Practical Guidance for Clinical Microbiology Laboratories: Microbiologic diagnosis of implant-associated infections.

SUMMARYImplant-associated infections (IAIs) pose serious threats to patients and can be associated with significant morbidity and mortality. These infections may be difficult to diagnose due, in part, to biofilm formation on device surfaces, and because even when microbes are found, their clinical significance may be unclear. Despite recent advances in laboratory testing, IAIs remain a diagnostic challenge. From a therapeutic standpoint, many IAIs currently require device removal and prolonged courses of antimicrobial therapy to effect a cure. Therefore, making an accurate diagnosis, defining both the presence of infection and the involved microorganisms, is paramount. The sensitivity of standard microbial culture for IAI diagnosis varies depending on the type of IAI, the specimen analyzed, and the culture technique(s) used. Although IAI-specific culture-based diagnostics have been described, the challenge of culture-negative IAIs remains. Given this, molecular assays, including both nucleic acid amplification tests and next-generation sequencing-based assays, have been used. In this review, an overview of these challenging infections is presented, as well as an approach to their diagnosis from a microbiologic perspective.

Comparative transcriptomic analysis of Staphylococcus epidermidis associated with periprosthetic joint infection under in vivo and in vitro conditions.

Staphylococcus epidermidis is part of the commensal microbiota of the skin and mucous membranes, though it can also act as a pathogen in certain scenarios, causing a range of infections, including periprosthetic joint infection (PJI). Transcriptomic profiling may provide insights into mechanisms by which S. epidermidis adapts while in a pathogenic compared to a commensal state. Here, a total RNA-sequencing approach was used to profile and compare the transcriptomes of 19 paired PJI-associated S. epidermidis samples from an in vivo clinical source and grown in in vitro laboratory culture. Genomic comparison of PJI-associated and publicly available commensal-state isolates were also compared. Of the 1919 total transcripts found, 145 were from differentially expressed genes (DEGs) when comparing in vivo or in vitro samples. Forty-two transcripts were upregulated and 103 downregulated in in vivo samples. Of note, metal sequestration-associated genes, specifically those related to staphylopine activity (cntA, cntK, cntL, and cntM), were upregulated in a subset of clinical in vivo compared to laboratory grown in vitro samples. About 70% of the total transcripts and almost 50% of the DEGs identified have not yet been annotated. There were no significant genomic differences between known commensal and PJI-associated S. epidermidis isolates, suggesting that differential genomics may not play a role in S. epidermidis pathogenicity. In conclusion, this study provides insights into phenotypic alterations employed by S epidermidis to adapt to infective and non-infected microenvironments, potentially informing future therapeutic targets for related infections.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Vancomycin trough concentration in adult patients with periprosthetic joint infection: A machine learning-based covariate model.

AIMS: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients. METHODS: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). RESULTS: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. CONCLUSION: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.

Preoperative dental screening can reduce periprosthetic infections of hip and knee endoprostheses in the first month after surgery: results of a cohort study.

PURPOSE: The oral cavity and, in particular, potential oral foci might pose a risk of periprosthetic joint infection (PJI). The aim of this cohort study was to determine whether practical preoperative dental screening would reduce the prevalence of early PJI in the first month after surgery. METHODS: Patients attending a specialized endoprosthesis implantation clinic between 2018 and 2022 were recruited. Two groups were examined. The test group consisted of patients attending the clinic between 2020 and 2022 and who were referred to their family dentist using a standardized form. The comparison group consisted of patients who were treated in the clinic between 2018 and 2020. They were not referred to their family dentist. The two groups were compared for the prevalence of PJI. Univariate analysis followed by multiple logistic regression was performed to confirm risk factors for PJI in this cohort. RESULTS: 2560 individuals (test group: 1227, comparison group: 1333) were included. The prevalence of PJI was significantly lower in the test group (0.8% vs. 1.8%, p = 0.04). Multiple logistic regression with PJI as the dependent variable showed that a dental referral was a strong predictor of a lower prevalence of PJI (OR: 0.43, CI95 0.205-0.917, p = 0.03). Male gender was also strongly associated with a higher frequency of PJI (OR: 2.68, CI95 1.32-5.42, p = 0.01). Age (OR: 1.06, CI95 1.01-1.10, p = 0.01) and BMI (OR: 1.11, CI95 1.05-1.17, p < 0.01) had little effect on the risk of PJI. CONCLUSION: Dental referral using a standardized form can reduce the prevalence of early PJI. Accordingly, orthopedists and dentists should collaborate in this practical way.

