Treatment Of Prosthetic Joint Infections Research Articles

Phage therapy in prosthetic joint infections caused by Staphylococcus aureus - A literature review.

Prosthetic joint infections (PJIs) are dreaded arthroplasty complications often caused by Staphylococcus aureus. Due to methicillin-resistant S. aureus (MRSA) strains or biofilm formation, successful treatment remains difficult. Currently, two-stage revision surgery constitutes the gold standard therapy of PJIs, sometimes replaced or supplemented by debridement, antibiotics, and implant retention (DAIR). Given the dire consequences of therapeutic failure, bacteriophage therapy might be another treatment option. Here we provide a comprehensive literature review addressing theefficacy of phages applied against S.aureus as causative agent of PJIs. The included 17 publications had in common that the applied phages proved to be effective against various S. aureus isolates including MRSA even in biofilms. Experiments with mice, rats, rabbits, and moth larvaeconfirmed favorable features of phage preparations in PJI treatment in vivo; including its synergistic with antibiotics. Case reports of PJI patients unanimously described the bacterial eradication following, alongside other measures, intravenous and intra-articular phage administration. Generally, no major side effects occurred, but in some cases elevated liver transaminases were observed. To conclude, our review compiled promising evidence suggesting the safety and suitability of phage therapy as an adjuvant to DAIR in S. aureus PJIs, and thus, underscores the significance of further research.

Effect of non-contact induction heating on HA coatings and bone cement, an ex vivo study

Background Prosthetic joint infection is a serious complication that can arise after total joint replacement surgery. When bacteria colonise an orthopaedic implant, they form biofilms that protect them from their environment, making them difficult to remove. Treatment is further complicated by a global rise of antimicrobial resistance. These protective mechanisms make treatment of prosthetic joint infection increasingly complex. Non-contact induction heating is an upcoming technology that uses heat to eradicate bacteria that are present on the surface of metallic implants. This study aims to provide insight into the feasibility of using non-contact induction heating on metallic implants that are in direct contact with other biomaterials, such as coatings composed of hydroxyapatite and bone cement composed of poly (methyl methacrylate) (PMMA). Methods Characterisation of hydroxyapatite coatings and adhesion strength tests were conducted according to standards set by the International Organisation for Standardisation (ISO 13779-2). The fixation strength of acrylic bone cement was tested according to an adapted method from ISO. Results It was found that non-contact induction heating did not significantly affect the adhesion strength of hydroxyapatite coatings (p=0.697). In contrast to hydroxyapatite coatings, acrylic bone cement softened temporarily as the temperature exceeded the glass transition temperature (83.38 ± 10.88°C). However, the induction heating temperature had no significant effect on the fixation strength after the cement was allowed to cool down (p=0.535). Conclusion This study shows the feasibility of using non-contact induction heating up to 80°C when bone cement or ceramic coatings are present in contact with infected metallic implants.

A Meta-Analysis of Success Rates of One-Stage Versus Two-Stage Revisions in Knee Prosthetic Joint Infections.

Prosthetic joint infections (PJIs) pose significant challenges following total joint arthroplasties and cause profound complications. They are associated with significant morbidity and mortality. One-stage revision involves the removal of the infected implant and simultaneous re-implantation of a new prosthesis in a single surgical procedure. The two-stage approach is traditionally more common in the United States and follows a deliberate sequence: the infected implant is first removed, followed by a period of antibiotic therapy, and then a second surgery for implant reinsertion. While two-stage revisions were traditionally considered the gold standard, recent advancements have introduced one-stage revisions as a viable alternative. One-stage revision offers the advantage of being a single procedure, significantly reducing the patient's downtime without a functioning knee. Currently, there has not been a comprehensive exploration of the comparative outcomes between two-stage revisions and one-stage revisions. This systematic review and meta-analysis aimed to assess the outcomes of both one- and two-stage revisions for total knee arthroplasties (TKAs), by utilizing comparison studies as the foundation for analysis. Our search encompassed databases such as MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, and Cochrane to identify articles examining the comparative efficacy and outcomes of one- and two-stage revision procedures between January 2000 and June 2023. We employed keywords relevant to knee PJIs to identify comparative studies reporting on success rates, reinfection rates, microbiological findings, and other pertinent outcomes. Statistical analysis for this investigation was performed using Review Manager 5.4 (The Cochrane Collaboration, 2020) with a standard significance threshold set at a p-value less than .05. This meta-analysis incorporated six comparison articles and 802 patients. Two-stage revisions (547 patients) were associated with greater success rates (i.e., infection eradication) than one-stage revisions (255 patients) (p = .03). The studies did not suggest a difference in the microbiology of the infections. Two-stage revisions are associated with higher success rates than one-stage revisions in the treatment of knee PJIs. Future randomized controlled trials should evaluate the optimization of the management of these complications.

Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Systemic Absorption Resulting from Tobramycin-Loaded Antibiotic Cement Spacers Used in the Treatment of Prosthetic Joint Infection.

Antimicrobial cement spacer (ACS) placement has been a cornerstone of two-stage management of prosthetic hip and knee infection. Pharmacokinetic modelling has described peak systemic antibiotic concentrations within the first 24-48h post-operatively, followed by rapid clearance. A few studies have, however, identified detectable tobramycin levels in patients with a post-operative decline in creatinine clearance. Our study sought to determine how frequently detectable serum tobramycin levels occurred within the first 72h following ACS placement in all patients regardless of baseline or subsequent changes in renal function, whether these levels correlated with tobramycin spacer dosage, creatinine clearance, or potential nephrotoxicity risk factors, and whether any patients developed acute kidney injury within the 14-day post-operative period. We prospectively enrolled patients with prosthetic hip or knee infections and subsequent ACS placement from October 2017 to February 2020. Patient comorbidities (chronic kidney disease, diabetes mellitus, chronic liver disease, chronic obstructive pulmonary disease, and atrial fibrillation), Charleston Comorbidity Index score, risk factors for post-operative nephrotoxicity (perioperative hypotension and nephrotoxic agent receipt), total tobramycin dosage, post-operative days 1 and 3 serum tobramycin concentrations, and serum creatinine and creatinine clearance throughout a 14-day post-operative period were recorded. A total of 20 patients were enrolled, comprising 20 spacers with a median total tobramycin dosage of 4.80g with an interquartile range (IQR) of 4.13-7.20g. Thirteen patients had a median detectable post-operative day 1 serum tobramycin concentration of 0.80 (IQR 0.50-1.60) mcg/mL. Five of these 13 patients had a median detectable post-operative day 3 serum tobramycin concentration of 0.80 (IQR 0.50-1.10) mcg/mL. A correlation was not found between serum tobramycin drug levels and patient comorbidities, receipt of nephrotoxic medications, or baseline and subsequent post-operative creatinine clearance up to day 14. The majority of patients who underwent tobramycin ACS placement had detectable serum tobramycin levels in the immediate post-operative period, but most reached undetectable levels within 72h. There were no reliable perioperative predictors of detectable drug levels.

Socioeconomic Disadvantage Predicts Decreased Likelihood of Maintaining a Functional Knee Arthroplasty Following Treatment for Prosthetic Joint Infection

BackgroundProsthetic joint infection (PJI) carries major morbidity and mortality as well as a complicated and lengthy treatment course. In patients who have high degrees of socioeconomic disadvantage, this may be a particularly devastating complication. Our study sought to evaluate the impact of socioeconomic deprivation on outcomes following treatment for PJI of the knee. MethodsWe conducted a retrospective review of revision total knee arthroplasty (TKA) procedures performed for the treatment of initial PJI between 2008 and 2020 at a single tertiary care center in the United States. The Area Deprivation Index (ADI) was used to quantify socioeconomic deprivation. The primary outcome measure was presence of a functional knee joint at the time of most recent follow-up defined as TKA components or an articulating spacer. A total of 96 patients were included for analysis. The median follow-up duration was 26.5 months. ResultsThere was no significant difference in the rate of treatment failure (P = .63). However, the proportion of patients who had a functional knee arthroplasty (in contrast to having undergone arthrodesis, amputation, or retention of a static spacer) declined significantly with increasing ADI index (81.8% for the least disadvantaged group, 58.7% for the middle group, 42.9% for the most disadvantaged group, P = .021). ConclusionsPatients who have a higher socioeconomic disadvantage as measured by ADI are less likely to maintain a functional knee arthroplasty following treatment for TKA PJI. These findings support continued efforts to improve access to care and optimize treatment plans for patients who have socioeconomic disadvantage.

