Orthopedic Infections Research Articles

Microbial Persistence, Replacement and Local Antimicrobial Therapy in Recurrent Bone and Joint Infection.

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.

Application value of combined detection of serum IL-6, SDF-1 and CD64 in the diagnosis of early postoperative infection after limb fractures

ABSTRACT Objective. To explore the application value of combined detection of serum interleukin-6 (IL-6), stromal cell-derived factor-1 (SDF-1) and neutrophils CD64 (CD64) in the diagnosis of early postoperative infection after limb fractures. Methods. 419 patients with limb fractures un erwent surgical treatment in our hospital were selected as study subjects, and they were divided into infection group (n = 104) and non-infection group (n = 315) according to postoperative pathological results of puncture to detect the levels of serum IL-6, SDF-1 and CD64 in the two groups on the 1st, 3rd, 5th and 7th day after surgery, and to analyze the clinical diagnostic efficacy of single and combined detection of the three indexes in early postoperative infection after limb fractures by ROC curve. Results. The levels of serum IL-6, SDF-1 and CD64 in infection group were overtly higher than those in non-infection group at different time after surgery (P < 0.05), and the AUC value, specificity and sensitivity of combined detection were higher than those of single diagnosis. In this study, 14 patients in infection group underwent reoperation, 22 patients received conservative treatment in the later period, 6 patients had postoperative muscular dystrophy, and the remaining patients had a good prognosis. Conclusion. Serum IL-6, SDF-1 and CD64 are closely related to the occurrence of early postoperative infection after limb fractures, and their combination is helpful to improve diagnostic accuracy of early postoperative infection and provide effective reference value for the treatment of postoperative infection in orthopedics.

Interest in the combination of antimicrobial therapy for orthopaedic device-related infections due to Enterococcus spp.

The objective of this study was to evaluate the management of orthopaedic device-related infections (ODRIs) due to Enterococcus spp. We performed a retrospective cohort study in a French tertiary university hospital. Patients with prosthetic joint- or osteosynthesis-associated infections caused by enterococci from 2013 to 2020 were included. Patients who died within 5days after surgery; who were in palliative care; or who had osteosynthesis of the hand, foot or vertebra were excluded. Thirty-six patients were included, with 24 in the arthroplasty group and 12 in the osteosynthesis material group. Most infections were polymicrobial (63.9%, n = 23). Debridement, antibiotics and implant retention (DAIR) was performed in 30.6% (n = 11), withdrawal of material in 16.7% (n = 6), one-stage exchange in 30.6% (n = 11) and two-stage exchange in 22.2% of cases (n = 8). The antibiotic regimen was amoxicillin in 41.6% (n = 15), rifampicin in 27.8% (n = 10), linezolid in 25% (n = 9) and/or fluoroquinolones in 30.6% (n = 11). Clinical success at 1year was 67% (18/27). The only variable statistically associated with a decreased risk of clinical failure was a duration of antibiotic therapy of 12weeks (p = 0.04). Patients with a lower body mass index and age tended to decrease the risk of clinical failure (p = 0.05 and 0.06 respectively). The management of enterococcal ODRIs is complex, and ODRI patients are at high risk for relapse. In our small study, a better outcome was not demonstrated for patients with combination therapy and rifampicin use. Further studies are needed to improve the medico-surgical strategy for treating these infections.

Does Having a Beard Matter? An Analysis of Orthopaedic Surgical Site Infection Rates in Outpatient Orthopaedic Surgery

