Viral Etiology Research Articles

Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC).

605 Background: Casdozo is the first in class and only clinical-stage IL-27 targeting antibody, which induces increased serum IFN-γ and NK cell gene activation, leading to reversal of IL-27-mediated immune suppression. A phase (Ph) 1 study demonstrated a favorable safety profile and antitumor activity of casdozo alone and in combination with PD-1 blockade in indications with known high levels of IL-27 pathway activation, including HCC (NCT04374877). This open-label Ph 2 trial examined the potential antitumor activity and safety of casdozo with PD-L1 and VEGF blockade in uHCC (NCT05359861). Updated clinical and biomarker data are presented. Methods: Patients (Pts) with untreated uHCC received casdozo 10 mg/kg, atezolizumab (atezo) 1200 mg, and bevacizumab (bev) 15 mg/kg IV Q3W. Primary endpoints were safety and tolerability, with key secondary endpoints of investigator-assessed ORR by RECIST1.1 and mRECIST, PFS, and OS. Results: As of Sept 4, 2024, 30 pts received casdozo/atezo/bev. Most pts were male (77%), Asian (67%), had viral etiology (53% HBV, 17% HCV), and poor-prognosis disease assessed by metastatic spread (67%) and/or macrovascular invasion (13%). Median follow-up was 15 months (mo). Median time on therapy was 8 mo. The most common (>20%) adverse events related to any study drug were proteinuria (43%), hypertension (27%), fatigue (23%), and diarrhea (20%); Grade ≥3 events occurred in 67%, with only hypertension (20%), arising in >10% of pts. Treatment-emergent adverse events (TEAEs) resulting in any study drug discontinuation occurred in 30% of pts. No treatment-related deaths were reported. In the 29 RECIST1.1 response-evaluable pts, ORR was 38% with 17% of pts achieving a CR (5 CRs, 6 PRs); mPFS (95% CI) was 8.1 mo (1.9, 13.6); landmark PFS rates at 6, 12 and 18 mo were 58.6%, 36.1% and 27.1%, respectively; mDoR (95% CI) was NR (6.1, -). In the 28 pts evaluable for mRECIST, ORR was 43% (5 CRs, 7 PRs); mPFS (95% CI) was 8.4 mo (2.0, 14.5); mDoR was NR (12.7, -). mOS (95% CI) was 19.9 mo (14.2, -); the 12-mo survival rate (95% CI) was 85% (65, 94). More than 40% of pts remain on study, and 16.7% remain on study treatment. Available archival tissue of responders expressed IL-27+ TAMs by IHC, including tumors of viral and nonviral etiologies. Conclusions: Triplet blockade of IL-27, PD-(L)1, and VEGF pathways with casdozo/atezo/bev continues to show a manageable safety profile with promising antitumor activity in uHCC that warrants continued exploration. Toxicity was consistent with the known profiles of the agents, with no new safety signals identified. Biomarker analysis to evaluate immune response and associations of IL-27 pathway and clinical outcomes is ongoing. Additional clinical studies of casdozo in combination with toripalimab are planned. Clinical trial information: NCT05359861 .

Real-world (RW) experience with atezolizumab + bevacizumab (A+B) for the treatment of unresectable HCC (uHCC): A multicenter study.

537 Background: A+B is the preferred first-line (1L) standard of care for uHCC, with emerging RW evidence supporting its use in a broad patient (pt) cohort. We evaluated pt characteristics, clinical and treatment outcomes in pts treated at five U.S. institutions: Mayo Clinic, Houston Methodist, Moffitt Cancer Center, Mays Cancer Center, and University of Arizona. Methods: This is a retrospective study of uHCC pts who initiated A+B after January 1, 2019. De-identified pt data were extracted by treating oncologists. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed using Kaplan-Meier methods for all pts and for a “trial-like” subgroup with characteristics similar to those in the IMbrave150 trial (ECOG performance status [PS] 0-1, Child-Pugh [CP] class A, albumin-bilirubin [ALBI] grade 1-2). HCC-related hospitalizations were evaluated within 1 year of A+B initiation. Results: A total of 300 eligible pts were treated with 1L A+B (median age 68 years, 79% male, 79% White, 82% BCLC C, 44% viral etiology,12% ECOG PS >1). Liver function was CP A in 73% (36% A5, 31% A6, 6% not reported), CP B in 26% pts (15% B7, 7% B8, 5% B9), and CP C in 2 (<1%) pts. Compared with CP A, more CP B pts had characteristics of compromised liver function (CP A vs B: cirrhosis: 61% vs 91%; ascites: 7% vs 46%; encephalopathy: 4% vs 17%; esophageal varices: 14% vs 32%), bile duct invasion (2% vs 11%), and ECOG PS>1 (8% vs 22%), all Ps<0.001. Over a median follow-up of 8.7 mos, 244 (81%) pts discontinued A+B, primarily due to disease progression. Toxicity-related treatment discontinuation and hospitalizations due to treatment-related adverse events (TRAE) were similar between the two groups (Table). Median OS (mOS) was 14.4 mos (95% CI: 12.3, 18.2) and median rwPFS was 6.8 mos (95% CI: 5.8, 8.4). In the trial-like subgroup (n=194), mOS was 19.5 mos (95%CI: 14.6, 24.7) and median rwPFS was 8.8 mos (95% CI: 7.6, 12.1). In the CP B subgroup, mOS was 5.6 mos (95% CI: 4.6, 11.3) and median rwPFS was 3.1 mos (95% CI: 2.4, 5.8). Conclusions: This study demonstrates the RW outcomes of 1L A+B in a diverse pt cohort. Results from the “trial-like” pts further confirm the reproducible efficacy of A+B in clinical practice. Although pts with CP-B had higher hospitalization rates due to disease progression or symptoms, consistent with their underlying liver complications, they had similar rates of toxicity-related treatment discontinuation and TRAE-related hospitalizations compared to CP-A. Further characterization of safety for A+B in CP B pts within a prospective, controlled trial is warranted. N (%) CP A (n=219) CP B (n=79) Treatment discontinuation* 167 (76) 75 (95) Atezolizumab-related toxicity 20 (12) 13 (17) Bevacizumab-related toxicity 26 (16) 16 (21) Hospitalization* 87 (40) 58 (73) Symptom-related 42 (48) 35 (60) Progression 8 (9) 11 (19) TRAE 7 (8) 6 (10) *P-value comparing CP A vs CP B <0.001.

