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Prosthetic joint infection (PJI) is a major complication following total arthroplasty. Rising antimicrobial resistance (AMR) to antibiotics will further increase therapeutic insufficiency. New antibacterial technologies are being developed to prevent PJI. In vivo models are still needed to bridge the translational gap to clinical implementation. Though rabbit models have been used most frequently, there is no consensus about methodology and measured outcomes. The PubMed, Scopus, and EMBASE databases were searched for literature on PJI in rabbit models. Data extraction included bias control, experimental design, and outcome measures of the NZW rabbit models in the articles. A total of 60 articles were included in this systematic literature review. The articles were divided into six groups based on the PJI intervention: no intervention used (21%), revision surgery (14%), prevention with only antibiotics (21%), prevention with surface modifications (7%), prevention with coatings (23%), and others (14%). Despite the current availability of guidelines and recommendations regarding experimental design, bias control, and outcome measures, many articles neglect to report on these matters. Ultimately, this analysis aims to assist researchers in determining suitable clinically relevant methodologies and outcome measures for in vivo PJI models using NZW rabbits to test new antimicrobial technologies.

Prosthetic joint infections caused by Campylobacter are uncommon, with the majority of cases being attributed to C. fetus. This case report represents the third instance of a prosthetic hip infection caused by C. coli following an episode of gastroenteritis and, notably, in an immunocompetent patient. The infection was successfully managed by surgical debridement and lavage with retention of the prosthesis and 12 weeks of antibiotics. Furthermore, we present the first whole-genome sequence of a Campylobacter strain responsible for prosthetic joint infection and offer a comprehensive review of the literature on such infections.

Increasing antibiotic resistance has been reported as an issue in the treatment of periprosthetic joint infection (PJI). A repeat two-stage revision for recurrent PJI is at high risk of reinfection. However, it is unclear if the microorganism profile plays a role with potentially more resistant or polymicrobial infections. This is a retrospective, single-center analysis of two-stage revisions performed between 2011 and 2017. We identified 46 patients who underwent a repeat resection arthroplasty for recurrent PJI of the same joint after a previous two-stage revision of the same joint at the same department. All microbiological findings were analyzed focusing on microbiological spectrum and resistance testing as well as the potential impact on reinfection-free survival. The most common organism found at the time of recurrent PJI were coagulase-negative Staphylococci (39%) followed by Gram-negative organisms (28%). The risk of polymicrobial infections, difficult-to-treat resistant organisms, and Gram-negative infections increased significantly. Among staphylococcal infections, there was a high percentage of methicillin-resistant species and resistance to oral antibiotics. Patients with Gram-negative organisms had a reduced infection-free survivorship, while resistant organisms were not associated with decreased survival. Patients who undergo a repeat two-stage revision for recurrent PJI have more polymicrobial and resistant organisms, although the impact on survivorship is unclear.

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus. Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches.

Robinsoniella peoriensis is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, R. peoriensis is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of Robinsoniella, describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by Robinsoniella. The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was R. peoriensis, and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections’ clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective.

Prosthetic joint infection (PJI) is one of the most serious complications of joint replacement surgery among orthopedic surgeries and occurs in 1 to 2% of primary surgeries. Additionally, the cause of PJIs is mostly bacteria from the Staphylococcus species, accounting for more than 98%, while fungi cause PJIs in only 1 to 2% of cases and can be difficult to manage. The current gold-standard microbiological method of culturing synovial fluid is time-consuming and produces false-negative and -positive results. This study aimed to identify a novel, accurate, and convenient molecular diagnostic method. The DreamDX primer–hydrolysis probe set was designed for the pan-bacterial and pan-fungal detection of DNA from pathogens that cause PJIs. The sensitivity and specificity of DreamDX primer–hydrolysis probes were 88.89% (95% CI, 56.50–99.43%) and 97.62% (95% CI, 87.68–99.88%), respectively, compared with the microbiological method of culturing synovial fluid, and receiver operating characteristic (ROC) area under the curve (AUC) was 0.9974 (*** p < 0.0001). It could be concluded that the DreamDX primer–hydrolysis probes have outstanding potential as a molecular diagnostic method for identifying the causative agents of PJIs, and that host inflammatory markers are useful as adjuvants in the diagnosis of PJIs.

Background and Objectives: Despite the promise of phage therapy (PT), its efficacy in prosthetic joint infection (PJI) management is unknown. Much of the current literature is largely limited to case reports and series. Materials and Methods: In order to help inform power calculations for future clinical trials and comparative analyses, we performed a systematic review and proportional meta-analysis of early PT outcomes to provide a preliminary assessment of early phage therapy treatment outcomes for cases of PJI. Results: In a search of available literature across MEDLINE (Ovid, Wolters Kluwer, Alphen aan den Rijn, The Netherlands), Embase (Elsevier, Amsterdam, The Netherlands), the Web of Science Core Collection (Clarivate, London, UK), and Cochrane Central (Wiley, Hoboken, NJ, USA) up to 23 September 2023, we identified 37 patients with PJIs receiving adjunctive PT. Patients most frequently reported Staphylococcal species infection (95%) and intraarticular phage delivery (73%). Phage cocktail (65%) and antibiotic co-administration (97%) were common. A random-effects proportional meta-analysis suggested infection remission in 78% of patients (95% CI: 39%, 95%) (I2 = 55%, p = 0.08) and 83% with a minimum 12-month follow-up (95% CI: 53%, 95%) (I2 = 26%, p = 0.26). Conclusions: Our study provides a preliminary estimate of PT’s efficacy in PJIs and informs future comparative studies.

