Improved cure rate of periprosthetic joint infection through targeted antibiotic therapy based on integrated pathogen diagnosis strategy.

Objectives: This study aimed to determine whether combined of pathogen detection strategies, including specimen acquisition, culture conditions, and molecular diagnostics, can improve treatment outcomes in patients with periprosthetic joint infections (PJI). Methods: This retrospective study included suspected PJI cases from three sequential stages at our institution: Stage A (July 2012 to June 2015), Stage B (July 2015 to June 2018), and Stage C (July 2018 to June 2021). Cases were categorized into PJI and aseptic failure (AF) groups based on European Bone and Joint Infection Society (EBJIS) criteria. Utilization of pathogen diagnostic strategies, pathogen detection rates, targeted antibiotic prescription rates, and treatment outcomes were analyzed and compared across the three stages. Results: A total of 165 PJI cases and 38 AF cases were included in this study. With the progressive implementation of the three optimization approaches across stages A, B and C, pathogen detection rates exhibited a gradual increase (χ2 = 8.282, P=0.016). Similarly, utilization of targeted antibiotic therapy increased stepwise from 57.1% in Stage A, to 82.3% in Stage B, and to 84% in Stage C (χ2 = 9.515, P=0.009). The 2-year infection control rate exceeded 90% in both stages B and C, surpassing stage A (71.4%) (χ2 = 8.317, P=0.011). Combined application of all three optimized protocols yielded the highest sensitivity of 91.21% for pathogen detection, while retaining higher specificity of 92.11%. Conclusion: The utilization of combined pathogen diagnostic strategies in PJI can increase pathogen detection rates, improve targeted antibiotic prescription, reduce the occurrence of antibiotic complications, and achieve better treatment outcomes.

Infectious mass debulking in lead-associated endocarditis with a percutaneous aspiration system.

AIMS: Debulking of infective mass to reduce the burden if infective material is a fundamental principle in the surgical management of infection. The aim of this study was to investigate the validity of this principle in patients undergoing transvenous lead extraction in the context of bloodstream infection (BSI). METHODS AND RESULTS: We performed an observational single-centre study on patients that underwent transvenous lead extraction due to a BSI, with or without lead-associated vegetations, in combination with a percutaneous aspiration system during the study period 2015-22. One hundred thirty-seven patients were included in the final analysis. In patients with an active BSI at the time of intervention, the use of a percutaneous aspiration system had a significant impact on survival (log-rank: P = 0.0082), while for patients with a suppressed BSI at the time of intervention, the use of a percutaneous aspiration system had no significant impact on survival (log-rank: P = 0.25). CONCLUSION: A reduction of the infective burden by percutaneous debulking of lead vegetations might improve survival in patients with an active BSI.

Antibiotic calcium sulphate beads lower the bacterial burden and prevent infection in a mouse model of periprosthetic joint infection.

Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.

Sonication protocols and their contributions to the microbiological diagnosis of implant-associated infections: a review of the current scenario.

Addressing the existing problem in the microbiological diagnosis of infections associated with implants and the current debate about the real power of precision of sonicated fluid culture (SFC), the objective of this review is to describe the methodology and analyze and compare the results obtained in current studies on the subject. Furthermore, the present study also discusses and suggests the best parameters for performing sonication. A search was carried out for recent studies in the literature (2019-2023) that addressed this research topic. As a result, different sonication protocols were adopted in the studies analyzed, as expected, and consequently, there was significant variability between the results obtained regarding the sensitivity and specificity of the technique in relation to the traditional culture method (periprosthetic tissue culture - PTC). Coagulase-negative Staphylococcus (CoNS) and Staphylococcus aureus were identified as the main etiological agents by SFC and PTC, with SFC being important for the identification of pathogens of low virulence that are difficult to detect. Compared to chemical biofilm displacement methods, EDTA and DTT, SFC also produced variable results. In this context, this review provided an overview of the most current scenarios on the topic and theoretical support to improve sonication performance, especially with regard to sensitivity and specificity, by scoring the best parameters from various aspects, including sample collection, storage conditions, cultivation methods, microorganism identification techniques (both phenotypic and molecular) and the cutoff point for colony forming unit (CFU) counts. This study demonstrated the need for standardization of the technique and provided a theoretical basis for a sonication protocol that aims to achieve the highest levels of sensitivity and specificity for the reliable microbiological diagnosis of infections associated with implants and prosthetic devices, such as prosthetic joint infections (PJIs). However, practical application and additional complementary studies are still needed.