Prevalence and clinical characteristics of patients with brain metastases at diagnosis with advanced hepatocellular carcinoma in a retrospective registry.

540 Background: Hepatocellular carcinoma (HCC) is a cancer with poor prognosis and rising incidence. The combination of atezolizumab plus bevacizumab (A+B) prolongs survival as 1 st line therapy in advanced HCC (aHCC) but confers a rare risk of serious bleeding. HCC brain metastases (BM) have high hemorrhage rates and contraindicate the A+B regimen. Alternative immunotherapies also prolong survival without increased bleeding risk. We conducted a retrospective review of a large, diverse, cancer center registry to estimate the prevalence of and identify clinical characteristics associated with BM in aHCC. Methods: The University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center (HDFCCC) registry was queried for new cases of HCC between 2004 and 2022. AJCC stage III or IV were defined as aHCC. Cases with central nervous system (CNS) metastases (including brain as well as skull, face, or orbit as adjacent high-risk sites) at diagnosis were identified. Key clinical covariates including demographics, liver disease etiology, and symptomatology were described. Results: Among 4002 new HCC cases, 832 were classified as aHCC. 12/832 (1.4%, 95% CI: 0.8, 2.5) had synchronous BM. Key demographics are displayed in Table. 10/12 (83%) patients with BM were symptomatic, including headache (25%), neurologic deficits (67%), and/or syncope (8%). Bleeding complications and/or hemorrhagic features were reported in 17%. Conclusions: BM are rare at diagnosis with aHCC, present in only 1.4% of this registry dataset. The majority (83%) were symptomatic, suggesting that routine CNS imaging may not have clinical utility in asymptomatic patients. A high proportion with BM at diagnosis had viral etiology. Limitations of this retrospective registry analysis include potential for underdiagnosis in asymptomatic patients and incomplete data for clinical covariates. Clinical characteristics of aHCC cases with BM at diagnosis between 2004-2022 in UCSF HDFCCC Registry. Overall aHCC Cases (N=832) Cases with BM (n=12) Median age (range) (yrs.) 61 (8-92) 60 (48-65) Race/ethnicity (%)AsianBlackCaucasianHispanic (any race) 29105715 2586717 Gender (%)MaleFemale 7921 7525 Etiology (%)Viral hepatitisUnknown/negative 2971 7525 Symptomatic BM (%)HeadacheNeurologic deficitsSyncope NA 8325678 Hemorrhagic BM (%) NA 17

Clinical outcomes of camrelizumab + rivoceranib vs sorafenib (CARES-310) as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC) of non-viral and viral etiology.

578 Background: CARES-310 (NCT03764293) evaluated the combination of PD-1 inhibitor, camrelizumab (cam), and VEGFR-1-3 inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC. Cam + rivo significantly improved median overall survival (mOS) and median progression-free survival (mPFS) compared to sor (mOS, 23.8 months [mo] [95% CI 20.6, 27.2] vs 15.2 mo [95% CI 13.2, 18.5] hazard ratio [HR] 0.64 [95% CI 0.52, 0.79]; one-sided p<0.0001; mPFS, 5.6 mo [95% CI 5.5, 7.4] vs 3.7 mo [95% CI 3.1, 3.7]; HR 0.54 [95% CI 0.44, 0.67]; one-sided p<0.0001). The most common (≥10%) grade ≥3 treatment-related adverse events in the cam + rivo arm were hypertension (38.6%) and AST increased (20.2%). Methods: A post-hoc analysis of CARES-310 was performed, where mOS and mPFS were estimated using the Kaplan-Meier method and compared between the 3 etiology groups of non-viral, hepatitis C virus (HCV), and hepatitis B virus (HBV) using the log-rank test. Results: mOS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.68 [95% CI 0.39, 1.19]), HCV (HR 0.37 [95% CI 0.162, 0.84]), and HBV etiologies (HR 0.70 [95% CI 0.55, 0.89]) (Table). Similarly, mPFS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.55 [95% CI 0.34, 0.91]), HCV (HR 0.50 [95% CI 0.23, 1.06]), and HBV etiologies (HR 0.57 [95% CI 0.45, 0.72]) (Table). Conclusions: Cam + rivo in CARES-310 suggested clinically meaningful mOS benefit in non-viral and viral HCC vs sor and provides assurance of clinical benefit for first line treatment to patients with uHCC independent of etiology. Clinical trial information: NCT03764293 . Etiology Group Camrelizumab + Rivoceranib (n=272) Sorafenib(n=271) Non-viral, n (%) 42 (15.4%) 45 (16.6) mOS, mo (95% CI) 26.8 (10.3, NR) 15.2 (9.6, 23.2) mPFS, mo (95% CI) 6.1 (4.1, 13.8) 3.7 (2.4, 5.5) HCV, n (%) 22 (8.1) 29 (10.7) mOS, mo (95% CI) 31.7 (10.8, NR) 13.3 (8.0, 21.5) mPFS, mo (95% CI) 12.7 (3.7, NR) 3.7 (1.8, 9.1) HBV, n (%) 208 (76.5) 197 (72.7) mOS, mo (95% CI) 23.0 (18.9, 26.0) 15.6 (13.3, 19.2) mPFS, mo (95% CI) 5.6 (5.5, 7.3) 3.7 (2.7, 3.7) HCC, hepatocellular carcinoma; mOS, median overall survival; mPFS, median progression-free survival; mo, months; HR, hazard ratio; HCV, hepatitis C virus; HBV, hepatitis B virus, NR, not reached. Results used Cox proportional hazard model. Confidence Intervals (CI) used the Brookmeyer and Crowley method.