The stability of Staphylococcal bacteriophages with commonly used prosthetic joint infection lavage solutions.

The aim of this study was to assess the viability of four Staphylococcal bacteriophages when exposed to different concentrations of commonly used lavage solutions in the surgical treatment of prosthetic joint infections (PJI). Four tailed Staphylococcal bacteriophages and six different lavage solutions (chlorhexidine 4%, hydrogen peroxide 3%, acetic acid 3%, povidone iodine 10%, sodium hypochlorite 0.5%, and Vashe solution) at 100%, 1%, and 0.01% concentrations were used in this experiment. In addition, the temporal impact of exposing bacteriophages to these lavage solutions was also evaluated at 5-min exposures and 24-h exposures. The results show that the titers of the four bacteriophages were statistically significantly decreased for all lavage solutions (100% and 1%) at 5-min exposures and 24-h exposures. However, with 0.01% concentrations of the lavage solutions, only acetic acid caused a statistically significant decrease in bacteriophage titers compared to normal saline control. Our findings suggest that tailed Staphylococcal bacteriophages do not remain stable in high concentrations of the most commonly used lavage solutions. However, at very dilute concentrations the bacteriophages do remain viable. This has important clinical ramifications in that it shows when using bacteriophage therapy for PJI it is critical to thoroughly wash out any lavage solutions before the introduction of therapeutic bacteriophages especially when acetic acid is used.

High Rates of Treatment Failure and Amputation in Modular Endoprosthesis Prosthetic Joint Infections Caused by Fungal Infections With Candida.

Fungal prosthetic joint infections (PJIs) are rare yet severe events associated with high rates of recurrent infection. Although bacterial PJIs associated with megaprostheses are known to be associated with higher rates of recurrence and amputation, little is known about fungal PJIs near megaprostheses. In patients with fungal megaprosthesis PJIs from one institutional registry, We asked: (1) what were the most common microorganisms isolated? (2) What were the reoperation-, revision-, and amputation-free survival rates 1 and 2 years after surgery? We conducted a retrospective analysis of megaprostheses in our institutional database. Between 2000 and 2022, 86 patients with a diagnosis of PJI after megaprosthesis implantation were surgically treated at our institution. We considered patients with microbiological cultures that were positive for fungal organisms and who had a minimum follow-up of 2 years from the initial treatment for PJI. Ten patients with fungal megaprosthesis PJIs were included. Although four patients had a follow-up shorter than 2 years, all reached one of the study endpoints at that earlier interval, and therefore were included. All included patients were treated between 2016 and 2022, and the diagnosis of PJI was made in accordance with the 2011 Musculoskeletal Infection Society criteria. Patients were treated with either debridement, antibiotics, and implant retention (DAIR), DAIR-plus (debridement, antibiotics, modular implant component exchange, and stem retention), or one-stage or two-stage revision. In general, DAIR was used for acute PJIs, while DAIR-plus was performed in patients with chronic PJIs who were deemed medically unfit to endure the high morbidity associated with removal of the stems. In cases of prior unsuccessful DAIR-plus or patients with fewer comorbidities, one-stage or two-stage revision was the main treatment approach. The median age at diagnosis was 67 years (range 32 to 84 years), 5 of 10 patients were female, and the median BMI was 31 kg/m2 (range 20 to 43 kg/m2). The median follow-up was 26 months (range 1 to 54 months). A Kaplan-Meier survival analysis was performed to calculate reoperation-, revision-, and amputation-free survival at 1 and 2 years from the index surgery for PJI. The two most common organisms were Candida albicans (5 of 10 patients) and C.parapsilosis (3 of 10). Six of 10 patients had coinfection with a bacterial organism. One-year reoperation-free and revision-free survival were 35% (95% CI 9% to 64%) and 42% (95% CI 11% to 71%), respectively. Two-year reoperation-free and revision-free survival were 12% (95% CI 1% to 40%) and 14% (95% CI 1% to 46%), respectively. Amputation-free survival was 74% (95% CI 30% to 93%) at the 1-year interval and 40% at the 2-year interval (95% CI 7% to 73%). At the final follow-up interval, four patients had undergone amputations and four were being administered chronic antifungal suppression. Megaprosthesis fungal PJIs are rare but devastating. Arthroplasty surgeons should consider treatment efficacy, which appears to be low across surgical strategies, and the patient's capacity to withstand it. A lower decision threshold for performing amputation may be considered in patients who require rapid infection control to initiate immunosuppressive treatments. Future studies should aim to compare the surgical and clinical outcomes of fungal PJIs with those of other etiologies while controlling for potential variables. Efforts should be made to establish multi-institutional collaborations to achieve larger study samples. Level IV, therapeutic study.

