Lower Mortality Research Articles

P-1144. Low prevalence of neonatal sepsis due to Streptococcus agalactiae in two large Mexican NICUs: multicenter retrospective study from 2021-2023

Abstract Background Group B Streptococcus (GBS), or S. agalactiae, is reported as a leading cause of neonatal sepsis in several regions including the United States. Although in recent years its incidence has shown a steady decline, current treatment guidelines still consider it a predominant cause of neonatal sepsis. Its prevalence varies according to geographical and racial factors; however, information regarding the epidemiology and clinical presentation of neonatal GBS infection in Mexico is scarce. Methods Retrospective multicenter study conducted in the NICUs of the two pediatric reference hospitals in NL, Mexico. Data of all newborns ≤28 days (d) diagnosed with blood culture-proven GBS infection from 2021-2023 were collected. Maternal premature rupture of membranes (PROM) was defined as >12h. GBS infection was classified as early (< 7 d) and late-onset (≥7 d). LBWIs were defined as newborns < 2500 g and very LBWI (VLBWI) as < 1500 g at birth, respectively. Clinical scenarios were classified as sepsis, pneumonia and meningitis. Sepsis was classified as early (≤3 d) and late-onset ( >3 d). Descriptive statistical analyses were performed to determine frequencies. Results A total of 928 positive blood cultures were included. 28 blood cultures (3%) from 27 patients were positive for GBS. Maternal PROM was documented in 11.1%. Most patients were term infants (77%) and 92.6% of the cases were early-onset. The most common presentation was sepsis (92.6%). One patient (3.7%) had pneumonia and one (3.7%) had meningitis due to GBS. Low mortality was documented (3.7%). Table 1 shows clinical characteristics of patients with GBS infection. As expected, all isolates were susceptible to Ampicillin. Conclusion We report a low prevalence of culture-proven GBS infection (3%) in two large Mexican NICUs during the studied period. This is consistent with previous single-center reports from Mexico, which date back to more than two decades. Although the international epidemiology and treatment guidelines consider GBS a predominant cause of neonatal sepsis, its frequency in Mexico remains low. The vast majority of cases were early-onset infections, and the most common clinical presentation was sepsis, which is consistent with global epidemiology. Disclosures All Authors: No reported disclosures

P-2281. Impact of Immunosuppression on Clinical Outcomes in Critically Ill Pneumonia Patients

Abstract Background Nosocomial lower respiratory infections (nLRTI) are linked to poorer clinical outcomes and a significant healthcare cost. Nevertheless, there remains uncertainty regarding the risk factors for mortality among critically ill individuals, particularly those with varying degrees of immunosuppression. Thus, this study aims to comprehensively describe immunocompromised patients, assess its impact on clinical outcomes, and conduct a comparative survival analysis. Figure 1 Identified microorganisms in A) the Immunosuppression group and B) Non- the Immunosuppression group Methods This analysis used data from the prospective, multicenter, and multinational cohort developed by the European Network for ICU-related respiratory infections (ENIRRI), including 1060 adult patients diagnosed with nLRTI. Descriptive statistics were utilized to compare the immunosuppressed group against the non-immunosuppressed group, while also detailing the microorganisms predominantly identified in both groups. A survival analysis adjusted for infection severity using a Cox proportional hazards model was performed to explore mortality within these subgroups further. Figure 2 Kaplan-Meier survival curve stratified by Immunosuppression status: Probability of survival from ICU admission Results Immunosuppression was observed in 25% of the patients (264/1060). In both cohorts, Pseudomonas aeruginosa was the predominant microorganism, particularly affecting immunosuppressed patients, (25.3% vs. 16.7%, p = 0.032), followed by Klebsiella spp and Acinetobacter baumanii (Figure 1). Interestingly, the survival analysis revealed a lower probability of survival in the non-immunosuppressed after admission to the ICU (Figure 2). Additionally, the Cox regression analysis adjusted by disease severity found that no-immunosuppressed patients had lower mortality. Figure 3 Adjusted Kaplan-Meier Survival Curve following Cox Regression: Survival Probability Adjusted for SAPS II Score. Conclusion This description sheds light on the intricate relationship between immunosuppression, microbial etiology, and clinical outcomes in patients with nLRTI. Interestingly, immunosuppression was not associated with worse clinical outcomes, even after adjusting for disease severity. Disclosures All Authors: No reported disclosures

P-459. Length Of Hospital Stay, In-patient Mortality And Factors Associated With Mortality Among HIV-Cryptococcal Meningitis Patients Receiving Liposomal Amphotericin B At Tertiary Hospitals in Uganda

Abstract Background Cryptococcal meningitis (CM) remains the second lethal opportunistic infection among People Living with HIV (PLWHIV) in sub-Saharan Africa. Currently, the patients are managed on single high-dose liposomal amphotericin B and flucytosine. However, there is no sufficient data on whether the new treatment regimen has an effect on reducing inpatient mortality and length of hospital stay in the real-world setting. We aimed to investigate the proportion of inpatient mortality, length of hospital stay (LOS), and factors associated with mortality among patients with HIV-associated CM receiving liposomal amphotericin B-flucytosine regimen. Methods This was a cross-sectional study conducted to review medical records of patients admitted between December 2022 and May 2023 at 11 tertiary hospitals in Uganda. Medical records of 173 HIV-CM patients were reviewed. Univariate descriptive statistics were used to summarize the background characteristics. Modified Poisson regression was used to ascertain factors associated with mortality at bivariable and multivariable levels. Associations were presented through adjusted prevalence ratios with their 95% confidence intervals. Data were analyzed using STATA v15. Results Of the 173 patients’ medical records reviewed, 58.4% were males with a median age of 38 years (IQR= 30, 48) and over 55.5% were married. Patients with altered mental status (GCS< 15) were 40%. Overall, inpatient mortality for liposomal amphotericin B was 35.8% and this varied by health facility. The median LOS was 7 days (IQR = 3, 12). Factors associated with mortality were convulsion [APR, 1.86, 95%CI (1.21-2.86), p-value=0.005)], altered mental status [APR; 1.66, 95%CI (1.07-2.57), p-value=0.023], and a comorbid condition [APR, 2.26 95%CI (1.44-3.53), p-value=0.006]. Therapeutic lumbar punctures were significantly associated with reduced mortality [APR; 0.47, 95%CI (0.29-0.73), p-value=0.001]. Conclusion Liposomal amphotericin B regimen has lower mortality than deoxycholate in the real-world setting. Patients on average spend more than a week in hospital. Male sex, convulsion, altered mental status, and comorbid conditions were independently associated with mortality. Therapeutic LPs significantly reduced inpatient mortality. Disclosures All Authors: No reported disclosures