Investigation of the pathogen-specific antibody response in periprosthetic joint infection.

PURPOSE: Periprosthetic joint infections (PJIs) are a very demanding complication of arthroplasty. Diagnosis of PJI and pathogen identification pose considerable challenges in clinical practice. We hypothesized that the pathogen-specific immune response to PJI reflects the infection process, provides clinically relevant information on disease course, and has the potential to further optimize antimicrobial therapy. METHODS: We conducted a prospective matched cohort pilot study with 13 patients undergoing two-stage septic revision arthroplasty (PJI patients) between 06/2020 and 06/2021, as well as 11 control patients undergoing one-stage aseptic revision arthroplasty (Non-PJI patients). Pre-, intra- and postoperative serum samples were collected at standardized time points. We developed a custom Luminex®-based quantitative bead-based suspension array (Infection Array; IA), and used it for simultaneous measurement of antibody specificities against 32 pathogens commonly associated with PJI in 267 serum samples. RESULTS: The IA was able to trace the dynamics of the pathogen-specific humoral immune response in all patients against PJI-related pathogens, prominently coagulase-negative staphylococci and streptococci. Pathogen-specific serum antibody titers declined in 62% of PJI patients over the course of treatment, while no changes in antibody titers were observed in 82% of Non-PJI patients during this study. Our serological data strongly suggested that antibody signatures reflect an immune response to microbial invasion. CONCLUSION: Our results provide insights into the pathophysiology of PJI and information on the individual disease courses. The IA is therefore a promising and novel serological tool of high resolution for monitoring the immunoproteomic footprints of infectious pathogens in the course of PJI.

Relationship between biofilm-forming microorganisms (BFM: Staphylococcus aureus and Pseudomonas aeruginosa) and DEFB1 gene variants on ß-defensin levels in periprosthetic joint infection (PJI).

BACKGROUND: The purpose of this study was to investigate the relationship between biofilm-forming microorganisms (BFM) and DEFB1 gene variants on ß-defensin levels in patients with periprosthetic joint infection (PJI) of Mexican origin. METHODS AND RESULTS: One hundred and five clinical aspirates were obtained from patients with suspected PJI. After microbiologic culture, samples were classified as non-septic and septic; of the latter, only those positive for Staphylococcus aureus and Pseudomonas aeruginosa were selected. ß-Defensin levels were quantified by ELISA, DNA was extracted from total leukocytes of the samples, and - 20G > A (rs11362) and - 44 C > G (rs1800972) variants were genotyped using TaqMan probes. Forty-one clinical aspirates were non-septic, 18 were positive for S. aureus and 18 were positive for P. aeruginosa. It was observed that ß-defensin levels were higher in the P. aeruginosa group compared to S. aureus group (2339.0 pg/mL IQR = 1809.2 vs. 1821.3 pg/mL IQR = 1536.4) and non-septic group (2339.0 pg/mL IQR = 1809.2 vs. 1099.7 pg/mL IQR = 1744.5, P < 0.001). The CG genotype of the rs1800972 variant was associated with higher ß-defensin levels compared to the CC genotype for both P. aeruginosa and S. aureus (1905.8 vs. 421.7 pg/mL, P = 0.004; and 1878.2 vs. 256.4 pg/mL, P = 0.006, respectively). CONCLUSIONS: Our results show that ß-defensin levels are significantly elevated in patients with BFM-associated PJI compared to those without infection. Furthermore, carriers of the CG genotype of the rs1800972 variant have an increased risk of PJI. Further research is needed to replicate these findings in a larger population.

