Little is known about the clinical use of antifungal-loaded acrylic bone cement in the treatment of periprosthetic hip and knee joint infections (PJIs). Hence, we performed a literature search using PubMed/MEDLINE from inception until December 2021. Search terms were “cement” in combination with 13 antifungal agents. A total of 10 published reports were identified, which described 11 patients and 12 joints in which antifungal-loaded cement was employed. All studies were case reports or case series, and no randomized controlled trials were identified. In 6 of 11 patients, predisposing comorbidities regarding the emergence of a fungal PJI were present. The majority of the studies reported on infections caused by Candida species. In six cases (seven joints), the cement was solely impregnated with an antifungal, but no antibiotic agent (amphotericin B, voriconazole, and fluconazole). In the other five joints, the cement was impregnated with both antibiotic(s) and antifungals. Great discrepancies were seen regarding the exact loading dose. Four studies investigated the local elution of antifungal agents in the early postoperative period and observed a local release of antifungals in vivo. We conclude that there is a paucity of data pertaining to the clinical use of antifungal-loaded bone cement, and no studies have assessed the clinical efficacy of such procedures. Future studies are urgently required to evaluate this use of antifungals in PJI.

Accurate diagnosis of orthopedic infection is crucial in guiding both antimicrobial therapy and surgical management in order to optimize patient outcomes. A variety of microbiological and nonmicrobiological methods are used to establish the presence of a musculoskeletal infection. In this minireview, we examine traditional culture-based and newer molecular methodologies for pathogen detection, as well as systemic and localized assays to assess host response to maximize diagnostic yield.

Background: A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI. Methods: We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as “prosthetic joint infection”, “PJI”, and “metagenomic sequencing”. Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis. Results: We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97). Conclusion: Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.

Accurate diagnosis ensures appropriate therapy of periprosthetic joint infection (PJI). Since mycobacterial PJI is rare, routine testing is inappropriate. We reviewed hip and knee PJI at our institution over 28 months. Mycobacterial cultures were routinely sent with rare positivity. Mycobacterial cultures should be sent only when there is clinical suspicion.

Debridement, antibiotic, and implant retention (DAIR) can be used as a first surgical procedure for acute infections in patients who have well-fixed components. However, its use in hematogenous or late acute infections is still debated. This systematic review of literature aims to clarify the effectiveness of DAIR procedure in the treatment of hematogenous periprosthetic knee infections. DAIR is an effective way to treat acute hematogenous PJIs of the knee and reaches its best efficacy when performed within one week from the onset of symptoms, modular components are exchanged, and a pathogen-oriented antibiotic therapy can be set. It is safe, economic, and effective technique, but has to be performed in a very narrow temporal window.

Background: Debridement, antibiotic agents, and implant retention (DAIR) is a currently accepted approach for the treatment of early prosthetic joint infections (PJI). The success of a DAIR procedure has shown variable results throughout the published literature. Scoring systems such as the Kidney, Liver, Index surgery, Cemented prosthesis, and C-reactive protein value (KLIC) score for the selection of patients that are likely to benefit from DAIR have proved to be helpful in decision making. Our study aims to further validate the KLIC score using a large external multicentric cohort and to evaluate other risk factors for failure. Patients and Methods: A retrospective analysis of patients with an early acute PJI who were treated with DAIR and recorded in a database of eight Spanish university hospitals was performed. According to pre-operative variables of the KLIC study, patients were categorized into five groups: group A, ≤2 points; group B, 2.5–3.5 points; group C, 4–5 points; group D, 5.5–6.5 points; and group E, ≥7 points. Failure rates were compared between groups at 60 days and after 60 days of DAIR. Further variables for risk of failure were also analyzed. Results: A total of 455 patients with early acute PJI were included in the analyses. At 60 days, patients presenting with pre-operative elevated C-reactive protein serum levels, Staphylococcus aureus, and polymicrobial infections were associated with failure. Failure rates recorded were 12% for group A (n = 210), 18% for group B (n = 83), 26% for group C (n = 89), 24% for group D (n = 66), and 0% for group E (n = 7). Univariable analysis between consecutive groups of the KLIC score showed no differences for failure before 60 days of the DAIR procedure. Scheduled surgery and having the procedure performed by a specialized unit were also identified as important factors for DAIR success. Conclusions: Our results suggest the KLIC score was not useful for predicting failure in our cohort. Furthermore, our results indicate a specialized unit should conduct DAIR procedures.

