Propensity of Candida spp. prosthetic joint infection clinical isolates to form aggregates in synovial fluid and the clinical ramifications.

BACKGROUND: Bacterial aggregation has been shown to occur in synovial fluid which are resistant to high concentrations of antibiotics. Yet the propensity of Candida spp. to form aggregates is unknown. OBJECTIVE: To assess the ability of numerous Candida spp. to form synovial fluid aggregates and the clinical ramifications of the aggregates. METHODS: Nine different Candidal prosthetic joint infection clinical isolates were evaluated for their ability to form aggregates at static and dynamic conditions and their resistance to high concentrations of amphotericin. Furthermore, the ability of tissue plasminogen activator (TPA) to disrupt the aggregates and enhance amphotericin activity was assessed. RESULTS: The results show that all species of Candida spp. evaluated formed aggregates in synovial fluid under dynamic conditions that were resistant to amphotericin. Yet no aggregates formed in tryptic soy broth under any conditions or in synovial fluid under static conditions. As well, when TPA was combined with amphotericin there was a statistically significant decrease (p < .005) in the amount of colony forming units per mL for all Candidal species evaluated. Interestingly, for Candida krusei there was no colony forming units observed after exposure to TPA and amphotericin. CONCLUSION: Our findings suggest that Candidal species form synovial fluid aggregates that are resistant to high dose amphotericin similar to those that occur with bacteria. However, the varying ability of the different Candida spp. to form hyphae and pseudohyphae compared to yeast cells may have direct impacts on the hardiness of the aggregates and thereby have clinical ramifications with respect to treatment durations.

Efficacy of Commercially Available Irrigation Solutions on Removal of Staphylococcus Aureus and Biofilm From Porous Titanium Implants: An In Vitro Study.

BACKGROUND: Periprosthetic joint infection remains a major problem. The bactericidal efficacy of commercial irrigation solutions for the treatment of infection is not well established in the presence of porous titanium (Ti) implants. This study compared the in vitro efficacy of five irrigation solutions on infected three-dimensional-printed porous Ti discs. METHODS: Titanium discs (2 × 4 mm, 400, 700, and 1,000 µm) were infected with S. aureus (1 × 106 colony-forming unit/mL) and incubated for 3 hours or 3 days to create acute or chronic infection with biofilm. Discs were irrigated with saline, antibiotic, or antiseptic solutions, then repeatedly sonicated. Sonicates were cultured for bacterial quantification. Statistical analyses were performed using one-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc testing (P < .05 significance). Biofilms were visualized by scanning electron microscopy. RESULTS: Saline irrigation was ineffective in both groups. In acute infections with 400 µm pores, differences were found with saline versus solution #3 (P = .015) and #4 (P = .015). Solution #4 had the lowest bacterial counts for all pore sizes. For biofilm, irrigation with saline, solutions #1, #2, and #3 inadequately cleared bacteria in all pore sizes. Lower remaining concentrations were observed in #4 with 400µm pores compared to saline (P = .06) and #2 (P = .039). The scanning electron microscopy showed a reduction of biofilm in samples washed with #4. CONCLUSIONS: Irrigation of infected porous Ti discs with saline, solutions #1 and #2 failed to reduce the bacterial load. The 400 µm discs consistently had more bacteria despite irrigation, highlighting the difficulty of removing bacteria from small pores. Solutions #3 and #4 reduced bacteria acutely, but only #4 demonstrated efficacy in clearing biofilm compared to saline. These results should be considered when treating periprosthetic joint infection in the presence of porous components and the potential presence of biofilm.

Semaglutide Use Prior to Total Hip Arthroplasty Results in Fewer Postoperative Prosthetic Joint Infections and Readmissions.

BACKGROUND: Semaglutide, a novel diabetes management medication, is known for its efficacy in inducing weight loss. Despite this, its impact on outcomes after total hip arthroplasty (THA) remains unclear. The aim of this study was to evaluate if THA patients on semaglutide demonstrate: (1) fewer medical complications; (2) fewer implant-related complications; (3) fewer readmissions; and (4) lower costs. METHODS: Using a national claims database from 2010 to 2021, we retrospectively examined diabetic patients prescribed semaglutide who underwent primary THA. This yielded 9,465 patients (Semaglutide = 1,653; Control = 7,812). Multivariable logistic regression was used to evaluate the following outcomes: 90-day postoperative medical complications, 2-year implant-related complications, 90-day readmissions, in-hospital lengths of stay, and day-of-surgery and 90-day episode of care costs. RESULTS: Semaglutide users exhibited lower 90-day readmission rates (6.2 versus 8.8%; odds ratio 0.68; P < .01) and reduced prosthetic joint infections (1.6 versus 2.9%; odds ratio 0.56; P < .01). However, medical complication rates, hospital stays, same-day surgical costs, and 90-day episode costs showed no significant differences. CONCLUSIONS: This study highlights semaglutide users undergoing THA with fewer 90-day readmissions and 2-year prosthetic joint infections. Although no variance appeared in medical complications, hospital stays, or costs, the medication's notable glycemic control and weight loss benefits could prompt pre-surgery consideration. Further research is essential for a comprehensive understanding of semaglutide's impact on post-THA outcomes.

