Proactive therapeutic monitoring of dalbavancin concentrations in the long-term management of chronic osteoarticular/periprosthetic joint infections.

Here, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments.

Evaluation of a BioFire multiplex PCR panel for detection of joint infections using retrospective and prospectively collected specimens.

The BioFire Joint Infection Panel (JI panel) is a newly FDA-approved multiplex PCR assay for detection of common bone and joint pathogens with 39 targets which include select Gram-positive and Gram-negative bacteria, yeast, and antimicrobial resistance genes. We evaluated the performance of the JI panel in detecting joint infections in our patient population. Sixty-three frozen, residual joint fluid specimens were retrospectively tested using the JI panel. An additional 104 residual joint fluid specimens were de-identified and prospectively tested within 1 week of collection. Results from routine bacterial cultures were used as the reference standard, which included inoculation to agar plates and blood culture bottles. For the frozen specimens, the JI panel showed a positive percent agreement (PPA) of 92.8% and a negative percent agreement (NPA) of 97.1%. PPA was 71.4% and NPA was 94.8% for fresh specimens. A total of 12 discrepancies were observed among the 167 specimens tested. The JI panel demonstrated good overall agreement with routine culture for the detection of joint infections and may improve timely diagnosis when used in conjunction with bacterial culture. However, potential false-positive and false-negative results were observed in both retrospective and prospective testing of specimens.IMPORTANCEThe BioFire JI panel is a new commercially available multiplex PCR assay for detecting common pathogens causing bone and joint infections. The test is performed directly on joint fluids with a fast turnaround time of 1 hour. Our study shows that while the JI panel overall shows good agreement with routine culture, discrepancies were observed in 7% of cases and results should be interpreted with appropriate clinical context.

Rapid high-throughput processing of tissue samples for microbiological diagnosis of periprosthetic joint infections using bead-beating homogenization.

Enrichment of periprosthetic tissue samples in blood culture bottles (BCBs) for microbiological diagnosis of periprosthetic joint infections (PJI) is more reliable than the use of an enrichment broth. Nevertheless, the extremely time-consuming homogenization of the samples for BCB processing has so far limited its use, especially in high-throughput settings. We aimed to establish a highly scalable homogenization process of tissue samples for long-term incubation in BCBs. A protocol for homogenization of tissue samples using bead beating was established and validated. In a second step, the use of the homogenate for enrichment in BCBs was compared to the use of thioglycolate broth (TB) in terms of diagnostic accuracy using clinical tissue samples from 150 patients with suspected PJI. Among 150 analyzed samples, 35 samples met the microbiological criteria for PJI. Using BCB, 32 of 35 (91.4%) PJI were detected compared to 30 of 35 (85.7%) by TB. The use of BCB had a lower secondary contamination rate (2/115; 1.7% vs 4/115; 3.5%) but the trend was not significant due to low numbers of samples (P = 0.39). The time to process a batch of 12 samples using the established homogenization method was 23 ± 5 min (n = 10 batches). We established and validated a homogenization workflow that achieves the highest sensitivity in the microbiological diagnostic of PJI. The enrichment of the tissue homogenate in BCBs showed equally good results as the use of enrichment broth and allows semi-automated high-throughput processing while demonstrating lower contamination rates in our study.

The burden of skin and soft tissue, bone and joint infections in an Australian cohort of people who inject drugs.

