Prevention, Diagnostic and Antibiotic Treatment of Periprosthetic Joint and Fracture Related Infection

Background: The number of periprosthetic joint infections caused by vancomycin-resistant pathogens is increasing. Currently, no PMMA cement is commercially available to cover VRE. Daptomycin shows promising results in treating infection, offering a good safety profile and a reduced risk of developing resistance. The purpose of this in vitro study was to investigate the mechanical stability, handling properties, elution behavior, and antimicrobial effectiveness of PMMA cement loaded with three different daptomycin concentrations in comparison to commercially available antibiotic-loaded bone cement (ALBC). Methods: Mechanical properties and handling characteristics (ISO 5833, DIN 53435), HPLC elution, antimicrobial effectiveness with proliferation assay (DIN 17025), and inhibition zone testing were investigated. Results: All tested daptomycin concentrations met the ISO and DIN standards for mechanical strength. Loading of 40 g of PMMA cement with 0.5 g of daptomycin did not show any antimicrobial effectiveness, in contrast to 1.0 g and 1.5 g. PMMA cement with 1.5 g of daptomycin was the best in terms of elution and effectiveness, and it showed good ISO mechanical strength; ISO doughing was sticky for a little longer and setting was faster compared to the vancomycin-containing reference cement. Conclusion: PMMA cement containing 0.5 g of gentamicin and 1.5 g of daptomycin could be a good alternative to the already established COPAL^® (Wehrheim, Germany) G+V for the treatment of PJIs caused by VRE. Full article

Periprosthetic Joint Infection (PJI) is a significant contributor to patient morbidity and mortality, and it can be addressed through a range of surgical interventions coupled with antibiotic therapies. Following surgical intervention(s), prolonged administration of oral antibiotics is recommended to cure PJI. There is a lack of reports on the adverse events (AEs) associated with oral antibiotics, particularly rifampin. This investigation sought to elucidate the occurrence of antibiotic-related AEs after an initial regimen of intravenous antibiotic administration, supplemented by an extended course of oral antibiotics. A prospective study of patients diagnosed with PJI of the hip, knee, or shoulder who underwent single-stage exchange arthroplasty (SSE) (10%), two-stage exchange arthroplasty (TSE) (81%), or debridement, antibiotics, and implant retention (DAIR) (6%) was performed. The primary outcome of interest was the detection of AEs, the secondary outcome the detection of a correlation between rifampin use and the incidence of AEs, and the tertiary outcome was whether oral antibiotic treatment needed to be adjusted or discontinued due to AEs. In addition, subjective tolerability was monitored throughout the study. A total of 336 events were identified for 73 out of 80 patients. The most frequently used antibiotics were rifampin and co-trimoxazole. Most AEs occurred in the gastrointestinal tract (46%). The most frequent AEs were nausea, inappetence, diarrhea, and skin rash. In 6% of cases, the AEs led to antibiotic discontinuation, and in 29% of cases, a dose adjustment of the oral therapy occurred, mainly with amoxicillin or co-trimoxazole. The majority of patients (55%) rated the subjective tolerability as good. In conclusion, AEs during antibiotic treatment for PJI are common. They mainly affect the gastrointestinal tract. Rifampin use might be a reason for the higher incidence of AEs compared to non-rifampin antibiotic treatment. Full article

(1) Background: intraoperative cell salvage (ICS) devices can provide a valuable contribution to patient blood management. An infection of the surgical site presents a formal contraindication to the use of ICS. To date, there is no recommendation for the use of ICS in the context of reimplantation in two-stage septic exchange arthroplasty. (2) Methods: at two hospitals of maximum endoprosthetic care, a retrospective evaluation of patients who had received ICS blood during reimplantation of hip arthroplasties was performed. Patients’ and surgical characteristics, intraoperative cultures, and the occurrence of septic complications in the short- and long-term follow-up were recorded. (3) Results: 144 patients were included. Detection of positive cultures during reimplantation occurred in 13 cases. A total of 127 patients showed no complication, 8 patients showed a non-specific septic complication, 6 patients a local persistence of infection, and 3 patients a possible bloodstream-associated infection. No significant correlation was found between the occurrence of complications and the detection of positive intraoperative cultures. (4) Conclusions: no clustering of septic complications due to the use of ICS during reimplantation was found. In the risk-benefit analysis, we considered the use of ICS during reimplantation to be indicated in terms of patient blood management, while the safety of the procedure during septic first-stage resection arthroplasty or septic one-stage exchange arthroplasty was not investigated. Given the paucity of comparative literature, further studies are needed on ideal patient blood management in the setting of septic revision arthroplasty. Full article