Use of thioglycolate broth as a pre-analytic transport medium in the diagnosis of prosthetic joint infection.

OBJECTIVES: This study aimed to investigate whether adding tissue samples directly into thioglycolate (TG) broth yielded a greater number of anaerobic organisms than freshly sampled tissue in suspected hip and knee prosthetic joint infections (PJIs). PATIENTS AND METHODS: Between January 2017 and December 2020, a total of 90 patients (46 males, 44 females; median age: 71.7 years; range, 50.8 and 87.8 years) who underwent revision hip or knee arthroplasty were included. Intraoperative samples were taken, with five placed in TG broth and five in standard containers (PC) with subsequent aerobic and anaerobic culturing conducted. Demographic and baseline data of the patients were recorded. The primary outcome was positive bacterial growth from a PJI specimen inoculated directly into TG broth at the time of collection or standard PJI specimen processing. Secondary outcomes investigated were the presence of Cutibacterium acnes (C. acnes) and the curative success of revision procedure. RESULTS: A total of 900 samples (450 PC and 450 TG) were taken from 90 revision arthroplasty patients (47 knees and 43 hips). There was no statistically significant difference in the number of positive bacterial growth samples between TG broth and standard processing (p=0.742). This was consistent with subgroup analysis analyzing C. acnes (p=0.666). CONCLUSION: In hip and knee arthroplasty, there is no benefit in substituting or adding TG broth as a culture medium to better identify both general bacterial species and C. acnes infections specifically. However, the use of TG may be useful in confirming a true positive result for infection.

Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study.

BACKGROUND: This study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI). METHODS: A retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed. RESULTS: mNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37). CONCLUSIONS: Metagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.

Triggered Release of Ampicillin from Metallic Implant Coatings for Combating Periprosthetic Infections.

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin ß-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the ß-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the ß-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

In vitro models for studying implant-associated biofilms - A review from the perspective of bioengineering 3D microenvironments.

Biofilm research has grown exponentially over the last decades, arguably due to their contribution to hospital acquired infections when they form on foreign body surfaces such as catheters and implants. Yet, translation of the knowledge acquired in the laboratory to the clinic has been slow and/or often it is not attempted by research teams to walk the talk of what is defined as 'bench to bedside'. We therefore reviewed the biofilm literature to better understand this gap. Our search revealed substantial development with respect to adapting surfaces and media used in models to mimic the clinical settings, however many of the in vitro models were too simplistic, often discounting the composition and properties of the host microenvironment and overlooking the biofilm-implant-host interactions. Failure to capture the physiological growth conditions of biofilms in vivo results in major differences between lab-grown- and clinically-relevant biofilms, particularly with respect to phenotypic profiles, virulence, and antimicrobial resistance, and they essentially impede bench-to-bedside translatability. In this review, we describe the complexity of the biological processes at the biofilm-implant-host interfaces, discuss the prerequisite for the development and characterization of biofilm models that better mimic the clinical scenario, and propose an interdisciplinary outlook of how to bioengineer biofilms in vitro by converging tissue engineering concepts and tools.

Risk factors of periprosthetic joint infection after hemiarthroplasty for displaced femoral neck fracture in the elderly: Analysis of 1619 cases in the multicenter database.