Purpose: While tuberculosis remains a significant global health concern, prosthetic joint infections (PJIs) caused by members of the Mycobacterium tuberculosis complex are exceptionally rare. Our objective is to perform a retrospective search of new cases of this disease and analyze all cases available in the literature of tuberculous PJIs, aiming to detect factors that may influence patient outcomes. Methods: The ESGIAI and ESGMYC study groups were used to collect information on non-published cases of tuberculous prosthetic joint infections (PJIs). Additionally, a literature review of all published cases of tuberculous PJIs was conducted. All identified cases in the retrospective study and in the literature review were merged and included in the statistical analysis, involving both univariate and multivariate analyses. Results: Fifteen previously unreported cases of tuberculous prosthetic joint infections (PJIs) from four countries were detailed. Among them, ten patients were female, with a median age of 76 years. The hip was affected in 13 cases. Seven patients experienced co-infection with another microorganism. Treatment approaches varied, with 13 patients undergoing implant removal, one treated with DAIR (debridement, antibiotics, and implant retention), and one case was treated with an unknown treatment method. All patients received antibiotic therapy and achieved a cure. The literature review that was conducted detected 155 published cases. Univariate analysis revealed a statistical significance for previous tuberculosis, joint, and no importance of surgery for cure. Conclusions: Tuberculous prosthetic joint infection (PJI) is a rare condition, typically presenting as a localized chronic infection. Antibiotic treatment is essential for the management of these patients, but neither surgical treatment nor duration of treatment seems to have importance in the outcome.

We aimed to evaluate the occurrence of infective endocarditis (IE) among patients with bone and joint infections (BJIs) and Staphylococcus aureus bacteraemia. This observational study was conducted at Lausanne University Hospital, Switzerland, from 2014 to 2023, and included episodes involving BJI, S. aureus bacteraemia, and cardiac imaging studies. The endocarditis team defined IE. Among the 384 included episodes, 289 (75%) involved native BJI (NBJI; 118 septic arthritis, 105 acute vertebral or non-vertebral osteomyelitis, 101 chronic osteitis), and 112 (29%) involved orthopedic implant-associated infection (OIAI; 78 prosthetic joint infection and 35 osteosynthesis/spondylodesis infection). Fifty-one episodes involved two or more types of BJI, with 17 episodes exhibiting both NBJI and OIAI. IE was diagnosed in 102 (27%) episodes. IE prevalence was 31% among patients with NBJI and 13% among patients with OIAI (p < 0.001). The study revealed a high prevalence of IE among S. aureus bacteraemic patients with NBJI, with notably lower prevalence among those with OIAI.

Introduction: Periprosthetic joint infection (PJI) remains a serious complication after total knee arthroplasty (TKA). While debridement, antibiotics, and implant retention (DAIR) are considered for acute PJI, success rates vary. This study aims to assess a new scoring system’s accuracy in predicting DAIR success. Methods: 119 TKA patients (2008–2019) diagnosed with PJI who underwent DAIR were included for analysis. Data were collected on demographics, laboratory values, and clinical outcomes. This was used for validation of the novel classification system consisting of PJI acuteness, microorganism classification, and host health for DAIR indication. Statistical analysis was carried out using SPSS programming. Results: Mean follow-up was 2.5 years with an average age of 65.5 ± 9.1 years, BMI of 31.9 ± 6.2 kg/m2, and CCI of 3.04 ± 1.8. Successful infection eradication occurred in 75.6% of patients. The classification system demonstrated 61.1% sensitivity, 72.4% specificity, and 87.3% positive predictive value (PPV) when the DAIR cutoff was a score less than 6. For a cutoff of less than 8, sensitivity was 100%, specificity was 37.9%, and PPV was 83.3%. Conclusions: To date, no consensus exists on a classification system predicting DAIR success. This novel scoring system, with high PPV, shows promise. Further refinement is essential for enhanced predictive accuracy.

(Background) The diagnosis and the antimicrobial treatment of orthopedic infection are challenging, especially in cases with culture-negative results. New molecular methods, such as next-generation sequencing (NGS), promise to overcome some limitations of the standard culture, such as the detection of difficult-to-grow bacteria. However, data are scarce regarding the impact of molecular techniques in real-life scenarios. (Methods) We included cases of suspected orthopedic infection treated with surgery from May 2021 to September 2023. We combined traditional cultures with NGS. For NGS, we performed a metagenomic analysis of ribosomal 16s, and we queried dedicated taxonomic libraries to identify the species. To avoid false positive results, we set a cut-off of 1000 counts of the percentage of frequency of reads. (Results) We included 49 patients in our study. Our results show the presence of bacteria in 36/49 (73%) and 29/49 (59%) cases studied with NGS and traditional cultures, respectively. The concordance rate was 61%. Among the 19/49 discordant cases, in 11/19 cases, cultures were negative and NGS positive; in 4/19, cultures were positive and NGS negative; and in the remaining 4/19, different species were detected by traditional cultures and NGS. (Conclusions) Difficult-to-grow microorganisms, such as slow-growing anaerobic bacteria, were better detected by NGS compared to traditional culture in our study. However, more data to distinguish between true pathogens and contaminants are needed. NGS can be an additional tool to be used for the diagnosis of orthopedic infections and the choice of appropriate antimicrobial therapy.

Background: Periprosthetic joint infection (PJI) after shoulder arthroplasty remains a significant complication. This study aimed to explore the epidemiology and risk factors of shoulder PJI in patients aged 60 and younger, analyze treatment options, and evaluate outcomes after 1-year follow-up. Methods: In this retrospective multicentric observational study, data from 1404 shoulders in patients under 60 who underwent primary shoulder arthroplasty were analyzed. Patients with PJI and at least 1-year follow-up after infection treatment were included. Results: The study identified 55 shoulders with PJI, resulting in a 2.35% infection rate after primary shoulder arthroplasty in the young population. Male gender and reverse shoulder arthroplasty were risk factors for infection, while previous surgeries did not significantly contribute. The most common causative agents were Cutibacterium acnes and Staphylococcus epidermidis. Open washout had a 52.9% success rate for acute infections, while one-stage and two-stage revisions achieved infection control rates of 91.3% and 85.7%, respectively. Resection arthroplasty had an 81.8% success rate but poorer functional outcomes. Conclusions: PJI following shoulder arthroplasty in young patients is a significant concern. Preoperative planning should be carefully considered to minimize infection risk. Treatment options such as open washout and one-stage and two-stage revisions offer effective infection control and improved functional outcomes. Resection arthroplasty should be reserved for complex cases where reimplantation is not a viable option.