Background: Following revision shoulder arthroplasty, postoperative antibiotics are selected before the results of intraoperative cultures become available. We determined infection-free survival, revision-free survival, complications, and patient-reported outcomes for patients selected to receive oral or intravenous (IV) antibiotics after revision arthroplasty. Methods: This study included 92 patients who had revision shoulder arthroplasty. IV antibiotics were administered if the surgeon had a high index of suspicion for infection, and oral antibiotics were given if there was a low suspicion. Antibiotic therapy was modified based on intraoperative culture results. Patient-reported outcomes and adverse events were documented at a mean of 4.1 years. Results: In selecting antibiotic therapy, surgeons correctly predicted the presence or absence of multiple positive cultures of specimens from the revision surgery in 72% of the 92 cases. Subsequent re-revision surgery was required in 17 (18%) of the patients; 8 of these 17 patients had ≥2 positive cultures at re-revision. Patients who initially received IV antibiotics and those who initially received oral antibiotics had similar revision-free (p = 0.202) and infection-free (p = 0.155) survivorship. Patients requiring a change from oral to IV antibiotics based on positive cultures had similar survivorship compared with those initially treated with IV antibiotics. The IV and oral antibiotic groups had similar postoperative Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES), and satisfaction scores. Patients receiving IV antibiotics had a higher rate of antibiotic-related adverse events. Conclusions: Post-revision antibiotic therapy was associated with an infection-free survival rate of 91% at a mean of >4 years of follow-up. Infection-free survival, revision-free survival, and patient-reported outcomes were similar in high-risk patients placed on IV antibiotics and low-risk patients placed on oral antibiotics. Further study is needed to define the indications for IV or oral antibiotics after revision arthroplasty.

Abstract Background Vertebral osteomyelitis is a serious condition that requires prompt diagnosis to avoid delays in proper management. There is no well-defined gold standard for diagnosis. We describe the current diagnostic approach at our institution, with a focus on the yield of image-guided vertebral biopsy. Methods We performed a single-centre 10-year retrospective case series, including adults with imaging suggestive of vertebral osteomyelitis/discitis, with either positive blood cultures, and/or a vertebral biopsy. We defined positive histopathology as our gold standard for test characteristic evaluation of biopsy cultures. Results Out of 694 patients identified, 221 met our inclusion criteria, and 173/221 (78.2%) patients underwent a spinal biopsy. Of those patients with biopsies, 113 (65%) had received antibiotics within 2 weeks preceding their evaluation. Six of 43 (13.9%) bone specimens were positive by culture, while 66/152 (43.4%) of disc specimens were culture positive. Forty-seven of 84 (55.9%) histopathology (bone or disc) specimens were diagnostic for osteomyelitis/discitis. The sensitivity of bone and disk culture were 30.0% and 56.0%, respectively, with specificities of 92.8% and 75.0%, respectively. Twenty-three (13.4%) patients had repeat biopsies, including 10 bone specimens and 14 disc specimens, and 11 (47.8%) specimens had histopathology performed which diagnosed an additional 3/23 patients (13% additional diagnostic yield). Conclusions Culture of percutaneous biopsy of disc resulted in the highest diagnostic yield. Histopathology added to the diagnostic yield in culture-negative specimens. Histopathologic evaluation of bone had better yield than bone culture. A repeat biopsy can add to the diagnostic yield.

Background: Surgical site infection (SSI) is a major complication in spinal instrumentation that is often difficult to treat. The purpose of this study was to identify and determine prognostic indicators for successful treatment of spine instrumentation SSI. Methods: Retrospectively, spine surgery cases were examined on SSI diagnosis. Post-instrumentation SSI patients were categorized as “Successful” if SSI subsided after single debridement. Patients in whom SSI did not subsided and/or required removal of instrumentation were classified as “Challenging”. We investigated the relation of treatment outcomes to patients and treatment factors. Results: A total of 1832 spinal instrumentation cases were recognized with 44 (2.40%) SSI cases. White blood cell count, C-reactive protein (CRP) levels, causative bacteria (i.e., S. Aureus or MRSA), trauma injury, and early-stage antimicrobial agent sensitivity correlated with treatment prognosis. Multivariate analysis highlighted CRP levels and applying early-stage sensitive antibiotics as potential impactful predictive factors for successful treatment. Conclusions: Our results demonstrated that early selection of sensitive antimicrobial agents is critical and emphasizes the potential for early-stage classification methods such as Gram staining. Additionally, S. Aureus and MRSA SSI formed significantly more challenging infections to treat, thus requiring consideration when deciding on instrumentation retention. These factors offer promising aspects for further large-scale studies.