PURPOSE: This multicenter retrospective study focuses on understanding the incidence, causative bacteria, and risk factors for Periprosthetic Joint Infection (PJI) following hemiarthroplasty in elderly patients with displaced femoral neck fractures (FNF). METHODS: From 2016 to 2020, 1,619 patients were diagnosed with displaced FNFs and treated surgically across 11 centers. After exclusions, 1,438 patients (399 men and 1,039 women) were included in the study, averaging 82.1 years in age and 20.2 kg/m² in BMI, observed over 25.7 months on average. Data on demographics, medical history, surgical details, and complications were described. RESULTS: PJI occurred in 20 of the 1438 patients (1.4%). The causative organism was methicillin-susceptible Staphylococcus aureus in 6 patients and methicillin-resistant S. aureus in 6 patients. In patients' backgrounds, the average age was slightly higher in the non-PJI group (82.1 years) compared to the PJI group (80.4 years). There was a higher percentage of males in the PJI group (45%) than in the non-PJI group (27.5%). Drug history showed that the prevalence of anticoagulant use in the PJI group was 25%. Peripheral vascular disease and diabetes mellitus were more prevalent in the PJI group. Most patients in both groups were independent in daily activities. The blood transfusion rate was significantly higher in the PJI group (50%) than in the non-PJI group (23.8%). Notably, the incidence of hematoma was higher in the PJI group (40%). CONCLUSION: This multicenter retrospective study demonstrates a low incidence (1.4%) of PJI in elderly patients undergoing hemiarthroplasty for FNF, primarily due to Staphylococcus aureus. Increased usage of antiplatelets and anticoagulants, as well as comorbidities related to atherosclerosis, like peripheral vascular disease and diabetes mellitus, were observed in patients with PJI. Additionally, these patients experienced higher rates of blood transfusion and postoperative hematomas, highlighting the need for careful management. It should be noted, however, that this finding is a conclusion limited by study design issues, including the retrospective design, small PJI sample size, and variability in treatment approaches.

Biofilm on total joint replacement materials can be reduced through electromagnetic induction heating using a portable device.

BACKGROUND: Periprosthetic joint infection is a serious complication following joint replacement. The development of bacterial biofilms bestows antibiotic resistance and restricts treatment via implant retention surgery. Electromagnetic induction heating is a novel technique for antibacterial treatment of metallic surfaces that has demonstrated in-vitro efficacy. Previous studies have always employed stationary, non-portable devices. This study aims to assess the in-vitro efficacy of induction-heating disinfection of metallic surfaces using a new Portable Disinfection System based on Induction Heating. METHODS: Mature biofilms of three bacterial species: S. epidermidis ATCC 35,984, S. aureus ATCC 25,923, E. coli ATCC 25,922, were grown on 18 × 2 mm cylindrical coupons of Titanium-Aluminium-Vanadium (Ti6Al4V) or Cobalt-chromium-molybdenum (CoCrMo) alloys. Study intervention was induction-heating of the coupon surface up to 70ºC for 210s, performed using the Portable Disinfection System (PDSIH). Temperature was monitored using thermographic imaging. For each bacterial strain and each metallic alloy, experiments and controls were conducted in triplicate. Bacterial load was quantified through scraping and drop plate techniques. Data were evaluated using non-parametric Mann-Whitney U test for 2 group comparison. Statistical significance was fixed at p ≤ 0.05. RESULTS: All bacterial strains showed a statistically significant reduction of CFU per surface area in both materials. Bacterial load reduction amounted to 0.507 and 0.602 Log10 CFU/mL for S. aureus on Ti6Al4V and CoCrMo respectively, 5.937 and 3.500 Log10 CFU/mL for E. coli, and 1.222 and 0.372 Log10 CFU/mL for S. epidermidis. CONCLUSIONS: Electromagnetic induction heating using PDSIH is efficacious to reduce mature biofilms of S aureus, E coli and S epidermidis growing on metallic surfaces of Ti6Al4V and CoCrMo alloys.