Prosthetic joint infection in the hip and knee

Prosthetic joint infection (PJI) is one of the worst complications of joint arthroplasty with an incidence of around 1% following primary arthroplasty, 3% following aseptic revision, and 20% following septic revision. It can occur following direct inoculation, haematogenous or contiguous spread. The majority of PJIs are secondary to bacterial infection although fungal PJI may be seen in multiply operated or immune compromised patients. Risk factors for PJI include patient, pathology and procedure-related factors which, where possible, should be optimized prior to surgery. The diagnosis of PJI remains a challenge and is based on patient history, clinical examination, laboratory tests, and imaging studies. No diagnostic assessment is 100% accurate with various diagnostic criteria used clinically. Investigation and treatment of PJI should be guided by a multi-disciplinary team. Surgical treatment remains the gold standard with the aim of eradicating infection. During surgery the causative organism is sought through a rigorous standardized tissue sampling technique. Surgical approaches including debridement, antibiotics and implant retention (DAIR), single-stage revision, two-stage revision, excision arthroplasty, arthrodesis and amputation. The approach used is tailored to the individual patient with the optimum surgical strategy being one that successfully eradicates the infection, but at the same time minimizes morbidity to the patient.

Outcomes after débridement, antibiotics, and implant retention for prosthetic joint infection in shoulder arthroplasty

Patients who undergo total shoulder arthroplasty usually have excellent long-term outcomes. However, a subset of patients is diagnosed with a prosthetic joint infection (PJI) requiring revision procedures and prolonged recovery. The purpose of this study was to evaluate rates of recurrent shoulder PJI in patients undergoing débridement, antibiotics, and implant retention (DAIR), single-stage revision, and 2-stage revision. We also sought to compare outcomes and complications across procedures. Retrospective chart review was conducted for patients diagnosed with PJI after primary shoulder arthroplasty between January 2010 and August 2021. Patients were included if they underwent treatment with DAIR, single-stage revision, or 2-stage revision. Demographic information, surgical details, complications, laboratory data, postoperative antibiotic regimen, and infectious pathogen were collected. Postoperative patient-reported outcomes were collected: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, Shoulder Activity Scale, and PROMIS Upper Extremity. Chi-square, t test, and 1-way analysis of variance were used as appropriate to evaluate each factor. Sixty-five patients were included in the study, 26% treated with DAIR, 9% treated with single-stage revision, and 65% treated with 2-stage revision. There were no significant differences in patient comorbidities. Patients undergoing DAIR were diagnosed significantly earlier than those undergoing single- and 2-stage revision procedures (12.6±22.9 months vs. 49.6±48.4 vs. 25.0±26.6, P=.010). Recurrent PJI was noted in 23.1% of patients: 29.4% of DAIR patients, no single-stage patients, and 23.8% of 2-stage patients (P=.330). Patients undergoing 2-stage revision with treatment failure had a significantly higher Elixhauser Comorbidity Index (0.2±3.7 vs. 3.7±3.9, P=.027). There was no significant difference in patient-reported outcomes across groups. Patients undergoing treatment of shoulder PJI with DAIR did not have an increased rate of reinfection compared with single-stage and 2-stage revision procedures. Patients treated with DAIR were diagnosed with PJI significantly earlier than those undergoing single-stage and 2-stage revision procedures. There was no difference in complication rates between groups. This information adds to the body of work detailing outcomes after DAIR for shoulder PJI and provides encouraging data for use in this patient population. Future studies with a larger sample size may be conducted to further investigate specific pathogens, infection timelines, and antibiotic regimens that reduce the risk of treatment failure.

