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329. Performance of Next Generation Sequencing in Isolating a Pathogen in Pediatric Osteoarticular Infections

Abstract Background Osteoarticular infections are often encountered in the pediatric population. Therapy is guided by isolation of a putative organism, however, operative cultures are often negative. Next generation sequencing (NGS) allows for more sensitive sampling of body compartments generally considered sterile. We sought to evaluate the utility of NGS in comparison to culture in detecting a pathogenic organism in acute osteomyelitis and septic arthritis in children. Methods This was a single-site study to evaluate the utility of NGS in comparison to culture in detecting a pathogenic organism in acute osteomyelitis and septic arthritis in children. Eligible patients were all patients with osteomyelitis or septic arthritis admitted to Rady Children’s Hospital from July 2019 through July 2020. We excluded any patients with bone or joint surgery within 30 days prior to admission. Operative samples were chosen at the surgeon’s discretion (joint aspirate, synovium, or bone) based on operative findings. We compared NGS testing to standard care culture from the same site. Results We enrolled 41 subjects. NGS of the operative samples identified a pathogen in 26 (63.4%) patients versus 18 (43.9%) by culture. Operative culture missed the diagnosis in 10 cases, though PCR identified the organism in 6 of those cases (5 were cases in which Kingella kingae was identified). In 4 subjects, NGS identified a putative organism where standard care testing (either PCR or culture) was negative. NGS was falsely positive in 1 subject and falsely negative for one other subject. Sensitivity was 96.3% (CI 95%, 81.0–99.9%) and Specificity was 92.9% (CI 95%, 66.1–99.8) for NGS versus 64.3% (CI 95%, 44.1–81.4) and 84.6% (CI 95%, 54.6–99.9%) for culture respectively. Conclusion In this single site prospective study of pediatric osteoarticular infections, we demonstrate improved sensitivity and specificity of NGS testing when compared to standard culture. Disclosures All Authors: No reported disclosures