The Application of the Vesikari and Modified Vesikari Severity Scores in Complicated Pediatric Gastroenteritis of Viral Origin: An Observational Study

Background/Objectives: Viral gastroenteritis can have a potentially fatal outcome at young ages and the recognition of severe cases could be aided by clinically derived severity scores. Methods: This observational study intended to conduct a comparative assessment of the utility of the Vesikari and modified Vesikari score in the evaluation of viral gastroenteritis severity and for the possible prediction of the dehydration degree. A total number of 113 children diagnosed with gastroenteritis were retrospectively enrolled and divided based on viral etiology into group 1 (34 children with unknown viral etiology), group 2 (60 children with rotavirus) and group 3 (19 children with adenovirus). Results: The highest mean Vesikari and modified Vesikari scores were found in group 2 (p<0.01; p=0.01). A significant increase in liver enzymes was also identified in patients infected with rotavirus. The highest mean diarrhea, vomiting duration and body temperature were found in group 3 (p<0.01; p<0.01; p=0.02), as well as the highest mean inflammatory markers, such as C-reactive protein (CRP; p=0.01) and the erythrocyte sedimentation rate (p<0.01). Significant linear associations were found between pH, bicarbonate level, base excess and the Vesikari scores, whereas urea, CRP and aspartate aminotransferase levels were associated with both severity scores. ROC curve analysis revealed a significant correlation between the Vesikari scores and dehydration degree (p<0.01), with numeric cut-off values of 11.5 being proposed for the differentiation between mild and moderate gastroenteritis and 13.5 for the distinction between moderate and severe gastroenteritis. Conclusions: Both severity scores are useful in clinical settings, but more studies enrolling populations with various enteral infections could provide more insight into their etiology-based performance and reflection of paraclinical changes.

Radiomics-based prediction of HCC response to atezolizumab/bevacizumab.

636 Background: Advanced hepatocellular carcinoma (HCC) treatment has evolved with the introduction of atezolizumab/bevacizumab, showing improved outcomes over sorafenib. However, the response varies among patients, particularly between viral and non-viral etiologies. This study aimed to develop and evaluate multimodal prediction models combining quantitative imaging and clinical markers to predict treatment response in HCC patients. Methods: From March 2020 to May 2023, patients with advanced HCC treated with atezolizumab/bevacizumab were retrospectively identified from six centers in Germany and Austria. Patients underwent baseline contrast-enhanced liver MRI and follow-up imaging to assess therapy response. Machine learning models, including RandomForestClassifier, were developed for radiomics, clinical, and combined datasets. Hyperparameter tuning was performed using RandomizedSearchCV, followed by cross-validation to evaluate model performance. Results: The study included 103 patients, with 70 achieving disease control (DC) and 33 experiencing disease progression (PD). Key findings included significant differences in treatment response and progression-free survival between DC and PD groups. The radiomics model, using 14 selected features, achieved 73.1% accuracy and a ROC AUC of 0.635 on the test set. The clinical model, with 4 selected features, achieved 73% accuracy and a ROC AUC of 0.649 on the test set. The combined model showed improved performance with 69% accuracy and a ROC AUC of 0.753 on the test set. Hyperparameter tuning further enhanced the combined model's accuracy to 80.1% and ROC AUC to 0.771 on the test set. Conclusions: The hybrid model combining clinical and radiological data outperformed individual models, providing better predictions of response to atezolizumab/bevacizumab in HCC patients.

A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia.

Pneumonia stands as the primary cause of death among children under five, yet current diagnosis methods often result in inadequate or unnecessary treatments. Our research seeks to address this gap by identifying host transcriptomic biomarkers in the blood of children with definitive viral and bacterial pneumonia. We performed RNA sequencing on 192 prospectively collected whole blood samples, including 38 controls and 154 pneumonia cases, uncovering a 5-transcript signature (genes FAM20A, BAG3, TDRD9, MXRA7, and KLF14) that effectively distinguishes bacterial from viral pneumonia (area under the curve (AUC): 0.95 [0.88-1.00]). Initial validation using combined definitive and probable cases yielded an AUC of 0.87 [0.77-0.97], while full validation in a new prospective cohort of 32 patients achieved an AUC of 0.92 [0.83-1.00]. This robust signature holds significant potential to enhance diagnostics accuracy for pediatric pneumonia, reducing diagnostic delays and unnecessary treatments and potentially transforming clinical practice.

Effects of disease aetiology on outcomes for unresectable HCC treated with lenvatanib or atezobev: A real world retrospective study.