Background : The microbiological profile of bone and joint infections is important for determining the empiric choice of both systemic and local antimicrobial therapy. This study assessed whether there was a difference in the bacterial species that were isolated on culture in osteomyelitis (OM), fracture-related infection (FRI) or prosthetic joint infection (PJI). This was a retrospective, observational cohort study of patients who had surgical intervention for PJI or OM or FRI with a positive microbial culture between 2019 and 2022. Methods : Data including patient demographics, the site of injury, JS-BACH score, organism classification and antibiotic resistance to vancomycin and gentamicin were extracted from the medical records. Results : A total of 440 patients were included in this study: 163 patients with osteomyelitis, 109 with fracture-related infection with fixation implants and 168 with prosthetic joint infection. The patients with PJI were older, more likely to be female and had a higher BMI and ASA score compared to those with OM. Patients with PJI were more likely to have a higher JS-BACH score and more complex infections. Staphylococcus aureus was the most commonly isolated organism in all three groups. It was more frequently isolated in osteomyelitis than in PJI ( p = 0.016). In both osteomyelitis and FRI, after Staphylococcus aureus, the next most common organisms were Gram-negatives, whilst for PJIs, the most commonly isolated organisms were Staphylococcus aureus , followed by coagulase-negative Staphylococci and then Streptococcus species. The rates of other organisms were broadly similar between the three groups. When adjusted for confounders, including symptom duration, JS-BACH score, the location of injury, age and BMI, there was no statistically significant difference in the presence of Staphylococcus aureus (OR = 0.765; 95% CI 0.633-1.232; p = 0.465) or polymicrobial infection (OR = 1.175; 95% CI 0.803-1.721; p = 0.407). Conclusions : Causative pathogens are similar across bone and joint infections and are independent of the presence of prosthetic material.

Replacement of native joints aims to restore patients’ quality of life by relieving pain and improving joint function. While periprosthetic joint infection (PJI) affects a small percentage of patients, with an estimated incidence of 1–9% following primary total joint replacement, this postoperative complication necessitates a lengthy hospitalisation, extended antibiotic treatment and further surgery. It is highlighted that establishing the correct diagnosis of periprosthetic infections is critical in order for clinicians to avoid unnecessary treatments in patients with aseptic failure. Of note, the PJI diagnosis could not purely rely upon clinical manifestations given the fact that heterogeneity in host factors (e.g., age and comorbidities), variability in infection period, difference in anatomical location of the involved joint and discrepancies in pathogenicity/virulence of the causative organisms may confound the clinical picture. Furthermore, intra-operative contamination is considered to be the main culprit that can result in early or delayed infection, with the hematogenous spread being the most prevalent mode. To elaborate, early and hematogenous infections often start suddenly, whereas chronic late infections are induced by less virulent bacteria and tend to manifest in a more quiescent manner. Last but not least, viruses and fungal microorganisms exert a role in PJI pathogenesis.

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

Background: Increasing antibiotic resistance has been reported as an issue in the systemic treatment of periprosthetic joint infection (PJI). Linezolid offers the advantages of high oral bioavailability and little resistance; however, efficacy in the treatment of PJI varies considerably, and studies reporting consistent surgical treatment are scarce. Methods: This is a retrospective, single-center analysis of two-stage revisions performed between 2008 and 2017. We identified 111 patients who met the inclusion criteria. Oral linezolid was given for 28 days following 14 days of intravenous tailored antibiotics in resistant gram-positive PJI. A total of 64% of the patients had methicillin-resistant coagulase-negative staphylococci. The median follow-up was 43 (interquartile range (IQR) 30–57) months. Results: 22% (24/111) of the patients underwent surgery for subsequent infection. The 5-year infection-free survival probability was 77% (95% confidence interval (CI) 69–85). A total of 5% of the patients (6/111) had the same organism at the time of reinfection. The patients with infections caused by other organisms than Coagulase-negative staphylococci tended to have a worse reinfection-free survivorship at five years (70% vs. 81%, p = 0.09). Furthermore, the patients with obesity tended to have reduced reinfection-free survivorship at five years (69% vs. 84%, p = 0.08). Overall, 5% (6/111) of the patients had blood count abnormalities with no treatment discontinuations. Conclusion: Two-stage revision arthroplasty with systemic oral linezolid treatment for resistant gram-positive PJI results in an infection control of 77% at the mid-term.

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton–Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of “Casa di Cura Santa Maria Maddalena”, from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA–PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31–7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22–4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

Infection of prosthetic joints is one of the biggest challenges to a successful replacement of the joint after a total joint arthroplasty. Such infections are caused by bacterial colonies that are difficult to treat by systemic delivery of antibiotics. Local delivery of antibiotics can prove to be the solution to such a devastating outcome that impacts patients’ health and ability to regain function in their joints as well as costs the healthcare system millions of dollars every year. This review will discuss prosthetic joint infections in detail with a focus on the development, management, and diagnosis of the infections. Surgeons often opt to use polymethacrylate cement locally to deliver antibiotics; however, due to the rapid release of antibiotics, non-biodegradability, and high chance of reinfection, the search for alternatives is in high demand. One of the most researched alternatives to current treatments is the use of biodegradable and highly compatible bioactive glass. The novelty of this review lies in its focus on mesoporous bioactive glass as a potential alternative to current treatments for prosthetic joint infection. Mesoporous bioactive glass is the focus of this review because it has a higher capacity to deliver biomolecules, stimulate bone growth, and treat infections after prosthetic joint replacement surgeries. The review also examines different synthesis methods, compositions, and properties of mesoporous bioactive glass, highlighting its potential as a biomaterial for the treatment of joint infections.

