Bone Cultures Research Articles

Does complete resection of infected bone improve clinical outcomes in patients with diabetic foot osteomyelitis?

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1.

Methicillin-resistant Staphylococcus aureus in diabetic and non-diabetic foot infections.

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = <0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p < 0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes.

Yield and clinical impact of image-guided bone biopsy in osteomyelitis of the appendicular skeleton: a systematic review and meta-analysis.

To assess the yield and clinical impact of image-guided bone biopsy for osteomyelitis of the appendicular skeleton. A literature search of several databases was conducted from inception to August 2023. Eligible studies reported patients who underwent image-guided bone biopsy for investigation of osteomyelitis of the appendicular skeleton. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023466419). From 370 initial studies screened, eight met the eligibility criteria, with a total of 700 patients. The pooled technical success rate was 99.6% (95% CI: 0.992, 1.001; I2 = 0%). Positive bone cultures were pooled at 31.9% (95% CI: 0.222, 0.416; I2 = 87.83%) and negative cultures at 68.1% (95% CI: 0.584, 0.778; I2 = 87.83%). Methicillin-Sensitive Staphylococcus Aureus and Methicillin-Resistant Staphylococcus Aureus yield was 24.5% (95% CI: 0.096, 0.394; I2 = 90.98%) and 7.6% (95% CI: 0.031, 0.121; I2 = 34.42%) respectively. Group A Streptococcus yield was 7.0% (95% CI: 0.014, 0.127; I2 = 70.94%). Polymicrobial culture yield was 15.7% (95% CI: 0.018, 0.297; I2 = 88.90%). Post-procedural management change rate was 36.5% (95% CI: 0.225, 0.504; I2 = 92.39%). No complications were reported across studies. For patients under investigation of osteomyelitis of the appendicular skeleton, image-guided bone biopsy demonstrates a good rate of technical success. Additional studies may provide further support for the use of image-guided bone biopsy in this population. Image-guided bone biopsy results lead to change in antibiotics therapy in a portion of patients with suspected osteomyelitis suggesting its potential utility in select patients.

Ex vivo organotypic bone slice culture reveals preferential chondrogenesis after sustained growth plate injury

Postnatal bone growth primarily relies on chondrocyte proliferation and osteogenic differentiation within the growth plate (GP) via endochondral ossification. Despite its importance, the GP is vulnerable to injuries, affecting 15–30 % of bone fractures. These injuries may lead to growth discrepancies, influence bone length and shape, and negatively affecting the patient's quality of life. This study aimed to investigate the molecular and cellular physiological and pathophysiological regeneration following sustained growth plate injury (GPI) in an ex vivo rat femur organotypic culture (OTC) model. Specifically, focusing on postnatal endochondral ossification process. 300 μm thick ex vivo bone cultures with a 2 mm long horizontal GPI was utilized. After 15 days of cultivation, gene expression analysis, histological and immunohistochemistry staining's were conducted to analyze key markers of endochondral ossification. In our OTCs we observed a significant increase in Sox9 expression due to GPI at day 15. The Ihh-PTHrP feedback loop was affected, favoring chondrocyte proliferation and maturation. Ihh levels increased significantly on day 7 and day 15, while PTHrP was downregulated on day 7. GPI had no impact on osteoclast number and activity, but gene expression analysis indicated OTCs' efforts to inhibit osteoclast differentiation and activation, thereby reducing bone resorption.In conclusion, our study provides novel insights into the molecular and cellular mechanisms underlying postnatal bone growth and regeneration following growth plate injury (GPI). We demonstrate that chondrocyte proliferation and differentiation play pivotal roles in the regeneration process, with the Ihh-PTHrP feedback loop modulating these processes. Importantly, our ex vivo rat femur organotypic culture model allows for the detailed investigation of these processes, providing a valuable tool for future research in the field of skeletal biology and regenerative medicine.