554 Background: Hepatocellular Carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-death worldwide. 1 Standard of care first line treatment for unresectable HCC is Atezolizumab plus Bevacizumab (AtezoBev) 1 while the multi-kinase inhibitor Lenvatinib 2 is also available in the first line setting. No randomised studies have compared these treatments directly. Real world data suggests similar overall survival (OS) with AtezoBev possibly superior in patients with a viral hepatitis aetiology and Lenvatinib superior in NAFLD. 3,4,5,6,7 Methods: We evaluated patients treated with Lenvatinib or AtezoBev in a retrospective cohort of patients who commenced first-line treatment in the West of Scotland from 04/12/2015 to 28/11/2023. 102 received Lenvatinib and 52 AtezoBev. We collected data on progression free survival (PFS), OS, demographics and disease aetiology- classified primarily as viral hepatitis, acholic liver disease (ALD) or NAFLD. Results: AtezoBev patients had improved mOS compared with Lenvatinib (13.8 vs 9. 1 months, p = 0.04). No statistically significant differences were observed in mPFS (5.5 vs 3.5 months, p = 0.31). Of the three aetiologies considered, the only statistically significant (p<0.05) difference between the treatments was OS in the NAFLD group (24.1 vs 9.1 months, p = 0.04). When considering patient demographic and disease factors, Child-Pugh score was most significant. Patients with Childs=5 liver disease had much longer OS and PFS compared with Childs≥6 disease. Similarly, patients with ECOG PS=0 had improved survival than PS≥1. There were no statistically significant (p<0.05) differences between AtezoBev and Lenvatinib. Age, sex and social deprivation (SIMD) score had minimal effects on survival although high levels of social deprivation and male sex were over-represented in our population. Conclusions: In contrast to other real world analyses, our patients demonstrated improved mOS with Atezo/Bev vs Lenvatinib. 3 However, mPFS was similar for the two regimes. The difference in OS may be explained by differences in patient selection, with the Lenvatinib group disproportionately representing patients with a poorer performance status (PS>0) and higher Childs-Pugh scores (CP>5). Furthermore, patients in the AtezoBev group who progressed were often offered Lenvatinib second-line, possibly improving mOS, whereas Lenvatinib patients who progressed were offered either Sorafenib, a clinical trial or best supportive care. However, we cannot rule out a direct survival benefit from the use of AtezoBev vs Lenvatinib in the first line setting. The choice of first line therapy for HCC remains complex and must account for patient preferences such as convenience and side effect profile in addition to observed trial outcomes and the increasing body of real world evidence. 1. Finn RS et. al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020 May 14;382(20):1894-1905. 2. Kudo, Masatoshi et. al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018. Volume 391, Issue 10126, 1163 – 1173. 3. Wang, BC. et. al. Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies. Targ. Oncol. 2024. 19, 203–212. 4. Casadei-Gardini A et. al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur. J. Cancer. 2023; 180:9-20. 5. Rimini M et. al. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis. ESMO Open. 2022 Dec;7(6):100591. 6. Su CW et. al. Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. Cancer Med. 2023. 12(6):7077-7089. 7. Rimini, M., et al. Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients. J. Cancer. Res. Clin. Oncol. 2023. 149, 7565–7577.

Etiology of infectious keratitis.

Analyze the etiology of infectious keratitis in our hospital. Retrospective study in which the medical records of patients were reviewed in which a keratitis-producing microorganism was detected during the last 9 years (January 2014-December 2022). The sample was obtained by corneal scraping and seeded in non-selective media. Bacterial and fungal identification was carried out by mass spectrometry and viral identification by polymerase chain reaction (PCR). Sensitivity was obtained using disk-plate antibiograms, E-test or broth microdilution systems. A total of 433 samples of corneal scrapings belonging to 416 patients were processed. Of the total samples, 196 were positive (44,3%). The average age was 55 years, with 51% being women. Regarding the etiology, we found the following isolates: Gram-positive bacteria (N = 83) (44%), highlighting Staphylococcus aureus (N = 33), coagulase-negative staphylococci (N = 26), being Staphylococcus epidermidis the most frequent (N = 19). Gram-negative bacteria (N = 67) (35%), including: Pseudomonas aeruginosa (N = 31), 42% associated with the use of contact lenses and Enterobacterales (N = 16). Anaerobes (N = 19), which 18 isolates were Cutibacterium acnes. Regarding viral etiology (N = 10): herpes simple type 1 (N = 7). Varicella-zoster virus (N = 3). Finally, the fungal etiology (N = 13), highlighting Candida spp. (N = 10). The main agents of infectious keratitis are Staphylococcus aureus and Pseudomonas aeruginosa. The causative agent was detected in 44,3% of the samples, so microbiological analysis of these samples is highly advisable.