Hematogenous prosthetic knee joint infection with Klebsiella pneumoniae caused by asymptomatic gallbladder abscess: a case report and literature review

Abstract Klebsiella pneumoniae has the ability to form biofilm; therefore, the treatment of prosthetic joint infection involving K. pneumoniae is often challenging. This report describes the first case of acute hematogenous prosthetic knee joint infection with K. pneumoniae that occurred as a result of an asymptomatic gallbladder abscess. The patient was a 78-year-old man who underwent bilateral total knee arthroplasty 6 years ago. He had pain and swelling in his right knee. The synovial fluid culture of the right knee revealed K. pneumoniae and prosthetic joint infection was diagnosed. Computed tomography revealed a gallbladder abscess in the absence of right upper abdominal pain. The patient underwent simultaneous debridement of the knee and open cholecystectomy. The treatment was successful and the prosthesis was retained. In cases of hematogenous prosthetic joint infection with K. pneumoniae, other sources of infection should be suspected and investigated regardless of whether they are symptomatic.

Failed 2-Stage Revision Knee Arthroplasty for Periprosthetic Joint Infection—Patient Characteristics and Outcomes

BackgroundChronic prosthetic joint infection (PJI) is most frequently treated with 2-stage revision in conjunction with antibiotic treatment. The aims of this study were 1) to investigate the characteristics of patients who have recurrent infection following 2-stage revision for PJI and 2) to identify risk factors associated with treatment failure. MethodsA multicenter retrospective review of 90 total knee arthroplasty (TKA) patients who underwent 2-stage revision for treatment of PJI from March 1, 2003 to July 31, 2019, and had recurrent PJI was conducted. The minimum follow-up was 12 months (median follow up of 2.4 years). Microorganisms, subsequent revision, PJI control status, and final joint status were collected. The infection-free survival after initial 2-stage revision was plotted utilizing the Kaplan–Meier method. ResultsMean survival time to reinfection was 21.3 months (range, 0.3 to 160.5). There were 14 recurrent infections that were acute PJIs treated with debridement, antibiotics, and implant retention (DAIR), while 76 were chronic and treated with repeat 2-stage revision. The most common pathogen identified for both index and recurrent PJI was coagulase-negative Staphylococci. Pathogen persistence was observed in 14 (22.2%) of recurrent PJIs. In total, 61 (67.8%) patients possessed a prosthetic reimplantation at their most recent follow-up, and 29 (35.6%) patients required intervention following repeat 2-stage. ConclusionOverall, 31.1% of the patients obtained infection control after treatment of a failed 2-stage revision due to PJI. The high rate of pathogen persistence and the relatively low survival time to recurrence suggests a need to more closely monitor PJIs cases within 2 years.

The Impact of Antimicrobial Therapy Duration in the Treatment of Prosthetic Joint Infections Depending on Surgical Strategies: A Systematic Review and Meta-analysis.

The aim of this systematic review was to address the question if short antibiotic treatment (SAT; at least 4 but <12 weeks) versus long antibiotic treatment (LAT) affects outcomes in prosthetic joint infections (PJIs). Database research (Medline, Embase, Web of Science, Scopus, Cochrane) retrieved 3740 articles, of which 10 studies were included in the analysis. Compared to LAT, 11% lower odds of treatment failure in the SAT group were found, although the difference was not statistically significant (pooled odds ratio, 0.89 [95% confidence interval, .53-1.50]). No difference in treatment failure was found between SAT and LAT once stratified by type of surgery, studies conducted in the United States versus Europe, study design, and follow-up. There is still no conclusive evidence that antibiotic treatment of PJIs for 12 weeks or longer is associated with better outcomes, irrespective of the type of surgical procedure. Most recent, high-quality studies tend to favor longer antibiotic courses, making them preferable in most situations.

ROUTINE SURGICAL ANTISEPTIC AGENTS ARE INEFFECTIVE IN THE ERADICATION OF TYPICAL PJI BIOFILM FORMED ON ORTHOPAEDIC IMPLANT MATERIAL IN VITRO AND THE ABSENCE OF AN ANTISEPTIC NEUTRALIZATION STAGE GIVES THE FALSE IMPRESSION OF EFFICACY