Development of a multiplex Loop-Mediated Isothermal Amplification (LAMP) for the diagnosis of bacterial periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most serious and debilitating complications that can occur after total joint arthroplasty. Therefore, early diagnosis and appropriate treatment are important for a good prognosis. Recently, molecular diagnostic methods have been widely used to detect the causative microorganisms of PJI sensitively and rapidly. The Multiplex Loop-Mediated Isothermal Amplification (LAMP) method eliminates the complex temperature cycling and delays caused by temperature transitions seen in polymerase chain reaction (PCR) methods, making it faster and easier to perform compared to PCR-based assays. Therefore, this study developed a multiplex LAMP assay for diagnosing bacterial PJI using LAMP technology and evaluated its analytical and clinical performance. METHODS: We developed a multiplex LAMP assay for the detection of five bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Escherichia coli, frequently observed to be the causative agents of PJI. The method of analytical sensitivity and cross-reactivity were determined by spiking standard strains into the joint synovial fluid. The analytical sensitivity of the multiplex LAMP assay was compared with that of a quantitative real-time PCR (qPCR) assay. Clinical performance was evaluated using 20 joint synovial fluid samples collected from patients suspected of having bacterial PJI. RESULTS: The analytical sensitivity of the gram-positive bacterial multiplex LAMP assay and qPCR were 105/104 CFU/mL, 103/103 CFU/mL, and 105/104 CFU/mL against S. agalactiae, S. epidermidis, and S. aureus, respectively. For P. aeruginosa and E. coli, the analytical sensitivity of the multiplex LAMP and qPCR assays were 105/104 and 106/104 CFU/mL, respectively. The multiplex LAMP assay detects target bacteria without cross-reacting with other bacteria, and exhibited 100% sensitivity and specificity in clinical performance evaluation. CONCLUSIONS: This multiplex LAMP assay can rapidly detect five high-prevalence bacterial species causing bacterial PJI, with excellent sensitivity and specificity, in less than 1 h, and it may be useful for the early diagnosis of PJI.

An In Vitro Study on the Application of Silver-Doped Platelet-Rich Plasma in the Prevention of Post-Implant-Associated Infections.

Implant therapy is a common treatment option in dentistry and orthopedics, but its application is often associated with an increased risk of microbial contamination of the implant surfaces that cause bone tissue impairment. This study aims to develop two silver-enriched platelet-rich plasma (PRP) multifunctional scaffolds active at the same time in preventing implant-associated infections and stimulating bone regeneration. Commercial silver lactate (L) and newly synthesized silver deoxycholate:ß-Cyclodextrin (B), were studied in vitro. Initially, the antimicrobial activity of the two silver soluble forms and the PRP enriched with the two silver forms has been studied on microbial planktonic cells. At the same time, the biocompatibility of silver-enriched PRPs has been assessed by an MTT test on human primary osteoblasts (hOBs). Afterwards, an investigation was conducted to evaluate the activity of selected concentrations and forms of silver-enriched PRPs in inhibiting microbial biofilm formation and stimulating hOB differentiation. PRP-L (0.3 µg/mm2) and PRP-B (0.2 µg/mm2) counteract Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans planktonic cell growth and biofilm formation, preserving hOB viability without interfering with their differentiation capability. Overall, the results obtained suggest that L- and B-enriched PRPs represent a promising preventive strategy against biofilm-related implant infections and demonstrate a new silver formulation that, together with increasing fibrin binding protecting silver in truncated cone-shaped cyclic oligosaccharides, achieved comparable inhibitory results on prokaryotic cells at a lower concentration.

A comparison of the prevalence of respiratory pathogens and opportunistic respiratory pathogenic profile of 'clean' and 'unclean' removable dental prostheses.

OBJECTIVES: To determine and compare the opportunistic respiratory pathogenic index (ORPI) and prevalence of respiratory pathogens between clean and unclean removable prostheses. METHODS: A cross-sectional study was conducted among 97 removable prosthesis wearers at a teaching dental hospital. Participants' prosthesis hygiene was grouped into clean and unclean. After prosthesis plaque samples were sequenced using the Type IIB Restriction-site Associated DNA Sequencing for Microbiome method, the prevalence was assessed for the presence of respiratory pathogens on each sample. The ORPIs for clean and unclean prostheses were quantified based on the sum of the relative abundance of respiratory pathogenic bacteria in a microbiome using a reference database that contains opportunistic respiratory pathogens and disease-associated information. RESULTS: A total of 30 opportunistic respiratory pathogens were identified on the removable prostheses. Eighty-one (83.5 %) removable prostheses harboured respiratory pathogenic bacteria. Stenotrophomonas maltophilia (34.0 %), Pseudomonas aeruginosa (27.8 %), and Streptococcus agalactiae (27.8 %) were the top three prevalent respiratory pathogens detected in plaque samples. There was a significantly higher prevalence of respiratory pathogens residing on unclean than clean prostheses (P = 0.046). However, the ORPIs in both groups showed no statistically significant difference (P = 0.516). CONCLUSIONS: The ORPIs for both clean and unclean prostheses demonstrated a similar abundance of respiratory pathogens. However, the high prevalence of respiratory pathogens residing on unclean prostheses should not be underestimated. Therefore, maintaining good prosthesis hygiene is still important for overall oral and systemic health, even though the direct link between prosthesis cleanliness and reduced abundance of respiratory pathogens has not been established. CLINICAL SIGNIFICANCE: The association between the prevalence of respiratory pathogens and unclean removable prostheses has been demonstrated and might increase the theoretical risk of respiratory disease development.