Abstract 4226: Human-derived hydrogels for 3D models of bone and osteosarcoma organoids and adipose tissue interactions

Abstract The goal of the study was to determine the metabolic and morphological changes, via high Content Imaging, in 3D models of osteosarcoma cancer cells using human derived hydrogels with different protein composition, Obagel and Obagel ECM. Furthermore, we evaluated the relevance of the adipose tissue microenvironment in Adipose Derived Stem Cells (ADSC) linage and Tumoroids development. Methods: Adipose derived Stem cells were cultured in a modified 3D human and fat and bone linage differentiation as studied via histology and Immunofluorescence. Osteosarcoma spheroids were cultured in Obatala Sciences’ human-derived hydrogels ObaGel and ObaGelECM and control media. Organoid structure and phenotypic changes were analyzed via live cell imaging on the Incucyte S3 and Nikon high content imaging device. Then, adipocyte- cancer cell crosstalk was evaluated using pooled adipocytes co-cultured with KHOS spheroids. Adipose derived Stem cells were cultured in a modified 3D human derived hydrogel dictates that promotes the differentiation potential toward fat and adipose tissue simultaneously in microenvironments within the organoid. Furthermore, the results demonstrated that ObaGel and ObaGel-ECM 3D cultures can support the growth and proliferation of KHOS tumor spheres during an extended culture period. Metabolic changes and phenotypic changes associated to ObaGel and ObaGel-ECM differentially facilitated tumoroids growth and migratory behavior. Conclusions: Human derived hydrogels are developed to support 3D culture of Bone and Osteosarcoma cells to recapitulate the phenotypic changes associated with their metastatic potential. The use of human derived 3D culture systems can accelerate the understanding of the role of the microenvironment in bone development and the pathogenesis and progression of Cancers like Osteosarcoma as well as screening for drug development. Citation Format: Cecilia G. Sanchez, Arman Raz, Haley Lassiter, Trivia Frazier. Human-derived hydrogels for 3D models of bone and osteosarcoma organoids and adipose tissue interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4226.

TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment.

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

MRSA infection, re-infection and clinical outcomes in diabetic foot infections.

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens.

Mechanical loading of ex vivo bovine trabecular bone in 3D printed bioreactor chambers

Previous ex vivo bone culture methods have successfully implemented polycarbonate (PC) bioreactors to investigate bone adaptation to mechanical load; however, they are difficult to fabricate and have been limited to a 5 mm maximum specimen height. The objective of this study was to validate a custom-made 3D printed MED610TM bioreactor system that addresses the limitations of the PC bioreactor and assess its efficacy in ex vivo bone culture. Twenty-three viable trabecular bone cores (10 mm height by 10 mm diameter) from an 18-month-old bovine sternum were cultured in MED610TM bioreactors with culture medium at 37 °C and 5% CO2 for 21-days. Bone cores were ranked based on their day 0 apparent elastic modulus (Eapp) and evenly separated into a “Load” group (n = 12) and a control group (n = 11). The Load group was loaded five times per week with a sinusoidal strain waveform between −1000 and −5000 με for 120 cycles at 2 Hz. Eapp was assessed on day 0, 8, and 21 using quasi-static tests with a −4000 με applied strain. Over 21-days, the Eapp of Load group samples tended to increase by more than double the control group (53.4% versus 20.9%) and no visual culture contamination was observed. This study demonstrated that bone organ culture in 3D printed MED610TM bioreactors replicated Eapp trends found in previous studies with PC bioreactors. However, further studies are warranted with a larger sample size to increase statistical power and histology to assess cell viability and bone mineral apposition rate.

Exploring the Role of Intraoperative Positive Culture of Allograft Bone in Subsequent Postoperative Infections among Donors and Recipients in Bone Bank Processing.

Allografts have been frequently used in orthopedic procedures. The purposes of this study were to evaluate the discard rates and bacterial contamination of a bone bank, and to assess the clinical outcomes of recipients with bacterial culture-positive donor allografts. We retrospectively reviewed 1764 allografts which were harvested from living donors and stored in a bone bank from 2018 to 2022. The donors whose allografts displayed bacterial contamination at retrieval of the primary hip or knee arthroplasty were followed for microbiology and subsequent prosthetic joint infection analysis. The infected pathogens, antibiotic treatment and subsequent infection were reviewed for the intraoperative positive culture group. The discard rate was 17%, and the bacterial contamination rate of bone retrieval was 2.15%. Thirty-eight allografts at retrieval displayed confirmed bacterial growth, and 37 patients did not reveal infective signs at 6 months follow-up. A total of 1464 allografts were stored and implanted, among which 28 allografts (1.91%) were confirmed to be positive for bacterial growth and 13 cases (0.89%) were confirmed as surgical site infections. Our results validate the suggestion that our bone bank system performs good quality monitoring to eliminate the risk of dissemination of viral and bacterial diseases and to decrease surgical site infection after allograft implantation. By ensuring aseptic conditions and contamination-reducing strategies during harvesting and thawing, the allografts can be safely stored and implanted while limiting bacterial contamination. Our findings confirm that the intraoperative positive cultures of allografts did not contribute to subsequent postoperative surgical site infection in donors and recipients.