. Composite Definition for Pressure Injury-related Osteomyelitis
Results: A total of 78 patients, accounting for 113 hospitalizations, and 138 unique PI, were identified (table 2). Patients had a mean age of 59 years at index admission and male predominance (97%). Of the 138 PI, 49% were ischial and 88% were stage 4. There were 27 FP and 51 NFP. The mean Charlson Comorbidity Index was 4.9 overall and significantly higher in the NFP vs. FP (5.2 vs. 4.3,p=0.05). Diagnostics included at least one imaging study in 76% (n=86) of hospitalizations and a bone biopsy in 45% (n=51). Bone biopsy cultures were commonly polymicrobial (47%, n=24), with anaerobes, Staphylococcus aureus, and Streptococcus species being the most predominant organisms. A diagnosis of definite, probable, or possible PIrOM was made in 14%, 16%, and 41% of hospitalizations, respectively (table 3). Healthcare utilization was high, with a mean length of antibiotic therapy of 54 days and mean length of stay of 122 days per hospitalization. The rates of healed PI overall at discharge and at 1 year were 27% and 39%, and 12% and 40% in the NFP group. The 1-year mortality for NFP was 22%, while all FP were alive at one year. Background: Osteoarticular infections are often encountered in the pediatric population. Therapy is guided by isolation of a putative organism, however, operative cultures are often negative. Next generation sequencing (NGS) allows for more sensitive sampling of body compartments generally considered sterile. We sought to evaluate the utility of NGS in comparison to culture in detecting a pathogenic organism in acute osteomyelitis and septic arthritis in children.
Methods: This was a single-site study to evaluate the utility of NGS in comparison to culture in detecting a pathogenic organism in acute osteomyelitis and septic arthritis in children. Eligible patients were all patients with osteomyelitis or septic arthritis admitted to Rady Children's Hospital from July 2019 through July 2020. We excluded any patients with bone or joint surgery within 30 days prior to admission. Operative samples were chosen at the surgeon's discretion (joint aspirate, synovium, or bone) based on operative findings. We compared NGS testing to standard care culture from the same site.
Results: We enrolled 41 subjects. NGS of the operative samples identified a pathogen in 26 (63.4%) patients versus 18 (43.9%) by culture. Operative culture missed the diagnosis in 10 cases, though PCR identified the organism in 6 of those cases (5 were cases in which Kingella kingae was identified). In 4 subjects, NGS identified a putative organism where standard care testing (either PCR or culture) was negative. NGS was falsely positive in 1 subject and falsely negative for one other subject. Sensitivity was 96.3% (CI 95%, 81.0-99.9%) and Specificity was 92.9% (CI 95%, 66. Background: As the number of joint replacement surgeries continues to rise, so does the number of joint infections. Many patients end up needing the implantation of antibiotic loaded bone cement (ALBC) to treat their infection. The use of localized high dose vancomycin, tobramycin, and gentamicin may be linked to acute kidney injury (AKI) in certain patients. Our hypothesis is that patients who developed AKI after receiving a joint spacer had a predisposition to AKI due to other comorbidities, high antibiotic doses in ALBC, immunosuppression, or the use of other nephrotoxic drugs pre-op. These patients may need close monitoring of their renal function and serum antibiotic levels after surgery.
Methods: We performed a chart review of 428 patients who underwent an orthopedic surgery that involved insertion of ALBC at our institution between 2015 and 2018. We excluded patients under age 18, those who had antibiotic irrigation only, trauma patients, non-arthroplasty surgeries (such as fractures and debridement of deep wounds), and patients with missing data for 30 days after the surgery. We identified 57 patients who fit our inclusion criteria and received a bone cement spacer or beads to treat an infection of the hip, knee, shoulder, or ankle. We matched patients who had AKI to 2 patients who did not have AKI. Matching was based on age (± 5 years), joint operated on, and antibiotics used.
Results: 15 patients showed an elevated serum creatinine level of over 1.2 within 30 days of surgery. 86.7% of these patients were male, their average age was 64.1 ± 6.2 years old, 40% had hip surgery, 46.7% knee surgery, 6.7% ankle, and 6.7% shoulder. All received vancomycin and tobramycin in Palacos bone cement. Compared to their case-control matches, these patients had more frequent use of immunosuppressive medication, a history of malignancy, a history of previous kidney disease, and obesity. The use of combined intravenous vancomycin and piperacillin-tazobactam post-operatively may also be linked to higher rates of AKI.
Conclusion: Immunosuppression, obesity, male gender, and history of kidney injury and cancer are factors associated with AKI after ALBC spacer implantation. Further analysis and study are needed to identify potential causation between ALBC use and AKI.
Disclosures: All Authors: No reported disclosures

Session: P-10. Bone and Joint
Background: Septic arthritis is an orthopedic emergency that requires debridement. Previous authors reported that patients with inflammatory arthropathy, diabetes, infection with S. aureus, involvement of a large joint, and synovial fluid WBC >85,000 are associated with >1 debridements. The purpose of this study was to determine factors associated with 1 vs >1 debridements.
Methods: This is a retrospective cohort of adult patients hospitalized at Denver Health Medical Center with large joint septic arthritis between 7/1/2012 and 4/13/20. Patients with implanted orthopedic material, osteomyelitis, and recurrent septic arthritis were excluded. Septic arthritis was defined as a patient presenting with acute arthritis and positive culture OR negative culture and no other etiology. Both electronic capture and manual chart review were performed. Descriptive statistics were used to characterize the population. Statistical analyses included bivariate and multivariate analyses.
Results As compared to those who had 1 debridement, those with >1 debridements were more likely to be male (95% vs 61.9%, p=0.02) and to have a higher synovial fluid leukocyte count (102,761 vs 49,154, p=0.001), CRP at admission (162.5 vs 97.7, p=0.039), and WBC the day prior to debridement (13.4 vs 9.8, p=0.007). Intra-operative purulence trended to association with >1 debridements. Pre-to post-operative changes in opiate use, temperature, and ability to work with physical therapy were not associated with 1 vs >1 debridements. Both higher synovial fluid leukocyte counts and CRP value at admission were independently associated with >1 debridements (OR 2.31, p=0.015; OR 1.01, p=0.036 respectively).
Conclusion: Patients with higher synovial fluid leukocytes and CRP at admission were more likely to have >1 debridements. Additional studies with functional outcome scores are necessary to determine if >1 debridements are associated with better clinical outcomes.
Disclosures: All Authors: No reported disclosures