Prada, Libardo Rueda

Abstract Background: Clostridium ramosum ( C. ramosum ) is an anaerobic gram-positive bacillus of the human intestine and a rare cause of bacteremia. This retrospective cohort study evaluated clinical characteristics and outcomes of a multicenter cohort of adults with C. ramosum bacteremia. Methods: This multicenter retrospective cohort included adults (≥ 18 years) with true C. ramosum bacteremia at Mayo Clinic hospitals in Arizona, Florida, Minnesota, and Wisconsin from September 1, 2012, through December 31, 2025. Data were collected through search for C. ramosum in microbiological culture records. Clinical characteristics assessed included immune status, source of bacteremia, presence of sepsis, neutropenic fever, monomicrobial vs. polymicrobial bacteremia, antimicrobial resistance patterns, antimicrobial therapy, length of stay and 30-day all cause mortality. Exploratory odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results: Among 90 patients with a positive C. ramosum blood culture, 17 were classified as contaminants and 73 comprised the study cohort. Median age was 66.0 years (IQR, 56.0–75.0); 44 (60.3%) were male and 33 (45.2%) were immunocompromised (including 26 with active malignancy, while the remaining 7 were received biologic immunosuppression). The most common infection sources were gastrointestinal (32/73, 43.8%) and central line-related (8/73, 11%). At presentation, 50.7% of patients met criteria for sepsis and 15/73 (20.5%), were in septic shock. Of 73 isolates tested, 31/73 (44.3%) were clindamycin resistant and 9/73 (12.9%) tested intermediate. Anaerobic-active antimicrobial therapy was received by 53/73 (72.6%). Thirty-day mortality was 11/73 (15.1%). Mortality was 30.0% (6/20) with therapy without reliable anaerobic activity and 9.4% (5/53) with anaerobic-active antimicrobial therapy (OR, 4.02; 95% CI, 0.88–19.46; P = 0.060). The median hospital LOS was 8.0 days. Among 30-day survivors, anaerobic active antimicrobial therapy was associated with a shorter median LOS compared to therapy without reliable anaerobic activity (8.5 vs. 12.0 days). Immunocompromised patients had higher odds of monomicrobial C. ramosum bacteremia than immunocompetent patients (OR 3.16, 95% CI 1.19–8.39; p = 0.03). Patients with polymicrobial bacteremia had higher odds of sepsis (OR, 3.89; 95% CI, 1.43–10.55; P = 0.008) and septic shock (OR, 5.66; 95% CI, 1.17–27.36; P = 0.020). Patients with malignancy or neutropenia demonstrated significantly lower odds of presenting in septic shock (p = 0.018; p = 0.029 retrospectively). Microbiological clearance was achieved in 91.3% (42/46) of evaluable cases. Conclusions: This largest reported cohort defines the clinical and microbiological profile of C. ramosum bacteremia. Frequent clindamycin nonsusceptibility is clinically actionable. Several clinical associations found on univariable analysis should be further investigated in larger studies.

Background: Spinal epidural abscesses (SEA) are rare, occurring 2.5–3 times per 10,000 hospital admissions. While streptococcus species comprise 7% of reported SEAs, Group A Streptococcus (GAS) has been described only once in the medical literature to our knowledge. Case presentation: We present a case of GAS pharyngitis with subsequent paraplegia from a GAS SEA. A 33-year-old female presented to the emergency department (ED) and was initially diagnosed with GAS pharyngitis and a suspected strained lower back. Following treatment with amoxicillin, she returned with worsened back pain, radiculopathy, and leukocytosis, for which she was treated with cyclobenzaprine. On her third presentation, she had new bilateral lower extremity weakness with decreased sensation, bilateral ankle clonus, and hyperreflexia. MRI of the thoracic and lumbar spine revealed a multiloculated SEA at T5-T10 requiring laminectomy and abscess evacuation. Intraoperative cultures grew Streptococcus pyogenes. Despite surgery, medical management, and physical therapy, she remained paraplegic. Conclusions: To our knowledge, this is the first report of SEA preceded by GAS pharyngitis. This case exposes the critical association between a recent infection, progression of back pain, eventual neurologic symptoms, and inflammatory markers that should trigger concern for SEA and early evaluation with MRI.