Objectives Post-operative infections cause significant morbidity and mortality in outpatient orthopaedic surgery. Orthopaedic surgical site infections have been estimated to occur in up to 5.6% of patients. Prior research has evaluated infection prevention related to operating room attire and hygiene, but no study has evaluated the effect on postoperative infection rates from surgeons having a beard. Methods Two fellowship-trained orthopaedic surgeons operated on a total of 940 patients during a consecutive 12-month period. During the first six months, surgeons were clean-shaven, and in the last six months, surgeons maintained a beard. A standard mask was worn at all times. Infectious complication data were collected retrospectively. Major infection was defined as hospitalization and/or return to the operating room, and minor infection was classified using the Centers for Disease Control and Prevention (CDC) Surveillance Criteria for surgical site infections (SSI). Results Three (0.31%) patients developed a major infection, and 57 (6.05%) patients developed a minor infection. Of 471 patients operated on when surgeons were clean-shaven, two (0.42%) and 30 (6.62%) developed a major or minor infection, respectively. Of the 469 patients operated on when surgeons had beards, one (0.21%) and 27 (5.75%) patients developed a major or minor infection. The difference in major (P=1.00) and minor (P=0.80) infection rates between the 6-month periods was insignificant. Conclusions Similar infection rates for outpatient surgery were found when the surgeons did and did not have a beard. These findings indicate that while wearing a standard surgical mask, a surgeon having a beard at the time of surgery does not affect the postoperative infection rate.

A Review on Human Monkeypox Virus

The human monkeypox is an emerging zoonotic orthopoxvirus with a clinical presentation similar to that of smallpox. It is difficult to differentiate monkeypox from other orthopedic infections, and laboratory diagnosis is the primary component of disease identification and monitoring. However, current diagnostics are time-consuming, and new tests are needed for rapid and precise diagnosis. Most cases have been reported in Central Africa; however, an increasing number of cases have been reported in Europe, the United States of America (USA), Australia, and the United Arab Emirates. Although investigation of the current global outbreak is still ongoing, viral transmission seems to have occurred during crowded events in Spain and Belgium. New therapeutics and vaccines are being deployed for the treatment and prevention of monkeypox, and more research on the epidemiology, biology, and ecology of the virus in endemic areas is required to understand and prevent further global outbreaks.

&lt;i&gt;Stenotrophomonas maltophilia&lt;/i&gt; Infection in Trauma and Orthopedic Patients: Clinical Experience and Review

Background. Stenotrophomonas maltophilia (S. maltophilia) is a gram-negative non-fermenting bacillus and is a rare pathogen of orthopedic infection. Due to the relatively low virulence of S. maltophilia, many clinicians are still faced with the question of whether this bacterial species is simply a colonizing agent or the true cause of infection.&#x0D; Aim of the study to raise the awareness of practitioners about S. maltophilia as a rare pathogen of orthopedic infection.&#x0D; Methods. A retrospective analysis was performed concerning the frequency of S. maltophilia isolation from patients treated at the Vreden Center for periprosthetic infection and/or osteomyelitis from January 1, 2009 to October 31, 2022. The literature search by keywords was carried out in the PubMed/MEDLINE, Scopus, eLIBRARY, and Cyberleninka databases. The search retrieved 587 articles published in Russian or English over the period from 2012 to November 2022.&#x0D; Results. During the study period, 9 cases of orthopedic monoinfection with S. maltophilia were identified in 9 patients aged 36 to 83 years. At the time of admission, no leukocytosis was detected in patients, and only 2 of 9 patients had elevated C-reactive protein level. S. maltophilia is naturally resistant to many broad-spectrum antibiotics. Co-trimoxazole is considered the drug of choice for the treatment of S. maltophilia infection. The limited choice of drugs for targeted therapy, the presence of multiple determinants of antibiotic resistance, the existence of microbial associations and patient risks including implantation, chronic nature of infection, elderly age, as well as the presence of significant concomitant somatic pathology can lead to the ineffectiveness of the ongoing treatment of infections caused by S. maltophilia. Our experience shows that in the case of sensitivity of S. maltophilia strain to co-trimoxazole it is possible to prescribe this drug for a long course as monotherapy, provided that the radical surgical treatment of the focus is performed.