304. Global Incidence of Viral Lower Respiratory Tract Disease (LRTD) Episodes and Hospitalizations (2010–2021)

Abstract Background The COVID-19 pandemic highlighted the impact of viruses on lower respiratory tract diseases (LRTD); however, the global burden of viral LRTD is undefined. To bridge this gap, we estimated the global incidence of viral LRTD and hospitalizations in 2010–21. Figure 1. Global incident count of viral LRTD episodes by viral etiology (2010–2021). Non-viral causes are shown for comparison. Methods We used the Global Burden of Diseases, Injuries, and Risk Factors 2021 (GBD) framework and a Bayesian meta-regression tool (DisMod-MR 2.1) to estimate the global incidence of viral LRTD. We defined viral LRTD as clinician-diagnosed pneumonia/bronchiolitis, capturing symptoms such as cough, difficulty breathing, fever, and chest discomfort. Viral LRTD were categorized by pathogen (SARS-Cov2; influenza; respiratory syncytial virus [RSV]; ‘other’). We estimated hospitalizations by applying a country-specific scalar, informed by inpatient admission data and a country-specific healthcare access and quality index from the GBD, on pathogen-specific estimates of LRTD for each country. In data sparse regions, estimates were generated by extrapolation.Figure 2.Global incident count of viral LRTD hospitalizations, by viral etiology (2010–2021). Non-viral causes are shown for comparison. Results Average global incidence (per 100,000 person-years [PY]) of viral-associated LRTD episodes was 1,198 in 2010–19 and 25,716 in 2020–21. The number of viral LRTD cases was 880 million in 2010–19 and 4 billion in 2020–21. Average overall global incidence (per 100,000 PY) of viral LRTD hospitalizations was 170 (123 in 2010–19; 388 in 2020–21). The total number of hospitalizations was 90 million in 2010–19 and 61 million in 2020–21. Influenza and ‘other’ viruses accounted for most viral LRTD episodes (Figure 1) and hospitalizations in 2010–19 (Figure 2). Viral LRTD episode rates remained stable until 2019, while hospitalization rates increased. A decrease in influenza- and RSV-related episodes and hospitalizations was noted in 2020–21. Conclusion Viral LRTD are common and incur substantial global healthcare burden. Year-on-year increases in severe cases requiring hospitalization, most recently compounded by the COVID-19 pandemic, are alarming. Given the previously underappreciated scale of the problem, increased surveillance and novel therapeutic options may help reduce the burden of viral LRTD. Disclosures Ekaterina Maslova, ScD, AstraZeneca: Employee of AstraZeneca|AstraZeneca: Stocks/Bonds (Private Company) Malin Fageras, PhD, AstraZeneca: Full time employee|AstraZeneca: Stocks/Bonds (Private Company) Lisa White, PhD, AstraZeneca: Advisor/Consultant Pratik Sinha, MBChB/PhD, AstraZeneca: Advisor/Consultant|Prenosis Inc: Board Member

P-1122. Impact of an Antimicrobial and Diagnostic Stewardship Program in Children with Lower Respiratory Tract Infection admitted to Intensive Care Unit in Argentina

Abstract Background Lower respiratory tract infection (LRTI) is a common cause of admission and antibiotic (ATB) overuse in children. Adequate use of diagnostic methods and ATB prescription in intensive care units (ICU) remain a challenge for antimicrobial stewardship programs. Aims to evaluate the impact of a multilevel intervention to improve diagnostic testing and ATB use in children with LRTI admitted to ICU. Methods Quasi-experimental, before-after study. Patients admitted to ICU from April to June 2023 (Pre Intervention period: PreI) and July to October 2023 (Post Intervention: PostI) with community acquired LRTI were included. Intervention consisted in educational activities, daily review and feedback of ATB prescription, development and dissemination of an institutional Guideline of ATB use in LTRI, including a Clinical Score to distinguish viral from bacterial pneumonia. Results 95 patients were included. Median age was 11 months (IQR 4-19).Fifty eight (61%) had any underlying condition, including: previous bronchiolitis N:16 (17%), Asthma N:8(8%) and Neurological Disorders N:7 (7%). Clinical diagnosis upon ICU admission was: bronchiolitis (N:42, 44%), asthmatic crisis (N: 33, 35%) and Pneumonia (N: 11, 12%). A viral etiology was documented in 76 patients (80%). The most common was RSV (N: 52, 55%) followed by Rhinovirus (N: 19, 20%). Viral coinfection was detected in 15 patients (16%). Sixty-three patients were admitted during PreI and 32 during PostI. Children admitted to ICU during PreI were more frequently healthy (PreI: 48% vs PostIn 22%, p 0.015), with bronchiolitis as admission diagnosis (PreI 56% vs PostI 23%, p 0.002) and confirmed respiratory infection (PreI 87% vs PostI 66%, p 0.01). In PreI more Blood cultures (PreI 61% vs PostI 51%, p 0.06) and tracheal aspirate cultures (PreI 48% vs PostI 22%, p 0.04) were performed. Empirical ATB were started on admission in 39 patients (62%) during PreI, and in 13 patients (41%) in PostI (p: 0.04). Adequate ATB prescription increased from 14% in the PreI to 37% in the PostI (p 0.01). Patients in PostI had shorter hospital length of stay (8 vs 14 days, p 0.02) Conclusion A multilevel intervention in children with LRTI on admission to ICU improved the use of blood and tracheal aspirate cultures and ATB prescription. Length of stay decreased in PostI. Disclosures All Authors: No reported disclosures

P-2358. Viral etiologies of bronchiolitis, pneumonia, and croup in children less than 5 years old, New Vaccine Surveillance Network, 2016-2022