Background: Periprosthetic infections represent a major challenge for doctors and patients. The aim of this study was therefore to determine whether the risk of infection can be positively influenced by preoperative decolonization of the skin and mucous membranes. Methods: In a retrospective analysis of 3082 patients who had undergone THA between 2014 and 2020, preoperative decolonization with octenidine dihydrochlorid was performed in the intervention group. In an interval of 30 days, soft tissue and prosthesis infections were detected, and an evaluation between the study groups was made by using a bilateral t-test regarding the presence of an early infection. The study groups were identical with regard to the ASA score, comorbidities, and risk factors. Results: Patients treated preoperatively with the octenidine dihydrochloride protocol showed lower early infection rates. In the group of intermediate- and high-risk patients (ASA 3 and higher), there was generally a significantly increased risk. The risk of wound or joint infection within 30 days was 1.99% higher for patients with ASA 3 or higher than for patients with standard care (4.11% [13/316] vs. 2.02% [10/494]; p = 0.08, relative risk 2.03). Preoperative decolonization shows no effect on the risk of infection that increases with age, and a gender-specific effect could not be detected. Looking at the body mass index, it could be shown that sacropenia or obesity leads to increased infection rates. Preoperative decolonization led to lower infection rates in percentage terms, which, however, did not prove to be significant (BMI < 20 1.98% [5/252] vs. 1.31% [5/382], relative risk 1.43, BMI > 30 2.58% [5/194] vs. 1.20% [4/334], relative risk 2.15). In the spectrum of patients with diabetes, it could be shown that preoperative decolonization leads to a significantly lower risk of infection (infections without protocol 18.3% (15/82), infections with protocol 8.50% (13/153), relative risk 2.15, p = 0.04. Conclusion: Preoperative decolonization appears to show a benefit, especially for the high-risk groups, despite the fact that in this patient group there is a high potential for resulting complications. Full article

In elderly patients with femoral neck fractures, preoperative serum C-reactive protein (CRP) values might be elevated due to active infections. Although there are limited data on CRP as a predictor of periprosthetic joint infection (PJI), out of concern, this could lead to delayed surgery. Therefore, we aim to investigate whether elevated serum-CRP levels justify delayed surgery for femoral neck fractures. A retrospective analysis was performed of the records of patients undergoing arthroplasty who were found to have an elevated CRP level of 5 mg/dL or more between January 2011 to December 2020. The patients were stratified to three groups, according to initial serum CRP levels at a cut off of 5 mg/dL and the time between admission and surgery (<48 vs. ≥48 h after admission). This study revealed that the patients with elevated serum CRP levels and delayed surgery showed a worse survival rate and significantly more postoperative complications than the patients on whom surgery was performed immediately. There were no significant differences in terms of PJI and prolonged wound healing in the inter-group comparison. Therefore, delays to surgery on the basis of elevated CRP values offer no benefits to patients with femoral neck fractures. Full article

Objectives: Fracture-related infection (FRI) is a major complication in orthopedic and trauma surgery. The management and choice of treatment can be difficult depending on multiple factors. Therefore, we implemented a weekly multidisciplinary team discussion to determine diagnostic and treatment strategies in FRI patients and aimed to analyze its effect on clinical outcomes. Methods: Clinical outcomes of FRI patients treated before and after implementation of a structured multidisciplinary treatment (MDT) approach with a weekly case discussion were compared at a follow-up of 12 months. Results: In total, n = 117 were eligible for enrolment, whereby n = 58 patients (72.4% male, mean age 56.7 ± 16.8 years) constituted the MDT group and n = 59 patients (72.9% male, mean age 55.0 ± 16.5 years) the control group. In the MDT group more cases were treated with local antibiotics (67.2% vs. 27.1%, p < 0.001) and significant less amputations (3.4% vs. 6.8%, p = 0.014), as well as less revision surgeries (1.5 ± 1.2 (0–5) vs. 2.2 ± 1.2 (0–7), p = 0.048) were performed. A trend towards less debridement, antibiotics and implant retention (DAIR) procedures, lower rates of recurrence of infection and less treatment failures in the MDT group was observable, even though not statistically significant. Conclusion: An MDT approach providing a patient tailored treatment concept in the treatment of FRI patients appears to be beneficial for the affected patients. Quality and efficacy of implemented MDT meetings should further be evaluated to provide sufficient evidence to further implement this valuable tool in clinical practice and decision making. Full article