Diagnostic Performance of Ultrasonography for Diabetic Foot Osteomyelitis.

Objective: This study aims to analyze the potential diagnostic capability of ultrasonography (US) in detecting diabetic foot osteomyelitis (DFO) in patients with diabetic foot ulcers (DFUs). Approach: A 1-year prospective study was conducted on 47 consecutive patients with active DFUs and suspicion of DFO at a specialized diabetic foot unit. The following ultrasonographic features were evaluated at baseline: (1) periosteal reaction; (2) periosteal elevation; (3) cortical disruption; (4) sequestrum; and (5) positive power Doppler. The primary outcome measure aimed to establish the effectiveness of ultrasonographic features compared with aseptic bone culture for diagnosing DFO. Receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic performance of ultrasonographic features. Sample size could not be determined as it is the first study to assess ultrasonographic features for the diagnosis of DFO. The research adhered to the guidelines for diagnostic accuracy studies (Standards for Reporting of Diagnostic Accuracy Studies [STARD] 2015). Results: All patients (n = 24) diagnosed with DFO exhibited positive power Doppler, resulting in a sensitivity (S) and specificity (SP) of 1 and an area under the curve (AUC) of 1 (p < 0.001 [1-1]). Cortical disruption was present in 23 patients (95.8%) with DFO, yielding an S of 0.93, SP of 1, and AUC of 0.96 (p < 0.001 [0.88-1]). Innovation: It validates the diagnostic value of US for DFO as it is the first and largest study of its kind to establish a clear reference standard to guide clinician decision-making. Conclusion: This study demonstrates the effectiveness of cortical disruption and positive power Doppler in assessing DFO through US.

Osteoinductive activity of photobiomodulation in an organotypic bone model

Photobiomodulation (PBM) is a technique that harnesses non-ionizing light at specific wavelengths, triggering the modulation of metabolic pathways, engendering favourable biological outcomes that reduce inflammation and foster enhanced tissue healing and regeneration. PBM holds significant promise for bone tissue applications due to its non-invasive nature and ability to stimulate cellular activity and vascularization within the healing framework. Notwithstanding, the impact of PBM on bone functionality remains largely undisclosed, particularly in the absence of influencing factors such as pathologies or regenerative therapies. This study aims to investigate the potential effects of PBM using red (660 nm) (RED) and near-infrared (808 nm) (NIR) wavelengths within an ex vivo bone culture system - the organotypic embryonic chicken femur model. A continuous irradiation mode was used, administering a total energy dose of 1.0 J, at an intensity of 100 mW for 10 s, which was repeated four times over the course of the 11-day culture period. The primary focus is on characterizing the expression of pivotal osteoblastic genes, the maturation and deposition of collagen, and the formation of bone mineral. Exposing femora to both RED and NIR wavelengths led to a notable increase in the expression of osteochondrogenic transcription factors (i.e., SOX9 and RUNX2), correlating with enhanced mineralization. Notably, NIR irradiation further elevated the expression of bone matrix-related genes and fostered enhanced deposition and maturation of fibrillar collagen. This study demonstrates that PBM has the potential to enhance osteogenic functionality within a translational organotypic bone culture system, with the NIR wavelength showing remarkable capabilities in augmenting the formation and maturation of the collagenous matrix.