Importance Dentists in the United States are under pressure from orthopedic surgeons and their patients with prosthetic joints to provide antibiotic prophylaxis before invasive dental procedures (IDP) to reduce the risk of late prosthetic joint infection (LPJI). This has been a common practice for decades, despite a lack of evidence for an association between IDP and LPJI, a lack of evidence of antibiotic prophylaxis efficacy, cost of providing antibiotic prophylaxis, and risk of both adverse drug reactions and the potential for promoting antibiotic resistance. Objective To quantify any temporal association between IDP and subsequent LPJI. Design, Setting, and Participants This cohort study used a case-crossover and time trend design to examine any potential association between IDP and LPJI. The population of England (55 million) was chosen because antibiotic prophylaxis has never been recommended to prevent LPJI in England, and any association between IDP and LPJI would therefore be fully exposed. All patients admitted to hospitals in England for LPJI from December 25, 2011, through March 31, 2017, and for whom dental records were available were included. Analyses were performed between May 2018 and June 2021. Exposures Exposure to IDP. Main Outcomes and Measures The main outcome was the incidence of IDP in the 3 months before LPJI hospital admission (case period) compared with the incidence in the 12 months before that (control period). Results A total of 9427 LPJI hospital admissions with dental records (mean [SD] patient age, 67.8 [13.1] years) were identified, including 4897 (52.0%) men and 4529 (48.0%) women. Of these, 2385 (25.3%) had hip prosthetic joints, 3168 (33.6%) had knee prosthetic joints, 259 (2.8%) had other prosthetic joints, and 3615 (38.4%) had unknown prosthetic joint types. There was no significant temporal association between IDP and subsequent LPJI. Indeed, there was a lower incidence of IDP in the 3 months prior to LPJI (incidence rate ratio, 0.89; 95% CI, 0.82-0.96; P = .002). Conclusions and Relevance These findings suggest that there is no rationale to administer antibiotic prophylaxis before IDP in patients with prosthetic joints.

Aims Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative. Methods We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not. Results There were 2,067 episodes of PJI diagnosed within the study period. A total of 3,629 fungal cultures and 2,923 mycobacterial cultures were performed, with at least one of these performed in 56% of episodes (n = 1,157). Test positivity rates of fungal and mycobacterial cultures were 5% (n = 179) and 1.2% (n = 34), respectively. After a comprehensive review, there were 40 true fungal and eight true mycobacterial PJIs. BCB were 90% sensitive in diagnosing true fungal PJI and 100% sensitive in detecting rapidly growing mycobacteria (RGM). Fungal stains were performed in 27 true fungal PJI but were only positive in four episodes (14.8% sensitivity). None of the mycobacterial stains was positive. Conclusion Routine fungal and mycobacterial stains and cultures should not be performed as they have little clinical utility in the diagnosis of PJI and are associated with significant costs. Candida species and RGM are readily recovered using BCB. More research is needed to predict rare non- Candida fungal and slowly growing mycobacterial PJI that warrant specialized cultures. Cite this article: Bone Joint J 2022;104-B(1):53–58.

Background: Periprosthetic joint infection (PJI) can be a devastating complication following shoulder arthroplasty. PJI following hip and knee arthroplasties has been found to increase mortality. However, anatomical and bacteriologic differences could potentially result in a different trend after shoulder arthroplasties. Thus, the purpose of the present study was to determine whether there is an association between shoulder PJI and all-cause mortality. Methods: Our institutional Total Joint Registry Database was queried to identify patients who underwent revision shoulder arthroplasty procedures between 2000 and 2018. A total of 1,160 procedures were then classified as either septic (21.8%) or aseptic (78.2%). Septic revisions were further subdivided into (1) debridement, antibiotics, irrigation, and implant retention (9.1%); (2) 2-stage reimplantation for deep infection (61.3%); (3) implant resection without reimplantation (3.6%); and (4) unexpected positive cultures at revision surgery (26.1%). The most common bacterium isolated was Cutibacterium acnes (64.4%). All-cause patient mortality was determined with use of our registry and confirmed with use of a nationwide mortality database. All-cause crude and adjusted mortality rates were then compared between groups. Results: The 1-year crude mortality rate was 1.8% (95% confidence interval [CI], 0.9% to 2.6%) for the aseptic group and 2.8% (95% CI, 0.7% to 4.8%) for the septic group (p = 0.31). Multivariate Cox regression analysis demonstrated an elevated but statistically similar adjusted hazard ratio for 1-year all-cause mortality of 1.9 (95% CI, 0.8 to 4.6) when comparing the septic to the aseptic group (p = 0.17). The risk of 2-year all-cause mortality was significantly higher in the septic group, with a hazard ratio of 2.2 (95% CI, 1.1 to 4.5; p = 0.029). In univariate analyses, increased 5-year mortality in the septic revision group was associated with age, Charlson Comorbidity Index, and methicillin-resistant Staphylococcus aureus infection, whereas C. acnes infection was associated with lower mortality. Conclusions: Shoulder PJI is associated with an adjusted 2-year all-cause mortality rate that is double that of aseptic patients. The results of the present study should be utilized to appropriately counsel patients who are considered to be at risk for infection following shoulder arthroplasty.