Abstract Background Acute respiratory illness (ARI) is a leading cause of medically attended visits among children. A multi-season, multicenter, prospective evaluation of viral etiologies for different ARI syndromes is lacking. We describe the epidemiology of respiratory viruses (RV) detected among children with bronchiolitis, pneumonia, and croup in the New Vaccine Surveillance Network (NVSN).Table 1.Demographic characteristics of children less than 5 years with different acute respiratory illness syndrome (n=14,590), New Vaccine Surveillance Network, 2016-2022 Methods NVSN is a population-based, prospective, active surveillance network conducted at 7 pediatric hospitals. During 2016-2022, children < 5 years old with ARI were enrolled in the emergency department (ED) or inpatient unit. Respiratory samples obtained at enrollment were tested by RT-PCR for 8 RV (Figure 1). Demographic and clinical data were collected by caregiver surveys and chart review. ICD-10 codes were used to identify cases of bronchiolitis, pneumonia, and croup; cases with multiple ARI syndromes of interest were excluded. Descriptive statistics were used to summarize the proportion of viral detections by ARI syndrome and age group.Figure 1.Respiratory virus detection across different acute respiratory illness syndromes, stratified by age , New Vaccine Surveillance Network, 2016-2022 Results Of 44,194 children enrolled, 14,590 were diagnosed with one ARI syndrome of interest, including 10,450 (71.6%) with bronchiolitis, 2,305 (15.8%) with pneumonia, and 1,835 (12.6%) with croup (Table 1). Of 14,590 children with one ARI syndrome, 12,138 (83%) had at least one virus detected. Among children with bronchiolitis or pneumonia, respiratory syncytial virus (RSV) and rhinovirus/enterovirus (RV/EV) were the most commonly detected viruses (Figure 1), whereas among children with croup, parainfluenza viruses (PIV) and RV/EV were most commonly detected. Among hospitalized children, children with pneumonia had the highest proportion of supplemental oxygen administration (69%), mechanical ventilation (7%), and death (0.3%). No deaths were reported for children with bronchiolitis or croup.Table 2.Severity and respiratory support across different acute respiratory illness syndromes evaluated in inpatient units (n=10,879), NVSN, 2016-2022 Conclusion From 2016-2022, RSV was commonly detected among children with bronchiolitis or pneumonia in the ED and inpatient settings and PIV was commonly detected among children with croup; RV/EV was commonly detected for all syndromes. Respiratory virus detections among common ARI diagnoses may evolve with the introduction of new respiratory virus prevention products underscoring the importance of continued evaluation. Disclosures Christopher J. Harrison, MD, GSK: Grant/Research Support|Medscape: Honoraria|Merck: Grant/Research Support|Pfizer: Grant/Research Support|UpToDate: Honoraria Geoffrey A. Weinberg, MD, Inhalon: Advisor/Consultant|Merck & Company: Honoraria for textbook chapter preparation Janet A. Englund, MD, Abbvie: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Speaker at meeting|SanofiPasteur: Advisor/Consultant|Shinogi: Advisor/Consultant Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Grant/Research Support|Abbott: Honoraria|BioMerieux: Grant/Research Support|Cepheid: Grant/Research Support|Diasorin: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Luminex: Grant/Research Support|Qiagen: Grant/Research Support Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria

P-2284. "Low Incidence of Bacterial and Viral Infection after Robotic Surgery Kidney Transplant"

Abstract Background Kidney and kidney-pancreas transplantation should benefit patients with end-stage kidney disease and diabetes mellitus. Immunosuppressive medication are required to prevent rejection and maintain graft. However, immunosuppression increases the risk of infection. Surgical procedures also lead to inflammation post-kidney transplant, which results in opportunistic viral/fungal infections. Robotic surgery is well established to be less invasive and cause less harm in the short term for patients. However, it has never been investigated for infectious disease complications post-kidney transplantation. Methods This was a single-center, retrospective cohort study conducted at a large kidney transplant center in the US. We included all recipients who had received kidney or kidney-pancreas transplants through robotic surgery between November 15th, 2022, and March 14th, 2023. We investigated the incidence of infection and its pathogen and the duration from transplant to infection for bacterial, fungal, and viral etiologies within 6 months post transplantation. Results Thirty-four, and 2 kidney and kidney/pancreas transplants were performed during the study period. Thirteen (36.1%) and 4 (11.1%) of urine culture positivity (predominantly Pseudomonas and E.coli) and bacteremia were identified. The causative pathogen of 4 bacteremia includes two Staphylococcus aureus, E.coli, and Morganella. Only 6/36 (16.7%) and 3/36 (8.3%) of clinically significant CMV and BK Polyomavirus DNAemia, which required treatment, including adjusting immunosuppression, were identified. Six cases of SARS-CoV-2 and one case of influenza were also identified. Conclusion We conducted a retrospective cohort study regarding infections after robotic kidney and kidney/pancreas transplant surgery. A very low surgical site infection and relatively low BK Polyoma viral infection rate were noted. Further study should be required to compare the incidence between robotic and traditional surgery. Disclosures Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant

P-2235. Implementation of a Host-Protein Test (MMBV) Into Routine Care for Children Hospitalized with Symptoms of Lower Respiratory Tract Infection

Abstract Background Infectious etiology is often unclear in children hospitalized with symptoms of lower respiratory tract infection (LRTI), driving antibiotic misuse. A host-protein test (MMBV) exhibits high diagnostic accuracy for differentiating bacterial from viral etiology. Best practices for test implementation should be established. We evaluate the effectiveness of implementing MMBV into routine care without specific antimicrobial stewardship (AMS) education by assessing impact on antibiotic administration to children hospitalized with LRTI symptoms. Patient flow Eligibility required age 3 months to 5 years old and hospitalized with 1 or more of the following signs or symptoms that concern for lower respiratory tract infection (LRTI): accessory muscle use, chest pain, cough, crepitation or rales, decreased breath sound, dyspnea, prolonged expiration, wheezing. MMBV, MeMed BV. Methods Retrospective pragmatic study of MMBV implementation at a single medical center without specific AMS education. Children 3 months to 5 years old hospitalized with LRTI symptoms were included. In the non-interventional arm (2014-2017) MMBV results were not available in time to impact antibiotic decisions. In the interventional arm (2021-2022) MMBV results were rapidly available. Patients were assigned into discharge diagnosis classes: bronchiolitis, community acquired pneumonia (CAP), viral diagnosis and other diagnosis. Antibiotic administration was compared between arms per diagnosis class. The relative reduction in antibiotic administration in the interventional arm versus the non-interventional arm according to discharge diagnosis class There was a relative reduction in antibiotic administration in the interventional arm relative to the non-interventional arm from 60.0% (12/20) to 22.5% (9/40) for bronchiolitis; from 98.7% (74/75) to 97.3% (71/73) for CAP; from 15.0% (12/80) to 13.3% (6/45) for viral diagnosis; and from 60.7% (51/84) to 51.8% (43/83) for other diagnosis. P-values were calculated using Richardson’s method. CAP, community-acquired pneumonia. Results Age, sex and MMBV results were similar across arms. Viral MMBV rates were high (39%-90%) across all diagnosis classes in the non-interventional (n=259) and interventional (n=241) arms. A significant relative reduction in antibiotic administration of 62.5% (p=0.004) was attained in patients discharged with bronchiolitis without impacting length of stay (p=0.530). Non-significant reductions in antibiotic administration were observed for CAP, viral diagnosis and other diagnosis. Conclusion MMBV availability is associated with judicious antibiotic administration to children hospitalized with bronchiolitis without AMS education. Combining MMBV introduction with AMS education is required to reduce potentially unwarranted antibiotics in children hospitalized with CAP. Disclosures All Authors: No reported disclosures