Crohn's disease is associated with higher rates of implant-related complications following primary total knee arthroplasty.

INTRODUCTION: In Western countries, there has been a rise in the prevalence of Crohn's Disease (CD) and primary total knee arthroplasty (TKA). This study delves deeper into the effects of CD on TKA patients by examining (1) the length of in-hospital stay (LOS); (2) the rates of readmission; (3) complications related to implants; and (4) the costs associated with care. METHODS: A retrospective analysis using the PearlDiver database was conducted, encompassing the time frame between January 1st, 2005 and March 31st, 2014, focusing on patients who underwent TKA and were either diagnosed with CD or not. Patients with CD were paired with control subjects at a 1:5 ratio based on age, gender, and medical comorbidities. The analysis comprised a total of 96,229 patients (CD = 16,039; non-CD = 80,190). RESULTS: Patients with CD had a notably longer hospital stay (3 v. 2 days, p < 0.0001) and faced significantly higher rates of 90-day readmissions and complications (19.80% v. 14.91%, OR: 1.40, p < 0.0001; 6.88% v. 4.88%, OR: 1.43, p < 0.0001 respectively). Additionally, CD patients incurred greater expenses on the surgery day ($18,365.98 v. $16,192.00) and within 90 days post-surgery ($21,337.46 v. $19,101.42). CONCLUSION: This study demonstrates longer in-hospital LOS, higher rates of readmissions, implant-related complications, and costs of care among CD patients following primary TKA.

Do All Prosthetic Joint Infection Clinical Isolates Form Aggregates in Synovial Fluid That Are Resistant to Antibiotic Agents?

Background: Chronic prosthetic joint infections (PJI) are associated with substantial morbidity because conventional antibiotic agents lack activity to bacteria in biofilms that necessitates prosthetic removal to attempt definitive cure. However, these are complex infections that go beyond biofilms and bacteria can be present in various other different states such as synovial fluid aggregates. Consequently, the purpose of this study was to assess the propensity of historically preserved PJI clinical isolates to form synovial fluid aggregates and if aggregation occurred then what is proclivity to be tolerant to high doses of antibiotic agents. Patients and Methods: Historically preserved chronic PJI clinical isolates from 2021 were evaluated for their ability to form synovial fluid aggregates under static and dynamic conditions in 24-microwell plates. Tolerance to vancomycin, gentamicin, or amphotericin was conducted by adding high concentrations of these antibiotic agents to synovial fluid microbial aggregates. Results: All clinical isolates formed synovial fluid aggregates under dynamic conditions, which with the use of scanning electron microscopy showed dense collections of bacteria with synovial fluid polymers. However, under static conditions only Staphylococcus aureus formed aggregates. Importantly, all the microbes in these aggregates were tolerant to high concentrations of antibiotic agents. Conclusions: This study demonstrates that synovial fluid aggregation occurred with all bacterial and fungal species assessed. Therefore, the findings here have important clinical ramifications given the extent that this phenomenon occurs across microbial species and the propensity for the microbes in these aggregates to be tolerant to antibiotic agents.

Genotypic and phenotypic characterization of Enterococcus faecalis isolates from periprosthetic joint infections.

Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1-2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity. The Gram-positive bacterium Enterococcus faecalis, which can be highly antibiotic-resistant and is a robust biofilm producer on indwelling medical devices, accounts for 2-11% of PJIs. E. faecalis PJIs are understudied compared to those caused by other pathogens, such as Staphylococcus aureus. This motivates the need to generate a comprehensive understanding of E. faecalis PJIs to guide future treatments for these infections. To address this, we describe a panel of E. faecalis strains isolated from the surface of prosthetic joints in a cohort of individuals treated at the Mayo Clinic in Rochester, MN. Here, we present the first complete genome assemblage of E. faecalis PJI isolates. Comparative genomics shows differences in genome size, virulence factors, antimicrobial resistance genes, plasmids, and prophages, underscoring the genetic diversity of these strains. These isolates have strain-specific differences in in vitro biofilm biomass, biofilm burden, and biofilm morphology. We measured robust changes in biofilm architecture and aggregation for all isolates when grown in simulated synovial fluid (SSF). Finally, we evaluated the antibiotic efficacy of these isolates and found strain-specific changes across all strains when grown in SSF. Results of this study highlight the existence of genetic and phenotypic heterogeneity among E. faecalis PJI isolates which will provide valuable insight and resources for future E. faecalis PJI research. IMPORTANCE: Periprosthetic joint infections (PJIs) affect ~1-2% of those who undergo joint replacement surgery. Enterococcus faecalis is a Gram-positive opportunistic pathogen that causes ~10% of PJIs in the United States each year, but our understanding of how and why E. faecalis causes PJIs is limited. E. faecalis infections are typically biofilm-associated and can be difficult to clear with antibiotic therapy. Here, we provide complete genomes for four E. faecalis PJI isolates from the Mayo Clinic. These isolates have strain-specific differences in biofilm formation, aggregation, and antibiotic susceptibility in simulated synovial fluid. These results provide important insight into the genomic and phenotypic features of E. faecalis isolates from PJI.

