Central Nervous System Infection Research Articles

Infectious Causes of Death: An Autopsy-Based Study of 546 cases

Abstract Background Diagnostic accuracy in cases of infectious diseases is crucial for appropriate patient management and public health interventions. This retrospective study aimed to evaluate the most common causes of death caused by infectious diseases and the rate of agreement between clinical diagnoses and autopsy findings in individuals diagnosed with infectious diseases in Mashhad, Iran. Methods Autopsy reports from March 2009 to February 2018 were analyzed for patients diagnosed with infectious diseases. Demographic data, clinical diagnoses, and autopsy results were collected and compared. Discrepancies between clinical and autopsy diagnoses were assessed, and potential predictors of diagnostic discrepancy were examined. Results Among 28,451 autopsied cases, 546 (1.9%) were diagnosed with infectious diseases. Pleuropulmonary infections were the most common cause of death (69.8%) as determined by autopsy, followed by bloodstream infections (14.1%) and intra-abdominal infections (10.4%). Discrepancies between clinical and autopsy diagnoses were identified in 22.4% of cases. Pleuropulmonary infections had the highest frequency of diagnostic discrepancies (29.1%), followed by central nervous system infections (15.8%). Conclusion This study underscores the importance of autopsy in identifying diagnostic discrepancies and improving clinical practice in cases of infectious diseases. They also highlight the need for ongoing efforts to enhance diagnostic capabilities, particularly in challenging cases such as pleuropulmonary and CNS infections, to reduce the burden of misdiagnosis and improve patient outcomes.

Revealing the diagnostic value of cerebrospinal fluid presepsin (sCD14) as a new biomarker for postneurosurgical and nosocomial central nervous system infections: A systematic review and meta-analysis of diagnostic test accuracy studies.

Central nervous system (CNS) infections represent life-threatening conditions. Emerging evidence suggests cerebrospinal fluid (CSF) presepsin (sCD14) as a promising biomarker for these infections. However, its diagnostic accuracy remains controversial. This study aimed to systematically evaluate the reliability of CSF presepsin in diagnosing CNS infections through a comprehensive meta-analysis. A systematic search of PubMed, Scopus, and Web of Science databases was conducted up to November 2024. Five prospective studies involving 384 participants were included. CSF presepsin levels were compared between infected and non-infected patients. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive predictive value (PPV), and negative predictive value (NPV) were calculated using a random-effects model. Publication bias and clinical utility were assessed through Deek's funnel plot and Fagan's nomogram, respectively. Infected patients exhibited significantly higher CSF presepsin levels (mean difference: 760.16 pg/mL; 95 % confidence interval (CI): 426.26-1094.05, p < 0.01). Pooled sensitivity and specificity were 87 % (95 % CI: 82-91 %) and 67 % (95 % CI: 60-74 %), respectively, with a DOR of 13.04 (95 % CI: 7.51-22.64). The pooled PPV and NPV were 79 % (95 % CI: 73-84 %) and 79 % (95 % CI: 71-85 %), respectively. The area under the curve of the summary receiver operating characteristic curve was 86 %, emphasizing high diagnostic accuracy. No statistically significant publication bias was detected (P = 0.12). CSF presepsin demonstrated potential as a diagnostic biomarker for CNS infections, demonstrating high sensitivity and moderate specificity. Further large-scale studies are needed to refine its clinical applicability and establish standardized thresholds.

Protective effects of wogonin in the treatment of central nervous system and degenerative diseases.

Wogonin, an O-methylated flavonoid extracted from Scutellaria baicalensis, has demonstrated profound neuroprotective effects in a range of central nervous system (CNS) diseases. This review elucidates the pharmacological mechanisms underlying the protective effects of wogonin in CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, epilepsy, anxiety, neurodegenerative diseases, and CNS infections. Wogonin modulates key signaling pathways, such as the MAPK, NF-κB, and ROS pathways, contributing to its anti-inflammatory, antioxidant, and antiapoptotic properties. In ischemic stroke models, wogonin reduces infarct size and enhances neurological outcomes by mitigating inflammation and oxidative stress. For patients with hemorrhagic stroke and traumatic brain injury, it accelerates hematoma regression, mitigates secondary brain damage, and promotes neurogenesis, making it an entirely new treatment option for patients with limited access to this type of therapy. Its anticonvulsant and anxiolytic effects are mediated through GABA-A receptor modulation. Moreover, wogonin shows promise in treating neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease by promoting autophagy and reducing neuroinflammation. Additionally, it exhibits antiviral properties, offering potential benefits against CNS infections. Despite extensive preclinical evidence, further clinical studies are warranted to confirm its efficacy and safety in humans. This review highlights the great therapeutic potential of wogonin in terms of CNS protection. However, despite the substantial preclinical evidence, further large-scale clinical studies are necessary. Future researchers need to further explore the long-term efficacy and safety of wogonin in clinical trials and translate it for early application in the clinical treatment of true CNS disorders.