Unexpected positive culture (UPC) in adults revision spine surgery: a systematic review and meta-analysis of incidence, risk factors, and management.

BACKGROUND: Without clear signs of infection, spinal implant failure is attributed to mechanical overloads and aseptic loosening. However, how low-grade infections contribute to seemingly aseptic implant failure is unclear. PURPOSE: The systematic review examined unexpected positive cultures (UPCs) in revision spine surgery regarding prevalence, isolated pathogens, risk factors, and strategies to reduce infection among asymptomatic patients undergoing revision spine surgery. METHODS: We followed the PRISMA guidelines and searched four main databases (PubMed, EMBASE, SCOPUS, Web of Science) comprehensively until January 2023 for articles reporting UPC after presumed aseptic adult revision spine surgery. The UPC rates were pooled, and risk factors were compared with the culture-negative control group and represented as odds ratio (OR) or mean difference (MD). RESULTS: Fifteen studies of 1057 individuals were included in two groups: culture-positive or UPCs (n = 317) and culture-negative or control (n = 740). The overall UPC prevalence was 33.2% (317/1057, range: 0 to 53%, 95% CI = 30.2%-36.4%), and Cutibacterium acnes (43.0%, 95% CI = 37.4%-48.8%), Coagulase-negative Staphylococci (CoNS), (39.5%, 95% CI = 33.2%-46.2%), and Staphylococcus species in general (49.5%, 95%CI = 43.7%-55.4%) were reported the most common isolated microbes. 16.1% of the UPCs were polymicrobial. Risk factors associated with UPC rates were female sex (OR = 2.62, 95%CI = 1.76-3.90, P < 0.001), screw loosening (OR = 4.43, 95%CI = 1.31-15.02, P = 0.02), number of operated levels (MD = 0.77, 95%CI = 0.33-1.22, P = 0.0007), and shorter time since index surgery (MD = - 8.57 months, 95%CI = - 14.76, -2.39, P = 0.02). CONCLUSIONS: One-third of patients undergoing spine revision surgery revealed UPC in this study. Each UPC pathogen interpretation and antibiotic use decision should be interpreted case by case. LEVEL OF EVIDENCE: IV.

Role of bariatric surgery in reducing periprosthetic joint infections in total knee arthroplasty. A systematic review and meta-analysis.

BACKGROUND: Obesity represents an epidemic of rising numbers worldwide year after year. In the Orthopedic field, obesity is one of the major causes leading to osteoarthritis needing Total Joint Arthroplasty (TJA). Still, contextually, it represents one of the most significant risk factors for joint replacement complications and failures. So, bariatric Surgery (BS) is becoming a valuable option for weight control and mitigating obesity-related risk factors. This review of the literature and meta-analysis aims to evaluate periprosthetic joint infections (PJI) and surgical site infections (SSI) rates in patients who underwent TKA after BS compared to obese patients without BS. METHODS: Systematic review was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines up to October 2023. We included longitudinal studies comparing obese patients who underwent total knee arthroplasty after bariatric surgery (study group) and obese patients who underwent TKA (control group). The surgical site infection and Periprosthetic joint infection rate were compared among groups using a meta-analytical approach. RESULTS: The online database and references investigation identified one hundred and twenty-five studies. PJI rate differed significantly among groups, (z = -21.8928, p < 0.0001), with a lower risk in the BS group (z = -10.3114, p < 0.0001), for SSI, instead, not statistically significance were recorded (z = -0.6784, p = 0.4975). CONCLUSIONS: The current Literature suggests that Bariatric Surgery can reduce infectious complications in TKA, leading to better outcomes and less related costs treating of knee osteoarthritis in obese patients.