1280. Retrospective Chart Review of Diabetic Foot Infection Microbiologic Data at UnityPoint Health Des Moines

Abstract Background Foot infections are a common and serious complication in people with diabetes. Pseudomonas aeruginosa has traditionally been considered a common pathogen in diabetic foot infections (DFI). However, newer data has not found this to be true in clinical practice. In addition, the 2012 Infectious Diseases Society of America guideline for DFI states that “empiric therapy directed at Pseudomonas aeruginosa is usually unnecessary except for patients with risk factors for true infection with this organism”. Methods This study is a retrospective chart review of patients presenting with diabetic foot infections at regional teaching hospitals in the Midwest between August 1, 2021 and August 1, 2022. All the patients had either a bone, tissue, or wound culture obtained by podiatric medicine. Descriptive statistics were used to determine relationships between variables and the frequency of P. aeruginosa in culture. The primary objectives of this study were to quantify the prevalence of and determine predictors of pseudomonas DFI. Results There were 460 cultures reviewed in the specified time period with 168 cultures meeting criteria for inclusion in the final review. The most commonly isolated organisms were streptococci (29.8%) and methicillin-susceptible Staphylococcus aureus (26.2%). Pseudomonas was isolated in 21 of the 168 cultures reviewed (12.5%), with 17 of them being from non-bone cultures and 3 from bone cultures. The risk for pseudomonas appeared to increase with recurrent or relapsed diabetic foot infections (90.5%), having a previously isolated gram-negative pathogen in the last year (38%), and having a known pseudomonas colonization within one year (33.3%). Conclusion Streptococcus and Staphylococcus remain the most common organisms in DFI. Pseudomonas is a less common organism in DFIs; however, our study suggests rates of PSAR may be higher than previous studies have discovered. Risk factors for pseudomonas in our study appear to be recurrent or relapsed diabetic foot infections, having a previously isolated gram-negative pathogen in the last year, and having a known pseudomonas colonization within one year. Though some individualized risk factors can be useful, local epidemiology and resistance patterns remain essential for antibiotic treatment considerations. Disclosures All Authors: No reported disclosures

2219. Guiding stewardship interventions through tracking of bone cultures in diabetic lower extremity infections

Abstract Background Lower extremity infections (LEIs) of diabetic patients poses a challenge to addressing over-utilization of broad spectrum antibiotics (BSA). To guide the development of educational and behavioral initiatives, we employed ASP quality improvement surveillance practices to explore podiatric-surgery collected bone cultures (BC), pre-procedural tissue cultures (PTC) and results of resection margin pathology. Methods Washington DC VAMC is an urban medical center with 220 acute and LTC beds with acute and outpatient surgical Podiatry Service and supported by an active ASP (PharmD/MD/NP). Between 2020-2022 positive BCs collected in podiatric LEI procedures for presumed osteomyelitis were reviewed by ASP with CDSS (TheraDoc, Inc) and EMR (VISTA_CPRS). A positive post-resection margin (Margin+), empiric antibiotic selection and microbiology including regimen altering organisms such as MRSA and P. aeruginosa (PSAR) were collected. Results Diabetic individuals had 94 positive BCs in 296 procedures among nearly 2,000 total cultures. Subjects were predominately male (97%), mean age 68 ± 8.7 (45-93y); and nearly a third had &amp;gt; 1 BC. Intraoperative BCs made up 79% of episodes and half were Margin+. Subjects had high rates of PVD (45%), insulin-dependence (49%) and HbA1c &amp;gt; 10 mg/dL (21%). Empiric BSA selection consisted mainly of MRSA and PSAR coverage with no deaths &amp;lt; 30d from BC. Among BC with PTC, 61% had partial or complete correlation in microbiology; MRSA and PSAR incidence were the same if PTC:BC findings were concordant or not. PTC:BC microbiologic non-concordance vs concordance for Margin+ was not significantly different between the groups (45.8% vs 59.4%, P=NS) and among PTC:BC concordant samples, PSAR rates trended higher (12.9% vs 4.8%, P=NS) with no difference in MRSA incidence. Conclusion Providers have limited information in predicting LEI results in advance of path and micro. Empiric BSAs remains a challenge for ASPs. Less than half of patients had a BC finding that would have been predicted by the PTC and for those with a concordant prior to procedure sample, the finding of organisms that directed the empiric selection were not reflective of final cultures. There are opportunities for ASP interventions that address empiric selection in diabetic LEIs. Disclosures All Authors: No reported disclosures