Review of the aetiologies of central nervous system infections in Vietnam

Review of the aetiologies of central nervous system infections in Vietnam

P-914. Clinical Outcomes and Predictors of Mortality among Hospitalized HIV/ AIDS Adult Patients Diagnosed with Central Nervous System Infections in a National Tertiary Referral Hospital in the Philippines: A 5-year Retrospective Study

Abstract Background HIV infection remains a significant global health concern despite the major advances in its understanding and treatment. Central nervous system (CNS) infections are common complications among HIV-infected patients. In the Philippines, limited local data on the clinical profile and outcome among HIV-infected patients with CNS infections is available. Case Distribution of CNS Infections among HIV-infected patients in the Philippines Methods This is a 5-year retrospective study of confirmed HIV-infected patients hospitalized and managed as CNS Infections at San Lazaro Hospital, Manila Philippines between 2018 and 2022. Demographics and clinical data were extracted from medical records and the association with clinical outcome and length of hospital stay were analyzed. Incidence and Case Fatality Rate of CNS Infections among HIV-infected patients in the Philippines Results One hundred twenty-eight (128) HIV-infected patients, mostly male (95%), were included, with a mean age of 31 years, and a mean CD4 lymphocyte count of 56.8 (0-282) cells/mm3. Forty-one patients (32%) were newly diagnosed with HIV, and 51% (n=65) were not on antiretroviral therapy (ART). The mean duration of HIV diagnosis among those known to have HIV before admission was 1.4 years. The most common CNS infection was Tuberculous Meningitis (TBM) (35%), followed by Cryptococcal Meningitis (CM) (29%), and Toxoplasma Encephalitis (TE) (17%). The presence of dual CNS Infection was diagnosed among 20 patients (15.6%), of which a total of 16 (12.5%) had co-infection of TBM and TE, while 4 (3.1%) had co-infection of TBM and CM. The most common clinical manifestations were headache (87.5%), fever (61%), and sensorial changes (60%). The overall in-hospital mortality rate was 30.4% (n=39), with the highest case-fatality rate among those infected with Cryptococcal Meningitis at 53% (n=19). Among those diagnosed with CM, 23 patients (62%) had concomitant Cryptococcal Fungaemia. Those with CM and dual CNS infection had a longer hospital stay of &amp;gt;31 days ( &amp;gt;1 month). Conclusion In the Philippines, the most common CNS infection among HIV-infected patients was Tuberculous Meningitis, followed by Cryptococcal Meningitis, and Toxoplasma Encephalitis. Early diagnosis of HIV infection with timely initiation of ART, together with an effective diagnostic and management approach to these conditions is needed to decrease the risk of further complications and death. Disclosures All Authors: No reported disclosures

P-1257. Cefazolin Dosage Considerations for Methicillin-Susceptible Staphylococcus aureus (MSSA) Central Nervous System Infections: Exploring Optimal Regimens

Abstract Background Historically, cefazolin (CFZ) has not been considered an appropriate agent to treat central nervous system (CNS) infections. Recent studies have shown that standard CFZ dosing achieves concentrations above the epidemiologic cutoff of minimum inhibitory concentration ≤ 2 mg/L for Staphylococcus aureus, but literature describing optimal dosing for CNS infections is lacking. This study aimed to identify CFZ dosing regimens necessary to achieve adequate probability of target attainment (PTA) for treatment of a methicillin-susceptible S. aureus (MSSA) CNS infection. Methods CFZ plasma and cerebral spinal fluid (CSF) pharmacokinetic parameters were obtained from a previous published study. Monte Carlo simulations were performed utilizing PD targets of 40%fT &amp;gt; MIC for intermittent infusions and 100%fT &amp;gt; MIC and 100%fT &amp;gt; 4xMIC for continuous infusions (CI) to determine probability of target attainment (PTA) for seven CFZ dosing regimens at an MIC of 0.5 mg/L, 1 mg/L, and 2 mg/L. Adequate target attainment, defined as ≥ 90% PTA, was evaluated for CFZ dosing regimens ranging from 6-12g/day administered intermittently every 4-8 hours over 30 minutes or as a CI over 24 hours (Table 1). Results The standard intermittent regimen of 2g q8h did not achieve ≥ 90% PTA for any MIC evaluated. Furthermore, no CI regimen achieved ≥ 90% PTA when using the PD target of 100%fT &amp;gt; 4xMIC. All continuous and intermittent regimens achieved ≥ 90% PTA when the MIC remained ≤ 0.5 mg/L. Only the 10 g and 12 g CI regimens achieved ≥ 90% PTA for 100%fT &amp;gt; MIC when the MIC was 1 mg/L while no regimen achieved the desired target when the MIC was 2 mg/L. Conclusion These findings underscore the inadequacy of standard intermittent CFZ regimens in achieving desired PD targets for MSSA CNS infections. Higher total daily doses or CI CFZ is necessary to achieve satisfactory PD targets for MSSA CNS infections. When comparing the same total daily dose administered as an intermittent versus continuous infusion, our results suggest that continuous infusions are more likely to achieve PD target attainment for MSSA CNS infections, particularly when the cefazolin MIC exceeds 0.5 mg/L. Further clinical studies are warranted to evaluate the safety and efficacy of CFZ for CNS infections caused by MSSA. Disclosures All Authors: No reported disclosures

208. Exposure-response relationship of ceftazidime/avibactam in adults with central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae: a prospective observational study