We report microbiological results from a cohort of recurrent bone and joint infection to define the contributions of microbial persistence or replacement. We also investigated for any association between local antibiotic treatment and emerging antimicrobial resistance. Microbiological cultures and antibiotic treatments were reviewed for 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection, and osteomyelitis) at two UK centres between 2007 and 2021. At re-operation, 48/125 (38.4%) individuals had an organism from the same bacterial species as at their initial operation for infection. In 49/125 (39.2%), only new species were isolated in culture. In 28/125 (22.4%), re-operative cultures were negative. The most commonly persistent species were Staphylococcus aureus (46.3%), coagulase-negative Staphylococci (50.0%), and Pseudomonas aeruginosa (50.0%). Gentamicin non-susceptible organisms were common, identified at index procedure in 51/125 (40.8%) and at re-operation in 40/125 (32%). Gentamicin non-susceptibility at re-operation was not associated with previous local aminoglycoside treatment (21/71 (29.8%) vs. 19/54 (35.2%); p = 0.6). Emergence of new aminoglycoside resistance at recurrence was uncommon and did not differ significantly between those with and without local aminoglycoside treatment (3/71 (4.2%) vs. 4/54 (7.4%); p = 0.7). Culture-based diagnostics identified microbial persistence and replacement at similar rates in patients who re-presented with infection. Treatment for orthopaedic infection with local antibiotics was not associated with the emergence of specific antimicrobial resistance.

Prosthetic Joint Infection (PJI) causes significant morbidity and mortality for patients globally. Delivery of antibiotics to the site of infection has potential to improve the treatment outcomes and enhance biofilm eradication. These antibiotics can be delivered using an intra-articular catheter or combined with a carrier substance to enhance pharmacokinetic properties. Carrier options include non-resorbable polymethylmethacrylate (PMMA) bone cement and resorbable calcium sulphate, hydroxyapatite, bioactive glass, and hydrogels. PMMA allows for creation of structural spacers used in multi-stage revision procedures, however it requires subsequent removal and antibiotic compatibility and the levels delivered are variable. Calcium sulphate is the most researched resorbable carrier in PJI, but is associated with wound leakage and hypercalcaemia, and clinical evidence for its effectiveness remains at the early stage. Hydrogels provide a versatile combability with antibiotics and adjustable elution profiles, but clinical usage is currently limited. Novel anti-biofilm therapies include bacteriophages which have been used successfully in small case series.

An accurate and fast microbiological diagnosis is key for a proper management and results when facing prosthetic joint infection (PJI). The purpose of this study is to assess the role of direct Matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS) for early identification of the pathogens causing PJI from sonication fluid inoculated in blood culture bottles (BCB-SF). This prospective multicentric study included 107 consecutive patients from February 2016 to February 2017. Among them, 71 prosthetic joint revision surgeries were undergone for aseptic and 36 for septic reasons. Prostheses were sonicated and the resulting fluid inoculated into blood culture bottles, regardless the suspicion for infection. We assessed the diagnostic performance of direct MALDI-TOF MS identification of the pathogens in BCB-SF and compared it with periprosthetic tissue and conventional sonication fluid cultures. The sensitivity of direct MALDI-TOF MS of BCB-SF (69%) was higher compared to conventional sonication fluid (69% vs. 64%, p > 0.05) or intraoperative tissue cultures (69% vs. 53%, p = 0.04), especially for patients receiving antimicrobial treatment. This approach also reduced the time for identification but the specificity was compromised (100% vs. 94%) and polymicrobial infections were missed. In conclusion, BCB-SF improves the sensitivity and reduces the time of PJI diagnosis when used in combination with conventional cultures under strict sterility conditions.

Arthroplasty surgery is a common procedure that significantly improves quality of life. The most feared complication is prosthetic joint infection (PJI), which occurs more often following revision surgery. Staphylococci are the most prevalent bacteria in PJIs, although many other pathogens have been reported. We describe a case of PJI in a 75-year-old farmer following revision surgery caused by Corynebacterium striatum, an unusual agent which normally occurs in the normal human skin microbiota with perceived low pathogenicity. Following a cemented right-sided total hip arthroplasty in 2006, a one-stage revision due to an osteolytic process in the right femur took place in 2020 with negative intraoperative tissue cultures. Three weeks later, the patient presented a fulminant infection which was treated with debridement, antibiotics, and implant retention (DAIR). Tissue biopsies showed C. striatum in 6/6 samples including small colony variants. Genome sequencing showed that all isolates differed by ≤6 SNPs with the same gene content related to resistance (tet(W) and erm(X)). The patient was sequentially treated with vancomycin, linezolid, and daptomycin, but due to side effects, treatment was changed to 12 weeks of dalbavancin as a 1000 mg loading dose followed by 500 mg intravenously/week. Impaired renal function during vancomycin treatment was normalized, and >1 year after finishing antibiotic treatment the outcome was still favourable. In conclusion, a case of a fulminant early post-interventional PJI due to C. striatum was successfully treated with DAIR and long-term dalbavancin therapy without any adverse reactions.

The analysis of synovial fluid is a crucial step in the diagnosis of prosthetic joint infections (PJIs). Recently several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI. In this study, synovial calprotectin was analyzed by a commercial stool test to explore whether it might accurately predict PJIs. The synovial fluids of 55 patients were analyzed and calprotectin levels were compared to other synovial biomarkers of PJI. Of the 55 synovial flu-ids, 12 patients were diagnosed with PJI and 43 with an aseptic failure of the implant. Specificity, sensitivity, and AUC of calprotectin resulted in 0.944, 0.80, and 0.852 (95%CI: 0.971–1.00), respectively, with a set threshold of 529.5 µg/g. Calprotectin had a statistically relevant correlation with the synovial leucocyte counts (rs = 0.69, p < 0.001) and the percentage of synovial neutrophils (rs = 0.61, p < 0.001). From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicators of local infection, and the use of a commercial lateral flow stool test could be a cost-effective strategy delivering rapid and reliable results and supporting the diagnostic process of PJI.

Prosthetic joint infection (PJI) is a major complication following total arthroplasty. Rising antimicrobial resistance (AMR) to antibiotics will further increase therapeutic insufficiency. New antibacterial technologies are being developed to prevent PJI. In vivo models are still needed to bridge the translational gap to clinical implementation. Though rabbit models have been used most frequently, there is no consensus about methodology and measured outcomes. The PubMed, Scopus, and EMBASE databases were searched for literature on PJI in rabbit models. Data extraction included bias control, experimental design, and outcome measures of the NZW rabbit models in the articles. A total of 60 articles were included in this systematic literature review. The articles were divided into six groups based on the PJI intervention: no intervention used (21%), revision surgery (14%), prevention with only antibiotics (21%), prevention with surface modifications (7%), prevention with coatings (23%), and others (14%). Despite the current availability of guidelines and recommendations regarding experimental design, bias control, and outcome measures, many articles neglect to report on these matters. Ultimately, this analysis aims to assist researchers in determining suitable clinically relevant methodologies and outcome measures for in vivo PJI models using NZW rabbits to test new antimicrobial technologies.