P-933. Combination Antibiotic Therapy in Infective Endocarditis: A systematic Review and Meta Analysis

Abstract Background Infective endocarditis (IE) is serious disease with 20% in-hospital mortality and significant morbidity. The role of combination therapy in managing patients with IE is controversial. We aimed to determine the effectiveness of combination antibiotic therapy compared to monotherapy in IE. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram; summarizes the study selection process Methods MEDLINE, Embase, Cochrane and Web of Science were searched from inception to July 28, 2023. Papers reporting mortality of combination therapy versus monotherapy in adult patients with IE were included. Non-English papers and studies with < 10 patients in combination therapy group were excluded. Two reviewers independently assessed the studies. Summary of odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated using a random-effects model. Sub-group analyses based on timing of mortality, bacterial species/group, geographic location, and study design were conducted. Forest Plot of all-cause Mortality at any time point of patients with infective endocarditis compared between combination therapy and monotherapy Results Out of 4323 studies identified, 27 studies (2462 patients) were included in the meta-analysis. There was no significant difference in the risk of all-cause mortality between the two groups (OR, 0.92; 95% CI, 0.59-1.43). Subgroup analysis focusing on one-year mortality demonstrated a decrease in mortality risk with combination therapy (OR, 0.54; 95% CI, 0.33-0.87). Additionally, combination therapy demonstrated a favorable outcome in studies involving gram-negative bacteria (OR, 0.38; 95% CI, 0.18-0.79). Studies conducted in Europe reported a statistically significant decrease in overall mortality risk with combination therapy (OR, 0.52; 95% CI, 0.32-0.86). Forest Plot of one-year Mortality of patients with infective endocarditis compared between combination therapy and monotherapy Conclusion Combination therapy in patients with infective endocarditis (IE) was associated with reduced one-year mortality rates and lower mortality among cases involving gram-negative bacteria. The observed significance in European studies may be attributed to a higher proportion of papers focusing on gram-negative infections and reporting one-year mortality outcomes. Forest Plot of all-cause Mortality at any time point of patients with infective endocarditis compared between combination therapy and monotherapy (only studies from Europe) Disclosures Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) Joshua T. Thaden, MD, PhD, National Institutes of Health K08 AI171183 (Thaden): Grant/Research Support

P-818. Unraveling Mortality Drivers in Gram-negative Bloodstream Infections to Guide Antimicrobial Stewardship Efforts

Abstract Background Bloodstream infections (BSIs) represent a significant clinical challenge due to their association with substantial morbidity and mortality. This study aimed to identify predictors of mortality in Gram-negative BSIs to guide more effective antimicrobial stewardship strategies. Methods Adult inpatients with Gram-negative BSIs from our academic medical institution between July 2022 and August 2023 were included. Data collected included patient demographics, microbiological data, clinical management variables (qPitt, Charlson Comorbidity Index (CCI), ICU admission, length of stay), ID consultation, and clinical outcomes. Logistic regression and CART analysis identified mortality predictors. Results In total, 441 predominately Caucasian patients (85.7%), with a mean age 58.5 yrs and 49.4% male, were included. Majority (61.5%) of infections were community-acquired, with 43.1% requiring ICU admission and 43.8% receiving an ID consultation. Overall mortality was 20.0% with the following prevalence and mortality rates: E. coli (39.7%, 14.9%), K. pneumoniae (14.1%, 17.7%), P. aeruginosa (9.1%, 35.0%), S. marcescens (7.5%, 24.2%), and E. cloacae (5.2%, 17.4%). Multivariable regression identified hospital-acquired infection (p < 0.001), qPitt > 2 (p < 0.001), and ICU admission (0.001) as independently associated with increased mortality. Additionally, renal disease (p=0.025), cancer (p = 0.026), and cardiovascular disease (p=0.040) were significant contributors to mortality. CART highlighted ICU admission as the primary driver of mortality, with higher mortality rates compared to non-ICU admissions (32.1% vs 10.8%, p< 0.001). Among ICU patients, a CCI >4 was identified as a secondary driver of mortality, with rates of 14.5% for CCI < 4 and 39.0% for CCI >4, p=0.001. Non-ICU patients with a length of stay < 8 days had lower mortality (3.3% vs 16.6%, p = 0.001). ICU patients received fewer ID consultations compared to non-ICU patients (49.3% vs 36.7%, p =0.007). Conclusion This study underscores the impact of Gram-negative BSIs, particularly regarding ICU admission’s role in mortality. Addressing disparities in ID consultations offers opportunities for optimization of patient outcomes through enhanced care coordination. Disclosures Sarah Cotner, PharmD, BCPS, Gilead Sciences, Inc: Advisor/Consultant

P-1579. Prediction of Prognosis of Visceral and Subcutaneous Fat Areas in Pyelonephritis