Systematic review and meta-analysis of single-stage vs two-stage revision for periprosthetic joint infection: a call for a prospective randomized trial.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication of joint arthroplasty that causes significant pain and economic loss. This study aimed to determine whether the current evidence supports single-stage revision for PJI based on reinfection and reoperation rates. METHODS: We searched the PubMed, EBSCO, Medline, and Cochrane Library databases from inception to 30 May 2023 to identify studies that compared single-stage revision and two-stage revision for PJI. Data on reinfection and reoperation rates were pooled. RESULTS: This meta-analysis included a total of 40 studies with 8711 patients. Overall, there was no significant difference between single- and two-stage revision regarding the postoperative reinfection rate and reoperation rate. Subgroup analysis by surgery period and different surgical sites revealed no difference between the two groups in the reinfection and reoperation rates. CONCLUSIONS: Based on the available evidence, our study did not identify a significant difference in reinfection and reoperation rates between single- and two-stage revision for PJI. Given the limitations in inclusion/exclusion criteria and the observed heterogeneity, we acknowledge the complexity of drawing strong conclusions. Therefore, we suggest that the choice between single- and two-stage revision should be carefully considered on an individual basis, taking into account patient-specific factors and further research developments.

Efficacy and safety of two-stage revision for patients with culture-negative versus culture-positive periprosthetic joint infection: a single-center retrospective study.

BACKGROUND: The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. METHODS: Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. RESULTS: The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24-123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). CONCLUSION: The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

The heavy burden and treatment challenges of fungal periprosthetic joint infection: a systematic review of 489 joints.

BACKGROUND: Fungal periprosthetic joint infection (FPJI) is an infrequent but devastating complication that imposes a heavy burden on patients. At present, a consensus regarding the most optimal surgical option for patients with FPJI, the ideal duration of systemic antifungal treatment, and many other issues has not been reached. METHODS: A comprehensive literature search was performed on the PubMed and Embase databases. The search criteria employed were as follows: (fungal OR candida OR mycotic) AND periprosthetic joint infection. Initially, the titles and abstracts were screened, and subsequently, studies deemed irrelevant or duplicative were eliminated. Following this, the complete texts of remaining articles were thoroughly examined. According to the inclusion and exclusion criteria, 489 joints in 24 articles were screened out. We further extracted the demographic characteristics (age, gender, body mass index, etc.), clinical presentation, fungal species, presence of bacterial coinfection, surgical methods, systemic and local antifungal therapy, and treatment outcomes. Subgroup data were analyzed according to fungal species and bacterial coinfection. Univariate logistic regression analysis was conducted to ascertain the risk factors associated with the infection recurrence. RESULTS: A total of 506 fungi were identified within 489 joints. The most prevalent fungal species were Candida albicans (41.5%). Out of 247 joints (50.5%) presenting with concurrent fungal and bacterial infections. Among the initial surgical interventions, two-stage exchange was the most common (59.1%). The infection recurrence rates of DAIR, resection arthroplasty, two-stage, one-stage, and three-stage exchange were 81.4%, 53.1%, 47.7%, 35.0%, and 30%, respectively. The mean duration of systemic antifungal therapy was 12.8 weeks. The most common drugs used both in intravenous (55.9%) and oral therapy (84.0%) were fluconazole. The proportion of patients who used antifungal drugs after replantation (two-stage and three-stage) was 87.6%. 33.2% of cement spacer or fixed cement contained antifungal drugs, of which amphotericin B was the main choice (82.7%). FPJI caused by candida albicans (OR = 1.717, p = 0.041) and DAIR (OR = 8.433, p = 0.003) were risk factors for infection recurrence. CONCLUSIONS: Two-stage exchange remains the most commonly used surgical approach. The reliability of one- and three-exchange needs further evaluation due to the small sample size. Antifungal-loaded cement spacers, and direct intra-articular injections of antimycotics after reimplatation should be strongly considered. Medication is not standardized but rather individualized according to microbiology and the status of patients.

