Search

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first‐line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug‐resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone–implant interface. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus. Methods: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria. Results: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min. Conclusion: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials. [ABSTRACT FROM AUTHOR]

Background:Staphylococcus lugdunensis is a coagulase-negative staphylococci that is considered normal skin microbiota. It has been described as a cause of soft tissue infections but is not a common micro-organism as the cause of orthopedic surgery-related infections. This study describes the characteristics, treatment, and results of musculoskeletal infection by Staphylococcus lugdunensis treated in our institution. Methods: We performed a descriptive, retrospective observational study. Clinical records of all musculoskeletal infections treated in our department between 2012 and 2020 were reviewed. We selected those patients with a positive monomicrobial culture for Staphylococcus lugdunensis. Risk factors for infection, patient's medical records, previous surgery performed, time from surgery to infection, culture antibiogram, antibiotic and surgical treatment for the infection, and recovery rate were registered for the analysis. Results: Of the 1,482 patients with musculoskeletal infections diagnosed in our institution, 22 had a monomicrobial positive culture of Staphylococcus lugdunensis after an orthopedic surgery representing 1.5% of all orthopedic infections. Ten patients underwent arthroplasty, six underwent fractures synthesis, three had foot surgeries, two had anterior cruciate ligament reconstructions, and one had spine surgery. All patients needed surgery and antibiotic treatment with a mean of two surgeries. The most used antibiotic scheme was levofloxacin-rifampicin. The mean follow-up was 36 months. Ninety-six percent of the patients achieved a complete clinical and analytical recovery. Conclusions: Although musculoskeletal infections caused by Staphylococcus lugdunensis are not common, we have observed a statistically significant incidence increase of Staphylococcus lugdunensis in recent years. If managed with appropriately aggressive surgical treatment and correct antibiotic therapy, good results can be obtained. [ABSTRACT FROM AUTHOR]

The increasing prevalence of antibiotic-resistant bacterial infections has led to the search for new approaches. This study aimed to evaluate the effects of carvacrol and N-acetyl cysteine, both individually and in combination, on the planktonic cells and biofilm formations of Staphylococcus aureus , including methicillin-resistant and methicillin-sensitive strains. Additionally, the study sought to perform cytotoxicity tests and chemical characterization to further understand the properties and potential applications of these substances. A total of 19 S. aureus strains were included in the study. Minimum inhibitory concentration and minimum bactericidal concentration were determined by assays. Synergy analysis tests were carried out. Cytotoxicity tests were conducted on the fibroblast cell line. Characterization test was performed. While Minimum inhibitory concentration and minimum bactericidal concentration values for carvacrol varied between 250 and 500 μg/ml, these values were in the range of 32–64 mg/ml for N-acetyl cysteine. Biofilm formation activities were identified. A total of eight strains, including six clinical and two standard strains with the highest biofilm-forming ability, were selected for combination studies. The combination of Carvacrol and N-acetyl cysteine exhibited synergistic and partially synergistic effects on the tested planktonic and biofilm strains, and these effects were dose-dependent. Carvacrol was found to be the most active drug at the end of 24, 48, and 72 h. Regarding the synergistic effect of N-acetyl cysteine + carvacrol, it was revealed to exhibit higher activity than N-acetyl cysteine and lower activity than carvacrol. The combination of carvacrol and N-acetyl cysteine demonstrated synergistic and partially synergistic effects against both planktonic and biofilm forms of Staphylococcus aureus. These results suggest potential for novel approaches in managing orthopedic infections, warranting further research to explore their therapeutic applications. • The CAR and NAC combination inhibits MRSA biofilm formation. • The NAC + CAR combination balances efficacy and safety for infections. • The study provides insights into the antimicrobial mechanisms of NAC and CAR through detailed chemical analysis. [ABSTRACT FROM AUTHOR]

Infection is a common cause of impaired fracture healing. In the clinical setting, definitive fracture treatment and infection are often treated separately and sequentially, by different clinical specialties. The ability to treat infection while promoting fracture healing will greatly reduce the cost, number of procedures, and patient morbidity associated with infected fractures. In order to develop new therapies, scientists and engineers must understand the clinical need, current standards of care, pathologic effects of infection on fractures, available preclinical models, and novel technologies. One of the main causes of poor fracture healing is infection; unfortunately, bone regeneration and infection research are typically approached independently and viewed as two separate disciplines. Here, we aim to bring these two groups together in an educational workshop to promote research into the basic and translational science that will address the clinical challenge of delayed fracture healing due to infection. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patie[Q2]nt well‐being is substantial. Outcome data suggests a long bone nonunion is as impactful on health‐related quality of life measures as a diagnosis of type 1 diabetes and fracture‐related infection has been shown to significantly l[Q3]ower a patient's quality of life for over 4 years. Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patient well‐being is substantial. Outcome data suggests a long bone nonunion is as impactful on health‐related quality of life measures as a diagnosis of type 1 diabetes and fracture‐related infection has been shown to significantly lower a patient's quality of life for over 4 years. Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system. [ABSTRACT FROM AUTHOR]