Genotypic and phenotypic characterization of Enterococcus faecalis isolates from periprosthetic joint infections.

Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1-2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity. The Gram-positive bacterium Enterococcus faecalis, which can be highly antibiotic resistant and is a robust biofilm producer on indwelling medical devices, accounts for 2-11% of PJIs. E. faecalis PJIs are understudied compared to those caused by other pathogens, such as Staphylococcus aureus. This motivates the need to generate a comprehensive understanding of E. faecalis PJIs to guide future treatments for these infections. To address this, we describe a panel of E. faecalis strains isolated from the surface of prosthetic joints in a cohort of individuals treated at Mayo Clinic in Rochester, MN. Here, we present the first complete genome assemblage of E. faecalis PJI isolates. Comparative genomics shows differences in genome size, virulence factors, antimicrobial resistance genes, plasmids, and prophages, underscoring the genetic diversity of these strains. These isolates have strain-specific differences in in vitro biofilm biomass, biofilm burden, and biofilm morphology. We measured robust changes in biofilm architecture and aggregation for all isolates when grown in simulated synovial fluid (SSF). Lastly, we evaluated antibiotic efficacy of these isolates and found strain specific changes across all strains when grown in SSF. Results of this study highlight the existence of genetic and phenotypic heterogeneity among E. faecalis PJI isolates which will provide valuable insight and resources for future E. faecalis PJI research.

Cutibacterium avidum: A Potent and Underestimated Pathogen in Prosthetic Hip Joint Infections.

Cutibacterium avidum has recently been reported as a rare cause of prosthetic joint infections (PJIs), contrary to Cutibacterium acnes, which is well established as a cause of PJIs, especially in shoulder arthroplasties. Two specific risk factors for PJI due to C. avidum have been reported: obesity and the skin incision approach. Here, we report four cases of hip PJIs caused by C. avidum admitted over a 30-month period at a single center. Whole-genome sequencing revealed that the four C. avidum strains were all individual strains and did not originate from a common source, such as an outbreak. Antibiotic susceptibility tests showed that the isolates were fully susceptible, and none carried known antibiotic resistance genes. In conclusion, the occurrence of four cases of PJI caused by C. avidum over a limited time at a single center may indicate that this pathogen is underestimated and is either emerging or more common than previously recognized. The patients presented overt signs of infection during surgery, indicating that C. avidum is a virulent pathogen. None of the previously reported risk factors for C. avidum PJI applied to these patients as only one was obese and none were operated on using a direct anterior skin incision approach.

Using nanopore sequencing to identify bacterial infection in joint replacements: a preliminary study.

This project investigates if third-generation genomic sequencing can be used to identify the species of bacteria causing prosthetic joint infections (PJIs) at the time of revision surgery. Samples of prosthetic fluid were taken during revision surgery from patients with known PJIs. Samples from revision surgeries from non-infected patients acted as negative controls. Genomic sequencing was performed using the MinION device and the rapid sequencing kit from Oxford Nanopore Technologies. Bioinformatic analysis pipelines to identify bacteria included Basic Local Alignment Search Tool, Kraken2 and MinION Detection Software, and the results were compared with standard of care microbiological cultures. Furthermore, there was an attempt to predict antibiotic resistance using computational tools including ResFinder, AMRFinderPlus and Comprehensive Antibiotic Resistance Database. Bacteria identified using microbiological cultures were successfully identified using bioinformatic analysis pipelines. Nanopore sequencing and genomic classification could be completed in the time it takes to perform joint revision surgery (2-3 h). Genomic sequencing in this study was not able to predict antibiotic resistance in this time frame, this is thought to be due to a short-read length and low read depth. It can be concluded that genomic sequencing can be useful to identify bacterial species in infected joint replacements. However, further work is required to investigate if it can be used to predict antibiotic resistance within clinically relevant timeframes.

Role of Routine Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infections.

Background: The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods: We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. Results: The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79-2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11-1.15; P = .09), which also had the highest risk of treatment failure. Conclusions: The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

Performance characteristics of genus or species-specific Polymerase Chain Reaction (PCR) for the microbial diagnosis of joint infections: A systematic review and meta-analysis.