Fabrication and in vitro characterization of antibacterial magneto-luminescent core-shell bioactive glass nanoparticles

When nanomaterials with antibacterial properties were sent to the infected area, it was predicted that infection and related complications could be prevented. The nanoparticles can be designed to possess magnetic and luminescence (magneto-luminescent) properties to be effectively targeted and localized at the infection foci without dispersing into the body. Simultaneously, the magneto-luminescent characteristic of particles allows visualization and confirmation of localized particles at the desired area. In this regard, there are no studies on the use of antibacterial magneto-luminescent bioactive glass for orthopedic applications and the treatment of orthopedic device-related infections. In this study, antibacterial magneto-luminescent 58S bioactive glasses were synthesized by the modified Stöber using coupled with a layer-by-layer assembly approach to possess core/shell particle morphology. SPION/Bioactive glass nanoparticles had an average size of 50 nm and displayed superparamagnetic behavior. While the saturation magnetization value (σs) of the undoped 58S sample was 25.32 emu/g, that of the co-doped sample (2% Eu, 2% Zn) was 21.74 emu/g; this showed that the doping slightly reduced the magnetization value. Europium (Eu) doping of SPION/Bioactive glass nanoparticles induced characteristic red emission originating from Eu emissions belonging to 5D0–7FJ (J = 1–4) transitions and the strongest peak was at 612 nm (electric-dipole transition, 5D0–7F2). Color chromaticity coordinates confirmed emission in the red region. XPS spectrum revealed the existence of Eu and Zn dopant elements in 58S bioactive glass. After soaking characteristic peaks at 31.74° and 45.43° belonging to the hexagonal hydroxyapatite phase were detected in the XRD data, confirming the SEM images. 2% Eu doped SPION/Bioactive glass nanoparticles had the highest osteoblast viability up to 7 days in vitro, while doping the samples with 2% zinc did not yield bone cell viability as high as the Eu doped ones. Importantly, Eu doped SPION/Bioactive glass nanoparticles inhibited gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) growth up to 48 h in vitro. The results showed that Eu doping of SPION/Bioactive glass nanoparticles increased osteoblast viability and inhibited bacterial growth, while possessing superparamagnetic properties and exhibiting red luminescence.

Vancomycin Loaded Amino-Functionalized MCM-48 Mesoporous Silica Nanoparticles as a Promising Drug Carrier in Bone Substitutes for Bacterial Infection Management.

Orthopedic infections due to biofilm formation in biomaterial-based implants have become challenging in bone tissue engineering. In the present study, in vitro antibacterial analysis of amino-functionalized MCM-48 mesoporous silica nanoparticles (AF-MSNs) loaded with vancomycin is analyzed for its potential as a drug carrier for the sustained/controlled release of vancomycin against Staphylococcus aureus. The effective incorporation of vancomycin into the inner core of AF-MSNs was observed by alternation in the absorption frequencies obtained by Fourier transform infrared spectroscopy (FTIR). Dynamic light scattering (DLS) and high resolution-transmission electron microscopy (HR-TEM) results show that all the AF-MSNs had homogeneous spherical shapes with a mean diameter of 165.2 ± 1.25nm, and there is a slight change in the hydrodynamic diameter after vancomycin loading. Furthermore, the zeta potential of all the AF-MSNs (+ 30.5 ± 0.54mV) and AF-MSN/VA (+ 33.3 ± 0.56mV) were positively charged due to effective functionalization with 3-aminopropyl triethoxysilane (APTES). Furthermore, cytotoxicity results show that the AF-MSNs have better biocompatibility than non-functionalized MSNs (p < 0.05), and results prove AF-MSNs loaded with vancomycin show better antibacterial effect against S. aureus than non-functionalized MSNs. Results confirm that bacterial membrane integrity was affected by treatment with AF-MSNs and AF-MSN/VA by staining the treated cells with FDA/PI. Field emission scanning electron microscopy (FESEM) analysis confirmed the shrinkage of bacterial cells and membrane disintegration. Furthermore, these results demonstrate that amino-functionalized MSNs loaded with vancomycin significantly increased the anti-biofilm and biofilm inhibitory effect and can be incorporated with biomaterial-based bone substitutes and bone cement to prevent orthopedic infections post-implantation.

Murine models of orthopedic infection featuring Staphylococcus aureus biofilm.