Abstract Background Central nervous system (CNS) infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant challenges for clinicians in ICU. Achieving optimal drug exposure in the cerebrospinal fluid (CSF) is crucial for good outcomes. This study aimed to evaluate the exposure-response relationship of ceftazidime/avibactam (CZA) in plasma and CSF. Methods All patients received CZA (2.5 g), IV infusion (over 2 hours), q8h. At steady-state after the fourth dose of CZA, the concentrations of CZA in the plasma and CSF were determined by ultra-performance liquid chromatography (UPLC) at 1, 2, 2.25, 2.5, 3, 4, 6, and 8 h post-dose. The PK/PD index of ceftazidime (CAZ) and avibactam(AVI) was calculated for each patient. Demographic, clinical efficacy, microbiological eradication, and 28-day mortality were reviewed. Blood and CSF samples were collected for calculation of PK parameters by non-compartmental pharmacokinetics (PK) modeling. The attainment of CAZ and AVI PK/PD targets in plasma and CSF was calculated to assess the exposure-response relationship of CZA and the corresponding clinical efficacy rate and bacterial eradication rate. Results CAZ and AVI demonstrated good penetration into CSF, evidenced by median CSF/plasma AUCtau ratio of 43.8 % and 55.8 %, respectively. CZA 2.5 g q8h achieved CAZ PK/PD target of 50%fT &amp;gt;MIC in both plasma and 50%T &amp;gt;MIC in CSF of all patients and reached AVI PK/PD target of 50%T &amp;gt;CT=1 mg/L in CSF of 80% (16/20) of patients. The dosing regimen also achieved CAZ PK/PD target of 100% fT &amp;gt;4MIC in plasma of 9 patients and 100% T &amp;gt;4MIC in CSF of 14 patients. At the end of the treatment, the overall clinical and microbiological efficacy rates were 80.0% and 100%, respectively. Only one case of CZA-related adverse event (Clostridioides difficile-associated diarrhoea) was reported. Conclusion The good CSF penetration of CZA enables the dosing regimen of CZA 2.5 g q8h a promising treatment option for CNS infections caused by CRKP. Disclosures Nanyang Li, Master of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator Jing Zhang, Doctor of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator

P-923. Characterization of the use of the FilmArray Molecular panel for the diagnosis of central nervous system infection

Abstract Background The Biofire FilmArray® Meningitis/Encephalitis Panel (FAME) has proven to be a valuable tool for etiological diagnosis. Despite this, we know little about its clinical impact.This investigation aims to characterize the clinical, epidemiological, therapeutic variables and outcomes of adults with suspected meningitis and/or encephalitis (ME) who underwent FAME panel, in two 3rd level hospitals in Medellín-Colombia. Central nervous system infection diagnosis Definitive diagnosis based on clinical and microbiologic criteria Methods Retrospective cohort study in 257 patients over 16 years of age, with suspected central nervous system infection with less than 4 weeks of symptoms who underwent FAME panel. Comparisons were made between those with positive and negative FAME panel results, and a medical record evaluation committee determined whether central nervous system infection was present. Identification of pathogens by Film Array meningitis encephalitis Pathogens identified Results 57.19% (147) of the patients presented central nervous system infection, with 70 patients (26.07%) with a positive FAME panel result; the most frequent involvement being bacterial meningitis 37 (52.9%), and among those with negative FAME panel it was aseptic meningitis 23 (15.64%) followed by meningeal tuberculosis 15 (10.2%). Altered consciousness (74.3%), fever (63.4%) and headache (63.4%) predominated in the FAME-positive group, as did higher cerebrospinal fluid (CSF) leukocyte count, glucose consumption and hyperproteinorrachia (p =0.0001). A positive FAME panel result was associated with greater modification of empirical to definitive antibiotic therapy and discontinuation of unnecessary antibiotics, while negative results were associated with shorter hospital stays, fewer neurological sequelae, and lower antibiotic consumption. Of the total number of patients with positive FAME, 9 had a CSF leukocytes of less than 5 cells/mm3. Additionally, of the total, eight (8) had pharmacological or disease-related immunosuppression, and only one case had a positive FAME for Varicella zoster without medical or pharmacological immunosuppression with normal CSF. Conclusion FAME panel in the appropriate context can provide valuable information for decision-making in patients with suspected central nervous system infection; a rational use and restrictive criteria in prescription could improve the benefits without incurring in excessive costs. Disclosures All Authors: No reported disclosures

299. Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for Central Nervous System Infections: Clinical Factors Associated with Increased Diagnostic Yield