Abstract Background Visceral fat accumulation has been regarded as a poor prognostic factor for coronary artery disease. Moderate overweight and mild obesity are associated with a lower mortality in patients with several infectious diseases on intensive care units, and this phenomenon is referred to as the obesity paradox. Pyelonephritis is one of the common infectious diseases, and although computed tomography (CT) imaging is frequently used in its localization, its prognostic value is limited. In this study, we analyze the relationship between the visceral and subcutaneous fat areas in CT scans and prognosis of patients with pyelonephritis.Fig. 1ROC curves using subcutaneous and visceral fat area to discriminating surviving pyelonephritis patients from deceased pyelonephritis patientsThe black line shows the curve using subcutaneous fat area and the gray line shows the curve using visceral fat area. Methods We included hospitalized patients with pyelonephritis who underwent computed tomography of the abdomen. Clinical data were obtained from the medical records. Subcutaneous and visceral fat aeras were analyzed at the umbilical level using the abdominal analysis (2D) function of the 3D image analysis system volume analyzer. Results 505 patients were included in the study. There were 497 survivors and 8 non-survivors, with both subcutaneous and visceral fat areas being lower in the non-survivors than in the survivors (subcutaneous fat area 49.3 ± 73.9 cm2 vs 123.7 ± 85.3 cm2, p=0.012; visceral fat area 42.2 ± 29.2 cm2 vs 98.4 ± 69.1 cm2, p< 0.01, respectively. ROC analysis using subcutaneous and visceral fat areas to discriminate survival and death showed that the areas under the curve of subcutaneous and visceral fat areas were 0.794 (p=0.002) and 0.770 (p< 0.001), respectively (Fig.1). Conclusion Patients with poor prognosis of pyelonephritis tended to have lower subcutaneous and visceral fat area at onset than patients with improved prognosis. The results suggest that both subcutaneous and visceral fat area using CT may have prognostic value for pyelonephritis. Disclosures All Authors: No reported disclosures

P-844. Bacteraemia Caused by High Risk AmpC-producing Enterobacterales: Influence of IDSA Guidelines Adequacy and Antimicrobial Stewardship Activity on Outcomes

Abstract Background Treatment of high risk AmpC-producing Enterobacterales bloodstream infections (BSIs) is challenging due to the posibility of development of antibiotic resistance during treatment. The aim of this study was to analyze the impact of antimicrobial stewardship activity and IDSA guidelines adequacy in patients with high risk AmpC-producing Enterobacterales BSIs. Methods Patients with Citrobacter spp, Enterobacter spp and Klebsiella aerogenes BSIs were included between June 2019-March 2024. Outcomes of death and relapse of infection at 30 days were assessed. Adequacy of definitive antimicrobial treatment according to IDSA guidelines was evaluated. The impact of antimicrobial stewardship activity in treatment adequacy and outcome was analyzed. Analysis was performed using SPSS version 25. Results 2049 BSIs were evaluated and 67 were finally included. 80% were monomicrobial. Median patient age was 74 years, 73% were male. The most frequent microorganism isolated was Enterobacter cloacae (55%). 50% were nosocomial and the most frequent origen was biliary tract (35,8%). 35% met sepsis criteria. 30% of cases presented cefotaxim resistance. Empiric and definitive antibiotic treatment was prescribed according IDSA guidelinesi n 34% and 91% of cases, respectively.. Death at 30 days was 6% and a combination outcome of death and relapse of infection at 30 days was 11,9%. Definitive antibiotic treatment adequacy according to IDSA guidelines was associated with lower mortality and relapse at 30 days (OR 0,04; IC95 0,003-0,6; P=0,02). Antimicrobial stewardship team did an intervention in 34% cases. This intervention was associated with a trend toward of lower mortality and relapse (4% vs 15%, P=0,2), a trend toward of higher IDSA guidelines adequacy (100% vs 86%, P=0,08), and a higher switch to oral treatment (78% vs 52%; P=0,03). Conclusion Adequacy of definitive antimicrobial treatment in high risk AmpC producing Enterobacterales BSIs according to IDSA guidelines was associated with a better outcome. Antimicrobial stewardship is desired for management of these patients. Disclosures All Authors: No reported disclosures

P-1626. Impact of Repeat Blood Cultures Among Adult Cancer Patients with Gram-Negative Bacilli Bacteremia on Patient-Oriented Outcomes

Abstract Background Gram-negative bacilli (GNB) bacteremia is a common and often fatal infection with mortality rates estimated to be 14-34%. Follow-up blood cultures (FUBCs) are blood cultures that are repeated after an initial positive culture. FUBCs are used to assess the appropriateness and duration of antimicrobial therapy. Currently, no guidelines exist regarding the use of FUBC for GNB bacteremia, and the utility is not well-studied in adults living with cancer. We aimed to characterize the impact of FUBC in GNB bacteremia on patient-centered outcomes in patients with cancer. Methods We conducted a single-center, retrospective study in patients ≥18 years, hospitalized during 2022, living with cancer, and with laboratory-confirmed GNB bacteremia. FUBC was defined as a blood culture performed within 7 days of initial positive blood culture. We gathered information on the source of bacteremia, identified organisms, presence of antimicrobial resistance, and comorbidities. Categorical variables were compared using Chi-square or Fisher’s exact test. Independent predictors of length of hospital stay were obtained via generalized linear model analysis. Logistic regression analysis was used to identify predictors of unplanned hospital readmission and mortality. Results Overall 94% (590/626) of patients with GNB bacteremia had a FUBC at our institution. Among those with FUBC, the majority were without growth (73%). 116/590 (20%) of patients had persistent GNB bacteremia. Patients with persistent or alternative growth on FUBC had higher mortality compared to those with negative FUBC (41% and 53% vs 17%, p< 0.001). Patients with a new organism on FUBC had longer length of stay compared to those with no growth on FUBC (aOR 1.55, 95% CI [1.09-2.20]). Patients with a single organism on repeat culture had a higher rate of mortality. Conclusion The majority of patients with FUBC did not show growth. We observed that patients who underwent FUBC had lower mortality than those without FUBC. Patients with new organisms identified on FUBC were associated with longer length of stay. Patients with positive FUBC may be characterized as high risk for mortality. Despite the majority of FUBC without growth, there may be a mortality benefit in identifying those patients with positive FUBC in patients living with cancer. Disclosures Natalie J Dailey Garnes, MD, MPH, MS, AlloVir: Grant/Research Support

