Aims. This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). Methods. A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. Results. The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Conclusion. Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics. Cite this article: Bone Joint Res 2024;13(9):441–451

The August 2024 Foot & Ankle Roundup³⁶⁰ looks at: ESWT versus surgery for fifth metatarsal stress fractures; Minimally invasive surgery versus open fusion for hallux rigidus; Diabetes and infection risk in total ankle arthroplasty; Is proximal medial gastrocnemius recession useful for managing chronic plantar fasciitis?; Fuse the great toe in the young!; Conservative surgery for diabetic foot osteomyelitis; Mental health and outcome following foot and ankle surgery.

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Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

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This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

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To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).

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Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

The June 2024 Trauma Roundup³⁶⁰ looks at: Skin antisepsis before surgical fixation of limb fractures; Comparative analysis of intramedullary nail versus plate fixation for fibula fracture in supination external rotation type IV ankle injury; Early weightbearing versus late weightbearing after intramedullary nailing for distal femoral fracture (AO/OTA 33) in elderly patients: a multicentre propensity-matched study; Long-term outcomes with spinal versus general anaesthesia for hip fracture surgery; Operative versus nonoperative management of unstable medial malleolus fractures: a randomized clinical trial; Impact of smoking status on fracture-related infection characteristics and outcomes; Reassessing empirical antimicrobial choices in fracture-related infections; Development and validation of the Nottingham Trauma Frailty Index (NTFI) for older trauma patients.

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The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

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Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

To date, few studies have investigated the feasibility of the loop-mediated isothermal amplification (LAMP) assay for identifying pathogens in tissue samples. This study aimed to investigate the feasibility of LAMP for the rapid detection of methicillin-susceptible or methicillin-resistant Staphylococcus aureus (MSSA or MRSA) in tissue samples, using a bead-beating DNA extraction method. Twenty tissue samples infected with either MSSA (n = 10) or MRSA (n = 10) were obtained from patients who underwent orthopedic surgery for suspected musculoskeletal infection between December 2019 and September 2020. DNA was extracted from the infected tissue samples using the bead-beating method. A multiplex LAMP assay was conducted to identify MSSA and MRSA infections. To recognize the Staphylococcus genus, S. aureus, and methicillin resistance, 3 sets of 6 primers for the 16S ribosomal ribonucleic acid (rRNA) and the femA and mecA genes were used, respectively. The limit of detection and sensitivity (detection rate) of the LAMP assay for diagnosing MSSA and MRSA infection were analyzed. The results of this study suggest that the LAMP assay performed with tissue DNA samples can be a useful diagnostic method for the rapid detection of musculoskeletal infections caused by MSSA and MRSA

Orthopedic Device-Related Infections (ODRIs) are a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current treatments, based on antibiotic administration, have proven to be ineffective. Consequently, there is a need for antibiotic-free alternatives. Antimicrobial peptides (AMPs) are a promising solution due to their broad-spectrum of activity, high efficacy at very low concentrations, and low propensity to induce resistance. We aim to develop a new AMP-based chitosan nanogel to be injected during orthopedic device implantation to prevent ODRIs. Chitosan was functionalized with norbornenes (NorChit) through the reaction with carbic anhydride and then, a cysteine-modified AMP, Dhvar5, a peptide with potent antibacterial activity, even against methicillin-resistant Staphylococcus aureus (MRSA), was covalently conjugated to NorChit (NorChit- Dhvar5), through a thiol-norbornene photoclick chemistry (UV= 365 nm). For NorChit-Dhvar5 nanogels production, the NorChit-Dhvar5 solution (0.15% w/v) and Milli-Q water were injected separately into microfluidic system. The nanogels were characterized regarding size, concentration, and shape, using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and Dynamic light scattering (DLS). The nanogels antibacterial properties were assessed in Phosphate Buffer (PBS) for 6 h, against four relevant microorganisms (Pseudomonas aeruginosa, S. aureus and MRSA, and in Muller- Hinton Broth (MHB), 50% (v/v) in PBS, supplemented with human plasma (1% (v/v)), for 6 and 24 h against MRSA. The obtained NorChit-Dhvar5 nanogels, presented a round-shaped and ∼100 nm. NorChit- Dhvar5 nanogels in a concentration of 10. 10. nanogels/mL in PBS were capable of reducing the initial inoculum of P. aeruginosa by 99%, S. aureus by 99%, and MRSA by 90%. These results were corroborated by a 99% MRSA reduction, after 24 h in medium. Furthermore, NorChit-Dhvar5 nanogels do not demonstrate signs of cytotoxicity against MC3T3-E1 cells (a pre-osteoblast cell line) after 14 days, having high potential to prevent antibiotic-resistant infection in the context of ODRIs

Aims

Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy.

Aim. Bacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA. Method. Two evolved bacteriophages (MRSA-R14 and COL-R23) with improved antibiofilm activity against a clinical isolate (MRSA3) were tested in combination with vancomycin and a carboxymethylcellulose (CMC) hydrogel in vitro and in vivo. MRSA3 bacterial biofilms were formed on sterile 4 mm sintered porous glass beads at 37 °C for 24 h. Biofilms were exposed to i-phage cocktail (10. 7. PFU/ml), ii-vancomycin at concentrations of 0.5, 1, 10 and 100 times the MIC, or iii-combination of phage cocktail and vancomycin. Recovered biofilm cells, were quantified by colony counting. The stability and release profiles of phage cocktail and vancomycin in co-delivery hydrogel were assessed in vitro for 8 days and 72 hrs, respectively, and subsequently tested in the treatment of 5-day-old MRSA3 infection of a femoral plate osteotomy in mice. Results. In vitro: The cocktail of evolved phages (10. 7. PFU/ml, 1:1) combined with 0.5 MIC vancomycin achieved 99.72% reduction in MRSA3 biofilm in vitro compared to the growth control. This combination was stable in the co-delivery hydrogel over 8 days. The release profile showed that 57% of phages and 80% of vancomycin were released after 72hrs, which was identical to the performance for gels loaded with phage or antibiotic alone. In the in vivo study, the bacterial load from animals that received co-delivery hydrogel and systemic vancomycin was significantly reduced compared to controls, animals that received systemic vancomycin and animals that received co-delivery hydrogel alone (p<0.05). Conclusions. Our study demonstrates the potential of using evolved phages in combination with vancomycin and hydrogel delivery systems for the treatment of MRSA-related infections. Further research in this area may lead to the development of specific therapies for biofilm-related infection