Abstract Background Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) can improve diagnostic yields in central nervous system (CNS) infections, but the most beneficial clinical indications have yet to be defined.Table 1.Factors evaluated by univariate analysis associated with a positive CSF mNGS test*P-value in bold are considered statistically significant (P &amp;lt; 0.05) Methods We analyzed CSF mNGS results and associated clinical, demographic, and laboratory metadata from a cohort of patients for whom mNGS testing was performed at University of California, San Francisco (UCSF) from 2016 to 2023. We assessed by chart-review positive CSF mNGS results that established definitive diagnoses of CNS infections in the cohort. We then used univariate and multivariate logistic regression analysis to identify clinical factors that were associated with positive mNGS results.Figure 1.Significant clinical factors associated with mNGS positivity selected by multivariate analysis.The odds ratio and associated confidence intervals are plotted for each row (clinical factors).*, P &amp;lt; 0.05; **, P &amp;lt; 0.01; ***, P &amp;lt; 0.001; NS, non-significant. Results Of 1,164 mNGS tests, 133 were positive for CNS infection-causing pathogens. By univariate analysis (Table 1), factors including hospitalization (P = 0.009), intensive care unit (ICU) admission (P = 0.02), immunosuppressed status (P &amp;lt; 0.0001), clinical meningitis or meningoencephalitis (P &amp;lt; 0.0001), and abnormal CNS imaging (P = 0.004) were significantly associated with a positive mNGS result. In contrast, demographic variables, including age, sex, race, and ethnicity, were not. For CSF, early mNGS testing performed by hospital day 7 (P &amp;lt; 0.002), elevated protein (P = 0.005), and low glucose (P = 0.001) were associated with a positive mNGS result, whereas the presence of red blood cells (P = 0.77), pleocytosis (P = 0.17), and neutrophil or lymphocyte predominance (P = 0.24) were not. Significant factors selected by multivariate analysis include ICU stay (OR = 1.8, 95%CI[1.2, 1.9]), acute abnormalities on imaging (OR = 2.3, 95%CI[1.3, 4.2]), early mNGS testing within 7 days of admission (OR = 2.8, 95%CI[1.5, 5.2]), meningitis or meningoencephalitis (OR = 10.7, 95%CI[1.4, 82.7] and OR = 14.4, 95%CI[1.9, 112.1]), and immunosuppressed status (OR = 4.3 95%CI[2.7, 7.0]) (Figure 1). Conclusion This study identified key factors for predicting positive CSF mNGS results that will be incorporated into a predictive scoring system to identify clinical scenarios for which testing is clinically indicated to maximize diagnostic yield. Real-time scoring metric will enhance diagnostic stewardship and optimize the cost-effectiveness of CSF mNGS testing. Disclosures Charles Chiu, MD, PhD, Abbott Laboratories, Inc: Grant/Research Support|Biomeme: Advisor/Consultant|Biomeme: Board Member|BiomeSense: Advisor/Consultant|BiomeSense: Board Member|Delve Bio: Advisor/Consultant|Delve Bio: Board Member|Delve Bio: Grant/Research Support|Flightpath Biosciences: Advisor/Consultant|Flightpath Biosciences: Board Member|Mammoth Biosciences: Advisor/Consultant|Mammoth Biosciences: Board Member|Pathogen detection using next generation sequencing: US patent 11380421|Poppy Health: Advisor/Consultant|Poppy Health: Board Member

P-916. Use of BCID2 on CSF in nosocomial CNS surgical site infections

Abstract Background Nosocomial intracranial infections, arising from surgical procedures or neuroinvasive devices like ventricular drains or shunts, present distinct risk factors and microbiologic etiologies compared to community-acquired meningitides. Pathogens typically include Staphylococcus spp., Gram-negative bacilli, and multidrug-resistant bacteria. The current diagnostic standard for nosocomial central nervous system (CNS) infections is cerebrospinal fluid (CSF) Gram stain and culture, but rapid molecular diagnostics could improve diagnosis and treatment, enhancing patient outcomes. This pilot study aimed to assess the validity of the BioFire® Blood Culture Identification Panel 2 (BCID2) panel used for blood culture positivity detection on CSF samples in patients presenting with nosocomial meningitis/ ventriculitis. Sensitivity and specificity were calculated, and patient characteristics and co-morbidities were reviewed. Microbiologic data comparing gold standard Gram stain and culture of CSF to BCID2 result. Methods Patients over 18, admitted to Thomas Jefferson University Health System hospitals between 4/1/2017 to 4/1/2024, were included if meeting Centers for Disease Control (CDC) criteria for intracranial infection or meningitis/ventriculitis. Positive CSF samples (n=30) from 28 patients with nosocomial infections included Gram-positive bacteria (13), Gram-negative bacteria (13), and fungi (4). Positive CSF samples included those positive on culture, while control samples (n=26) had negative cultures or cultures positive for Cutibacterium acnes, an organism not detected by the BCID2 panel. Results Across all positive CSF specimens, sensitivity for organism detection was 76.7%. When culture-positive samples were classified based on Gram Stain, samples with organisms detected on Gram Stain had a sensitivity of 94.7% compared to 45.5% for samples with no organisms seen. For samples with organisms detected on Gram Stain, sensitivity for Gram-negative organisms was 100% and 88.9% for Gram-positive organisms. Among all control specimens, specificity was 100%. Conclusion The ability to rapidly identify a pathogen is crucial for managing nosocomial CNS infections effectively. Our study found that the BCID2 panel offers a promising utility in the detection of nosocomial CNS infections through CSF analysis. Disclosures Matthew Pettengill, PhD, Cepheid: Grant/Research Support

P-973. Pediatric Infectious Diseases rotation for general pediatric residents in Washington DC: impact, benefits and pitfalls