Prosthetic joint infection (PJI) is a serious complication following joint replacement. Antiseptic solutions are often used for intraoperative wound irrigation particularly in cases of revision for PJI. Antiseptic irrigation is intended to eradicate residual bacteria which may be either free floating or in residual biofilm although there is no clear clinical efficacy for its use. Also, reviewing the scientific literature there is discordance in in vitro results where some studies questions antiseptic efficacy whilst others suggest that even at low concentration antiseptic agents are effective at eradicating bacterial biofilms.The aim of this in vitro study was to establish the efficacy of undiluted antiseptic agents at eradication of a typical PJI forming biofilm and determine the importance of an antiseptic neutralisation step in this assessment.Mature Staphylococcus epidermidis biofilms grown on TiAl6V4 discs were submerged in chlorohexidine (CHL) gluconate 4%, povidone-iodine (PI) 10% or phosphate-buffered saline (PBS) control solution. The discs were then rinsed, the biofilm bacteria suspended in solution using sonication and vortexing, and the viable count (CFU/ml) of the bacterial suspensions determined. The rinse/suspension solution was either (a) PBS or (b) Dey-Engley neutralization broth (NB).When PBS was used to rinse/suspend the biofilm a highly significant, 7.5 and 4.1, mean log reduction in biofilm vitality was observed from the control, for CHL 4% and PI 10%, respectively. However, when NB was the rinse/suspension solution the apparent antiseptic biofilm eradication efficacy was replaced with a statistically significant but clinically irrelevant less the one log-reduction in biofilm vitality.Clinical antiseptic agents are ineffective at eradicating S. epidermidis biofilm in an in vitro PJI model and absence of a neutralisation step gives the false impression of efficacy. Antiseptics alone are an ineffective treatment for biofilm related PJI and no substitute for meticulous debridement.

ANTIMICROBIAL ACTIVITY OF ION-SUBSTITUTED CALCIUM PHOSPHATES: A SYSTEMATIC REVIEW

Prosthetic Joint Infection (PJI) is a devastating complication that can occur after total joint replacement surgery. With increasing antimicrobial resistance, there is a need for non-antibiotic approaches to treat and prevent PJI. Doping calcium phosphates with antimicrobial ions shows promise for these purposes. This systematic review aims to search and summarise the evidence-base for the potential of calcium phosphates doped with different antimicrobial ions.A systematic review was conducted on PubMed, Embase, Web-Of-Science, Cochrane Library and Emcare of in vitro and animal studies on the antimicrobial activity of (co)substituted calcium phosphates according to PRIMSA guidelines.. The research protocol, listing search terms and in/exclusion criteria, was registered a priori at https://doi.org/10.7910/DVN/HEP18U. Data was extracted regarding ions, micro-organisms and antimicrobial activity.The search retrieved 1017 hits of which 148 papers were included. The substitution of 33 different ions was reported. Silver (n= 46), zinc (n=39), copper (n=18) and magnesium (n=14) were the most commonly doped ions. 36 different micro-organisms were studied of which E. coli (n=109), S. aureus (n=99), and C. albicans (n=22) were the most common. 6 different outcomes were reported, most commonly the K-ratio (n=53), the log CFU (n=41) and the bacterial inhibition zone (n=39). A validated outcome for the evaluation of biofilm prevention was lacking.There was considerable heterogeneity in studied ions, micro-organisms and reported outcomes. A lack of clearly defined reporting guidelines in the field of antimicrobial materials has led to the use of clinically irrelevant micro-organisms and a general lack of consistency of the methods used and the reported results. Currently, there is no universally accepted measure for the effectiveness required from biomaterials for treatment and prevention of PJI.

Dare to DAIR: Is Rifampin Always Necessary?

The treatment of early post-operative staphylococcal prosthetic joint infection (PJI) with debridement, antibiotics, and retention of the implant (DAIR) is becoming increasingly common. This approach has many advantages, primarily more rapid mobilization and return to normal activities compared to a one- or two-stage revision [1]. A recent prospective multicenter observational study conducted at 27 hospitals in Australia and New Zealand found that DAIR was as successful as one or two-stage revisions, especially in patients with acute infections [2]. However, there is still considerable confusion as to the best antibiotics and duration of therapy. Some guidelines have adopted rifampin combination therapy as the cornerstone antibiotic treatment for staphylococcal PJI treated with DAIR, based on experimental animal models, one randomized trial, and several cohort studies [3,4]. However, rifampin combination therapy is associated with significant side effects and drug–drug interactions. A common justification for adding rifampin is a prospective randomized trial of early MSSA PJI conducted by Zimmerli and published in 1998 [5]. This was a prospective, randomized, double-blind trial that showed 100% success with combination therapy compared to 58% in the non-rifampin arm. Only 33 patients were included in this trial and only 24 completed the study. Of the 18 patients in the rifampin arm, there were 5 hip replacements, 3 knee replacements and 10 internal fixation devices. In the placebo arm, there were 3 hip replacements, 4 knee replacements and 8 internal fixation devices. This study was certainly a remarkable accomplishment; however, arguably, it should not be considered the definitive word on how to treat PJI with DAIR and drive clinical practice for decades. Unfortunately, it seems that this has been the case given the recommendations of current guidelines.