INTRODUCTION: There are currently limited data regarding the clinical and economic significance of skin and soft tissue infections (SSTI) and bone and joint infections in Australian people who inject drugs (PWID). METHODS: Retrospective cohort study in adult PWID admitted to Monash Health, a large heath care network with six hospitals in Victoria, Australia. Inpatients were identified using administrative datasets and International Classification of Disease (ICD-10) coding for specific infection-related conditions. Cost analysis was based on mean ward, intensive care and hospital-in-the-home (HITH) lengths of stay. Spinal infections and endocarditis were excluded as part of previous studies. RESULTS: A total of 185 PWID (61 female, 124 male, median age 37) meeting the study criteria were admitted to Monash Health between January 2010 and January 2021. Admitting diagnoses included 78 skin abscesses, 80 cellulitis, 17 septic arthritis, 4 osteomyelitis, 3 thrombophlebitis and 1 each of necrotising fasciitis, vasculitis and myositis. Pain (87.5%) and swelling (75.1%) were the most common presenting complaints. Opioids (67.4%) and methamphetamine (37.5%) were the most common primary drugs injected. Almost half (46.5%) of patients had concurrent active hepatitis C (HCV) infection on admission. Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) were uncommon. The most significant causative organism was methicillin-susceptible Staphylococcus aureus (24.9%). In 40.0% (74/185) no organism was identified. Patients required a median acute hospital stay of 5 days (2-51 days). There were 15 patients admitted to the intensive care unit (ICU) with median duration 2 days. PICC line insertion for antibiotics was required in 16.8% of patients, while 51.4% required surgical intervention. Median duration of both oral and IV antibiotic therapy was 11 days. Almost half (48.6%) of patients were enrolled in an opioid maintenance program on discharge. Average estimated expenditure was AUD $16, 528 per admission. CONCLUSION: Skin and soft tissue and joint infections are a major cause of morbidity for PWID. Admission to hospital provides opportunistic involvement of addiction specialty services.

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.

Gloves Contamination During Revision Surgery for Periprosthetic Joint Infection.

BACKGROUND: The use of double gloving has become a standard practice for joint replacement surgeons. However, since there are limited data on how gloves are contaminated during both primary and revision arthroplasty, no precise protocol exists to direct surgeons on when, or if, to change their gloves. The goals of this preliminary study were to evaluate the contamination of gloves during total joint arthroplasties (TJAs). METHODS: We included 25 infected cases and 10 primaries, which were performed at the same institution using the same surgical protocol from 3 fellowship trained surgeons. Samples were taken every 20 minutes from the start of the surgery until the joint was irrigated. Procedural steps were noted. To evaluate cross-contamination during infected cases, we sampled gloves using blood agar plates. In primary cases, culture swabs of anterior chamfer cuts and sterile instruments on the back table were used as negative controls. Next-generation sequencing (NGS) was used as an adjunct to identify low virulence bacteria. RESULTS: In the primary cases, all samples were found culture negative but 3 (8.1%) of the 37 samples were found to have a low, unidentifiable bacterial mass via NGS testing. In the infected cases, 41 (59.4%) of the 69 samples yielded positive microbial results. The positivity rate was higher in the samples collected after the arthrotomy was performed (70%) compared to samples collected before the arthrotomy was performed (40%), and the surgeon was only dissecting superficial layers (P = .502). CONCLUSION: Gloves seem to be a common source of cross-contamination in the intraoperative field during revision TJA. Due to the higher percent of positive samples following the opening of the joint, we hypothesize that the arthrotomy allows for the spread of bacteria across the operative site. While further investigation is necessary to formulate a precise protocol for the changing of gloves during TJA, it may be beneficial to perform a thorough irrigation of the joint and change of the gloves immediately following arthrotomy.

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.

The Association of Dental Caries or Dental Implant Placement Within One Year of Primary Total Hip Arthroplasty on Medical and Implant Complications.

BACKGROUND: Total hip arthroplasty (THA) adverse events among patients who have dental diagnoses remain unclear. We sought to determine if dental caries or dental implant placements increased (1) 90-day medical complications, (2) 90-day readmissions, and (3) 2-year implant-related complications, including periprosthetic joint infections (PJIs) after THA. METHODS: A nationwide database for primary THAs from 2010 to 2021 was queried to compare 3 patient cohorts. Patients who had a history of dental implants or caries within 12 months prior to THA (n = 1,179) or 12 months after THA (n = 1,218) were case-matched to patients who did not have dental history (n = 6,090) by age and comorbidities. Outcomes included 90-day complications, 90-day readmissions, and 2-year implant-related complications. Logistic regression models computed the odds ratios (ORs) of complications and readmissions. P values less than .006 were significant. RESULTS: Patients who had dental caries or implant placement 12 months before or after THA experienced 1.6-fold greater odds of 90-day medical complications compared to case-matched patients. Readmissions within 90 days increased for patients who had a dental history before (11.7% versus 8.3%; OR: 1.49, P < .0001) and after (14.2% versus 8.3%; OR: 1.84, P < .0001) THA compared to case-matched patients. A dental caries diagnosis or dental implant placement within 12 months following THA increased 2-year implant complications compared to case-matched patients (15.2% versus 9.3%; OR: 1.69, P < .0001), including PJIs (5.3% versus 2.8%; OR: 1.98, P < .0001), dislocations (4.4% versus 2.7%; OR: 1.63, P = .002), and THA revisions (3.9% versus 2.5%; OR: 1.61, P = .005). CONCLUSIONS: Dental diagnoses within 12 months of THA are associated with increased medical complications. Dental diagnoses occurring 12 months after THA are associated with greater implant-related complications, including PJIs. Delaying invasive dental procedures for 12 months after THA may be advisable.