Incidence and Risk Factors for Acid-fast Bacillus/Fungal Culture Positivity in Primary, Conversion, and Revision Hip and Knee Arthroplasty.

INTRODUCTION: Previous literature has reported minimal incidences of positive fungal/AFB cultures, questioning the routine use of these tests. With growing concern for excessive use, predictive factors for patients at higher risk for intraoperative AFB/fungal infections would help surgeons limit unnecessary testing. This study evaluates the positivity rate and predictive factors of positive fungal and/or acid-fast bacillus (AFB) cultures after primary, conversion, or revision hip and knee arthroplasty. METHOD: Two hundred thirty-eight knee and hip procedures were done between January 2007 and 2022 where intraoperative AFB/fungal cultures were obtained. Procedures included primary total knee arthroplasty, primary total hip arthroplasty, conversion, first of two-stage, second of two-stage, irrigation and débridement polyexchange, and aseptic revision. Positivity rates of intraoperative AFB/fungal cultures were calculated as binomial exact proportions with 95% confidence intervals and are displayed as percentages. Univariable generalized linear mixed models estimated the unadjusted effects of demographics, individual comorbid conditions, and procedural characteristics on the logit of positive AFB/fungal cultures. RESULTS: Two hundred thirty-eight knee and hip procedures recorded an overall positivity rate of 5.8% for intraoperative AFB/fungal cultures. Aseptic revisions showed the lowest rates of positivity at 3.6%, while conversions showed the highest rates of positivity at 14.3%. The positivity rates are highest among patients who are male (9.0%), of Hispanic origin (12.0%), with body mass index <30 (6.4%), and a Charlson Comorbidity Index <5 (6.1%). History of a prior infection in the same surgical joint showed statistically significant influence of odds of culture positivity with an odds ratio of 3.47 ( P -value: 0.039). Other demographic factors that we investigated including age, sex, race, ethnicity, body mass index, and Charlson Comorbidity Index did not show any notable influence on AFB/fungal positivity rates. CONCLUSION: These results suggest utility in obtaining routine intraoperative AFB/fungal cultures, given the relatively high positivity and poor predictive factors.

Positive Culture of Atypical Mycobacterium Avium Following Revision Total Knee Arthroplasty.

CASE: We report a rare case of mycobacterial periprosthetic joint infection (PJI) after primary total knee arthroplasty 14 years earlier. Progressive knee pain over three years with a negative PJI infectious workup led to revision total knee arthroplasty. A surprising result was isolation of Mycobacterium avium from tissue cultures taken at time of revision surgery. After six months of antibiotic treatment, the patient is alive with well- functioning pain-free TKA at over one-year follow-up. CONCLUSION: Periprosthetic joint infection can present acutely or chronically years following total knee arthroplasty. Depending on the infecting organism, patients can present with sepsis, or a more indolent slower course that mimics aseptic loosening. In the absence of positive pre-operative labs and cultures, and based on the Musculoskeletal Infection Society (MSIS) criteria, aseptic loosening is a diagnosis of exclusion. An atypical infectious organism should be considered a possible cause and may require specialized cultures of operative specimens.

Outcomes in orthopedic device infections due to Streptococcus agalactiae: a retrospective cohort study.