1302. Impact of Insurance Coverage on the Route of Antibiotic Treatment for Forefoot Osteomyelitis

Abstract Background Recent studies suggest oral antibiotics can be a non-inferior alternative to intravenous antibiotics for treating bone and joint infections. In this study, we aimed to investigate whether insurance type affects the choice of antibiotic treatment routes and whether the route of antibiotic treatment influences the delivery of home health services. Methods We conducted a retrospective chart review of non-bacteremic patients who underwent amputations for forefoot osteomyelitis with residual signs of infection on proximal bone cultures and were discharged home from the hospital. Of 461 patients scheduled for hospital follow-up visits for bone and joint infections in our community practice infectious diseases clinic from January 2019 to December 2022, 40 met the inclusion criteria. Results were analyzed with multivariable logistic regression, selecting models with the lowest Akaike Information Criterion. Results The placement of PICC lines decreased significantly over time (OR 0.34, 95% CI: 0.14 - 0.71, p = 0.01), mirroring national trends favoring increased oral antibiotic use. After controlling for the year of treatment, we observed a trend towards patients with Medicaid insurance more frequently receiving IV antibiotics (OR 4.8, 95% CI: 1.0 - 29, p = 0.06). We found no evidence that the antibiotic administration route led to differences in the delivery of home health services at the time of discharge (p = 0.99). PICC Placement Percentage by Year and Insurance Percentage of PICC line Placement by year in patients with and without Medicaid Insurance during hospital encounter PICC Placement Frequency by Insurance and Home Nursing Frequency of PICC placement in patients during hospital encounters based on (A) if a patient has Medicaid insurance and (B) if home nursing is ordered at discharge Organisms Cultured by Year Frequency of organisms cultured on proximal bone cultures by year of study Conclusion Our findings suggest a trend towards patients with Medicaid insurance more frequently receiving IV antibiotics, despite the higher direct and indirect costs. It remains unclear whether this trend is due to differences in the severity of infections or microbiological resistance patterns. Future studies should assess the interaction of psychosocial and microbiological factors in influencing shared decisions regarding the route of antibiotic treatment outside of clinical trial settings. Organisms Cultured by Antibiotic Route, Insurance Type, and Home Nursing Orders Frequency of PICC line placement (A), Insurance coverage (B), and ordered for home nursing at discharge (C) by organisms cultured from proximal bone margins Disclosures All Authors: No reported disclosures

Dalbavancin as salvage therapy in difficult-to-treat patients for diabetes-related foot osteomyelitis

ObjectivesWe aimed to describe the efficacy and safety of dalbavancin in treatment of patients with diabetes-related foot osteomyelitis with bone culture confirmation. Patients and methodsBetween January 2019 and December 2021, all consecutive patients receiving at least one 1500 mg dose of dalbavancin for diabetes-related foot osteomyelitis were included in a retrospective study. Remission was defined as absence of relapsing infection or need for surgery at the initial or a contiguous site during 6-month follow-up from the last dose of dalbavancin. ResultsThirteen patients were included. Eleven (85%) patients were surgically treated. Six (46%) patients received dalbavancin as first-line treatment and 7 (54%) as second-line treatment due to adverse events related to previous treatments. One adverse event was reported. At 6-month follow-up, 11 patients were evaluable and 9 (82%) were in remission. ConclusionsIn the study, dalbavancin was well-tolerated and showed microbiological and clinical efficacy.

Infection after intramedullary nailing of femoral and tibial diaphyseal fractures

PurposeManagement of fracture-related infection (FRI) after intramedullary fixation (IF) is a challenge. The aim of the present study is to describe a series of 26 patients with FRI after IF and to evaluate factors possibly related to the outcome. MethodsBaseline variables were obtained at the time of IF: age, sex, body mass index, affected bone, open fracture, substance abuse, use of an external fixator, type of nail, reaming, soft-tissue reconstruction and surveillance culture result. After diagnosis of the infection, information was obtained about the time interval between IF and diagnosis and classification according to both the Willeneger and Roth and Makridis systems. Treatment modalities were grouped and analysed according to: use of antimicrobials, surgical debridement, nail removal or retention and spacer use. Cultures of bone or deep soft tissues were performed. Patients were followed up for 12 months, and outcomes (remission, relapse, death and loss of follow-up) were evaluated, as well as fracture consolidation. ResultsRemission was observed in 42.3% of patients. There was no significant association between any baseline variable and outcome. There was a significant association between Makridis stage 2 classification and recurrence or death. Treatment strategy was not significantly associated with outcome, and 65.4% of cases had positive culture results, with Enterobacter cloacae as the predominant agent. Consolidation was observed in 81.8% of patients and was not significantly related to the outcome. ConclusionThere was a significant association between Makridis classification and the outcome. Consolidation rate was not associated with the outcome regarding the treatment of the infection.