310. A comparative study on the effectiveness and safety between colistin-based and high-dose ampicillin/sulbactam-based combination therapy for nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii

Abstract Background There are differences between IDSA guidance and ESCMID guideline in the treatment of nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB). We compared differences in treatment outcomes between the colistin-based and high-dose ampicillin/sulbactam-based regimen in CRAB pneumonia. Methods A retrospective cohort study was conducted on adult patients diagnosed with nosocomial pneumonia (clinically defined pneumonia or pneumonia with specific laboratory findings according to the CDC/NHSN surveillance definition) by CRAB (with a meropenem MIC ≥16ug/ml, colistin MIC 1 ≤ug/ml, and ampicillin/sulbactam MIC ≥4ug/ml) in a university-affiliated hospital in Korea. The study enrolled those who received colistin-based regimen using a loading dose of colistin followed by a maintenance dose (June 2021 to May 2022) and high-dose ampicillin/sulbactam-based regimen using sulbactam 9g/day (October 2022 to September 2023). The primary outcome (all-cause mortality within 28 days) and secondary outcomes (including 14-day/28-day clinical success rates and 14-day/28-day kidney injury -RIFLE score) between the two groups were compared using a Log-binomial regression. Results A total of 170 CRAB pneumonia patients were enrolled in the study, including 87 patients receiving colistin-based regimen and 83 patients receiving high-dose ampicillin/sulbactam-based regimen. The 28-day mortality rate in the ampicillin/sulbactam group (27.7%) was significantly lower than the colistin group (57.5%) (adjusted RR = 0.48, 95% CI 0.33-0.71). The 14-day and 28-day clinical success rates of the ampicillin/sulbactam group (50.6% and 68.7%) were both significantly higher than those of the colistin group (23.0% and 32.2%) (aRR = 2.20, 95% CI 1.42-3.42 and aRR = 2.13, 95% CI 1.52-2.99). Also, both 14-day and 28-day kidney injury in the ampicillin/sulbactam group (0.6 ± 1.2 and 0.7 ± 1.4) were significantly lower than those in the colistin group (0.9 ± 1.2 and 1.0 ± 1.3) (aRR = 0.69, 95% CI 0.52-0.91 and aRR = 0.68, 95% CI 0.47-0.99). Conclusion In patients with CRAB nosocomial pneumonia, High-dose ampicillin/sulbactam-based combination therapy is a better treatment option because of its lower mortality, higher clinical success rate, and lower risk of kidney injury. Disclosures All Authors: No reported disclosures

P-661. Impact of Optimal β-lactam Treatment on the Outcomes of Patients with Pseudomonas Aeruginosa Pneumonia

Abstract Background P. aeruginosa is the most common cause of nosocomial pneumonia and accounts for a large proportion of antibiotic use in the ICU. Despite this, there are limited comparative-effectiveness data for β-lactam agents. Our objective was to compare outcomes of Pseudomonal pneumonia treated with piperacillin-tazobactam (TZP), cefepime (FEP) or meropenem (MEM). Methods We performed a retrospective cohort study of patients who met clinical criteria for pneumonia before (2017-2018) and after (2022-2023) dose optimization protocols were established.The primary outcome was 28-day all-cause mortality with secondary outcomes including 28-day clinical response, 90-day recurrence and development of new β-lactam resistance. Results In preliminary analyses, 118 patients were included; baseline characteristics shown in Figure 1. At diagnosis, 72% required mechanical ventilation and 42% had severe sepsis/shock. TZP was giving as a prolonged infusion (≥3h) throughout the study; 98.3% of patients received FEP or MEM as prolonged infusions after dose optimization, compared to 0% before (Figure 2). Clinical outcomes stratified by definitive treatment are shown in Figure 3. Mortality rates were numerically higher in patients treated with TZP (28.6%) compared to FEP or MEM (22.6%). Rates of treatment emergent resistance ranged from 28.9 – 47.1% across agents. Clinical response rates did not vary across patients before or after dose optimization (Figure 4); however, the 28-day mortality rates was 4.3% lower post-dose optimization of FEP and MEM. Across all patients, 24% died within 28 days of treatment initiation. Among those who survived (n=90), 26% developed recurrent pneumonia or bacteremia within 90 days. Conclusion Our preliminary data suggests that outcomes did not vary significantly between TZP, FEP, or MEM for treatment of P. aeruginosa pneumonia; however, some notable trends were identified, including higher mortality among patients who received TZP and lower mortality among patients receiving optimized doses of FEP or MEM. These data support further investigation through multicenter studies that include a larger number of patients. Consistent with prior reports, recurrent infections and treatment-emergent resistance are common challenges in managing P. aeruginosa pneumonia. Disclosures Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Ciadara: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Honoraria|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support

P-1891. What’s the Reason for the Consult? Identifying Clusters of Infectious Disease Consultations in an Academic Health System