Prosthetic joint infections caused by Campylobacter are uncommon, with the majority of cases being attributed to C. fetus . This case report represents the third instance of a prosthetic hip infection caused by C. coli following an episode of gastroenteritis and, notably, in an immunocompetent patient. The infection was successfully managed by surgical debridement and lavage with retention of the prosthesis and 12 weeks of antibiotics. Furthermore, we present the first whole-genome sequence of a Campylobacter strain responsible for prosthetic joint infection and offer a comprehensive review of the literature on such infections.

Increasing antibiotic resistance has been reported as an issue in the treatment of periprosthetic joint infection (PJI). A repeat two-stage revision for recurrent PJI is at high risk of reinfection. However, it is unclear if the microorganism profile plays a role with potentially more resistant or polymicrobial infections. This is a retrospective, single-center analysis of two-stage revisions performed between 2011 and 2017. We identified 46 patients who underwent a repeat resection arthroplasty for recurrent PJI of the same joint after a previous two-stage revision of the same joint at the same department. All microbiological findings were analyzed focusing on microbiological spectrum and resistance testing as well as the potential impact on reinfection-free survival. The most common organism found at the time of recurrent PJI were coagulase-negative Staphylococci (39%) followed by Gram-negative organisms (28%). The risk of polymicrobial infections, difficult-to-treat resistant organisms, and Gram-negative infections increased significantly. Among staphylococcal infections, there was a high percentage of methicillin-resistant species and resistance to oral antibiotics. Patients with Gram-negative organisms had a reduced infection-free survivorship, while resistant organisms were not associated with decreased survival. Patients who undergo a repeat two-stage revision for recurrent PJI have more polymicrobial and resistant organisms, although the impact on survivorship is unclear.

No consensus has been reached on the optimal antibiotic regimen to treat Cutibacterium acnes PJIs (Ca-PJIs). In vitro studies showed excellent rifampicin efficacy against biofilm-associated C. acnes infections, but clinical studies did not confirm the superiority of rifampicin-combined therapy over monotherapy. This prospective cohort study was undertaken to analyze the outcomes of 70 patients who underwent exchange arthroplasty for chronic monomicrobial Ca-PJI and were treated with rifampicin or without between 2004 and 2019. The 37 patients treated from January 2004 to August 2014 were prescribed rifampicin-combination therapy and the 33 treated from September 2014 to December 2019 received monotherapy without rifampicin. The primary endpoint was the 2-year Kaplan–Meier-estimated reinfection-free probability, including relapses and new-pathogen PJIs. The 2-year reinfection-free rate was high and not different for patients who had received rifampicin or not (89.2% vs. 93.8%, respectively; p = 0.524). None of the patients relapsed and six developed new-pathogen PJIs. Our results do not support a benefit of rifampicin-combination therapy for patients who underwent exchange arthroplasty for chronic Ca-PJIs.

Fungal prosthetic joint infection (fPJI) is a rare complication; nonetheless, it represents a significant diagnostic and therapeutic challenge. There are no official guidelines on the most effective approach to identify and treat fPJIs. This systematic review aims to review the current literature on fPJI management and provide a comprehensive overview of this topic, especially from an epidemiologic point of view. Studies eligible for this systematic review were identified through an electronic systematic search of PubMed, Scopus, and Web of Science until 30 September 2022. Further references were obtained by cross-referencing. Sixty-three studies met the inclusion criteria, reporting on 372 cases of fPJI; such cases were described mostly in case reports and small case series with only a few larger cohort studies. Diagnosis of fPJI is challenging because of its chronic and indolent clinical course; it is further complicated by the technical difficulty of harvesting fungal cultures. A two-stage revision was the primary procedure in 239 (64.2%) patients whereas DAIR and one-stage approaches were reported in 30 (8.0%) and 18 (4.8 %) cases. In conclusion, our study highlights the heterogeneity of the reported treatments of fPJI, particularly in terms of medical management. With concern to a surgical approach, a two-stage revision arthroplasty is generally suggested, considering fPJI a delayed or late infection. The need for multicenter, prospective studies to provide standardized protocols and improve the treatment of fungal PJI clearly emerges.

Debridement, antibiotics and implant retention (DAIR) remains a commonly utilized technique in the treatment of acute prosthetic joint infections despite its inconsistent outcomes. The performance of a second DAIR after a failed first debridement is controversial as outcomes are uncertain and the final prognosis in the event of failure may be unfavorable. This study analyzes 84 cases of acute prosthetic (hip & knee) joint infection treated with DAIR between 2011 and 2020 at the same institution. In 12 failed cases, a second DAIR was performed, whose success rate was significantly lower than that of the first procedure (8% [95% CI, 0–38] vs. 57% [46–68]). Moreover, the ultimate outcome of the second failed DAIRs was unfavorable with eradication of the infection being achieved in none of the patients. Due to the high likelihood of failure and the potentially grim final prognosis following a second debridement, removal of the components should be considered.

Prosthetic joint infection (PJI) presents several clinical challenges. This is in large part due to the formation of biofilm which can make infection eradication exceedingly difficult. Following an extensive literature search, this review surveys a variety of non-pharmacological methods of preventing and/or treating biofilm within the body and how they could be utilized in the treatment of PJI. Special attention has been paid to physical strategies such as heat, light, sound, and electromagnetic energy, and their uses in biofilm treatment. Though these methods are still under study, they offer a potential means to reduce the morbidity and financial burden related to multiple stage revisions and prolonged systemic antibiotic courses that make up the current gold standard in PJI treatment. Given that these options are still in the early stages of development and offer their own strengths and weaknesses, this review offers an assessment of each method, the progress made on each, and allows for comparison of methods with discussion of future challenges to their implementation in a clinical setting.