Introduction: Osteomyelitis remains a major clinical challenge. Many published rodent fracture infection models are costly compared with murine models for rapid screening and proof-of-concept studies. We aimed to develop a dependable and cost-effective murine bone infection model that mimics bacterial bone infections associated with biofilm and metal implants. Methods: Tibial drilled hole (TDH) and needle insertion surgery (NIS) infection models were compared in C57BL/6 mice (female, ). Metal pins were inserted selectively into the medullary canal adjacent to the defect sites on the metaphysis. FreeStaphylococcus aureus(ATCC12600) or biofilm suspension (ATCC25923) was locally inoculated. Animals were monitored for physiological or radiographic evidence of infection without prophylactic antibiotics for up to 14 d. At the end point, bone swabs, soft-tissue biopsies, and metal pins were taken for cultures. X-ray and micro-CT scans were performed along with histology analysis. Results: TDH and NIS both achieved a 100 % infection rate in tibiae when a metal implant was present with injection of free bacteria. In the absence of an implant, inoculation with a bacterial biofilm still induced a 40 %-50 % infection rate. In contrast, freely suspended bacteria and no implant consistently showed lower or negligible infection rates. Micro-CT analysis confirmed that biofilm infection caused local bone loss even without a metal implant as a nidus. Although a metal surface permissive for biofilm formation is impermeable to create progressive bone infections in animal models, the metal implant can be dismissed if a bacterial biofilm is used. Conclusion: These models have a high potential utility for modeling surgery-related osteomyelitis, with NIS being simpler to perform than TDH.

Success of staged revision reverse total shoulder arthroplasty in eradication of periprosthetic joint infection.

Management of periprosthetic joint infection (PJI) in shoulder arthroplasty remains a challenge, with no established gold standard treatment. This study presents the unique experience of a high-volume single-surgeon, single-institution approach on staged revision reverse total shoulder arthroplasty (RTSA) for infection. The authors theorize that staged revision RTSA is an effective treatment for PJI. Between 2013 and 2018, 38 patients underwent a staged RTSA for treatment of PJI. Patient histories were collected and classified using Cierny-Mader classification. Infection workup for all patients included radiographs, laboratory indices, and computed tomographic aspiration arthrogram. PJI was identified based on high clinical and radiographic suspicion, elevated serologic markers, and/or aspirate culture results per 2018 International Consensus Meeting Shoulder guidelines on Orthopedic Infections. All patients underwent first stage with implant removal, irrigation and débridement, and antibiotic spacer placement. Next, intravenous antibiotics were administered by infectious disease consultants for a minimum of 6 weeks. Infection workup was then repeated and, if normalized, final-stage revision commenced with antibiotic spacer removal and revision to RTSA. If indices were persistently abnormal, an additional stage of débridement and spacer placement procedure was performed. Treatment failure was defined as recurrent periprosthetic infection after final prosthesis implantation or persistently elevated indices despite adequate débridement and spacer placement. Mean age of the cohort was 68(standard deviation [SD] 8.9) years and mean follow-up was 33(SD 14) months with 34 Cierny-Mader C hosts and 4 B hosts. Patients underwent a mean of 2(SD 1.1) previous surgeries. The staged revision protocol was successful in 34 (89.5%) patients for management of PJI. Four patients (10.5%) were considered failures with recurrent infections at a mean of 13 months (range 2-26 months) after the final RTSA implantation and underwent repeat staged revisions. Of the 34 patients who had successful infection eradication, 31 had 2-stage treatment and 3 had to undergo 3 stages. There were no treatment-associated mortalities and 10 major complications (26%), including permanent neuropathy, instability, and periprosthetic fractures. The most common cultured microorganism was Cutibacterium acnes (18%), with no polymicrobial infections detected. Although there are multiple treatment options for PJI management, staged revision remains an effective means of treatment. Although there were several patients who required an additional stage of treatment, and a significant complication rate, staged revision RTSA proved successful in the ultimate eradication of the PJI.

The Antimicrobial Activity of Micron-Thin Sol-Gel Films Loaded with Linezolid and Cefoxitin for Local Prevention of Orthopedic Prosthesis-Related Infections.