Abstract Background In many institutions, infectious diseases (ID) consultations are requested via electronic order entry and the reason for consultation is included as free text in the order. We employed an unsupervised clustering algorithm to determine whether the consult order text can be used to ascertain clinically meaningful groups among patients for whom ID consultation is requested. Figure 1. Example Word Cloud ‘Clusters’ of Free-Text Reasons for Infectious Disease Consultation and Corresponding Subject Matter Expert Interpretation Methods We examined the initial ID consultation for all Duke University Health System inpatients receiving consultation from 1/1/2014 - 12/31/2023. The free text “Reason for Consult?” field in the consultation order was extracted, transformed into a weighted vector format using Term-Frequency Inverse-Document Frequency, and categorized using an unsupervised K-means clustering algorithm; Algorithm parameters were adjusted to optimize clinical relevance of the clusters. Within each patient cluster, we evaluated mortality and hospital length of stay, with patients censored at their time of last contact with the health system.Figure 2.Kaplan-Meier Survival Estimates for Each Cluster Results 37,848 unique patients with an ID consultation during the study period were evaluated, and 35,197 had free-text reasons associated with the electronic consult order. A combination of the K-means Elbow Method, silhouette score, and subject matter expert evaluation identified that approximately 10 clusters were optimal to categorize the dataset. Word clouds were generated for each cluster (Figure 1) and expert assessment identified the central theme of each cluster (Table 1). We identified unique patient characteristics or syndromes in nine of the patient clusters, while the final cluster was characterized as a ‘generic’ ID consult. One-year mortality varied according to cluster (Figure 2) with the highest mortality seen in the ‘Hematologic Malignancy’ category, and lowest mortality in the ‘Complicated Wound Infection’ and ‘HIV Management’ categories. Conclusion An unsupervised clustering algorithm allowed for the identification of clinically meaningful groups of ID consultations. If validated in other settings, this approach could present an accessible way to understand qualitative and prognostic trends in ID clinical practice.Table 1.Cluster Characteristics*Institutional policy at the end of study period requires Infectious Disease consultation for patients with HIV, new lung transplant recipients, patients with candidemia or Staphylococcus aureus bacteremia, and patients for whom restricted antibiotics are requested.**Infinite median survival times indicate that the Kaplan-Meier survival curve did not cross the 50% threshold through the evaluated period. Disclosures Kristen Dicks, MD, UpToDate: Advisor/Consultant Nicholas A. Turner, MD, MHSc, PDI: Research contract|Purio Labs: Research contract

P-2253. Epidemiology and Outcomes of Gram-Negative Bacteremia in a Diverse Immunocompromised Population

Abstract Background While gram-negative bloodstream infections (GN-BSI) carry significant risk of mortality and are of particular concern in neutropenic patients, relatively little is known about epidemiology and outcomes in contemporary immunocompromised populations. This study aims to assess the epidemiology of GN-BSI admitted to the National Institutes of Health Clinical Center (NIH CC). Methods Episodes of GN-BSI were identified through positive blood culture results from January 1 to December 31, 2023. Episodes not treated at the NIHCC were excluded. We performed chart review for baseline demographics, laboratory results, infectious disease consultation results, and clinical outcomes. Results Seventy-five episodes of GN-BSI admitted to the NIHCC were identified. All patients were immunocompromised by disease or treatment (Table 1). Forty-four (58.7%) were neutropenic at index culture with median duration of neutropenia 9 days after index culture (IQR 7-17.5) in survivors. Sixty-five (86.7%) had central venous access device (CVAD) and 16 (24.6%) were removed during the episode. Translocation (n=38, 50.8%) was the most frequently reported source followed by gastrointestinal (n=10, 13.3%) and pulmonary (n=9, 12%). Escherichia coli (n=25), Klebsiella pneumonia (n=17), and Pseudomonas aeruginosa (n=15) were the most frequently identified isolates. Twenty-one (28%) had polymicrobial bacteremia with 7 (33.3%) also containing a gram-positive isolate. Bacteremia duration was a single day in 64 (88.9%) episodes. Twenty-five (32.9%) had ICU admission and 7 (9.2%) experienced 30-day mortality. Neutropenic episodes had similar 30-day mortality (6.8% v 12.9%, OR 0.50, p=0.62) and ICU admission rate (OR 1.09, 0.37-3.28, p >0.99). Polymicrobial episodes had similar 30-day mortality (4.8% v 11.1%, p=0.45). Those with CVAD removal had lower rate of ICU admission (12.5% vs 37.3%, OR 0.16, p=0.03) and lower 30-day mortality (0% v 11.9%, p=0.22) though not statistically significant. Conclusion Enterobacteriaceae caused most of GN-BSI at an institution with a diverse immunocompromised population. CVAD removal remains important in the treatment of GN-BSI. Neutropenia is not associated with worse outcomes. Disclosures All Authors: No reported disclosures

P-825. Short Versus Long Treatment Duration for Streptococcal Bloodstream Infections