Aims and Methods: In septic two-stage revision arthroplasty, the timing of reimplantation is crucial for therapeutic success. Recent studies have shown that singular values of C-reactive protein (CRP) and white blood cell count (WBC count) display weak diagnostic value in indicating whether periprosthetic joint infection (PJI) is controlled or not during two-stage revision surgery of knee arthroplasty. Therefore, in addition to the values of CRP and WBC, the course of CRP and WBC counts were compared between groups with and without later reinfection in 95 patients with two-stage revision (TSR) of infected total knee arthroplasties (TKA). Of these patients, 16 had a reinfection (16.84%). Results: CRP values decreased significantly after the first stage of TSR in both the reinfection and no-reinfection groups. WBC count values decreased significantly in the no-reinfection group. Decrease in WBC count was not significant in the reinfection group. No significant difference could be found in either the CRP values or the WBC counts at the first stage of TSR, the second stage of TSR, or their difference between stages when comparing groups with and without reinfection. Area under the curve (AUC) values ranging between 0.631 and 0.435 showed poor diagnostic value for the calculated parameters. The courses of CRP over 14 days after the first stage of both groups were similar with near identical AUC. Conclusions: CRP and WBC count as well as their course over 14 days postoperatively are not suitable for defining whether a PJI of the knee is under control or not. Full article

Fracture-related infection is a serious complication in orthopedic surgery with severe consequences for the patient. We evaluated whether a novel noble metal nail-coating technology can prevent bacterial adhesion and biofilm formation without interfering with bony union. In this retrospective, single-center case series, we described the incidence of fracture-related infections and bony union achievement in patients who had Gustilo type IIIa or IIIb femoral or tibial fractures treated with noble metal alloy-coated titanium nails. Patients were treated between January 2017 and January 2019 at the Sultanah Aminah Hospital, Johor Bahru, Malaysia. Information on fracture-related infections and bone healing assessments was collected from patient records. Additionally, three independent experts retrospectively reviewed patient X-ray images from follow-up visits to further evaluate bony union achievement. Thirty-five patients were included. Infection developed in 3/35 (8.6%) patients; all cases were resolved by antibiotic therapy. Radiographs were available for 32 patients; these confirmed the presence of bone healing in 30/32 (93.8%) patients. However, according to patient records, bony union was achieved in all patients. No safety issues were recorded. This case series suggests that a noble metal alloy-coated titanium nail can prevent infection and facilitate bony union achievement in patients undergoing surgery for severe open fractures. Full article

Aims: This study evaluates the value of a new graphic representation of cell count data of synovial fluid in the diagnosis of acute periprosthetic joint infection (PJI). Methods: A total of 75 patients with revisions of 48 primary total knee and 27 hip arthroplasties within the first six weeks after surgery were analyzed with cultivation of the synovial fluid and determination of its cell count as well as microbiological and histological analyses of the periprosthetic tissue obtained during the revision surgery using the ICM classification. The synovial fluid was additionally analyzed for graphic representation of the measured cells using LMNE-matrices. Results: A total of 38 patients (50.7%) had an infection. The following types of LMNE matrices could be differentiated: the indeterminate type (IV) in 14.7%, the infection type (II) in 5.3%, the hematoma type (V) in 33.3%, and the mixed type (VI; infection and hematoma) in 46.7%. Differentiation of LMNE types into infection (types II and VI) and non-infection (types IV and V) resulted in a sensitivity of 100%, a specificity of 97.3%, and a positive likelihood ratio of 37.0. The cell count measurement showed a sensitivity of 78.9%, a specificity of 89.2%, and a positive likelihood ratio of 7.3 at a cut-off of 10,000 cells. The percentage of polymorphonuclear leukocytes showed a sensitivity of 34.2%, a specificity of 100%, and a positive likelihood ratio of >200 at a cut-off of 90%. Conclusion: The graphic representation of the cell count analysis of synovial aspirates is a new and helpful method for differentiating between genuine early periprosthetic infections and postoperative hemarthrosis. Full article