Abstract Background Although infectious diseases present significant challenges in pediatric care, formal training in pediatric infectious diseases is not mandated in categorical pediatric residency training. This research seeks to examine the self-assessed confidence levels of general pediatric residents in Washington DC in managing common infectious diseases. The study specifically compares the confidence levels of residents who have undergone elective infectious diseases training with those who have not. Subjective Confidence in the Management of Common Infectious Diseases Encounters Methods A cross-sectional study was conducted using voluntary surveys distributed among pediatric residents from various programs in Washington DC. The surveys aimed to assess subjective confidence levels in managing common infectious disease conditions and to explore motivation to pursue infectious disease training. Effect of infectious diseases elective rotation on interest in infectious diseases as a career. Are you more or less likely to pursue infectious diseases fellowship? Results Analysis of 20 completed surveys revealed that residents who completed infectious diseases rotations demonstrated significantly higher confidence levels in managing infectious disease conditions compared to their counterparts (P: &amp;lt; 0.001). Notably, residents with specialized training showed increased confidence in antibiotic selection and in their diagnostic abilities. Additionally, they exhibited enhanced confidence in managing specific presentations such as sexually transmitted diseases, fever of unknown origin, and central nervous system infections (all with P &amp;lt; 0.05). Finally, 22% of respondents expressed an increased likelihood of pursuing a career in infectious diseases following their rotation. Effect of infectious diseases rotation on the confidence in the management of inpatient and outpatient infectious diseases encounters Conclusion These findings underscore the potential benefits of incorporating infectious diseases rotations into pediatric residency programs, as evidenced by improved skills in antibiotic selection, diagnosis, and management of specific infectious disease scenarios. Additionally, the observed increased interest in pursuing a career in infectious diseases among a subset of residents highlights the positive impact of such training on career trajectory and specialty choice. Investigators plan to distribute the questionnaire more broadly across the US to see if these results are more widespread. Disclosures All Authors: No reported disclosures

298. Host Response Profiling from Clinical Metagenomic Sequencing Data for Diagnosis of Central Nervous System Infections

Abstract Background Clinical metagenomic next-generation sequencing (mNGS) testing of cerebrospinal fluid (CSF) increases diagnostic yield for suspected central nervous system (CNS) infections. Nevertheless, up to 45% of cases remain unknown despite extensive testing and 6 months of follow-up. We developed artificial intelligence-machine learning (AI-ML) classification models (classifiers) based on RNA gene expression / host response data from CSF mNGS testing to enhance diagnostic performance.Figure 1.An artificial intelligence machine learning classifier. (A) Schematic illustration of the different steps to generate the sub-classifiers then integrated into a consensus classifier. (B) The parasitic sub-classifier was generated using the "leave-one-out" algorithm due to the low sample numbers. (C) Performance metrics of the main classifiers. Methods From June 2016 and April 2023, 464 CSF mNGS results from UCSF patients with a confirmed viral (n=175), bacterial (n=91), fungal (n=44), or non-infectious (n=155) diagnosis were randomly divided into training and test subsets in an 80:20 ratio (Figure 1A). Clinicians adjudicated their confidence in the final diagnosis based on blinded medical chart review and laboratory test results. Gene (feature) selection was carried out using high-confidence samples, followed by 50-fold cross-validation. All possible pairwise comparisons were performed to generate sub-classifiers which were then integrated into a consensus classifier. Performance metrics were obtained by running the consensus classifier on the independent test subset. A separate classifier was developed for parasitic infections (n=24) using a “leave-one-out” algorithm to assess performance (Figure 1B). Classifier results were displayed as a score ranging from 0 to 10, corresponding to specificities of ≤70% to ≥99%.Figure 2.Differentially expressed gene analysis with pair-wise comparison between sub-classifiers. Left panel shows genes selected by the LASSO (least absolute shrinkage and selection operator) algorithm, and right panel the pathway/function these genes. Results Classifier accuracy based on the test set was 83%, with individual area under the curve (AUC) scores ranging from 0.88-0.93 for each category (Figure 1C). The function of the selected genes corresponded well with the category (Figure 2). Classifier examples include patients with (i) culture-negative CNS tuberculosis, (ii) persistent Toxoplasma gondii infection despite 19 days of treatment, (iii) a rare autoimmune syndrome, and (iv) a chronic enterovirus infection misclassified as an atypical bacterial infection, suggesting that acute and chronic host response profiles differ (Figure 3).Figure 3.Classifier examples. (i) culture-negative CNS tuberculosis, (ii) persistent Toxoplasma gondii infection despite 19 days of treatment, (iii) a rare autoimmune syndrome, and (iv) a chronic enterovirus infection misclassified as an atypical bacterial infection. Conclusion Host response profiling with AI-ML classifiers complements mNGS testing and can enhance diagnostic yield for unexplained CNS syndromes. Disclosures Charles Chiu, MD, PhD, Abbott Laboratories, Inc: Grant/Research Support|Biomeme: Advisor/Consultant|Biomeme: Board Member|BiomeSense: Advisor/Consultant|BiomeSense: Board Member|Delve Bio: Advisor/Consultant|Delve Bio: Board Member|Delve Bio: Grant/Research Support|Flightpath Biosciences: Advisor/Consultant|Flightpath Biosciences: Board Member|Mammoth Biosciences: Advisor/Consultant|Mammoth Biosciences: Board Member|Pathogen detection using next generation sequencing: US patent 11380421|Poppy Health: Advisor/Consultant|Poppy Health: Board Member

P-902. Etiology, Clinical Characteristics, Prognosis and Outcomes of Acute Central Nervous System Infections: A Prospective Study