Orthopedic prosthesis-related infections (OPRI) are an essential health concern. OPRI prevention is a priority and a preferred option over dealing with poor prognosis and high-cost treatments. Micron-thin sol-gel films have been noted for a continuous and effective local delivery system. This study aimed to perform a comprehensive in vitro evaluation of a novel hybrid organic-inorganic sol-gel coating developed from a mixture of organopolysiloxanes and organophosphite and loaded with different concentrations of linezolid and/or cefoxitin. The kinetics of degradation and antibiotics release from the coatings were measured. The inhibition of biofilm formation of the coatings against Staphylococcus aureus, S. epidermidis, and Escherichia coli strains was studied, as well as the cell viability and proliferation of MC3T3-E1 osteoblasts. The microbiological assays demonstrated that sol-gel coatings inhibited the biofilm formation of the evaluated Staphylococcus species; however, no inhibition of the E. coli strain was achieved. A synergistic effect of the coating loaded with both antibiotics was observed against S. aureus. The cell studies showed that the sol-gels did not compromise cell viability and proliferation. In conclusion, these coatings represent an innovative therapeutic strategy with potential clinical use to prevent staphylococcal OPRI.

Can Differently Stabilized Silver Nanoparticles Modify Calcium Phosphate Precipitation?

Calcium phosphates (CaPs) composites with silver nanoparticles (AgNPs) attract attention as a possible alternative to conventional approaches to combating orthopedic implant-associated infections. Although precipitation of calcium phosphates at room temperatures was pointed out as an advantageous method for the preparation of various CaP-based biomaterials, to the best of our knowledge, no such study exists for the preparation of CaPs/AgNP composites. Motivated by this lack of data in this study we investigated the influence of AgNPs stabilized with citrate (cit-AgNPs), poly(vinylpyrrolidone) (PVP-AgNPs), and sodium bis(2-ethylhexyl) sulfosuccinate (AOT-AgNPs) in the concentration range 5-25 mg dm-3 on the precipitation of CaPs. The first solid phase to precipitate in the investigated precipitation system was amorphous calcium phosphate (ACP). The effect of AgNPs on ACP stability was significant only in the presence of the highest concentration of AOT-AgNPs. However, in all precipitation systems containing AgNPs, the morphology of ACP was affected, as gel-like precipitates formed in addition to the typical chain-like aggregates of spherical particles. The exact effect depended on the type of AgNPs. After 60 min of reaction time, a mixture of calcium-deficient hydroxyapatite (CaDHA) and a smaller amount of octacalcium phosphate (OCP) formed. PXRD and EPR data point out that the amount of formed OCP decreases with increasing AgNPs concentration. The obtained results showed that AgNPs can modify the precipitation of CaPs and that CaPs properties can be fine-tuned by the choice of stabilizing agent. Furthermore, it was shown that precipitation can be used as a simple and fast method for CaP/AgNPs composites preparation which is of special interest for biomaterials preparation.

Study protocol: short against long antibiotic therapy for infected orthopedic sites — the randomized-controlled SALATIO trials

BackgroundFew studies address the appropriate duration of post-surgical antibiotic therapy for orthopedic infections; with or without infected residual implants. We perform two similar randomized-clinical trials (RCT) to reduce the antibiotic use and associated adverse events.MethodsTwo unblinded RCTs in adult patients (non-inferiority with a margin of 10%, a power of 80%) with the primary outcomes “remission” and “microbiologically-identical recurrences” after a combined surgical and antibiotic therapy. The main secondary outcome is antibiotic-related adverse events. The RCTs allocate the participants between 3 vs. 6 weeks of post-surgical systemic antibiotic therapy for implant-free infections and between 6 vs. 12 weeks for residual implant-related infections. We need a total of 280 episodes (randomization schemes 1:1) with a minimal follow-up of 12 months. We perform two interim analyses starting approximately after 1 and 2 years. The study approximatively lasts 3 years.DiscussionBoth parallel RCTs will enable to prescribe less antibiotics for future orthopedic infections in adult patients.Trial registrationClinicalTrial.gov NCT05499481. Registered on 12 August 2022.Protocol version: 2 (19 May 2022)