ЗНАЧЕНИЕ ПОЛИМЕРАЗНОЙ ЦЕПНОЙ РЕАКЦИИ В ВЫЯВЛЕНИИ ИНФЕКЦИОННЫХ АГЕНТОВ У КРУПНОГО РОГАТОГО СКОТА

The aim of our work was to identify bacterial and viral infectious agents in biological material from cows and calves with different clinical manifestations of diseases by PCR. Biological materials from animals were sent to the PCR laboratory from 23 agricultural organizations in the Ural Region. A total of 808 samples were studied, of which genomes of pathogens were found in 11.9 % of cases: Mycoplasma bovis DNA in 2.4 % of samples, Bovine virus diarrhoea RNA in 2.3 % of samples, Mycoplasma spp. and Chlamydia spp DNA in 2 % of samples, Mycoplasma bovigenitalium, Bovine herpesvirus (type 1), Chlamydophila abortus, Chlamydophila pecorum were found singly. Out of 80 samples in 36.2 % of biomaterials, specific DNA sites of Cl. difficile were found – 31.2 % of samples, Cl. perfringens – 20.0 % of samples, Cl. difficile + Cl. perfringens – 25.0 % of biosamples. Toxins were found in Cl. difficile: CDT toxin in 41.0 % of clostridia, toxin B in 6.0 % of pathogens, less often toxin A. In some cases, clostridia (Cl. perfringens, Cl. difficile B) were found in the biomaterial from dead calves, which confirmed the diagnosis – infectious anaerobic enterotoxemia of calves. Bacteria (E. coli, Salmonella enterica spp. entericaserogroup C (0:9, 2), Cl. perfringens and Cl. difficile CDT DNA) were detected in the biomaterial from dead cows, which confirmed the diagnosis of acute intestinal infection. All detected pathogens were presented in the form of monoinfection and singly in the form of mixed infections. Using PCR, it was possible to detect DNA and RNA of infectious agents in various clinical manifestations of diseases of bacterial and viral etiology in cattle herds in the Ural Region.

Herpetic Endotheliitis Induced Interface Fluid Syndrome 16 years After Laser in Situ Keratomileusis.

To report a case of herpes simplex virus (HSV) endotheliitis inducing acute interface fluid syndrome in a patient with a remote history of laser in situ keratomileusis (LASIK). Case report and literature review. A 51-year-old man with a history of LASIK 16 years prior presented with unilateral HSV endotheliitis and was found to have acute interface fluid syndrome secondary to endothelial decompensation. The patient was treated with oral valacyclovir 1 g 3 times daily, prednisolone acetate 1% drops 4 times daily, timolol maleate 0.5% drops twice daily, topical 5% sodium chloride hypertonic ophthalmic solution drops 4 times daily, and 5% sodium chloride hypertonic ophthalmic ointment nightly. At 1-month follow-up, the patient had full resolution of the interface fluid and returned to baseline visual acuity. This case underscores the importance of considering viral etiologies, such as HSV endotheliitis, in interface fluid syndrome beyond a decade after LASIK.

Frequency of viral etiology in community-acquired pneumonia.

The identification of etiology is very important when managing patients with community-acquired pneumonia (CAP). In Pakistan, studies regarding the viral etiology in CAP are scarce. The main objective of this study was to evaluate the frequency of viral etiology in CAP patients and analyze the clinical features and their impact on prognosis. Medical records of CAP patients admitted to Aga Khan University Hospital (Karachi, Pakistan) from March 2022 to February 2023 were retrospectively reviewed, patients who had microbiological tests performed within 48 hours of the hospital admission were included, and the frequency of viral and bacterial etiology was calculated. Patients who were immunocompromised were excluded. Epidemiological and clinical characteristics were examined, and the impact on prognosis was explored. A total of 166 patients were included; 115 (69.3%) patients were identified as having pneumonia with known causative microorganisms. A total of 83 (72.1%) patients had a viral etiology alone, 18 (15.6%) had only bacterial infection, and 14 (12.2%) had a viral and bacterial co-infection. Influenza A was most frequently detected (n=46/97; 47.4%), followed by Rhinovirus/Enterovirus (n=19/97; 19.6%). Staphylococcus aureus accounted for the majority (n=18; 56.3%) of cases among bacteria. Bacterial and viral-bacterial co-infection was significantly higher among non-survivors (38.1% vs. 16.6%, p=0.034). Confusion-Urea-Respiratory Rate-Blood Pressure-Age of 65 scores of 3-5 [odds ratio (OR) 4.234; 95% confidence interval 1.156-15.501], leukocytosis (OR 0.137; 0.030-0.636), high C-reactive protein (>10mg/L) (OR 1.008; 1.001-1.014), high serum procalcitonin level (≥0.5 ng/mL) (OR 10.731; 3.018-38.153), and mechanical ventilation required (OR 47.104; 13.644-162.625) were associated with mortality. Mechanical ventilation requirement was independently associated with increased odds of mortality (OR 43.407; 8.083-233.085). Of 166 patients, 21 (12.7%) had died, with the highest percentage (28.6%) seen in the viral-bacterial coinfection group (p=0.046). To conclude, respiratory viruses are increasingly being recognized as an important etiology in CAP, with higher mortality seen in bacterial infection, whether alone or with viral co-infection.