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.

Second-Line Antibiotic Agents in Patient-Reported Penicillin or Cephalosporin Allergy Have No Negative Impact on Antibiotic Resistance After Hip and Knee Arthroplasty.

BACKGROUND: The aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA). METHODS: We reviewed all cases of PJI occurring after primary THA and primary TKA/UKA, between 2011 and 2020 in a tertiary referral hospital. The standard preoperative prophylactic antibiotic for primary joint arthroplasty was cefuroxime and recommended second-line agent was clindamycin. Patients were divided by the replaced joint and analyzed independently. RESULTS: In the THA group, culture-positive PJI was detected in 61 of 3,123 (2.0%) cefuroxime-administered cases and 6 of 206 (2.9%) noncefuroxime-administered cases. In the TKA/UKA group, culture positive PJI was identified in 21 of 2,455 (0.9%) cefuroxime-administered cases and in 3 of 211 (1.4%) noncefuroxime administered cases. The most commonly isolated bacteria in both groups were coagulase negative staphylococci (CNS). There were no statistically significant differences of pathogen spectrum depending on the preoperative antibiotic regimen detected. Antibiotic resistance of isolated bacteria was significantly different in 4 of 27 (14.8%) analyzed antibiotics in THA and in 3 of 22 (13.6%) analyzed antibiotics in TKA/UKA. In all cohorts, a high occurrence of oxacillin-resistant CNS (50.0 to 100.0%) and clindamycin-resistant CNS (56.3 to 100.0%) has been observed. CONCLUSION: The use of the second-line antibiotic did not influence the pathogen spectrum or antibiotic resistance. However, an alarmingly high proportion of CNS strains was resistant to clindamycin.

Disability-adjusted life years from bone and joint infections associated with antimicrobial resistance: an insight from the 2019 Global Burden of Disease Study.

PURPOSE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.

Initiating chemotherapy in joint arthroplasty patients increases the risk of periprosthetic joint infections.

BACKGROUND: Total Joint Arthroplasties (TJAs) are becoming more popular, resulting in a growing economic burden due to potential postoperative complications, with periprosthetic joint infections (PJIs) playing a significant role. The effect of immunosuppression on PJI risk, particularly in cancer patients following chemotherapy, is unknown. The hypothesis of this study investigated whether chemotherapy increases PJI rates in patients who received post-arthroplasty chemotherapy within one year of surgery. METHODS: Data from the M161Ortho dataset of PearlDiver patient records database were utilized using ICD-9, ICD-10, and CPT codes. The cohort includes Total Knee Arthroplasty (TKA), Total Hip Arthroplasty (THA), and Total Shoulder Arthroplasty (TSA) patients who underwent post-arthroplasty chemotherapy within one year after surgery between 2010 and 2022. Patients in the matched control group did not receive post-arthroplasty chemotherapy. Pre-arthroplasty chemotherapy recipients, PJI, and post-op first year revisions were excluded. Analyses including the linear logistic regression were performed via R statistical software. RESULTS: Totally, 17,026 patients (8,558 TKAs, 6,707 THAs, and 1,761 TSAs) were included. At two (OR = 1.59, p = 0.034), three (OR = 1.57, p = 0.009), and four (OR = 1.40, p = 0.032) years for TKA, and two (OR = 2.27, p = 0.008), three (OR = 2.32, p < 0.001), and four (OR = 2.25, p0.001) years for THA, PJI rates were significantly higher in the chemotherapy group. TSA patients had a significant rise in PJI after four years (OR = 2.20, p = 0.031). CONCLUSIONS: This study reveals a possible relationship between postoperative chemotherapy and an increased incidence of PJI in patients with arthroplasty. Chemotherapy suppresses the immune system, rendering patients more vulnerable to infections. Additional research is required to confirm these findings.