Abstract Background The rise in antibiotic resistance, antimicrobial-related harms and emerging data have prompted a shift towards shorter antibiotic durations. However, there is a lack of data to inform durations of therapy for Streptococcal bloodstream infections (BSI). The need for clearer guidance led us to compare outcomes between short and long antibiotic durations for uncomplicated Streptococcal BSI with the goal of informing local and national practice. Effects of Long vs. Short Antibiotic Durations Methods This was a retrospective cohort study of unique adult patients admitted to University of Utah from January 1, 2014 to July 15, 2023 with uncomplicated Streptococcal BSI, defined as negative follow-up blood cultures, clinical resolution by day 3, absence of metastatic foci, source control if indicated, and no other complications. We used inverse probability of treatment weighting to estimate the average treatment effects (ATE) of in vitro active antibiotics administered for > 10 days (long duration) versus < 10 days (short duration), adjusting for pretreatment variables. The primary outcome was a composite of recurrent bacteremia, all-cause mortality, and readmissions at 30 days from end of treatment (EOT). Secondary outcomes were 90-day all-cause mortality and recurrent bacteremia from EOT. Results 209 patients met criteria for inclusion. The median duration in the long and short groups were 15 (IQR, 14-17) and 8 days (IQR, 7-9.75), respectively. In the propensity score weighted analysis (Table 1), the ATE of long versus short duration was not significant on the composite primary outcome (21% vs 22%; OR= 0.81 [95% CI: 0.34 to 1.91], p=0.62) or any secondary outcomes. Conclusion We found no appreciable difference in outcomes between patients treated with >10 days of antibiotics compared to those treated with <10 days for uncomplicated Streptococcal BSI. Given low absolute rates of mortality and recurrent bacteremia, paired with no appreciable difference related to treatment duration, it is reasonable to recommend shorter durations. Given limitations of this retrospective analysis, future research is needed to confirm our findings; however, our data could inform antimicrobial stewardship interventions aimed at decreasing treatment durations for uncomplicated Streptococcal BSI. Disclosures All Authors: No reported disclosures

P-282. Cost Effectiveness Analysis of Ceftolozane/Tazobactam for the Treatment of Patients with Ventilated Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia in the Philippines

Abstract Background Ceftolozane/tazobactam (C/T) was licensed by Philippine Food and Drug Administration for the treatment of ventilated hospital-acquired bacterial pneumonia (vHABP) and ventilator-associated bacterial pneumonia (VABP) last 2019. Increasing resistance rates to antibiotics available in the Philippine National Formulary (PNF) by Pseudomonas aeruginosa associated vHABP/VABP has concerned clinicians due to its overall morbidity and mortality. This study assessed the cost-effectiveness of C/T treatment compared with existing antimicrobials among adult patients with confirmed susceptibility profile of Pseudomonas aeruginosa associated vHABP/VABP. Methods An economic model was developed to compare the lifetime costs and quality-adjusted life-years (QALYs) associated with C/T and the currently listed antimicrobials (meropenem, aminoglycosides, colistin) in the PNF for the treatment of patients with Pseudomonas aeruginosa associated vHABP/VABP. A short-term decision tree was used for the in-hospital period, followed by a long-term Markov model to depict lifetime costs and outcomes. Pathogen susceptibility was sourced from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database; clinical efficacy was obtained from the published literature. The model assumed a public payer perspective, capturing direct costs incurred by the health system, and direct health outcomes for treated patients. Discount rates applied followed local HTA methods guide. Results On treating Pseudomonas aeruginosa associated vHABP/VABP, C/T was associated with a higher absolute cure rate (17%) and lower absolute mortality rate (-3%) than meropenem. The incremental cost-effectiveness ratio (ICER) for C/T compared to meropenem, amikacin, and colistin were ₱267,396, ₱164,570, and ₱47,504 per QALY gained, respectively. C/T generated more QALYs than exiting antimicrobials at an increased cost per patient, but resulting in ICER less than one times the Gross Domestic Product (GDP) of ₱233,902 for amikacin, and colistin, and ∼ 1.2x GDP per capita for meropenem. Conclusion C/T represents a cost-effective treatment for payers and an important option to be listed in the PNF for clinicians treating patients with Pseudomonas aeruginosa vHABP/VABP in the Philippines. Disclosures GEOVIN DEXTER C. UY, RPh, MPH, MSD Philippines: employee|MSD Philippines: Stocks/Bonds (Private Company) Karlo Paredes, RN, MPH, PhD (cand), MSD Philippines: employee|MSD Philippines: Stocks/Bonds (Private Company) Gillian Camille Abello, MD, MSD Philippines: employee Carolyn Cameron, MPH, MSD Australia: employee|MSD Australia: Stocks/Bonds (Private Company) Joe Yang, PhD, Merck & Co., Inc: employee|Merck & Co., Inc: Stocks/Bonds (Private Company)

Investigation of Virulence-Related Markers in Atypical Strains of Toxoplasma gondii from Brazil

Toxoplasma gondii is an obligate intracellular protozoan parasite distributed worldwide that infects a wide range of warm-blooded animals, including humans. Recent studies sought to clarify the relationship between the alleles GRA15, ROP5, ROP16, ROP17, and ROP18 and the virulence of T. gondii isolates in mice. This work aims to analyze the variability of genes that express T. gondii virulence proteins of 103 strains. Most strains were virulent for mice (76/103–73.79%); within these, 30 were 100% lethal, and 46 caused a cumulative mortality range from 20% to 93%. For the GRA15 marker, most strains presenting allele 2 were non-lethal. For the ROP17 marker, allele 4 was associated with mortality, compared to allele 1. For the ROP18 marker, alleles 1 and 4 were associated with mortality, compared to alleles 2 and 3. A combined analysis of alleles showed low cumulative mortality when the strains presented alleles 3 and 1 for ROP18 and ROP16, respectively. On the other hand, allele 4 of ROP17 was a determinant for virulence when associated with ROP18 allele 3 and ROP16 allele 1. Our analysis shows that ROP18 is the primary determinant of the virulence of atypical strains in mice. Additionally, ROP17 genotyping should not be overlooked, as it has proven critical to enhance this prediction.