C‐C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant‐associated infections (OIAI), but whether CCR2‐mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic‐grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2‐deficient mice. In vivo bioluminescent signals significantly increased in CCR2‐deficient mice compared with wt mice at later time points (Days 14–28), which was confirmed with ex vivo colony‐forming unit enumeration. S. aureus γ‐hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ‐hemolysin‐deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ‐hemolysin virulence. Although CCR2‐deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2‐deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus and Streptococcus agalactiae (Group B streptococcus, GBS) are common causes of deep musculoskeletal infections (MSKI) and result in significant patient morbidity and cost to the healthcare system. One of the major challenges with MSKI is the lack of faithful diagnostics to correctly identify the primary pathogen, as standard culture‐based assays are prone to false positives in the case of polymicrobial infections, and false negatives due to limitations in sample acquisition and antibiotic use before presentation. To improve upon our current diagnostic methods for MSKI, we developed a multiplex immunoassay for antigen‐specific IgGs in serum (Luminex), and medium enriched for newly synthesized antibodies (MENSA) for anti‐S. aureus and GBS generated from cultured peripheral blood mononuclear cells (PBMCs) of orthopedic infection patients undergoing surgical treatment. Samples were obtained from 110 MSKI patients: 80 diabetic foot ulcer, 21 periprosthetic joint infection, 5 septic arthritis, 2 spine, 1 hand, and 1 fracture‐related infection (FRI). Anti‐S. aureus and anti‐GBS antibody titers were compared to culture results to assess their concordance in identifying the pathogens. Immunoassay, particularly MENSA, showed high diagnostic potential for monomicrobial S. aureus and GBS orthopedic infections (AUC > 0.95). MENSA also demonstrated diagnostic potential for GBS polymicrobial orthopedic infection and for GBS DFU (AUC > 0.83 for both). Serum showed high diagnostic potential for S. aureus PJI (AUC > 0.95). Taken together, these findings support the development of species‐specific immunoassays for the identification of causal pathogens in active MSKI, especially in conjunction with standard culture. [ABSTRACT FROM AUTHOR]

Background: Currently, one of the most pressing problems in the field of orthopedic surgery is peri-prosthetic joint infection [PJI]. While there are numerous ways to detect PJI, current clinical detection methods differ across institutions and have varying criteria and protocols. Some of these methods include the Modified Musculoskeletal Infection Society system, culturing, polymerase chain reaction, the determination of the presence of certain biomarkers, testing for the presence of alpha defensin peptides, and leukocyte level testing. Methods: This review summarizes the most recent publications in the field of PJI detection to highlight current strengths as well as provide future directions to find the system for the quickest, cost-effective, and most accurate way to diagnose these types of infections. Results: The results of this literature review suggest that, while each method of diagnosis has its advantages, each has various drawbacks as well. Current methods can be expensive, take days to weeks to complete, be prone to contamination, and can produce ambiguous results. Conclusions: The findings in this review emphasize the need for a more comprehensive and accurate system for diagnosing PJI. In addition, the specific comparison of advantages and drawbacks can be useful for researchers and clinicians with goals of creating new diagnostic tests for PJIs, as well as in clinical scenarios to determine the correct treatment for patients. [ABSTRACT FROM AUTHOR]

Bacterial infection and antibiotic resistance are major threats to human health and very few solutions are available to combat this eventuality. A growing number of studies indicate that cold (non-thermal) plasma treatment can be used to prevent or eliminate infection from bacteria, bacterial biofilms, fungi and viruses. Mechanistically, a cold plasma discharge is composed of high-energy electrons that generate short-lived reactive oxygen and nitrogen species which further react to form more stable compounds (NO2, H2O2, NH2Cl and others) depending on the gas mixture and plasma parameters. Cold plasma devices are being developed for medical applications including infection, cancer, plastic surgery applications and more. Thus, in this review we explore the potential utility of cold plasma as a non-antibiotic approach for treating post-surgical orthopedic infections. [ABSTRACT FROM AUTHOR]