Abstract Background Various pathogens can cause central nervous system (CNS) infections. Early recognition and treatment significantly improves outcomes. Clinical features and outcomes vary by etiology and clinical phenotype, making diagnosis challenging. We report a single-center experience emphasizing the clinical profile and prognostic factors of this entity. Methods We conducted a two-year prospective, observational study at a tertiary care center in Western India. Patients suspected to have CNS infections underwent a standardized workup that included neuroimaging and CSF polymerase chain reaction panel testing. Patients were followed throughout the admission. The outcomes recorded were duration of intensive care unit (ICU) stay, hospital stay, modified Rankin Scale (mRS) at discharge and mortality. Results We included 75 patients (53 male, 22 female). The mean age was 43±19 years. Most infections were viral (69%) – 40% encephalitis, 17% meningitis and 12% meningoencephalitis. Viral infections surged in the monsoon and post-monsoon period (Fig. 1). Tuberculous meningitis accounted for 16% cases, pyogenic meningitis for 7%, and cryptococcal meningitis for 5%. Mucor cerebritis and brain abscesses accounted for 3%. Presenting symptoms, CSF, and neuroimaging findings are listed in Fig. 2-4. Mortality was highest for cryptococcal meningitis (25%); followed by pyogenic meningitis (20%); and viral encephalitis and tuberculous meningitis (16.7% each). Increased risk of mortality was observed with: new-onset seizures (relative risk [RR] 3.58, 95% confidence intervals [CI] 1.03-12.45, p&amp;lt; 0.001); a Glasgow Coma Scale (GCS) &amp;lt; 8 (RR: 6.85, 95% CI 2.00-23.40, p=0.002); and the presence of dilated ventricles on imaging (RR: 5.25, 95% CI 1.99-13.82, p&amp;lt; 0.001). Increasing age correlated with a longer ICU stay (r=0.37, p&amp;lt; 0.001), hospital stay (r=0.33, p=0.002), and worse functional status at discharge reflected by a higher mRS (p=0.04). GCS at presentation correlated inversely with functional recovery reflected by the mRS at discharge (p&amp;lt; 0.001). CSF findings varying by etiology CSF findings varying by etiology Conclusion The etiology and prognosis of acute CNS infectious varies by region and season. A detailed history, thorough physical examination, neuroimaging and CSF analysis are vital as each provides diagnostic and prognostic information. Disclosures All Authors: No reported disclosures

P-2294. Listeriosis in cancer patients: Uncommon and protean

Abstract Background Historically cancer patients (pts) are considered to be at an increased risk of Listeria monocytogenes infection (listeriosis, LT), especially those with ongoing chemotherapy or receipt of glucocorticoids (GCs). However, the features of this uncommon infection have not been described in contemporary cohorts of cancer pts. Methods We performed a 12-year retrospective chart review of cancer pts with LT as confirmed by positive culture from blood or other sterile clinical samples at MD Anderson Cancer Center (2011-2023). Results We identified 20 cancer pts with LT. Twelve (60%) had an underlying hematologic malignancy (Figure 1). Lymphopenia &amp;lt; 1000/µL (17, 85%, severe &amp;lt; 200/µL in 20%) and monocytopenia &amp;lt; 1000/µL (18, 90%, severe &amp;lt; 200/µL in 35%) were common at diagnosis, as well as chemotherapy (13, 65%) and GC use (11, 55%) within 30 days prior to LT diagnosis. Most (15 pts) were &amp;lt; 65 years old. Fever was seen in 10 pts. Vomiting/diarrhea were common (50%), while 45% of pts had headache or altered mental status. LT most often presented with bacteremia (17, 85%) and gastroenteritis (9, 45%) (Figure 2). 7/9 pts with gastroenteritis were bacteremic. Central nervous system (CNS) manifestations (meningitis, brain abscess) were documented in 2 pts who had a lumbar puncture. Focal non-CNS infections were seen in 30% of pts in unusual sites: cellulitis, abscess, endocarditis, cholangitis, urinary tract infection, and peritonitis. Of interest, 11pts (55%) had low SOFA score at presentation and were given antibiotics only after blood cultures were positive for Listeria. In fact, most pts (17, 85%) either did not receive empiric (n=11) or had inappropriate empiric antibiotics (n=6) until LT diagnosis. The 30-day mortality from LT diagnosis was 25% and correlated with high SOFA score ≥ 5 (5/8 pts, P = 0.0005). Delayed appropriate antibiotics were not significantly associated with increased 30-day mortality in this small cohort (Table 1). Conclusion Although uncommon, LT in cancer pts has pleotropic manifestations and variable morbidity, from non-bacteremic gastroenteritis to septicemia, CNS and non-CNS focal infections. Consider LT in ill cancer pts with lymphopenia/monocytopenia and recent chemotherapy or GCs, especially if they have GI symptoms, even in the absence of fever or CNS involvement. Disclosures Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant

385. Sepsis-Associated Encephalopathy and Dementia Outcome: A Retrospective Cohort Study of 30,378 Adult Sepsis Inpatient Survivors at a Tertiary Medical Center in Taiwan