Prosthetic joint infections (PJIs) caused by fungi, although relatively rare, represent a major surgery-related complication. An extremely rare fungal PJI, following revised total knee replacement (TKR) caused by Candida lusitaniae, is reported, and a meticulous review of similar cases is provided. A 74-year-old female, who underwent primary total knee arthroplasty 10 years ago and a revision surgery three weeks ago, presented with signs and symptoms of PJI. C. lusitaniae was eventually isolated from the periprosthetic tissue using the MALDI-TOF VitekMS–bioMérieux technique. Multiple strategies for managing this fungal PJI were performed, and finally, the patient was treated successfully with an intramedullary arthrodesis system and proper antifungal treatment, including fluconazole. A multidisciplinary approach is essential for the diagnosis and treatment of such severe infections. In persistent cases and in cases where revision surgery is extremely difficult to perform, arthrodesis seems to be an effective solution for the elimination of the infection. The efficacy of the therapeutic management of fungal PJIs remains unclear. Therefore, more research should be reported, focusing on proper treatment so that the optimal strategy in treating these severe infections may be established.

Background: Staphylococcus aureus is the main cause of haematogenous prosthetic joint infections (PJI). We aimed to describe the prevalence and factors associated with PJI in patients with documented S. aureus bacteraemia. Methods: Adult patients with S. aureus bacteraemia and presence of prosthetic joint hospitalized in Lausanne University Hospital during a seven-year period (2015–2021) were included. Results: Among 135 patients with S. aureus bacteraemia and prosthetic joints, 38 (28%) had PJI. Multivariate analysis revealed that the presence of PJI was associated with knee arthroplasty (P 0.029; aOR 3.00, 95% CI 1.12–8.05), prior arthroplasty revision (P 0.034; aOR 3.59, 95% CI 1.10–11.74), community-acquired bacteraemia (P 0.005; aOR 4.74, 95% CI 1.61–14.01) and age < 70 years (P 0.007; aOR 9.39, 95% CI 1.84–47.85). Conclusions: PJI was common among patients with documented S. aureus bacteraemia. PJI was associated with characteristics of the prosthesis, such as prior arthroplasty revisions and knee prosthesis.

Aims: This study aimed to characterize 79 Cutibacterium acnes strains isolated from prosthetic joint infections (PJIs) originated from eight European hospitals. Methods: Isolates were phylotyped according to the single-locus sequence typing (SLST) scheme. We evaluated the ability of the biofilm formation of C. acnes strains isolated from PJIs and 84 isolates recovered from healthy skin. Antibiotic susceptibility testing of planktonic and biofilm cells of PJI isolates and skin isolates was performed. Results: Most of the isolates from PJIs belonged to the SLST class H/phylotype IB (34.2%), followed by class D/phylotype IA1 (21.5%), class A/phylotype IA1 (18.9%), and class K/phylotype II (13.9%). All tested isolates were biofilm producers; no difference in biofilm formation was observed between the healthy skin group and the PJI group of strains. Planktonic and sessile cells of C. acnes remained highly susceptible to a broad spectrum of antibiotics, including beta-lactams, clindamycin, fluoroquinolones, linezolid, rifampin, and vancomycin. The minimal inhibitory concentrations (MICs) for planktonic and biofilm states coincided in most cases. However, the minimal biofilm eradication concentration (MBEC) was high for all antimicrobial drugs tested (>32 mg/L), except for rifampin (2 mg/L). Conclusions: C. acnes strains isolated from healthy skin were able to produce biofilm to the same extent as isolates recovered from PJIs. All C. acnes strains in planktonic and sessile states were susceptible to most antibiotics commonly used for PJI treatment, although rifampin was the only antimicrobial agent able to eradicate C. acnes embedded in biofilm.

Given the variable success of the debridement, antibiotics and implant retention (DAIR) procedure in patients with acute prosthetic joint infection (PJI), an accurate selection of candidates is critical. In this study, we set about calculating the predictive value of a novel algorithm for predicting outcome following DAIR developed by Shohat et al. Sixty-four patients who underwent debridement for (early and late) acute PJI in a tertiary-level university hospital were selected, and the aforementioned algorithm was retrospectively applied. Patients with model scores of 40–50%, 50–60%, 60–70%, 70–80% and 80–90% displayed success rates of 33.34%, 41.18%, 57.9%, 78.27% and 100%, respectively. The receiver operating characteristic curve showed an area under the curve of 0.69. The calibration intercept value was 0, and the calibration slope value was 1. Failure rates were significantly higher for the following variables: revision surgery (p = 0.012) index surgery for reasons other than osteoarthritis (p = 0.01), and C-reactive protein level >30 mg/L (p = 0.042). This analysis demonstrated that the Shohat algorithm is associated with an optimal calibration value and a moderate predictive value for failure of a DAIR procedure in patients with acute PJI. Its validation is recommended before it can be routinely applied in daily practice.

The incidence of total joint arthroplasty is increasing over time since the last decade and expected to be more than 4 million by 2030. As a consequence, the detection of infections associated with surgical interventions is increasing and prosthetic joint infections are representing both a clinically and economically challenging problem. Many pathogens, from bacteria to fungi, elicit the immune system response and produce a polymeric matrix, the biofilm, that serves as their protection. In the last years, the implementation of diagnostic methodologies reduced the error rate and the turn-around time: polymerase chain reaction, targeted or broad-spectrum, and next-generation sequencing have been introduced and they represent a robust approach nowadays that frees laboratories from the unique approach based on culture-based techniques.

Gemella morbillorum is a facultative anaerobic, catalase-negative and non-spore forming Gram-positive cocci. It can be found as part of the normal oropharyngeal flora, in the gastrointestinal tract and the female genital tract. However, it can be a causal agent of infections such as endocarditis, meningitis or brain abscesses, and very rarely can cause osteoarticular infections. Herein, a case report of an acute hematogenous prosthetic hip infection caused by Gemella morbillorum, successfully treated with a DAIR and beta-lactam antibiotic therapy, is presented. We provide a literature review of the other orthopedic-related infections caused by this microorganism.