Combination d-Amino Acid and Photothermal Hydrogel for the Treatment of Prosthetic Joint Infections.

Prosthetic joint infection (PJI) is a devastating complication requiring surgical intervention and prolonged antimicrobial treatment. The prevalence of PJI is on the rise, with an average incidence of 60,000 cases per year and a projected annual cost of $1.85 billion in the US. The underlying pathogenesis of PJI involves the formation of bacterial biofilms that protect the pathogen from the host immune response and antibiotics, making it difficult to eradicate such infections. Biofilms on implants are also resistant to mechanical brushing/scrubbing methods of removal. Since the removal of biofilms is currently only achievable by the replacement of the prosthesis, therapies aimed at eradicating biofilms while enabling retention of implants will revolutionize the management of PJIs. To address severe complications associated with biofilm-related infections on implants, we have developed a combination treatment that is based on a hydrogel nanocomposite system, containing d-amino acids (d-AAs) and gold nanorods, which can be delivered and transforms from a solution to a gel state at physiological temperature for sustained release of d-AAs and light-activated thermal treatment of infected sites. Using this two-step approach to utilize a near-infrared light-activated hydrogel nanocomposite system for thermal treatment, following initial disruption with d-AAs, we were able to successfully demonstrate in vitro the total eradication of mature Staphylococcus aureus biofilms grown on three-dimensional printed Ti-6Al-4V alloy implants. Using a combination of cell assays, computer-aided scanning electron microscopy analyses, and confocal microscopy imaging of the biofilm matrix, we could show 100% eradication of the biofilms using our combination treatment. In contrast, we were only able to see 25% eradication of the biofilms using the debridement, antibiotics, and implant retention method. Moreover, our hydrogel nanocomposite-based treatment approach is adaptable in the clinical setting and capable of combating chronic infections brought about by biofilms on medical implants.

Antimicrobials in polymethylmethacrylate: from prevention to prosthetic joint infection treatment: basic principles and risk of resistance

BackgroundExcellent revisions about antibiotic-loaded bone cement (ALBC) have been recently published. In the present article, we review the principles and limitations of local antibiotic delivery in the context of recent advances in the pathogenesis of prosthetic joint infections (PJI), with particular attention paid to the potential association between ALBC and antimicrobial resistance.Main bodyRecalcitrance of PJI is related to the ability of pathogens to adapt to particular environments present in bone tissue and protect themselves from host immunity in different ways. Accordingly, delivery of high local antimicrobial concentrations using ALBC is needed. Most relevant clinical data showing the efficacy of ALBC for PJI prophylaxis and treatment are reviewed, and we dissected the limitations on the basis of the recent findings from animal models and suggested that aminoglycosides, in particular, could not be the best option. One of the major concerns associated with ALBC is the emergence of resistance because of theoretical prolonged exposure to low antibiotic concentrations. We summarize the mechanisms for the selection of resistant microorganisms, and we critically reviewed the evidence from animal models and clinical data from observational and registry studies and concluded that there is no evidence to support this association.ConclusionWhile waiting for better evidence from well-designed clinical trials, ALBC shows a beneficial effect as a prophylaxis in arthroplasty, and to avoid the colonization of spacers used for two-stage revision in patients with PJI. Experimental models and clinical evidence suggest the need to achieve high local antimicrobial concentrations to obtain the highest prophylactic and therapeutic effect. The current evidence does not support the risk of increasing resistance with use of ALBC. In the future, it is necessary to evaluate new carriers and different antimicrobials to improve clinical outcomes.