Abstract Background Sepsis-associated encephalopathy (SAE) is commonly observed in critically ill patients without identifiable causes, potentially leading to neurological sequelae. Prior studies have associated the long-term risk of dementia with sepsis or in-hospital infections, or the short-term risk of mortality with SAE, rather than the short-term dementia risk with SAE. We aimed to assess the association between SAE and the 1-year risk of dementia among sepsis survivors.Figure 1.Flowchart of the selection process of adult sepsis inpatient survivors (n = 30,378). Methods This cohort included inpatients aged ≥ 18 years with first-time sepsis during 2010-2019, no prior dementia or central nervous system (CNS) infections, Glasgow Coma Scale (GCS) measurements within 7 days of sepsis, and who survived the index hospitalization (Figure 1). Sepsis was identified using Sepsis-3 criteria. SAE was defined as having at least two GCS measurements of either &amp;lt; 7 for patients with endotracheal tubes, tracheostomies, or aphasia, or &amp;lt; 12 for the remaining patients within the 7 days of sepsis. Dementia at 3 months and 1 year was defined by the presence of ICD-9 and ICD-10 diagnosis codes from 7 days to 3 months, and from 3 months to 1 year post-sepsis onset, respectively. Multivariable Cox models were used, considering death as the competing risk. Demographic, clinical characteristics, and outcomes of adult sepsis inpatient survivors, stratified by SAE status. Results Of 30,378 eligible sepsis inpatient survivors, 6.4% developed SAE within 7 days of sepsis onset. Patients with SAE tended to be older, female, and have more comorbidities compared to those without SAE (Table 1). Dementia occurred more frequently in patients with SAE than those without (10.9% vs 3.9% within 3 months; 3.6% vs 2.1% within 1 year). Similar patterns were observed in mortality rate. SAE was significantly associated with an increased risk of dementia for 3-month (adjusted hazard ratio [aHR] 1.81; 95% confidence interval [CI] 1.55-2.12) and for 1-year (aHR 1.54; 95% CI 1.18-2.01), compared to patients without SAE (Table 2). This association was significantly stronger among patients without chronic pulmonary disease, stroke, and with a qSOFA &amp;lt; 2, regarding the 3-month dementia risk (Figure 2). Risk of dementia and all-cause mortality associated with SAE among adult sepsis inpatient survivors. Conclusion Determining whether SAE is a trigger for the disease itself or merely triggers more intensive dementia surveillance requires more studies with standardized SAE diagnostic criteria and post-sepsis follow-up strategies. Subgroup analyses of the risk of dementia and all-cause mortality associated with SAE. Disclosures All Authors: No reported disclosures

P-1699. Antimicrobial Administration and 30-Day Outcomes in Patients Hospitalized with MRSA-Related Infections who Self-Discharge

Abstract Background Management of serious infectious diseases typically includes hospitalization and IV antibiotics, particularly where methicillin-resistant Staphylococcus aureus (MRSA) is the causative organism. When patients with these infections decide to self-discharge, it presents a challenging clinical decision for their providers. Here we describe antimicrobial prescribing practices for patients hospitalized with different infectious disease diagnoses and their 30-day outcomes. Methods This retrospective cohort study included patients 18 years and older admitted between January 1, 2010, and December 31, 2019, with admission blood cultures growing MRSA. Veterans Affairs (VA) electronic health data was extracted from the Veterans Informatics and Computing Infrastructure, microbiology data, inpatient antibiotic administration, discharge antibiotic prescriptions, ICD-9- and ICD-10-CM coded infectious disease discharge diagnoses, discharge type (self-discharge or regular discharge), as well as 30-day all-cause mortality and readmission. Descriptive statistics were used to compare antibiotic prescribing for specific infectious diseases between self- and regular discharges. Results While hospitalizations with patients self-discharging were lower for each infectious disease, their total antibiotic days were similar for most listed MRSA-related infections. However, for 30-day readmission rates, there was a higher rate among self-discharged patients for most all infections except cardiovascular. Conversely, 30-day mortality appeared to be higher among regular discharges for most infectious disease diagnoses except central nervous system and bloodstream infections. Conclusion While this analysis is preliminary, there is a concerning trend towards higher 30-day readmissions for patients with MRSA infections who self-discharge, despite similar durations of MRSA-directed antibiotic prescribing. This suggests additional factor(s) than antibiotic administration that play a role in readmissions for this patient population. Further research is needed to elucidate what factors contribute to readmission for patients who self-discharge from hospitalization for serious MRSA-related infections. Disclosures All Authors: No reported disclosures

Comparison of mNGS with conventional methods for diagnosis of cryptococcal meningitis: a retrospective study

The application of metagenomic next-generation sequencing (mNGS) in the diagnosis of cryptococcal meningitis is relatively under characterized. Here, we retrospectively evaluated data from cryptococcal meningitis patients who were tested using mNGS and/or routine testing, including fungal culture, India ink staining, and cryptococcal antigen (CrAg) testing. The performance of mNGS was then assessed. Initial cerebrospinal fluid (CSF) samples were collected from 65 patients with suspected central nervous system (CNS) infection and tested using conventional tests and/or mNGS. mNGS offers a culture-independent approach, facilitating a rapid and unbiased detection of a broad spectrum of pathogens. Patients with bacterial tuberculous or viral meningitis were used as mNGS-positive controls and one autoimmune encephalitis patient was used as an mNGS-negative control. In the 45 patients diagnosed with cryptococcal meningitis, the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of mNGS were 92%, 100%, 100%, 90.9%, and 95.6%, respectively. Compared to conventional methods, the sensitivity of mNGS was slightly lower than CrAg tests (96.7%) but higher than India ink (79.5%) and culturing (63.4%). Of the two negative mNGS cases (2/25, 8.0%), one was positive by India ink staining, culture, and CrAg testing, while the other was positive only by CrAg testing. A combination of mNGS and conventional methods enhanced the detection rate to 100%. Our study demonstrates that both CrAg and mNGS offer excellent diagnostic accuracy for cryptococcal meningitis, and utilizing both tests can enhance clinical assessment and patient management.