P-1482. Ceftazidime-Avibactam for Treating Bacteremic and Non-Bacteremic Carbapenemase-Producing Enterobacterales Infections in Immunocompromised Patients

Abstract Background Ceftazidime-avibactam (CA) and CA plus aztreonam (ATM) are the preferred treatment options for KPC and metallo-beta-lactamase (MBL) carbapenemase-producing Enterobacterales infections (KPC-CPE and MBL-CPE), respectively. There are not many studies in immunocompromised patients (IP). Methods Observational and prospective cohort study. All episodes of KPC-CPE and MBL-CPE infections in IP admitted to a university hospital from August 2018 to April 2023, who received definitive antibiotic therapy (DAT) with CA or CA+ATM for at least 48 hours, were included. Non-bacteremic episodes (NBE) were compared with those with bacteremia (BE). Logistic regression analysis was performed to identify risk factors for 30-day mortality (RFM). Results Seventy-six episodes were included (36 NBE and 40 BE). Hematological malignancies and neutropenia were more frequent in BE (NBE 13.9% vs. BE 50.2%, p< 0.001; and NBE 5.6% vs. BE 42.5%, p< 0.001), while solid organ transplantation was in NBE (NBE 66.7% vs. BE 32.5%, p=0.003). The urinary source was more frequent in NBE (NBE 72.2% vs. BE 30%, p< 0.001), while the abdominal source was in BE (NBE 2.8% vs. BE 17.5%, p=0.04). K. pneumoniae was the main isolated microorganism, and KPC-CPE was the most common resistance mechanism in both groups, followed by MBL-CPE, without significant differences. Septic shock at onset was higher in BE (NBE 8.3% vs. BE 30%, p=0.18). Empirical treatment was appropriate in 59.3% of NBE vs. 75% of BE, p=0.12. Seven-day mortality, 30-day overall and infection-related mortality in NBE and BE were 2.8% vs. 5%, p=0.40; 11.1% vs. 27.5%, p=0.07; and 0% vs. 10%, p=0.07; respectively. The RFM were APACHE II score >20 [OR 5.80 (95% CI 1.19-28.17)], and acute renal failure [OR 16.15 (95% CI 1.78-146)]. Conclusion KPC-CPE and MBL-CPE infections in IP with or without bacteremia who received DAT with CA or CA+ATM had low early and 30-day infection-related mortality. RFM were related to the severity and complications of the infections. Disclosures Diego Torres, Medical Doctor, Gador: Honoraria|GSK: Advisor/Consultant|Khight Therapeutics: Honoraria|MSD: Honoraria

P-1406. Racial Disparities in HIV Prevalence and Complications in Hospitalized Patients

Abstract Background Racial and ethnic disparities in HIV care and outcomes are well known. Multiple causes have been reported including inequalities in access to care and pre-exposure prophylaxis (PrEP), housing instability, lack of antiretroviral insurance coverage, and economic disadvantages. We aim to evaluate the disparities in HIV prevalence and outcomes in hospitalized patients. Methods We analyzed the 2020 United States National Inpatient Sample (NIS) data of all patients with a diagnosis of HIV admitted inpatient. The NIS database is the largest publicly available database of patients hospitalized in the United States and contains approximately 20% stratified samples of all hospital discharges in the United States. Results There were 38,666 admissions with a diagnosis of HIV in 2020, of which 30.3% were females. 51.6% of the HIV patients were Blacks, 30% Whites, 13.7% Hispanics, 0.7% Asians, 0.6% Native Americans, and 3.4% others. The mean age was 50.8 years, and the mean length of stay was 6.4 days. In the bivariate analysis, the Hispanics were more likely compared to others to have Kaposi Sarcoma (1.8% vs. 1.1%, p< 0.001), cryptococcal meningitis (1.5% vs. 0.6%, p< 0.001), disseminated coccidioidomycosis (0.2% vs 0.0%, p< 0.001), hepatitis C (6.7% vs. 5.3%, p< 0.001), Covid-19 infection (7.9% vs. 4.9%, p< 0.001) and pneumocystis jiroveci pneumonia (3.2% vs. 2.3%, p< 0.001). The multivariate analysis showed no statistically significant racial or ethnic difference in all-cause mortality (p=0.17). However, patients in the highest income quartile had significantly lower all-cause mortality compared to those in the lowest quartile after adjusting for variables including race, ethnicity, and HIV complications (OR 0.69, 95% CI 0.54-0.89, p=0.004). Conclusion Our study showed that the prevalence of HIV is still disproportionally high in Blacks. While about 16% of all patients in our dataset are Black, about 52% of the HIV patients are Black. However, Hispanic patients appear to have more HIV complications. Cultural appropriate interventions to prevent HIV acquisition, increase HIV screening, and early initiation of treatment in racial and ethnic minorities are warranted. Mining a national database can provide insights into morbidity and mortality trends in patients living with HIV. Disclosures All Authors: No reported disclosures

P-729. Prognostic Value of the Immunodeficiency Scoring Index for Respiratory Viral Infections in Hematopoietic Cell Transplant Recipients