Aim. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with serious cases of community-onset skin and musculoskeletal infections (Co-SMSI). Molecular epidemiology analysis of CA-MRSA recovered from skin and soft tissues specimens is lacking in Latin America. This study aimed to identify phenotypic and genotypic features of MRSA isolates recovered from patients presenting Co-SMSI. Methods. Consecutive MRSA isolates recovered from Co-SMSI of patients admitted from March 2022 to January 2023 in a Brazilian teaching hospital were tested for antimicrobial resistance and characterized by their genotypic features. Identification was carried out by automated method and through MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion, broth microdilution and E-test strips for determination of the minimal inhibitory concentration (MIC) according to recommendations from the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Gene mecA characterization and Sccmec typing were performed by multiplex polymerase chain reaction (PCR) assay, and gene lukF detection by single PCR. Patients were prospectively followed up for two months, in order to determine their clinical characteristics and outcomes. Results. Overall, 48 Staphylococcus aureus isolates were obtained from 68 samples recovered from patients with Co-SMSI. Twenty two (42%) were phenotypically characterized as MRSA, although mecA gene was only identified in 20 of those samples. Sccmec was untypable in 12 isolates, Sccmec was type II in 4 isolates and 2 were classified as type IVa. LukF gene was identified in 5 isolates. Antimicrobial resistance profile showed that all isolates were susceptible to linezolid and vancomycin with MIC = 1 and MIC = 2 in 66,7% and 33.3%, respectively. Susceptibility to quinolones was worryingly low and none of the isolates were sensitive to usual doses of ciprofloxacin and levofloxacin, and showed increased rates of resistance to increased exposure to these drugs, as well. Isolates were both susceptible to gentamicin and tetracycline in 85% and resistance to also Sulfamethoxazole/Trimethoprim occurred in only 2 isolates. Mortality rate evaluated within 1 month of the initial evaluation was 10% among MRSA isolates. Conclusions. Our results showed that CA-MRSA isolates causing Co-SMSI demonstrated an alarming pattern of multidrug resistance, including to β-lactam and quinolones, which have been commonly prescribed as empirical therapy for patients with skin, soft tissue and musculoskeletal infections

Aim. Antibiotics have limited activity in the treatment of multidrug-resistant or chronic biofilm-associated infections, in particular when implants cannot be removed. Lytic bacteriophages can rapidly and selectively kill bacteria, and can be combined with antibiotics. However, clinical experience in patients with surgical infections is limited. We investigated the outcome and safety of local application of bacteriophages in addition to antimicrobial therapy. Method. 8 patients (2 female and 6 male) with complex orthopedic and cardiovascular infections were included, in whom standard treatment was not feasible or impossible. The treatment was performed in agreement with the Article 37 of the Declaration of Helsinki. Commercial or individually prepared bacteriophages were provided by ELIAVA Institute in Tbilisi, Georgia. Bacteriophages were applied during surgery and continued through drains placed during surgery three times per day for the following 5–14 days. Follow-up ranged from 1 to 28 months. Results. Median age was 57 years, range 33–75 years. Two patients were diagnosed with a persistent knee arthrodesis infection, one chronic periprosthetic joint infection (PJI), one cardiovascular implantable electronic device (CIED) infection and four patients with left ventricular assist device (LVAD) infection. The isolated pathogens were multi-drug-resistant Pseudomonas aeruginosa (n=3), methicillin-sensitive Staphylococcus aureus (n=4), methicillin-resistant Staphylococcus aureus (MRSA) (n=1) and methicillin-resistant Staphylococcus epidermidis (MRSE) (n=1). 4 infections were polymicrobial. 5 patients underwent surgical debridement with retention of the implant, 1 patient with PJI underwent the exchange of the prosthesis and one patient with LVAD infection was treated conservatively. All patients received intravenous and oral antibiotic therapy and local application of bacteriophages. At follow-up of 12 month, 5 patients were without signs or symptoms of infection, whereas in one patient with LVAD infection, a relapse was observed with emergence of phage-resistant Pseudomonas aeruginosa. In this patient, no surgical revision was performed. Conclusions. Bacteriophage therapy may represent a valid additional approach, when standard antimicrobial and surgical treatment is not possible or feasible, including in difficult-to-treat infections. In our case series, 5 of 6 patients were infection free after 1 year. Further studies need to address the optimal bacteriophage administration route, concentration, duration of treatment and combination with antimicrobials

Aims

Achievement of accurate microbiological diagnosis prior to revision is key to reducing the high rates of persistent infection after revision knee surgery. The effect of change in the microorganism between the first- and second-stage revision of total knee arthroplasty for periprosthetic joint infection (PJI) on the success of management is not clear.

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The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

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The rate of day-case total knee arthroplasty (TKA) in the UK is currently approximately 0.5%. Reducing length of stay allows orthopaedic providers to improve efficiency, increase operative throughput, and tackle the rising demand for joint arthroplasty surgery and the COVID-19-related backlog. Here, we report safe delivery of day-case TKA in an NHS trust via inpatient wards with no additional resources.

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This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.