fusion was once considered the gold standard for the treatment of joint infections, and despite the inconvenience it caused to patients’ lives after fusion, there was no significant difference between the results of fusion and second-stage replacement in terms of Oxford scores. Although fusion is effective in eradicating infection, the success rate of arthrofusion in patients with uncontrolled infection is only 19%. Infections after TKA in hinged knees or with intramedullary prostheses are often combined with significant bone defects, and such patients are more likely to fail to heal after fusion. In this regard, Oostenbroek et al. staged 15 patients with bone defects and performed joint fusion using the Ilizarov method with a healing rate of 93%, a higher complication rate of 80%, and no recurrence of infection; three of the eight complications were other medical conditions, three cases of osteomyelitis with pin tract infection, one case of fracture during removal of the stent, one case of nonunion, and two cases of stent loosening. Amputation is the ultimate solution for patients with sepsis who have failed to eradicate the infection after all surgical options have been tried, or who have a life-threatening combination. Less than 5% of infected patients ultimately require amputation. The most common reasons for amputation are massive bone loss and intractable pain from repeated previous surgical operations. Therefore, surgeons should carefully assess the possibility of eradicating the infection preoperatively rather than blindly performing repeated surgeries to avoid unnecessary amputations.
4.Summary
Prompt and accurate diagnosis through history taking, physical examination and ancillary findings is a prerequisite for successful treatment of all joint infections. Eradication of infection and restoration of pain-free, functional artificial joints are the basic principles of treatment of joint infections. Although antibiotics are simple and inexpensive, the eradication of joint infections mostly requires a combination of surgical interventions, and the choice of surgical treatment is critical to consider the retention of the prosthesis, which is the core aspect of managing joint infections. At present, the combination of antibiotics, debridement and arthroplasty has become a complete set of procedures for the treatment of most complex joint infections, which needs to be supplemented and improved.