BACKGROUND: Group B streptococci (Streptococcus agalactiae) (GBS) is a rare cause of prosthetic joint infection (PJI) occurring in patients with comorbidities and seems to be associated with a poor outcome. Depiction of GBS PJI is scarce in the literature. METHODS: A retrospective survey in 2 referral centers for bone joint infections was done Patients with a history of PJI associated with GBS between 2014 and 2019 were included. A descriptive analysis of treatment failure was done. Risk factors of treatment failure were assessed. RESULTS: We included 61 patients. Among them, 41 had monomicrobial (67%) infections. The median duration of follow-up was 2 years (interquartile range 2.35) Hypertension, obesity, and diabetes mellitus were the most reported comorbidities (49%, 50%, and 36% respectively). Death was observed in 6 individuals (10%) during the initial management. The rate of success was 63% (26/41). Removal of the material was not associated with remission (p = 0.5). We did not find a specific antibiotic regimen associated with a better outcome. CONCLUSION: The results show that S. agalactiae PJIs are associated with high rates of comorbidities and a high treatment failure rate with no optimal treatment so far.

Detection value of third-generation sequencing to identify the pathogenic organisms in prosthetic joint infection.

To compare the detection value of third-generation sequencing (TGS) with pathogenic microbial culture in prosthetic joint infection (PJI). Arthrocentesis was performed on 29 patients who underwent hip and knee revision surgeries. In the PJI group, TGS detected 85.71 % of positive cases, while pathogenic microbial culture detected only 42.85 %. TGS identified 17 different pathogenic microorganisms, including Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus lactis, and Mycobacterium tuberculosis complex. In the loosening group, TGS was positive in one patient, while microbial culture was negative in all cases. TGS showed higher sensitivity (85.71 % vs. 42.85 %), comparable specificity (93.33 % vs. 100 %), and similar positive predictive value (92.31 % vs. 100 %) compared to culture.However, TGS had a higher negative predictive value (87.5 % vs. 65.22 %).Additionally, TGS provided faster results (mean time 23.8±3.6 h) compared to microbial culture (mean time 108.0±9.4 h).These findings suggest that TGS holds promise for detecting pathogenic microorganisms in PJI and has potential for clinical application.

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.

The Clinical Challenge of Prosthetic Valve Endocarditis: JACC Focus Seminar 3/4.

During the past 6 decades, there have been numerous changes in prosthetic valve endocarditis (PVE), currently affecting an older population and increasing in incidence in patients with transcatheter-implanted valves. Significant microbiologic (molecular biology) and imaging diagnostic (fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography) advances have been incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria, thus increasing the diagnostic sensitivity for PVE without sacrificing specificity in validation studies. PVE is a life-threatening disease requiring management by multidisciplinary endocarditis teams in cardiac centers to improve outcomes. Novel surgical options are now available, and an increasing set of patients may avoid surgical intervention despite indication. Selected patients may complete parenteral or oral antimicrobial treatment at home. Finally, patients with prosthetic valves implanted surgically or by the transcatheter approach are candidates for antibiotic prophylaxis before invasive dental procedures.

The Effect of Slime Factor in the Treatment of Spinal Implant Infections.

AIM: To investigate the effect of the biofilm-forming ability of the bacteria on treatment in rats by using biofilm-forming and nonbiofilm- forming strains of Staphylococcus aureus (S. aureus). MATERIAL AND METHODS: Forty rats were divided into four equal groups as Group 1A, 1B, 2A, and 2B. All rats underwent single distance lumbar laminectomy, and titanium implants were introduced. Group 1 rats were inoculated with Slime factor (-) S. aureus, while Group 2 rats were inoculated with biofilm Slime factor (+) S. aureus. None of the rats were given antibiotics. One week later, the surgical field was reopened and microbiological samples were taken. The implants of rats in Groups 1A and 2A were left in place, while the implants of rats in Groups 1B and 2B were removed. RESULTS: There was no statistically significant difference between the groups inoculated with slime factor (+) S. aureus; although, Groups 1A and 2A showed statistically significant difference. Statistical analysis with respect to bacterial count also showed a statistically significant difference between Groups 1A and 2A. There was a statistically significant difference between Group 1B and 2B. CONCLUSION: The results obtained in the present study reveal that in case of implant-dependent infection, the first sample taken can be checked for slime factor, and if there is infection with slime factor-negative bacterium, treatment without removing the implant may be recommended. S. aureus was used in the study because it is the most common cause of implant-related infection at surgical sites. Further studies using different bacterial species are needed to reach a definitive conclusion.