Prolonged efficacy of cefazolin in intraosseous regional prophylaxis for total knee arthroplasty: a rabbit model study.

BACKGROUND: A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. METHODS: Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. RESULTS: The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. CONCLUSIONS: Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Limited value of platelet-related markers in diagnosing periprosthetic joint infection.

OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.

Optimal reimplantation timing in two-stage exchange for periprosthetic joint infection: an observative cohort study in Asian population.

BACKGROUND: The optimal timing for reimplantation for periprosthetic joint infection (PJI) has not been established and varies from a few weeks to several months. The aim of this study was to assess the commendable time between implant removal and reimplantation in patients who underwent two-stage exchange arthroplasty for PJI. METHODS: We retrospectively reviewed 361 patients who were treated with two-stage exchange arthroplasty for hip and knee chronic PJI at our institution between January 2000 and December 2018. Patient characteristics, comorbidities, surgical variables, microbiology data, and time to reimplantation were recorded. All patients were followed for a minimum of one year. Treatment failure was defined by Delphi criteria. Logistic regression analyses were used to calculate survival rates and adjusted odds ratios (ORs) of treatment failure. RESULTS: In final analysis, 27 (7.5%) had treatment failure. Factors related to treatment failure including interim spacer exchange (OR, 3.13; confidence interval (CI), 1.04-9.09, p = 0.036), higher ESR level at reimplantation (OR, 1.85; CI, 1.05-3.57; p = 0.04), and time to reimplantation (OR, 1.00; CI, 1.003-1.005, p = 0.04). Performing revision arthroplasty surgery from 16 to 20 weeks had highest successful rate. The reimplantation over 24 weeks had a lower successful rate. However, no statistical significance in comparing each interval group. CONCLUSION: Our study emphasized the importance of timely reimplantation in achieving successful outcomes. Factors such as ESR levels, spacer exchange, and the duration of time to reimplantation influenced the likelihood of treatment failure in two-stage exchange arthroplasty for hip and knee PJI.

When to lavage in the absence of a sonographically visible joint effusion in painful total knee arthroplasty: a retrospective longitudinal study.

OBJECTIVE: To determine if knee arthroplasty without sonographically visible effusion needs to undergo lavage to rule out infection. METHODS: Patients were accrued by a retrospective search of a longitudinally maintained radiology database looking for patients referred for ultrasound guided aspiration of suspected TKA infection. Clinical presentations, laboratory tests, intraoperative findings, and follow-up were reviewed. RESULTS: Four hundred sixty-nine patients were included (mean age of 67 years (range, 36-91)) including 251 females. Four hundred three patients had effusions, of which 57 were infected based on ultrasound-guided and surgical aspirates. Sixty-four patients lacked effusions, of which 47 underwent lavage at the clinicians' request, with 6/47 infected. Nineteen patients without effusion were not lavaged at the clinicians' request due to low suspicion, and none were infected. Patients with positive lavage cultures all had clinical risk factors. Infection rates were significantly higher in patients with joint effusion and clinical suspicion for infection compared to absent joint effusion and absent clinical suspicion. A significantly higher proportion of patients with hyperemia or moderate-severe synovial thickening on ultrasound were symptomatic and had joint effusion and positive joint cultures. Aspiration of native fluid had 85% sensitivity and 100% specificity while lavage had a sensitivity of 57% and specificity of 100%. Negative predictive value for native aspirates was 94% compared to 86% for lavage. CONCLUSION: A TKA with low clinical suspicion of infection does not need to undergo lavage in the absence of a sonographically visible effusion.

Two-dimensional liquid chromatography measurement of meropenem concentration in synovial fluid of patients with periprosthetic joint infection.

Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery. One potential treatment approach for PJI could be the combination of one-stage revision and intra-articular infusion of antibiotics. Meropenem is one of the commonly used intra-articular antibiotics in our institution. Determining the concentration of meropenem in the joint cavity could be crucial for optimizing its local application, effectively eradicating biofilm infection, and improving PJI treatment outcomes. In this study, we developed a simple, precise, and accurate method of two-dimensional liquid chromatography (2D-LC) for determining the concentration of meropenem in human synovial fluid. The method was then validated based on the guidelines of the Food and Drug Administration and the Chinese Pharmacopoeia. Meropenem showed good linearity in the range of 0.31-25.01 µg/mL (r ≥ .999). Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, and stability validation results were all within the acceptance range. This method has been successfully applied to the determination of synovial fluid samples from PJI patients, providing a useful detection method for meropenem therapeutic drug monitoring (TDM) in PJI patients.

Comprehensive Guidance for the Prevention of Periprosthetic Joint Infection After Total Joint Arthroplasty and Pitfalls in the Prevention.

Total joint arthroplasty (TJA) is a surgical procedure, in which parts of damaged joints are removed and replaced with a prosthesis. The main indication of TJA is osteoarthritis, and the volume of TJA is rising annually along with the increase of aged population. Hip and knee are the most common joints, in which TJAs are performed. The TJA prosthesis is composed of metal, plastic, or ceramic device. Even though TJA is the most successful treatment for end-stage osteoarthritis, it is associated with various complications, and periprosthetic joint infection (PJI) is the most serious complication after TJA. With the increasing volume of TJAs, there is a simultaneous rise in the incidence of PJI. Contamination of the surgical wound and the adherence of bacteria to the surface of prosthetic component represent the initial step in the pathogenesis of PJI. The main sources of the contamination are 1) patient's own flora, 2) droplets in the operation room air, and 3) surgical gloves and instruments. Even though modern techniques have markedly reduced the degree of contamination, TJAs cannot be done in completely germ-free conditions and some degree of contamination is inevitable in all surgical procedures. However, not all contamination leads to PJI. It develops when the burden of contamination exceeds the immune threshold or the colony forming units (CFUs) and various factors contribute to a decrease in the CFU level. Surgeons should be aware of the germ burden/CFU concept and should monitor sources of contamination to maintain the germ burden below the CFU to prevent PJI.

Static spacers play a crucial role in the treatment of complex periprosthetic joint infections of the knee.

PURPOSE: To determine the superior spacer design, a growing number of studies are comparing treatment results between patients having been treated with articulating and static knee spacers in the setting of two-stage revision for periprosthetic joint infection (PJI). In contrast, the primary objective of this study was to compare preoperative characteristics between patients from both spacer groups and examine whether significant differences were present prior to spacer implantation. METHODS: This retrospective, single-centre, cohort study examined the preoperative situation of 80 consecutive knee PJIs between 2017 and 2020. All patients underwent two-stage revision, with 35 (44%) receiving an articulating and 45 (56%) a static spacer. RESULTS: No significant differences were observed in terms of patient gender (p = 0.083), age (p = 0.666), comorbidity (p = 0.1) and preoperative clinical function (p = 0.246). Static spacers were significantly more often used in the presence of a periarticular fistula (p = 0.033), infection of a revision implant (p < 0.001), higher degree of bone loss (p < 0.001) and infection caused by a difficult-to-treat pathogen (p = 0.038). Complication and revision rates were similar for both spacer types during the interim period, while patients with articulating spacers demonstrated a superior clinical function (p < 0.001) during the interim period and after reimplantation. CONCLUSION: Static spacers are being utilised in significantly more complex and unfavourable preoperative scenarios. Therefore, a preoperative selection bias may be at least partially accountable for any disparities observed in postoperative outcomes. To achieve the best possible results, surgeons should know and respect the distinct indications of static and articulating spacers and consequently understand and use them as complementary surgical options. LEVEL OF EVIDENCE: Level III.