e14545 Background: Durable antitumor immunity depends on the maintenance of stem-like CD8⁺ T cells capable of sustaining long-term effector responses. Oncolytic viruses (OVs) are potent immunomodulatory agents that reshape the tumor microenvironment and augment antitumor immunity. We hypothesized that platinum-based chemotherapy alters tumor-intrinsic type I interferon (IFN-I) signaling in a manner that can be functionally restored by OV therapy, thereby promoting the generation and persistence of stem-like CD8⁺ T cells. Methods: Tumor cells treated with platinum chemotherapy were evaluated in vitro for changes in IFN-I pathway activity, OV replication, and markers of immunogenic cell death (ICD). Syngeneic mouse tumor models were used to assess antitumor efficacy and immune remodeling following combination therapy. Tumor-infiltrating lymphocytes were analyzed by single-cell RNA sequencing and multiparameter flow cytometry to define CD8⁺ T-cell states and functional programs. Guided by these preclinical findings, a clinical trial combining XELOX, PD-1 blockade, and OV therapy was initiated (ChiCTR2500107607). Results: Platinum chemotherapy significantly suppressed tumor-intrinsic IFN-I signaling, while OV therapy restored antiviral responses, enhanced viral replication, and increased ICD in vitro. In vivo, the combination strategy resulted in superior tumor control and profound remodeling of the tumor immune microenvironment. The most pronounced immunologic effect was observed within the stem-like CD8⁺ T-cell compartment. Combination therapy induced a distinct population of TCF7⁺ ISG15^high NFATC1^low AP-1^low CD8⁺ T cells, characterized by restrained activation, enhanced persistence, and reduced propensity toward terminal exhaustion. In IRF7-deficient tumors, this stem-like CD8⁺ T-cell population failed to emerge and antitumor efficacy was significantly diminished, indicating that moderate tumor-intrinsic IFN-I signaling is required for this immune state. Conclusions: Tumor-intrinsic type I interferon signaling is a critical determinant of synergy between platinum chemotherapy and oncolytic virotherapy, enabling the maintenance of durable stem-like CD8⁺ T-cell immunity. These findings establish a mechanistic rationale for combining platinum chemotherapy, oncolytic viruses, and immune checkpoint blockade and support ongoing clinical translation. Clinical trial information: ChiCTR2500107607.

Background and Clinical Significance: Nonbacterial thrombotic endocarditis (NBTE) is a sterile fibrin-platelet valvular condition associated with malignancy and hypercoagulable states. It produces friable vegetations prone to systemic embolization, often presenting as multifocal ischemic stroke. While modestly linked to advanced adenocarcinomas, its association with melanoma is exceedingly rare; Case Presentation: We present a 43-year-old man with recently diagnosed metastatic melanoma who presented with fever, confusion and abdominal pain. Brain magnetic resonance imaging (MRI) revealed multifocal bilateral acute infarcts. Additional imaging demonstrated splenic and bilateral renal infarcts. Transesophageal echocardiography (TEE) revealed an 8 mm × 7 mm multilobar lesion on the posterior mitral valve leaflet. Blood cultures remained persistently negative; autoimmune and infectious workup were unrevealing, and positron emission tomography-computed tomography (PET-CT) showed no cardiac hypermetabolism. Despite empiric antibiotics for suspected infective endocarditis (IE), progressive embolic infarcts occurred. After exclusion of infection, NBTE was considered, and therapeutic enoxaparin was initiated, resulting in clinical stabilization without hemorrhagic conversion; Conclusions: Distinguishing NBTE from IE remains challenging due to overlapping and nonspecific imaging findings. TEE is the preferred diagnostic modality because of its high sensitivity for detecting small valvular vegetations. Adjunctive imaging modalities such as brain MRI and PET-CT may support the diagnosis by demonstrating embolic patterns or excluding metabolically active infectious vegetations. Management primarily relies on systemic anticoagulation, while percutaneous vegetation aspiration may represent a potential diagnostic and therapeutic strategy. Clinicians should maintain high suspicion of this condition in patients with advanced melanoma and other malignancies presenting with multifocal embolic phenomena and negative cultures to enable timely anticoagulation.

Background: Leprosy, caused by Mycobacterium leprae, presents on a spectrum ranging from tuberculoid to lepromatous disease. Borderline lepromatous leprosy represents an unstable immunological state that predisposes patients to immune-mediated reactions, including erythema nodosum leprosum (ENL), a severe inflammatory complication. Case Presentation: We report a case of a 62-year-old female with borderline lepromatous leprosy who presented with recurrent facial cellulitis and later developed disseminated ENL. She was initially diagnosed following a series of facial infections and confirmatory skin biopsy. Months later, she developed systemic inflammatory lesions consistent with ENL, requiring hospitalization. She was treated with high-dose corticosteroids for ENL and methotrexate to treat type 1 reaction and continued multidrug therapy (MDT) with minocycline, rifampin, and clarithromycin for leprosy, which led to significant clinical improvement. Conclusion: This case highlights the diagnostic challenges of leprosy in the United States and the importance of recognizing ENL as a severe immunologic complication requiring prompt intervention. A multidisciplinary approach is essential for optimal patient outcomes.

Background: Mycobacterium chelonae is a ubiquitous, rapidly growing, nontuberculous mycobacteria that primarily affects immunocompromised patients. The most common presentation is an atypical, chronic skin and soft tissue infection. Due to its high resistance rate, early diagnosis based on clinical suspicion, risk factor assessment, and exposure history is crucial for initiating appropriate multi-drug treatment. Methods: We report two cases of M. chelonae skin and soft tissue infections, one presenting with localized disease and the other with disseminated involvement. One case had a specific exposure to fish-related activities, a risk factor more commonly associated with Mycobacterium marinum infections rather than M. chelonae. Results: One of the cases involved osteomyelitis and tenosynovitis which are rare presentations of M. chelonae infection. While the limbs are the most commonly affected sites in disseminated M. chelonae infections, involvement of the lower extremities, as seen in one of our cases, is rarely reported. Treatment posed challenges due to antibiotic resistance and patient tolerance. However, in both cases where follow up was possible, prolonged multi-drug therapy led to complete resolution of the lesions. Conclusions: These cases highlight the importance of considering M. chelonae in chronic skin and soft tissue infections, especially in patient with relevant exposures or immunosupression. Uncommon presentations require a high index of suspicion. Given the challenges of treatment resistance and patient tolerance, prolonged multi-drug therapy remains essential for successful outcomes.