One-stage revision using intra-articular vancomycin infusion effectively treats chronic prosthetic joint infection caused by Enterococcal

Objective: To investigate the clinical effects of one-stage revision combined with intra-articular infusion of vancomycin in the treatment of chronic prosthetic joint infection (PJI) caused by Enterococcal. Methods: From May 2013 to June 2020,the clinical data of 9 patients (2 males and 7 females) with chronic Enterococcal PJI treated with one-stage revision using intra-articular infusion of vancomycin at Department of Orthopaedics,First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed,including 8 hips and 1 knee.A total of 9 patients with age of (63.9±11.7)years (range:43 to 76 years) were included, and the body mass index was (23.6±4.3)kg/m2 (range:18 to 30 kg/m2).There were 6 cases with antibiotic history and 5 cases with sinus tract.The joint fluid,infected tissue around the prosthesis and ultrasonic shock fluid of the prosthesis were collected during operation for microbial culture identification and drug sensitivity test.After thorough debridement of the infected site and removal of the infected prosthesis,a new prosthesis was implanted,then the drainage tube in the operation area was placed.After surgery,vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin(0.5 g,qd) in monomicrobial PJI,and vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin (0.5 g,qd) and imipenem/meropenem (0.5 g,qd),and the interval between the two drugs was 12 hours in polymicrobial PJI.Hip and knee functions were evaluated by Harris Hip Score or Knee Society Score(KSS),respectively.The comparison of hip function scores before and after operation was performed by paired t-test. Results: All patients were followed up for (60±39)months(range:24 to 110 months).Two cases were infected with Enterococcus faecium and 7 cases were infected with Enterococcus faecalis.There were 7 cases of monomicrobial infection and 2 cases of polymicrobial infection.Erythromycin(5/9),tetracycline(4/9),ciprofloxacin and β-lactam antibiotics(3/9) were the top three antibiotics in Enterococci resistance rate.The sensitive antibiotics for Enterococcal were vancomycin,linezolid and tigecycline.The average duration of intravenous antibiotics was (14±1)days (range:13 to 17 days),and the average duration of antibiotics in articular cavity was (15±2)days(range:11 to 20 days).Mean duration of oral antibiotic use after discharge was (2±1)months(range:1 to 3 months).One case of polymicrobial PJI treatment failed,with a failure rate of 1/9.At last follow-up,the Harris score of patients with hip PJI increased from (43±6)points to (84±6)points(t=-11.899, P<0.01). KSS score of knee function was improved from 33 point pre-operatively to 85 point post-operatively;overall function score was improved from 35 point pre-operatively to 80 point post-operatively.During the treatment,no formation of sinus tract of the hip joint caused by a catheter,skin necrosis at the knee puncture site or leakage of joint fluid;no complications such as deep vein thrombosis and pulmonary embolism occurred. Conclusions: One-stage revision combined with intra-articular infusion of vancomycin can achieve acceptable infection control rate and joint function in patients with chronic Enterococcus PJI.However,the treatment of polymicrobial PJI still needs to be further verified.

THE PROFILE OF CAUSAL PATHOGEN OF HIP/ KNEE PROSTHETIC JOINT INFECTION (PJI): A SINGLE CENTER STUDY

Introduction: One of the most challenging and serious complications associated with total joint arthroplasty is prosthetic joint infection (PJI). Advancements in prevention, diagnosis, and treatment of PJI seem promising. Accurate identification of the causal pathogen is a key factor for successful treatment and also for choosing antibiotic treatment. This study was aimed to evaluate the prevalence of PJI and distribution of causative pathogen using microbiological culture and pathological examination. Methods: A retrospective descriptive study was conducted by collecting data from our center registry from 2018 to 2020. The inclusion criteria of this study were patients diagnosed with hip or knee PJI based on the diagnostic criteria for PJI. The exclusion criteria were incomplete microbiology data which were either refusal to participate or loss of contact. The data extracted from medical records are demographic data such as age, sex, and microbiology and pathological examination data. Results: A total of 1359 total hip/ knee arthroplasty surgeries were performed during the years 2018–2020. Among them, 1031 were total knee arthroplasty (TKA) and 321 were total hip arthroplasties (THA). During the same period, a total of 52 patients with PJI were treated at our center. There were 31 knee PJI cases (59.61%) and 21 were hip PJI cases (40.38%). Microbiology culture and pathologic anatomy results showed gram positive Staphylococcus sp bacteria, which was the common causal pathogen of PJI. Negative culture results were found in 10/52 (19.23%) of cases. Conclusions: Staphylococcus sp was the most common causal pathogen of Hip/ Knee PJI in our center. Relatively high rate of culture-negative PJI was observed in this study, further strategies are needed to increase the rate of causal pathogen isolation in hip/ knee PJI cases in our center.