Introduction: Periprosthetic joint infections (PJI) following primary arthroplasty continue to be a serious complication, despite advances in diagnostics and treatment. Two-stage revision arthroplasty has been commonly used as the gold standard for the treatment of PJI. However, much discussion persists regarding the interim of the two-stage procedure and the optimal timing of reimplantation. Serology markers have been proposed as defining parameters for a successful reimplantation. The objective of this matched-pair analysis was to assess the role of serum C-reactive protein (CRP) and white blood cell count (WBC) in determining infection eradication and proper timing of reimplantation. We investigated the delta (∆) change in CRP and WBC values prior to both stages of two-stage revision arthroplasty as a useful marker of infection eradication. Methods: We analyzed 39 patients and 39 controls, matched by propensity score matching (BMI, age, ASA-classification), with a minimum follow-up of 24 months and treated with a two-stage revision THA or TKA in our institution. Data of serum CRP and WBC values were gathered at two selected time points: prior to the explantation of the implant (preexplantation) and following the completion of antibiotic treatment regimen, both systemic and with a drug-eluting cement spacer (prereimplantation). Patient records were reviewed electronically for preexisting comorbidities, overall health status, synovial fluid cultures, inflammatory serologies, revision surgeries, and recurrent or persistent infection based on the modified Musculoskeletal Infection Society criteria. Patient demographics, ∆CRP, ∆WBC, and time interval to reimplantation were statistically analyzed using receiver operator curves (ROC), Pearson’s correlation coefficient, Levene’s test, and Student’s t-test. Results: Infection-free patients exhibited higher mean CRP and WBC than did patients who were reinfected at both time points. When comparing preexplantation with prereimplantation values, the median ∆CRP was 9.48 mg/L (interquartile range (IQR) 2.3–36.6 mg/L) for patients who did not develop a reinfection versus 2.74 mg/L (IQR 1.4–14.2 mg/L) for patients who developed reinfection (p = 0.069). The median ∆WBC was 1.5 × 10⁹/L (IQR 0.6–4.0 × 10⁹/L) for patients who remained infection-free versus 1.2 × 10⁹/L (IQR 0.8–2.2 10⁹/L) for patients who developed reinfection (p = 0.072). Analysis of areas under the curve (AUC) using ROC demonstrated poor prediction of persistent infection by ∆CRP (AUC = 0.654) and ∆WBC (AUC = 0.573). Although a highly significant correlation was found between the interim interval and infection persistence (r = 0.655, p < 0.01), analysis using ROC failed to result in a specific threshold time to reimplantation above which patients are at significantly higher risk for reinfection (AUC = 0.507). Conclusion: No association could be determined between the delta change in serum CRP and WBC before and after two-stage revision arthroplasty for PJI and reinfection risk. Even though inflammatory serologies demonstrate a downtrending pattern prior to reimplantation, the role of CRP and WBC in determining the optimal timing of reimplantation seems to be dispensable. Planning a second-stage reimplantation requires assessing multiple variables rather than relying on specific numeric changes in these inflammatory marker values. Full article

The number of orthopedic procedures, especially prosthesis implantation, continues to increase annually, making it imperative to understand the risks of perioperative complications. These risks include a variety of patient-specific factors, including genetic profiles. This review assessed the current literature for associations between patient-specific genetic risk factors and perioperative infection. The PRISMA guidelines were used to conduct a literature review using the PubMed and Cochrane databases. Following title and abstract review and full-text screening, eight articles remained to be reviewed—all of which compared single nucleotide polymorphisms (SNPs) to periprosthetic joint infection (PJI) in total joint arthroplasty (TJA). The following cytokine-related genes were found to have polymorphisms associated with PJI: TNFα (p < 0.006), IL-6 (p < 0.035), GCSF3R (p < 0.02), IL-1 RN-VNTR (p = 0.002), and IL-1B (p = 0.037). Protein- and enzyme-related genes that were found to be associated with PJI included: MBL (p < 0.01, p < 0.05) and MBL2 (p < 0.01, p < 0.016). The only receptor-related gene found to be associated with PJI was VDR (p < 0.007, p < 0.028). This review compiled a variety of genetic polymorphisms that were associated with periprosthetic joint infections. However, the power of these studies is low. More research must be conducted to further understand the genetic risk factors for this serious outcome. Full article