The infected diabetes-related foot: Comparison of erythrocyte sedementation rate/albumin and C-reactive protein/albumin ratios with erythrocyte sedimentation rate and C-reactive protein to differentiate bone and soft tissue infections.

The objective of this study was to evaluate the effectiveness of C-reactive protein (CRP)/albumin, erythrocyte sedimentation rate (ESR)/albumin ratio, ESR, CRP and albumin to differentiate bone and soft tissue infection in persons with diabetes. We retrospectively evaluated 242 individuals admitted to hospital with diabetes-related foot infections (DFI). We categorised DFI cases as either bone (OM) or soft tissue infection based on bone culture and/or histology. We evaluated the diagnostic accuracy of CRP, ESR, albumin, CRP/albumin and ESR/albumin as biomarkers to diagnose OM in persons with diabetes. The median age was 53 years (74% male). There were 224 diabetes-related patients of which 125 had been diagnosed with osteomyelitis. The ESR/albumin and CRP/albumin ratios cut-points were >17.84 and >1.83, respectively. ESR/albumin and CRP/albumin ratios had similar diagnostic parameters: AUC (0.71, 0.71), sensitivity (70.0%, 57.0%), specificity (62.0%, 75.0%), positive predictive value (67.0%, 71.0%) and negative predictive value (66.0% and 71.0%). In contrast diagnostic efficiency of CRP and ESR were AUC 0.71 and 0.71, sensitivity (45.6%, 71.2%), specificity (85.5%, 60.7%), positive predictive value (70.0%, 65.9%) and negative predictive value (59.5%, 66.4%), respectively. When comparing area under the curves, the results showed that ESR/albumin was not significantly different to ESR alone (Delong test pvs ESR >0.1). Similarly, CRP/albumin was not significantly different to CRP alone (Delong test pvs CRP >0.1). In conclusion, ESR/albumin and CRP/albumin ratios provided comparable results as using ESR and CRP alone.

Epidemiology, clinical characteristics, and outcomes of nontuberculous mycobacterial skin, soft tissue, and bone infections from a single center over a 10-year period

IntroductionNon-tuberculous mycobacteria (NTM) cause a wide variety of clinical syndromes. Data guiding diagnosis and treatment of NTM skin and soft tissue infections (SSTI) and bone infections are limited. We sought to better understand SSTI and bone infections caused by NTM. MethodsAll NTM clinical isolates recovered at Brooke Army Medical Center from 2012 to 2022 were screened; SSTI and bone isolates were included. Electronic health records were reviewed for epidemiologic, microbiologic, and clinical data. Infections were defined as recovery of one or more NTM isolate from skin, soft tissue, or bone cultures with a corresponding clinical syndrome. ResultsForty isolates of skin, soft tissue, or bone origin from 29 patients were analyzed. Twenty (69 %) patients, majority female (14/20, 70 %), had infecting isolates, most commonly secondary to surgery (35 %) or trauma (35 %). Six of 20 (30 %) had bone infections. Time from symptom onset to isolate recovery was a median 61 days (IQR 43–95). Eight (40 %) had combined medical/surgical therapy, 8 (40 %) had surgery alone, and 4 (20 %) had medical therapy alone. M. abscessus was more frequently isolated from patients with true infections. ConclusionsData supporting diagnosis and treatment decisions in NTM SSTI/bone infections is sparse.In this study the majority of NTM isolated were true infections. We confirm that surgery and trauma are the most common routes of exposure. The delay between symptom onset and directed therapy and the wide variety of treatment regimens highlight a need for additional studies delineating criteria for diagnosis and treatment.

OR29-04 Vitamin D Signaling Prevents Glucocorticoid-Induced Musculoskeletal Tissue Loss And Cardiac Dysfunction By Targeting The Atrogene Pathway