One of the most commonly used treatments for acute prosthetic joint infection (PJI) is DAIR (debridement, antibiotics and implant retention), which comprises the debridement and the retention of the implant, followed by antibiotic treatment. The efficacy of DAIR remains unclear, as the literature has demonstrated variable success rates, ranging from 26% to 92%. The Staphylococcus aureus is one of the most closely related causative microorganisms, especially with acute and late-acute PJI; it has been identified as one of the most significant predictors of DAIR failure. The current guidelines consider the use of vancomycin as the therapy of choice, but it requires the close control of possible side effects. The aim of this study is to determine if a new combination of antibiotics (a highly bactericidal initial combination followed by an antibiofilm scheme) decreases the failure of DAIR-treated acute prosthetic joint infection (PJI) caused by Staphylococcus aureus. A retrospective analysis of cases of orthopedic infections during a nine-year period (2011–2019) was performed. A total of 45 acute PJI cases caused by S. aureus were diagnosed. The results of two antibiotic schemes were compared: a novel scheme comprising 5 days of daptomycin (10 mg/kg/24 h) + cloxacillin (2 g/6 h) followed by levofloxacin (500 mg/24 h) + rifampicin (600 mg/24 h), versus a traditional, less bactericidal scheme of vancomycin (1000 mg/12 h) plus rifampicin (600 mg/24 h) or levofloxacin (500 mg/24 h) plus rifampicin (600 mg/24 h). Twenty-two out of the twenty-four patients treated with the new scheme (91.6%) were free of infection after 24.8 months of mean follow-up, whereas fourteen out of twenty-one patients (66.6%) were free of infection after 46.6 months of follow-up. This difference was statistically significant (p = 0.036). Demographic comparisons demonstrated homogeneous features, except the Charlson score, which was higher in the novel scheme group (p = 0.047). The combination of high-dose daptomycin and cloxacillin, followed by levofloxacin plus rifampicin, together with surgical treatment, shows better results when compared with other antibiotic schemes for treating acute PJI caused by S. aureus in which DAIR was performed.

Prosthetic joint infections (PJIs) occurring in multiple joints at the same time (synchronous PJI) are an extremely rare complication, frequently associated with bacteremia, and are associated with high mortality rates. The presence of three or more prosthetic joints, rheumatoid arthritis, neoplasia, bacteremia and immune-modulating therapy seem to be the recurring risk factors for synchronous PJI. In case of PJIs, all other replaced joints should be considered as potentially infected and investigated if PJI is suspected. Treatments of synchronous multiple PJIs vary and must be decided on a case-by-case basis. However, the advantages of one-stage exchange seem to outweigh the two-stage protocol, as it decreases the number of necessary surgical procedures. Nonetheless, too few studies have been conducted to allow firm conclusions about the best handling of synchronous PJI. Thus, additional studies are needed to understand this devastating complication and to design the most appropriate diagnostic and therapeutic path.

Prosthetic joint infections are a devastating complication of joint replacement surgery. Consequently, novel therapeutics are needed to thwart the significant morbidity and enormous financial ramifications that are associated with conventional treatments. One such promising adjuvant therapeutic is bacteriophage therapy given its antibiofilm activity and its ability to self-replicate. Herein we discuss the case of a 70-year-old female who had a recalcitrant MRSA prosthetic knee and femoral lateral plate infection who was successfully treated with adjuvant bacteriophage therapy. Moreover, this case discusses the importance of propagating bacteriophage therapeutics on bacteria that are devoid of toxins and the need to ensure bacteriophage activity to all bacterial morphologies. Overall, this case reinforces the potential benefit of using personalized bacteriophage therapy for recalcitrant prosthetic joint infections, but more translational research is needed to thereby devise effective, reproducible clinical trials.

Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes) is the major causative agent of prosthetic joint infections (PJI). Treatment of PJI with antibiotics is difficult due to antibiotic resistance and adverse side effects on patients’ health. Proper disinfection of the surgical site using a variety of povidone iodine formulations could prevent C. acnes infection. In the current study, the efficacy of the three povidone iodine (PVP-I) formulations, viz: PVP-I 10% dermic solution, PVP-I 5% alcoholic solution and PVP-I 4% scrub, was tested against C. acnes, in vitro, in the presence of interfering substances mimicking soiling conditions. C. acnes strain ATCC 6919 was used to test the bactericidal activity of the povidone iodine formulations according to the modified dilution-neutralization method described in French Norm EN standard 13727. A 3-log reduction in the bacterial cell count in 60 s was considered to be significant. The results showed that under experimental conditions, the three PVP-I formulations displayed bactericidal activity against the micro-organism, Cutibacterium acnes, and that the lowest concentration of povidone-iodine active against C. acnes was 0.4%. These results are encouraging as PVP-I offers a low-cost and efficient method of disinfection.

Inflammatory arthritis affects the level of synovial inflammatory factors, which makes it more difficult to diagnose prosthetic joint infection (PJI) patients with inflammatory arthritis. The aim of this study was to analyze synovial interleukin levels to distinguish between PJI and active rheumatoid arthritis (RA) after a hip or knee arthroplasty. From September 2019 to September 2021, we prospectively enrolled patients with joint pain after arthroplasty due to aseptic prosthesis loosening (n = 39), acute RA (n = 26), and PJI (n = 37). Synovial fluid from the affected joint is obtained and tested with a standard enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was analyzed for each biomarker. Interleukin (IL)-1β, IL-6, and IL-8 showed promising value in differentiating of aseptic loosening from PJI, with areas under the curves (AUCs) of 0.9590, 0.9506, and 0.9616, respectively. Synovial IL-1β, IL-6, and IL-8 showed limited value in distinguishing between PJI and acute episodes of RA after arthroplasty, with AUCs of 0.7507, 0.7069, and 0.7034, respectively. Interleukins showed satisfactory efficacy in differentiating aseptic loosening from PJI. However, when pain after arthroplasty results from an acute episode of RA, current synovial interleukin levels do not accurately rule out the presence of PJI.