Background: Bacterial colonization of spinal implants may cause severe complications in patients with early-onset scoliosis. Correct diagnosis and detection of microbiologic formation is crucial to prevent delayed infections caused by bacterial colonization. The purposes of this study were to estimate the rate and risk factors of colonization of vertical expandable prosthetic titanium rib (VEPTR) implants in children and to compare the different methods for detecting microbiologic formation on the spinal implants.Methods: We evaluated prospectively a group of 42 children with spinal deformities with an overall of 95 lengthening surgeries and applied different methods to detect potential bacterial colonization of VEPTR implants: swab of the implant, swab with culture of tissue, analysis of the removed lock, polymerase chain reaction (PCR), and confocal microscopy. Potential risk factors were evaluated.Results: Of 42 patients, 17 (40%) were rated positive for bacterial colonization with Propionibacterium acnes and coagulase-negative staphylococci being the most commonly found bacteria. Risk factors for colonization were increasing age, body height, and weight. The swab with culture of removed tissue yielded most positive results, whereas direct microscopy and PCR were the least sensitive detection methods. Furthermore, commonly used infectious blood parameters were inconclusive.Conclusions: Although the impact of bacterial colonized implants on the health of the patients is not fully elucidated, clinicians aim for prevention of microbiologic formation on implanted devices. Therefore, reliable, inexpensive, and easy to apply diagnostic tools are indispensable to detect colonization. Based on our data, the swab together with tissue culture has the potential to become the method of choice for future diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: A new multiplex real-time polymerase chain reaction (PCR) assay was developed to detect methicillin-resistant Staphylococcus (MRS) and to distinguish between gram-positive and gram-negative bacteria. In this study, we validated the sensitivity and specificity of this assay with periprosthetic joint infections (PJIs) and evaluated the utility of PCR for culture-negative PJI. Methods: Forty-five samples from 23 infectious PJI cases and 106 samples from 64 non-infectious control cases were analyzed by real-time PCR using a LightCycler NanoVR system. Twenty-eight clinical samples, comprising bacteria of known species isolated consecutively in the microbiological laboratory of our hospital, were used to determine the spectrum of bacterial species that could be detected using the new multiplex primers and probes. Results: The sensitivity and specificity of the MRS- and universal-PCR assays were 92% and 99%, and 91% and 88%, respectively. Twenty-eight species of clinically isolated bacteria were detected using this method and the concordance rate for the identification of gram-positive or gram-negative organisms was 96%. Eight samples were identified as PCR-positive despite a culture-negative result. Conclusion: This novel multiplex real-time PCR system has acceptable sensitivity and specificity and several advantages; therefore, it has potential use for the diagnosis of PJIs, particularly in culture-negative cases. [ABSTRACT FROM AUTHOR]

Background: The purpose of this work was to compare pre-made antibiotic-loaded spacers with two commercially available antibiotic agents and custom-made cements with three antibiotic agents added. We evaluated: (a) the validity of our procedures, (b) the control of the rate of infection in the long term, (c) complications, and (d) quality of life and patient satisfaction.Methods: A retrospective cohort study was performed on 112 consecutively treated patients between January 2010 and December 2013; 56 patients were treated with a pre-formed cement spacer (clindamycin + gentamicin), and 56 patients were treated with a spacer loaded with three antibiotic agents (clindamycin + gentamicin + vancomycin). Demographic data were collected: Classification of infection according to criteria of Cierny-Mader; microbiologic results; number of previous operations; and years of disease. Infection control or relapse after at least 18 months of follow-up was evaluated. Complications were recorded. Every patient completed the SF-36 test and Oxford Knee Score.Results: With a follow-up of 32.87 months (standard deviation 12.04), at the end of treatment, amputation occurred in three of 112 patients because of recurrence of infection, and one patient died from other causes not related to the infection. The study population presented a rate of recurrence of infection of 2.70%.Conclusions: Our results suggest that a two stage re-implant with three antibiotic agents added to the spacer should be considered to avoid rescue procedures, especially in patients with multi-resistant micro-organism infections. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to evaluate the feasibility and clinical efficacy of bridging vein transplantation to deal with the vessel shortage during free vascularized fibular grafting for reconstructing infected bone defects of the femur.Methods: Twelve patients (aged 15-58 years) with infected bone defects of the femur (between 6.0 and 18.0cm) were recruited in this study. Vacuum sealing drainage were applied after extensive debridement of the infected bone defects and irrigated with 0.9% sodium chloride solution for 1-2 weeks. After the drainage was clear and the focal infections were controlled, the free vascularized fibula was harvested for reconstructing the femoral bone defects. The vascularized fibula was grafted and fixated appropriately at the recipient site. The autogenous great saphenous vein was harvested, one end was anastomosed and bridged the vascular pedicles of the fibular grafts, and the other end anastomosed the artery and/or the vein in the recipient healthy site.Results: Mean length of vein transplantation with vascularized fibular graft was 10.2 cm (range 7-15cm). All patients had good radiological healing without recorded nonunion or malunion. No patient developed deep infection or implant failure. Primary bone healing was achieved in 10 patients; however, 2 grafted fibular formed pseudarthrosis with the recipient femoral and then healed after a secondary surgery. One patient suffered from graft stress fracture after bone healing and healed after external fixation. After the mean follow-up of 30 months (9-72 months), according to the Enneking scoring system, clinical outcomes were excellent in 7 patients, good in 4 and fair in one. The functional recovery rate of the lesion limb was 89.4%.Conclusions: Free vascularized fibular graft with vein transplantation bridged vascular pedicle can effectively repair the infected bone, improve blood supply to the bone defect site, and help control infection. It is a feasible and effective treatment for infected bone defects of the femur with poor soft tissue conditions, or blood supply vessel shortage. [ABSTRACT FROM AUTHOR]