Abstract Disclosure: A. Sato: None. M. Cregor: None. B. Adhikari: None. M. Boerma: None. T. Bellido: None. Glucocorticoid excess increases the risk of bone fractures and induces cardiovascular events. Earlier studies demonstrated that glucocorticoids upregulate the expression of E3 ubiquitin ligases (atrogenes) in bone and skeletal/cardiac muscles, suggesting a common targetable pathway to prevent harmful glucocorticoid actions. Atrogenes stimulate proteasomal degradation of proteins, which promotes musculoskeletal tissue loss and cardiac dysfunction, known hallmarks of glucocorticoid disease. Here, we investigated whether Vitamin D receptor activation, which has beneficial musculoskeletal effects and may prevent falls, blocks glucocorticoid-induced activation of the atrogene pathway. Skeletally mature female 4-month-old C57Bl6 mice (N=12) were implanted with placebo or 2.1mg/kg/d prednisolone pellets for 8wks and received vehicle or 50ng/kg/d of 1,25D3 (calcitriol), 5x/wk, starting 3d before pellet implantation. In bone, 1,25D3 fully prevented decreases in spinal bone mineral density (BMD) and cancellous bone microarchitectural deterioration (low BV/TV and Tb.Th) induced by glucocorticoids. 1,25D3 prevented glucocorticoid-induced resorption, as quantified by circulating CTX and osteoclast number/surface. In contrast, 1,25D3 did not prevent glucocorticoid-induced suppression of bone formation, as quantified by circulating markers (P1NP and osteocalcin) and histomorphometric indexes (MS/BS and BFR). In skeletal muscle, 1,25D3 fully prevented glucocorticoid-induced loss of lean body mass, a muscle mass index measured by DEXA, and decreases in muscle strength, as determined by in vivo plantarflexion torque testing of the posterior hindlimb muscular compartment. Consistent with clinical evidence, cardiac echocardiography detected glucocorticoid dysfunction as exhibited by left ventricular (LV) wall thinning (anterior and posterior LVs at diastole and systole) and inefficient heart contraction (increased LV systolic volume, reduced ejection fraction and fractional shortening). Remarkably, 1,25D3 prevented the cardiac LV thinning and dysfunction induced by glucocorticoids. Neither glucocorticoid nor 1,25D3 altered heart mass, LV mass, or heart rate. 1,25D3 also prevented glucocorticoid increases in atrogene MuRF1 expression in cardiac and skeletal tissues. Additionally, 1,25D3 prevented glucocorticoid-induced increases in atrogene expression in separate ex vivo organ cultures of bone, skeletal muscle, and left ventricles of the heart, demonstrating direct Vitamin D actions. In conclusion, 1) atrogene upregulation is a central mechanistic hub underlying the damaging actions of glucocorticoid excess in bone, skeletal muscle, and the heart and 2) activation of Vitamin D receptor signaling preserves tissue structure and function by interfering with the atrogene pathway in musculoskeletal and cardiac systems. Presentation: Sunday, June 18, 2023

SAT190 The Effect Of Mechanical Loading On Bone Growth Ex Vivo

Abstract Disclosure: T. Aeppli: None. Z. Zhang: None. F. Zaman: None. L.S. Savendahl: None. Background: Bone growth is a multi-step process that involves proliferation and differentiation of chondrocytes within the growth plate. Apart from local regulation by various signaling pathways, chondrocytes respond also to external cues such as nutrition, inflammation and mechanical load that may increase or stunt growth. The Hueuter and Volkmann law describes the effect of mechanical loading on bone growth stating that bone growth is inhibited by increased mechanical compression and is promoted by reduced loading. To this date, no data is available investigating the local effects of mechanical loading on bone growth in the absence of systemic growth factors in small embryonic bones. Aim: The aim was to study the effects of mechanical loading on bone growth in an ex vivo bone culture model. Methods: Cultured femur and metatarsal bones from rats (E19.5) were studied and local/direct effects of mechanical loading on bone growth were investigated. A range of different mechanical forces was applied to femur and metatarsal bones every 2-3 days. To monitor bone growth, digital pictures were taken and bone length was measured every 2-3 days. The loaded bones were compared to control bones (sham-loaded). Results: When applying different mechanical load to metatarsal bones, bone growth was suppressed in a dose-dependent manner. On day 5, after applying mechanical loading (0.4 N) twice on day 0 and 2, metatarsal bone growth was significantly suppressed when compared to unloaded control bones (p&amp;lt;0.05). In contrast, when mechanical loading was applied repetitively to femur bones, bone growth was significantly stimulated (p&amp;lt;0.001) when compared to unloaded control bones. Conclusion: In conclusion, depending on the type of bone (embryonic rat metatarsal bone and the larger rat femur bone) mechanical loading exerts opposite effects on bone growth in an ex vivo culture model. The effect of mechanical loading on bone growth requires further in vivo investigations to increase our understanding on the role of mechanical loading in different bones and bone growth disorders. Presentation: Saturday, June 17, 2023