BACTERIOLOGICAL PROFILE AND THEIR SENSITIVITY PATTERN OF ANTIBIOTICS TO POST-OPERATIVE ORTHOPAEDIC IMPLANT INFECTIONS IN TERTIARY CARE HOSPITAL

Background: A correct information about most common causative organism and it sensitivity pattern in that clinical setup is essential for designing empirical therapy. Present study has been designed to study the microbiological prole and antibiotic sensitivity pattern of post-operative orthopaedic Implant infections in tertiary care teaching hospital. Material and Method: This prospective observational study. Patients who presented with the signs and symptoms of infections, conrmed by laboratory and other routine investigations, were included in present study. The demography, microbiological data sensitivity to antimicrobial agent of organism was recorded. Result: The most common pathogen isolated was pseudomonas aeruginosa that is 37 (41.1%), followed by staphylococcus aureus that is 36 (40%). Pseudomonas aeruginosa was sensitive to Piperacillin tazobactam 28(77.7%), Imipenem 26(72.2%), Imipenem+cilastatin 28(77.7%) and Meropenem 30(83.3%). Methicillin resistant staph aureus were sensitive to Cotrimoxazole 4(44.4%), Clindamycine 6(66.6%), Vancomycin 8(88.8%) and Linazolid 7(77.7%). Conclusion: Implant of femur was most commonly infected. Staphylococcus Aureus (MSSA) was commonly associated with biolm formation followed by Staphylococcus Aureus (MRSA). Pseudomonas aeruginosa isolated from implant infections were sensitive to Piperacillin+ tazobactam, Imipenem, Imipenem+cilastatin and Meropenem

In vitro elution characteristics of antibiotic-loaded polymethylmethacrylate cement and a calcium sulfate bone substitute using staphylococci isolated from orthopedic implant-associated infections.

Polymethylmethacrylate (PMMA) remains the gold standard antibiotic carrier in the management of osteomyelitis. However, biodegradable ceramic carriers may exhibit more efficient antibiotic elution properties. Through zone of inhibition (ZOI) testing and biofilm killing assays, we assessed the in vitro elution efficacy of vancomycin released from calcium sulfate (PG-CSH) and PMMA beads as carriers on clinical strains of Staphylococcus aureus and Staphylococcus epidermidis, which were isolated from sonication fluid of orthopedic implant-associated infections. Overall, vancomycin-loaded PMMA and PG-CSH beads showed potency (ZOI above 4cm2 ) for up to 14 days against ATCC and clinical strains. Vancomycin-loaded PG-CSH beads displayed higher rates, exhibited a more stable antibiotic elution, had greater impacts on bacterial colony-forming unit counts and produced higher ZOIs; additionally, statistically significant differences (Student's t test) were observed in different time sets during the experiment. In the biofilm killing assay, PG-CSH loaded with vancomycin resulted in more bacterial deaths. In conclusion, in the present study, both PG-CSH and PMMA beads acted as good carriers, but greater antimicrobial elution and biofilm bacterial killing were observed with PG-CSH than PMMA. Future in vitro research should focus on testing other difficult-to-treat clinical strains, including multidrug resistant coagulase-negative staphylococci and Gram-negative bacilli.

ANTIBITOIC HYDROGEL FOR SINGLE-STAGE REVISION IN ORTHOPAEDIC INFECTION: A PRECLINICAL STUDY

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability.In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI insheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem.There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits.This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

Current treatment and prevention of orthopaedic infections in the horse

SummaryOrthopaedic infections, including synovial sepsis, osteomyelitis and infection of orthopaedic implants are common in equine medicine. Infections can be caused by haematogenous spread of pathogens, trauma or penetrating injuries, extension of local infections and iatrogenic causes such as surgery and synovial injections. Horses with orthopaedic infections are generally markedly lame and often require aggressive and prolonged therapy. Early diagnosis can greatly impact treatment outcomes and can be facilitated by careful physical examinations, haematology, diagnostic imaging and timely synovial fluid sampling. Concerted efforts should always be made to obtain a positive bacterial culture and sensitivity. Treatment is focused on antimicrobial therapy with local therapy, including intravenous regional limb perfusion and intrasynovial injections, being employed whenever possible; lavage and debridement; and analgesia and supportive care. Responsible use of antimicrobials and antimicrobial stewardship are critical when treating orthopaedic infections. Prognosis will depend on the source and severity of the infection, the causative agent and the time to intervention. Foals and horses can respond well to treatment and return to soundness with early, aggressive and targeted treatment.

Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates.

Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.

Vancomycin-nanofunctionalized peptide-enriched silk fibroin to prevent methicillin-resistant Staphylococcus epidermidis-induced femoral nonunions in rats.

Implant-related infections and infected fractures are significant burdens in orthopedics. Staphylococcus epidermidis is one of the main causes of bone infections related to biofilm formation upon implants. Current antibiotic prophylaxis/therapy is often inadequate to prevent biofilm formation and results in antibiotic resistance. The development of bioactive materials combining antimicrobial and osteoconductive properties offers great potential for the eradication of microorganisms and for the enhancement of bone deposition in the presence of infections. The purpose of this study is to prevent the development of methicillin-resistant S. epidermidis (MRSE)-infected nonunion in a rat model. To this end, a recently developed in our laboratories bioactive material consisting of antibiotic-loaded nanoparticles based on carboxylic acid functionalized hyperbranched aliphatic polyester (CHAP) that are integrated into peptide-enriched silk fibroin sponges with osteoconductive properties (AFN-PSF) was employed, whose biocompatibility and microbiological tests provided proof of its potential for the treatment of both orthopedic and dental infections. In particular, non-critical femoral fractures fixed with plates and screws were performed in Wistar rats, which were then randomly divided into three groups: 1) the sham control (no infection, no treatment); 2) the control group, infected with MRSE and treated with peptide-enriched silk fibroin sponges incorporating non-drug-loaded functionalized nanoparticles (PSF); 3) the treated group, infected with MRSE and treated with peptide-enriched silk fibroin sponges incorporating vancomycin-loaded functionalized nanoparticles (AFN-PSF). After 8 weeks, bone healing and osteomyelitis were clinically assessed and evaluated by micro-CT, microbiological and histological analyses. The sham group showed no signs of infection and complete bone healing. The PSF group failed to repair the infected fracture, displaying 75% of altered bone healing and severe signs of osteomyelitis. The AFN-PSF treated group reached 70% of fracture healing in the absence of signs of osteomyelitis, such as abscesses in the cortical and intraosseous compartments and bone necrosis with sequestra. AFN-PSF sponges have proven effective in preventing the development of infected nonunion in vivo. The proposed nanotechnology for local administration of antibiotics can have a significant impact on patient health in the case of orthopedic infections.

Antibacterial Activity on Orthopedic Clinical Isolates and Cytotoxicity of the Antimicrobial Peptide Dadapin-1

In orthopedic surgery, biomaterial-associated infections represent a complication of serious concern. Most promising strategies to prevent these infections currently rely on the use of anti-infective biomaterials. Desirably, in anti-infective biomaterials, the antibacterial properties should be achieved by doping, grafting, or coating the material surfaces with molecules that are alternative to conventional antibiotics and exhibit a potent and highly specific activity against bacteria, without altering the biocompatibility. Antimicrobial peptides (AMPs) are among the most interesting candidate molecules for this biomaterial functionalization. Here, the potential expressed by the recently discovered peptide Dadapin-1 was explored by assaying its MIC, MBIC and MBC on clinical strains of relevant bacterial species isolated from orthopedic infections and by assessing its cytotoxicity on the human osteoblast-like MG63 cells. When appropriately tested in diluted Mueller Hinton Broth II (MHB II), Dadapin-1 exhibited significant antibacterial properties. MIC values were in the range of 3.1-6.2 µM for the gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri, and 12.4-24.9 µM for the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Interestingly, the peptide was found non-cytotoxic, with an IC50 exceeding the highest concentration tested of 179 µM. Overall, Dadapin-1 expresses considerable potential for future application in the production of anti-infective biomaterials.