Preventive strategies to reduce the rate of periprosthetic infections in total joint arthroplasty; a comprehensive review.

The increasing frequency of total hip (THA) and knee arthroplasties (TKA) is marred by the rise in periprosthetic joint infections (PJIs) and surgical site infections (SSIs), with PJIs incurring costs over $1.62 billion as of 2020 and individual case management averaging $90,000. SSIs additionally burden the U.S. healthcare economy with billions in expenses annually. PJI prevalence in primary THA and TKA ranges from 0.5% to 2.4%, spiking to 20% in revisions and representing 25% of TKA revision causes. Projections estimate up to 270,000 annual PJI cases by 2030. Often caused by gram-positive bacteria, particularly methicillin-resistant staphylococci, these infections demand preventive measures. This review dissects PJI prevention across preoperative, intraoperative, and perioperative phases, aligning with evidence-based CDC and WHO guidelines. Preoperative measures include managing diabetes, obesity, tobacco use, Staphylococcus aureus screening and nasal decolonization, nutritional optimization, and management of inflammatory arthropathies. Intraoperatively, antibiotic prophylaxis, skin preparation, operative room environmental controls, surgical technique precision, and irrigation options are scrutinized. Perioperative concerns focus on anticoagulation, blood management, and infection risk mitigation. Integrating these strategies promotes a patient-centric care model, aiming to reduce PJI incidence, improve patient outcomes, and increase care cost-effectiveness in joint arthroplasty.

What to Know about Antimicrobial Coatings in Arthroplasty: A Narrative Review.

Periprosthetic joint infections (PJIs) are one of the most worrying complications orthopedic surgeons could face; thus, methods to prevent them are evolving. Apart from systemic antibiotics, targeted strategies such as local antimicrobial coatings applied to prosthetics have been introduced. This narrative review aims to provide an overview of the main antimicrobial coatings available in arthroplasty orthopedic surgery practice. The search was performed on the PubMed, Web of Science, SCOPUS, and EMBASE databases, focusing on antimicrobial-coated devices used in clinical practice in the arthroplasty world. While silver technology has been widely adopted in the prosthetic oncological field with favorable outcomes, recently, silver associated with hydroxyapatite for cementless fixation, antibiotic-loaded hydrogel coatings, and iodine coatings have all been employed with promising protective results against PJIs. However, challenges persist, with each material having strengths and weaknesses under investigation. Therefore, this narrative review emphasizes that further clinical studies are needed to understand whether antimicrobial coatings can truly revolutionize the field of PJIs.

The stability of Staphylococcal bacteriophage in presence of local vancomycin concentrations used in clinical practice.

PURPOSE: To evaluate the stability of a clinically used Staphylococcal bacteriophage with doses of vancomycin that are encountered with local administration of vancomycin for musculoskeletal infections. METHODS: A Staphylococcal bacteriophage was evaluated for stability in different pH ranges. Then that same bacteriophage was evaluated for stability with different concentrations of vancomycin and with vancomycin biodegradable antibiotic beads. RESULTS: The bacteriophage had stability within a pH range of 4-10. There was a statistically significant (P < 0.05) decrease in the amount of bacteriophage over 24 h for vancomycin concentrations of 10 mg/mL and 100 mg/mL compared to lower vancomycin concentrations (1 mg/mL, 0.1 mg/mL and normal saline). However, no statistically significant decrease in the amount of bacteriophage was seen with biodegradable vancomycin beads over 24 h. CONCLUSION: These findings have important clinical ramifications in that they show local administration of bacteriophages with concomitant local vancomycin powder therapy should be avoided. Moreover, these findings should spearhead further research into bacteriophage stability in in vivo environments.

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.

Experience Using Adjuvant Bacteriophage Therapy for the Treatment of 10 Recalcitrant Periprosthetic Joint Infections: A Case Series.