Comparative analysis of iridian anterior segmentOCT and microbiological features in Fuchs Uveitis Syndrome and Posner-Schlossman Syndrome.

To compare iridian Swept-Source Anterior Segment OCT (SS-AS-OCT) and microbiological features in Aqueous Humor (AH) in patients with Fuchs Uveitis Syndrome (FUS) and Posner-Schlossman Syndrome (PSS). Comparative, retrospective-prospective single center study examining 131 eyes from 66 patients, including 33 eyes with PSS, 37 eyes with FUS, and 61 healthy eyes. AH samples were collected from affected eyes in all patients. Cross-sectional 6mm SS-AS-OCT B-scans were taken from iris quadrants and analyzed for Stromal Thickness (ST), Smooth Index (SI), and Optical Density (OD) with ImageJ®. Statistical analysis was performed using SPSS®. Among 32 PSS patients, Cytomegalovirus (CMV) was detected in 21 (65.5%). Of 34 FUS patients, 22 (64.7%) tested positive for Rubella Virus (RV) and one for CMV (2,9%). FUS eyes showed decreased ST compared to PSS ones in the superior (328.2 ± 49.4 vs 352.2 ± 47.4; p = 0.010) and temporal (322.6 ± 54.4 vs 294.3 ± 47.9; p = 0.024) quadrants. FUS eyes had a higher mean SI (p = 0.021), notably in the temporal quadrant (p = 0.002). Both FUS and PSS eyes showed significant differences in all parameters compared to healthy eyes, except for ST and OD in the temporal quadrant in PSS, and OD in the nasal quadrant in FUS. Quantitative analysis of iris OCT images showed that RV-related and non-RV-related FUS eyes were similar, as were CMV-associated and non-CMV-associated PSS eyes. CMV and RV were found to be the main etiologies of PSS and FUS respectively. Quantitative analysis of iris OCT images has proved to be an objective method to differentiate between these two syndromes. What is known The etiopathogenesis of Fuchs Uveitis Syndrome (FUS) and Posner-Schlossman Syndrome (PSS) remains under discussion. Viral etiology is the most widely accepted theory: Rubella virus (RV) has been associated mostly with FUS and cytomegalovirus (CMV) with PSS. Although FUS and PSS are distinct conditions, their differential diagnosis can be challenging at times due to clinical similarities, particularly iris damage. What is new The quantitative analysis of iris images from Swept Source Anterior Segment OCT is an objective, reliable, and non-invasive method that allows differentiation between FUS and PSS. In this study, RV in FUS and CMV in PSS have been detected in almost 2/3 of patients. This is the first study to perform a comparative analysis of aqueous humor results between PSS and FUS along with the examination of iris images using SS-AS-OCT.

Psychiatric manifestations of encephalitis.

Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment. This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. In our cohort of 642 patients, 318 (49.6%) had psychiatric symptoms at the time of initial presentation, including 78.2% with autoimmune etiologies and 35.2% with viral etiologies (P < 0.001). Those with psychiatric symptoms were younger (median age 47.5 vs. 51.5; P < 0.001), and more likely to have a history of documented psychiatric disorders, as well as longer lengths of hospital stay, and poorer discharge outcomes. Of patients initially admitted to a psychiatric service (n = 28), most had autoimmune causes, although 3 out of 28 (10.7%) had herpes viral infections; admission to a psychiatric service was associated with substantially longer interval to initiation of antivirals and immunotherapy. Autoimmune and infectious etiologies differed in the spectrum and frequency of psychiatric manifestations. Psychiatric symptoms are common across etiologies of encephalitis and are associated with longer lengths of hospital stay and worse clinical outcomes. Specific patterns and dimensionality of psychiatric symptoms distinguish autoimmune from infectious causes.

Development of a Reference Standard to Assign Bacterial Versus Viral Infection Etiology Using an All-inclusive Methodology for Comparison of Novel Diagnostic Tool Performance

Abstract Background Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools. Methods Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with high/moderate confidence or 2/3 adjudicators concur with high confidence), and all-inclusive (remaining unlabeled cases were reviewed by up to 7 additional adjudicators until reaching a leading label). Results Among 1016 patients, 156 difficult-to-diagnose cases required over 3 adjudicators. The area under the receiver operating characteristic curve in the microbiologically confirmed (n = 427), unanimous (n = 565), suspected (n = 860), and all-inclusive (n = 1016) cohorts for MMBV were 0.98 (95% confidence interval .94–1.00), 0.98 (.95–1.00), 0.95 (.92–.98) and 0.90 (.87–.93), respectively, and for procalcitonin were 0.69 (.57–.81), 0.77 (.68–.86), 0.74 (.68–.80) and 0.70 (.65–.75), respectively. A delta in performance between MMBV and procalcitonin was maintained across the different cohorts. Conclusions Creating a reference standard that includes difficult-to-diagnose cases demands an approach to addressing diagnostic uncertainty in acute infections. Tool performance depends on the reference standard applied and decreases as the difficulty to diagnose increases, highlighting the importance of using the same reference standard when comparing tools.