Joint infections cause significant morbidity and mortality. Rapid diagnosis enables prompt initiation of appropriate antimicrobial therapy and surgical treatment. We conducted a systematic review and meta-analysis to evaluate the accuracy of genus- or species-specific polymerase chain reaction (PCR) in diagnosing joint infections. The literature databases were searched for articles from January 2010 to December 2022. The meta-analysis using the split component synthesis (SCS) method, included 20 studies with 2,457 adult participants. The pooled sensitivity, specificity, diagnostic odds ratio, and AUC of PCR were 49 % (95 % CI [37.9-60.2]), 95.7 % (95 % CI [91.6-97.8]), 21.32, and 0.82 respectively. Sensitivity was highest for sonicate fluid and lowest for periprosthetic tissue. The mean turnaround time to results was 4.7 hours (SD 1.1). PCR is a favourable option for diagnosing joint infections due to its rapid results, but it has low sensitivity. To enhance diagnostic yield, the test should be used in conjunction with other methods.

A Review of Phage Therapy for Bone and Joint Infections.

There is a strong rationale for using phages in patients with bone and joint infections (BJIs). Indeed, specific phages can infect and replicate in bacterial pathogens and have also demonstrated their activity in vitro against biofilm produced by different bacteria. However, there is a high variability of the different clinical forms of BJI, and their management is complex and frequently includes surgery followed by the administration of antibiotics. Regardless of the availability of active phages, optimal ways of phage administration in patients with BJIs are unknown. Otherwise, all BJIs are not relevant for phage therapy. Except for diabetic foot infection, a BJI with bone exposure is potentially not a relevant indication for phage therapy. On the counterpart, prosthetic joint infections in patients for whom a multidisciplinary expert team judges a conservative approach as the best option to keep the patient's function seem to be a relevant indication with the hypothesis that phage therapy could increase the rate of infection control. The ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA) was created in 2022. One century after the first use of phages as a therapy, the phage therapy 2.0 era, with the possibility to evaluate personalized phage therapy in modern medicine and orthopedic surgery, is just open.

Next Generation Sequencing in orthopaedic infections - Where is the road headed?

Next-generation sequencing (NGS) has emerged as a game changer in the field of orthopaedic diagnostics, notably in the detection and management of infections associated with prosthetic joints and implants. This paper conducts an exhaustive examination of the pivotal role, outcomes, and prospective future uses of NGS in diagnosing orthopaedic infections. In comparison to conventional culture-based methods, NGS offers a marked improvement in sensitivity thereby facilitating prompt and comprehensive identification of pathogens. This encompasses the ability to detect polymicrobial infections, antibiotic-resistant strains, and previously imperceptible microorganisms. Furthermore, this article delves into the technology's contribution to advancing personalized medicine and promoting judicious antibiotic use. Nonetheless, the seamless integration of NGS into routine clinical practice is impeded by challenges such as substantial financial outlays, the requisite for specialized equipment and expertise, and the intricacy associated with data analysis. Notwithstanding these impediments, the potential for NGS to revolutionize orthopaedic diagnostics remains substantial, with ongoing advancements poised to address current limitations and broaden its scope within clinical applications.

Mycobacterium flavescens Infection - An Unusual Case of Prosthetic Joint Infection.

INTRODUCTION: The onset of prosthetic joint infections (PJIs) is characterized by early onset defined as within 90 days of the procedure, delayed onset defined as within 3 to 12 months, and late onset defined as over 12 months. In only a scant number of case reports, Mycobacterium flavescens associated infections are typically found in sputum cultures and associated with various forms of penetrating joint traumas, particularly post-surgical interventions. Due to its rarity in presentation among cases of PJIs, we have presented a case of PJI caused by Mycobacterium flavescens. CASE PRESENTATION: We have, herein, reported a case of a 70-year-old male presenting with stabbing left knee pain over the past several months along with accompanying erythema and swelling with the presence of purulent discharge. Outpatient cultures have shown the growth of Mycobacterium flavescent; subsequently, the patient underwent a 2-stage revision arthroplasty and was treated with a three-drug regimen and implant 5 months later. Although being an atypical cause of PJIs, we emphasize the importance of considering NTM as a differential for immunocompromised patients, especially those with prior surgical intervention. DISCUSSION: Mycobacterium spp. related PJIs manifest clinical features similar to other bacteriacausing PJIs, such as warm, indurated edema at the surgical site resulting in wound dehiscence and joint effusion. Diagnosis of Mycobacterium spp. related PJIs includes history and physical examination findings, serum inflammatory markers, synovial fluid analysis, and culture. Concurrently with surgical interventions, utilization of antimicrobial agents provides additional control in Mycobacterium- related PJI. Mycobacterium flavescens should be included among other NTMs as a possible cause of PJIs.