Background Periprosthetic joint infection (PJI) mortality rate is approximately 20%. The etiology for high mortality remains unknown. The objective of this study was to determine whether mortality was associated with preoperative morbidity (frailty), sequalae of treatment, or the PJI disease process itself. Methods A multicenter observational study was completed comparing 184 patients treated with septic revision total knee arthroplasty (TKA) to a control group of 38 patients treated with aseptic revision TKA. Primary outcomes included time and the cause of death. Secondary outcomes included preoperative comorbidities and Charlson Comorbidity Index (CCMI) measured preoperatively and at various postoperative timepoints. Results The septic revision TKA cohort experienced earlier mortality compared to the aseptic cohort, with a higher mortality rate at 90 days, 1, 2, and 3 years after index revision surgery (P = .01). There was no significant difference for any single cause of death (P > .05 for each). The mean preoperative CCMI was higher (P = .005) in the septic revision TKA cohort. Both septic and aseptic cohorts experienced a significant increase in CCMI from the preoperative to 3 years postoperative (P < .0001 and P = .002) and time of death (P < .0001 both) timepoints. The septic revision TKA cohort had a higher CCMI 3 years postoperatively (P = .001) and at time of death (P = .046), but not one year postoperatively (P = .119). Conclusion Compared to mortality from aseptic revision surgery, septic revision TKA is associated with earlier mortality, but there is no single specific etiology. As quantified by changes in CCMI, PJI mortality was associated with both frailty and the PJI disease process, but not treatment.

Objectives We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions. Methods We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort. Results In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort. Discussion Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.

Introduction Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. Results One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. Conclusions TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies.

Identification of the causative organism(s) in periprosthetic joint infection (PJI) is a challenging task. The shortcomings of traditional cultures have been emphasized in recent literature, culminating in a clinical entity known as “culture-negative PJI.” Amidst the growing burden of biofilm infections that are inherently difficult to culture, the field of clinical microbiology has seen a paradigm shift from culture-based to molecular-based methods. These novel techniques hold much promise in the demystification of culture-negative PJI and revolutionization of the microbiology laboratory. This article outlines the clinical implications of culture-negative PJI, common causes of this diagnostic conundrum, established strategies to improve culture yield, and newer molecular techniques to detect infectious organisms.

Purpose The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. Methods We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008–June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. Results A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d–11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10–12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. Conclusion Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

Background Deep tissue culture specimens obtained at the time of revision shoulder arthroplasty are commonly positive for Cutibacterium . Clinical interpretation of positive cultures can be difficult. This was a multi-institutional study evaluating the accuracy of cultures for Cutibacterium using positive control (PC) and negative control (NC) samples. The relationship between time to culture positivity and strength of culture positivity was also studied. Methods Eleven different institutions were each sent 12 blinded samples (10 PC and 2 NC samples). The 10 PC samples included 2 sets of 5 different dilutions of a Cutibacterium isolate from a failed total shoulder arthroplasty with a probable periprosthetic infection. At each institution, the samples were handled as if they were received from the operating room. Specimen growth, time to culture positivity, and strength of culture positivity (based on semiquantitative assessment) were reported. Results A total of 110 PC samples and 22 NC samples were tested. One hundred percent of specimens at the 4 highest dilutions were positive for Cutibacterium . At the lowest dilution, 91% of samples showed positive findings. Cutibacterium grew in 14% of NC samples. Cutibacterium grew in PC samples at an average of 4.0 ± 1.3 days, and all of these samples showed growth within 7 days. The time to positivity was significantly shorter ( P < .001) and the strength of positivity was significantly higher ( P < .001) in true-positive cultures compared with false-positive cultures. Conclusions This multi-institutional study suggests that different institutions may report highly consistent rates of culture positivity for revision shoulder arthroplasty samples with higher bacterial loads. In contrast, with lower bacterial loads, the results are somewhat less consistent. Clinicians should consider using a shorter time to positivity and a higher strength of positivity as adjuncts in determining whether a tissue culture sample is a true positive.