P-910. Enhancing Awareness: Early Detection of Varicella-Zoster in CNS Among Immunocompromised Patients

Abstract Background Varicella zoster virus (VZV) reactivation typically presents as herpes zoster, but central nervous system (CNS) involvement is more prevalent in immunocompromised individuals. Methods This retrospective study, conducted from January 2023 to March 2024 at two hospitals, aimed to characterize VZV CNS infections in this population. Twenty-seven immunocompromised patients with active herpes zoster were included. Clinical data, cerebrospinal fluid (CSF) analysis, and treatment outcomes were analyzed. Results The mean age was 45 years, with a predominance of males (60%). Most patients had HIV (16) with a mean CD4 count of 126, while others had cancer (5), autoimmune diseases (2), or diabetes mellitus (1). Headache was the most common symptom (64%), followed by fever (19%), altered consciousness, and behavioural changes (7%). Facial palsy was observed in 3 patients, but no seizures were reported. CSF analysis revealed hyperproteinorrachia (mean 75 mg/dL) and pleocytosis (mean 39 cells). All patients received intravenous acyclovir for an average of 14 days, with a 100% survival rate at 30 days. Conclusion This study highlights the importance of early suspicion and diagnosis of VZV CNS infections in immunocompromised individuals, even in the absence of classical neurological symptoms. Prompt initiation of intravenous acyclovir therapy is crucial for favourable outcomes. Disclosures Estefania Sienra-Iracheta, MD, PFIZER: Advisor/Consultant|STENDHAL: Advisor/Consultant Juan Pablo Ramírez-Hinojosa, MD, Abott: Honoraria|Jansen: Honoraria|Silanes: Honoraria Patricia Rodriguez-Zulueta, MD, PFIZER: Advisor/Consultant|STENDHAL: Advisor/Consultant

P-901. Clinical Characteristics and Outcomes of CNS Nocardiosis Differ by Nocardia Species: A Review of Published Cases

Abstract Background Nocardiosis is an opportunistic infection with a predilection for central nervous system (CNS) involvement. A large number of Nocardia species ( &amp;gt;50) have been associated with human infection. Efforts to compare the clinical characteristics of nocardiosis across Nocardia species have been limited by insufficient sample size. Distribution of Nocardia species/species complex among all patients with CNS nocardiosis. Methods A literature search of multiple databases (PubMed, Scopus, Google Scholar, Google) was conducted to identify potential cases of CNS nocardiosis published from 1/2000-3/2024. CNS nocardiosis was defined as either identification of Nocardia in a CNS specimen or identification of Nocardia at any site combined with clinical, laboratory, radiographic, or histopathologic evidence of CNS infection. Cases of CNS nocardiosis were included if Nocardia species was reported to at least the species complex level. Duplicate cases were excluded. Categorical variables were compared by chi-squared test with statistical significance defined as P&amp;lt; 0.05. Frequency of each Nocardia species/species complex stratified by risk factor group. Results In total, 826 cases of CNS nocardiosis were included; one-third were derived from the grey literature (sources not included in PubMed). Cases were reported in 54 countries with 81.1% from North America, Europe, or East Asia. Half of all cases were caused by N. farcinica (Figure 1). Brain abscess +/- meningitis was the most common manifestation of CNS nocardiosis (96.4%). The frequency of various characteristics differed across species (Table 1, Figure 2). N. paucivorans/brevicatena cases were disproportionately reported in Oceania. N. abscessus and N. paucivorans/brevicatena were overrepresented in immunocompetent individuals and among patients with pulmonary alveolar proteinosis (PAP). These species were associated with a lower mortality rate. N. nova was particularly among recipients of solid organ (SOT) or hematopoietic stem cell transplantation (HSCT). Skin and musculoskeletal involvement were more common in patients with N. brasiliensis. Frequency of clinical characteristics for each Nocardia species/species complex. Conclusion Patient population, clinical manifestations, and outcome of CNS nocardiosis varies according to the species of Nocardia responsible for infection. Knowledge of the causative species has important implications for clinical practice. Disclosures All Authors: No reported disclosures

Do routine antibiotics change the myelomeningocele infection rate? A case series.

Myelomeningocele (MMC) is the most common type of congenital spinal malformation, typically requiring surgical intervention. While prenatal repair is increasingly favored, postnatal repair remains the standard in many settings. This study aims to evaluate the antibiotics prescribed to neonates with MMC and their correlation with central nervous system (CNS) infection rates following postnatal surgical repair. A retrospective cohort study was conducted, including newborns who underwent postnatal MMC repair between August 2017 and June 2021 at the Children's Hospital of Goiânia. The study examined variables related to the pregnancy and birth periods, as well as anatomical and neurosurgical factors. Neonates were categorized into four groups based on the time interval between birth and surgical repair (within 24, 48, 72h, and beyond 72h) and were evaluated for CNS infection rates. A total of 38 neonates were included, with 24.32% diagnosed with CNS infections post-surgery. Notably, 22.86% of mothers did not receive prenatal care. Cesarean section was the predominant mode of delivery, accounting for 77.78% of cases. The average time from birth to surgery was 67h. At admission, 73.68% of MMC cases presented with a rupture of the MMC membrane, and 78.94% of newborns received intravenous antibiotics. The mean surgical time was 60min, with 78.94% of surgeries performed by experienced surgeons. Timely surgical intervention and the use of prophylactic antibiotics are critical in reducing CNS infection rates in neonates undergoing postnatal MMC repair. Delays in surgery and the lack of antibiotic prophylaxis were associated with higher infection rates, whereas factors such as delivery mode and surgeon experience had less impact on infection outcomes. These findings highlight the need for standardized care protocols and improved prenatal care to optimize neonatal outcomes.