Periprosthetic joint infections are a devastating complication of joint replacement surgery. One novel therapeutic that has potential to change the current treatment paradigm is bacteriophage therapy. Herein, we discuss our experiences with bacteriophage therapy for 10 recalcitrant periprosthetic joint infections and review the treatment protocols utilized to achieve successful outcomes.

Population Pharmacokinetics and Dosage Optimization of Vancomycin in Pediatric Patients with Skin and Soft Tissue Infections, Bone, and Joint Infections.

Vancomycin is recommended for the treatment of skin and soft tissue infections (SSTI) and bone and joint infections (BJI). However, a detailed investigation of the pharmacokinetic profile and optimal dosing regimens of vancomycin in pediatric patients with SSTI and BJI is lacking. We successfully developed a new PopPK model of vancomycin in this population by using scavenged blood samples with the typical values for clearance (CL) of 0.14 L/h/kg and volume of distribution (V) of 0.5 L/kg. Body weight was confirmed as the significant covariate on CL and V. The optimal dosing regimens of 75 mg/kg/day and 80 mg/kg/day were recommended for this specific population.

Rapid Diagnostics of Joint Infections Using IS-Pro.

Diagnosis of bone and joint infections (BJI) relies on microbiological culture which has a long turnaround time and is challenging for certain bacterial species. Rapid molecular methods may alleviate these obstacles. Here, we investigate the diagnostic performance of IS-pro, a broad-scope molecular technique that can detect and identify most bacteria to the species level. IS-pro additionally informs on the amount of human DNA present in a sample, as a measure of leukocyte levels. This test can be performed in 4 h with standard laboratory equipment. Residual material of 591 synovial fluid samples derived from native and prosthetic joints from patients suspected of joint infections that were sent for routine diagnostics was collected and subjected to the IS-pro test. Bacterial species identification as well as bacterial load and human DNA load outcomes of IS-pro were compared to those of culture. At sample level, percent positive agreement (PPA) between IS-pro and culture was 90.6% (95% CI 85.7- to 94%) and negative percent agreement (NPA) was 87.7% (95% CI 84.1 to 90.6%). At species level PPA was 80% (95% CI 74.3 to 84.7%). IS-pro yielded 83 extra bacterial detections over culture for which we found supporting evidence for true positivity in 40% of the extra detections. Missed detections by IS-pro were mostly related to common skin species in low abundance. Bacterial and human DNA signals measured by IS-pro were comparable to bacterial loads and leukocyte counts reported by routine diagnostics. We conclude that IS-pro showed an excellent performance for fast diagnostics of bacterial BJI.

Performance and Hypothetical Impact on Joint Infection Management of the BioFire Joint Infection Panel: a Retrospective Analysis.

Pathogen identification is key in septic arthritis. Culture-based techniques are challenging, especially when patients have been pretreated with antibiotics or when difficult-to-culture bacteria are encountered. The BioFire joint infection assay (BJA) is a multiplex PCR panel which detects 31 of the most prevalent bacterial and fungal pathogens causing septic arthritis. Here, 123 cryoconserved contemporary synovial fluid samples from 120 patients underwent BJA analysis. Results were compared to those of culture-based diagnostics (standard of care [SOC]). Clinical data were collected, and the possible impact of the molecular diagnostic application on patient management was evaluated. Fifteen of 123 synovial fluid cultures grew bacterial pathogens. All on-panel pathogens (9/15) were correctly identified by the BJA. The BJA identified four additional bacterial pathogens in four SOC-negative cases. BJA sensitivity and specificity were 100% (95% confidence interval [CI], 69.2% to 100%) and 100% (95% CI, 96.8% to 100%), respectively. Compared to the SOC, the BJA would have resulted in faster provision of species identification and molecular susceptibility data by 49 h and 99 h, respectively. Clinical data analysis indicates that in BJA-positive cases, faster species ID could have led to timelier optimization of antibiotic therapy. This retrospective study demonstrates high sensitivity and specificity of the BJA to detect on-panel organisms in bacterial arthritis. The usefulness of the BJA in prosthetic-joint infections is limited, as important pathogens (i.e., coagulase negative staphylococci and Cutibacterium acnes) are not covered. Evidence from patient data analysis suggests that the assay might prove valuable for optimizing patient management in acute arthritis related to fastidious organisms or for patients who received antibiotics prior to specimen collection.