Background: Periprosthetic joint infections (PJI) are among the most morbid complications in total hip arthroplasty (THA). The ideal incubation time, however, for intraoperative cultures for PJI diagnosis remains unclear. As such, the aim of this study was to determine if any differences existed in culture-positive rates and organism detection between five-day and fourteen-day cultures. Methods: This retrospective cohort study consisted of THA cases diagnosed with PJI performed between May 2014 and May 2020 at a single tertiary-care institution. Analyses compared five-day and fourteen-day cultures and carried out a pre-specified subgroup analysis by organism and PJI type. Results: A total of 147 surgeries were performed in 101 patients (57.1% females), of which 65% (n = 98) obtained five-day cultures and 34% (n = 49) obtained fourteen-day cultures. The positive culture rate was 67.3% (n = 99) with Staphylococcus aureus being the most common pathogen identified (n = 41 specimens, 41.4%). The positive culture rate was not significantly different between groups (66.3% five-day, 69.4% fourteen-day, p = 0.852). Fourteen-day cultures had a significantly longer time-to-positive culture (5.0 days) than five-day cultures (3.0 days, p < 0.001), a higher rate of fungi (5.6% vs. 0%), and a lower rate of Gram-negatives (4.5% vs. 18.7%, p = 0.016). Conclusions: Fourteen-day cultures did not increase the positivity rate, had higher rates of slow-growth pathogens, and had a longer time-to-positivization than five-day cultures. Prolonged culture holds may provide more thorough organism detection for PJI without increasing the diagnostic culture yield.

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus . Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches.

Robinsoniella peoriensis is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, R. peoriensis is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of Robinsoniella , describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by Robinsoniella . The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was R. peoriensis , and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections' clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective.

Prosthetic joint infection (PJI) is one of the most serious complications of joint replacement surgery among orthopedic surgeries and occurs in 1 to 2% of primary surgeries. Additionally, the cause of PJIs is mostly bacteria from the Staphylococcus species, accounting for more than 98%, while fungi cause PJIs in only 1 to 2% of cases and can be difficult to manage. The current gold-standard microbiological method of culturing synovial fluid is time-consuming and produces false-negative and -positive results. This study aimed to identify a novel, accurate, and convenient molecular diagnostic method. The DreamDX primer-hydrolysis probe set was designed for the pan-bacterial and pan-fungal detection of DNA from pathogens that cause PJIs. The sensitivity and specificity of DreamDX primer-hydrolysis probes were 88.89% (95% CI, 56.50-99.43%) and 97.62% (95% CI, 87.68-99.88%), respectively, compared with the microbiological method of culturing synovial fluid, and receiver operating characteristic (ROC) area under the curve (AUC) was 0.9974 (*** p < 0.0001). It could be concluded that the DreamDX primer-hydrolysis probes have outstanding potential as a molecular diagnostic method for identifying the causative agents of PJIs, and that host inflammatory markers are useful as adjuvants in the diagnosis of PJIs.

As the population ages, more and more patients with orthopaedic prostheses (OPs) require dental implant treatment. Surveys of dentists and orthopaedic surgeons show that prophylactic antibiotics (PAs) are routinely prescribed with a very high frequency in patients with OPs who are about to undergo dental procedures. The present study aims to determine the need to prescribe prophylactic antibiotic therapy in patients with OPs treated with dental implants to promote their responsible use and reduce the risk of antimicrobial resistance. An electronic search of the MEDLINE database (via PubMed), Web of Science, LILACS, Google Scholar, and OpenGrey was carried out. The criteria used were those described by the PRISMA® Statement. No study investigated the need to prescribe PAs in patients with OPs, so four studies were included on the risk of infections of OPs after dental treatments with varying degrees of invasiveness. There is no evidence to suggest a relationship between dental implant surgeries and an increased risk of OP infection; therefore, PAs in these patients are not justified. However, the recommended doses of PAs in dental implant procedures in healthy patients are the same as those recommended to avoid infections of OPs.

Gram-negative bacilli can be responsible for prosthetic joint infection (PJI) even if staphylococci are the main involved pathogens. Gram-negative PJIs (GN-PJI) are considered difficult-to-treat infections due to the increase in antimicrobial resistance and biofilm formation. To minimize the risk of infection in cases of arthroplasties with cemented prosthesis, bone cement can be loaded with antibiotics, especially gentamicin. In this study, we aimed to compare the prophylactic antibiofilm activity of ready-to-use antibiotic-loaded bone cements (ALBC), already commercialized or new prototypes. We compared ALBCs containing gentamicin alone, gentamicin plus vancomycin, gentamicin plus clindamycin, gentamicin plus Fosfomycin, and fosfomycin alone, to plain cement (no antibiotic); these comparisons were conducted to investigate the biofilm formation of three strains of Escherichia coli, three strains of Pseudomonas aeruginosa and two strains of Klebsiella pneumoniae, with or without specific resistance to gentamicin or fosfomycin. We reported that ALBC containing gentamicin and clindamycin (COPAL G+C) seems to be the most interesting ALBC of our tested panel for the prevention of biofilm formation by gentamicin-susceptible strains, even if clindamycin is not effective against Gram-negative bacteria. However, gentamicin-resistant strains are still a problem, and further studies are needed to identify an antibiotic to associate with gentamicin for an efficient dual ALBC against Gram-negative bacteria.

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being “GMP-like”) targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally “phage therapy 2.0” has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial–academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

Prosthetic joint infection (PJI) is the second most common cause of arthroplasty failure. Though infrequent, it is one of the most devastating complications since it is associated with great personal cost for the patient and a high economic burden for health systems. Due to the high number of patients that will eventually receive a prosthesis, PJI incidence is increasing exponentially. As these infections are provoked by microorganisms, mainly bacteria, and as such can develop a biofilm, which is in turn resistant to both antibiotics and the immune system, prevention is the ideal approach. However, conventional preventative strategies seem to have reached their limit. Novel prevention strategies fall within two broad categories: (1) antibiotic- and (2) heavy metal-based surface modifications of titanium alloy prostheses. This review examines research on the most relevant titanium alloy surface modifications that use antibiotics to locally prevent primary PJI.