Objectives: Outpatient parenteral antimicrobial therapy (OPAT) is an effective way of treating infections, but complications are common. We identified patient characteristics and OPAT treatment factors associated with increased risk of OPAT-related complications.Methods: We used a retrospective cohort design that assessed 337 adult patients treated with OPAT for orthopedic and neurosurgical infections between August 1, 2008 and May 30, 2010. Independent variables included demographics, infection characteristics, lead time factors, OPAT treatment factors, and comorbid conditions. Multivariable log-binomial regression was used to estimate the risk of OPAT complications.Results: The mean patient age was 55 years (range 19-87), 86% had an orthopedic infection, and 44% were treated with intravenous vancomycin. OPAT complications were seen in 45% (152/337) of the cohort. Risk ratios for OPAT complications were 1.9 (95% confidence interval 1.4-2.5) in patients having no primary care provider, 1.7 (95% confidence interval 1.3-2.1) for those treated with vancomycin.Conclusions: Identifying specific patient characteristics and OPAT treatment factors could facilitate OPAT process improvements to reduce the risk of OPAT complications for vulnerable patients. [ABSTRACT FROM AUTHOR]

Abstract: Blastomycosis commonly occurs following inhalation of Blastomyces dermatitidis conidia causing a pulmonary infection and can disseminate to extrapulmonary sites. Osseous involvement primarily results from hematogenous spread, but in rare cases, direct inoculation can occur. We describe a case of osseous blastomycosis without pulmonary or disseminated disease successfully treated with posaconazole. [Copyright &y& Elsevier]

Orthopedic biomaterial-associated infections remain a major clinical challenge, with Staphylococcus aureus being the most common pathogen. S. aureus biofilm formation enhances immune evasion and antibiotic resistance, resulting in a local, indolent infection that can persist long-term without symptoms before eventual hardware failure, bone non-union, or sepsis. Immune modulation is an emerging strategy to combat host immune evasion by S. aureus. However, most immune modulation strategies are focused on local immune responses at the site of infection, with little emphasis on understanding the infection-induced and orthopedic-related systemic immune responses of the host, and their role in local infection clearance and tissue regeneration. This study utilized a rat bone defect model to investigate how implant-associated infection affects the systemic immune response. Long-term systemic immune dysregulation was observed with a significant systemic decrease in T cells and a concomitant increase in immunosuppressive myeloid-derived suppressor cells (MDSCs) compared to non-infected controls. Further, the control group exhibited a regulated and coordinated systemic cytokine response, which was absent in the infection group. Multivariate analysis revealed high levels of MDSCs to be most correlated with the infection group, while high levels of T cells were most correlated with the control group. Locally, the infection group had attenuated macrophage infiltration and increased levels of MDSCs in the local soft tissue compared to non-infected controls. These data reveal the widespread impacts of an orthopedic infection on both the local and the systemic immune responses, uncovering promising targets for diagnostics and immunotherapies that could optimize treatment strategies and ultimately improve patient outcomes. [ABSTRACT FROM AUTHOR]

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections. [ABSTRACT FROM AUTHOR]

Summary: The combined 2005 meeting of the AO Switzerland and the Swiss AO Alumni Chapter took place in Liestal. Topics were the current standards in prevention and treatment of infections in orthopedic surgery and new developments in implant design and material (eg, surface modification) aiming to reduce implant-related infections. In addition, improved diagnostic methods for germ identification and current treatment algorithms were discussed. [Copyright &y& Elsevier]