Abstract Background Accurate prediction of the severity of respiratory viral infections (RVIs) may help in improving patients’ outcomes. The respiratory syncytial virus (RSV) immunodeficiency scoring index (ISI), which incorporates patients’ host factors, was predictive of progression to lower respiratory tract infection (LRI) or mortality in HCT recipients with RSV infections. Our study goal was to correlate the ISI with severe respiratory infection and 30-day mortality in HCT recipients infected with different respiratory viruses and with non-viral respiratory infections.Table 1:Baseline characteristics and clinical outcomes following respiratory infection.Abbreviations: BiPAP= bilevel positive airway pressure, BMI= Body mass index, CKD= chronic kidney disease, COPD= chronic obstructive pulmonary disease, CPAP= continuous positive airway pressure, ESRD= end-stage renal disease, GVHD= graft-versus-host disease, HCT= hematopoietic stem cell transplantation, HFNC= high-flow nasal cannula, ISI= immunodeficiency scoring index, IQR= interquartile range, LRI= lower respiratory tract infection, MRD= matched related donor, MUD= matched unrelated donor, RVI= respiratory virus infection, SD=standard deviation, URI= upper respiratory tract infection. Methods In this prospective study, we enrolled 50 patients who had undergone allogeneic or autologous HCT and were infected with RSV (n=10), influenza (n=10), parainfluenza (n=10), SARS-CoV-2 (n=10) or had a non-viral respiratory infection (n=10). We calculated the ISI at enrollment and followed the patients for 4 weeks. Primary outcomes of interest were progression to LRI, the severity of RVI (the use of a high-flow nasal cannula, BiPAP, CPAP, or mechanical ventilation), and 30-day all-cause mortality.Figure 1:Median immunodeficiency scoring index at presentation and severity of respiratory infection (n=50).*Mild-moderate infection is defined as the maximal O2 requirement of a nasal cannula or face mask, and severe infection as the need for high flow nasal cannula, BiPAP, CPAP, or mechanical ventilation. Abbreviations: BiPAP= bilevel positive airway pressure, CPAP= continuous positive airway pressure, ISI= immunodeficiency scoring index, PIV= parainfluenza virus, RSV= respiratory syncytial virus, RVI= respiratory virus infection. Results Among the 50 enrolled patients, the majority (78%) had undergone allogeneic HCT, while 22% had autologous HCT. Upon presentation, 44% were diagnosed with upper respiratory tract infection (URI), and 56% with LRI. Over the 30-day follow-up period, three patients with URI (14%) progressed to LRI, and four patients (8%) experienced severe infections leading to mortality (Table 1). For any viral pathogen, we observed higher ISI in patients with severe infections; in the non-viral respiratory infection group, relatively high ISI was noted at presentation but with no cases of severe infections (Figure 1). A higher ISI in HCT recipients with RVI was associated with 30-day mortality risk (median of 7 [IQR 5-8] vs. 3 [IQR 2-4], p=0.003) and severe infection (median of 7 [IQR 5-8] vs. 3 [IQR 2-4], p=0.003) (Figures 2, 3).Figure 2:Median immunodeficiency scoring index at presentation according to 30-day mortality status (among patients with RVI, n=40).Abbreviations: ISI= immunodeficiency scoring index, RVI= respiratory virus infection. Conclusion The ISI was associated with severe respiratory infections and 30-day mortality in a cohort of HCT recipients with different RVIs. The ISI can potentially be used to predict poor clinical outcomes in HCT recipients infected with any RVI and allow for early management of high-risk patients.Figure 3:Median immunodeficiency scoring index at presentation according to 30-day maximal oxygen requirements (among patients with RVI, n=40).Abbreviations: BiPAP= bilevel positive airway pressure, CPAP= continuous positive airway pressure, HFNC= high flow nasal cannula, ISI= immunodeficiency scoring index, RVI= respiratory virus infection. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor: Grant/Research Support|Symbio: Grant/Research Support Roy F. Chemaly, MD/MPH, AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Pharmaceuticals: Advisor/Consultant|Ansun Pharmaceuticals: Grant/Research Support|Astellas: Advisor/Consultant|Eurofins-Viracor: Grant/Research Support|InflaRX: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Roche/Genentech: Advisor/Consultant|Roche/Genentech: Grant/Research Support|Shinogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant

P-311. Shifts in Methicillin-Resistant Staphylococcus aureus Types in Bloodstream Infections: Nationwide and Regional Influences and Their Impact on Mortality

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bloodstream infections (BSI). In the USA and Japan, the New York/Japan clone (ST5-II) was historically prevalent, but recent studies in Japan have shown a shift towards ST8-IV and CC1-IV as the dominant strains. The extent to which these trends are mirrored in individual facilities and the variation in patient backgrounds across different MRSA types remains unclear. Methods We analyzed MRSA strains from blood cultures collected at Nagasaki University between 2012 and 2019. Whole-genome sequencing was utilized to determine sequence types, SCCmec, spa types, and resistance and virulence genes, complemented by phylogenetic analysis using core-genome MLST. Data were compared with earlier studies from 2003-2011 at the same hospital. Results Between 2003 and 2019, SCCmec type II decreased from 79.2% to 15.5%, whereas type IV increased from 18.2% to 65.5%. Severity and outcomes also changed: SOFA score decreased from 5.8 to 3.1, while in-hospital mortality decreased from 39.8% to 15.5%. No changes in the patient background, such as age, sex, or underlying diseases, were observed (Table 1). Further, the percentage of intravascular device-related BSI increased significantly from 18.1% during 2003–2007 to 46.6% during 2016–2019. The most common SCCmec type IV detected between 2012 and 2019 were ST8-IV and CC1-IV (Fig. 1A). ST8 was the predominant ST in both 2012–2015 and 2016–2019, but CC1 was detected only during 2016–2019 (Fig. 1B). In ST8-IV, MRSA/J and ST8-IV with spa type t5071 were identified, with MRSA/J being predominant. The detected MRSA/J, ST8-IV with spa type t5071, and CC1-IV subtypes were similar in terms of drug resistance, molecular characteristics, and phylogenetic features to those detected in the nationwide surveillance (Fig. 2). Patient characteristics across major MRSA types (ST8-IV, CC1-IV, ST8-I, ST5-II) revealed no significant differences, with lower SOFA scores and in-hospital mortality for CC1-IV (Table 2). Conclusion The evolving nature of MRSA types in bloodstream infections, correlating with improved outcomes over time and influenced by changes in nationally and regionally circulating strains, is highlighted. Disclosures Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi & Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees

Clinical outcomes and care for spontaneous bacterial peritonitis: A national cohort study.

SBP leads to high rates acute kidney injury (AKI) -hepatorenal syndrome and mortality. Population-based studies on contemporary SBP epidemiology are needed to inform care. In a large, national cohort of patients diagnosed with SBP and confirmed by ascitic fluid criteria, we characterized ascitic fluid characteristics, in-hospital and 12-month mortality, AKI, and recurrent SBP. We investigated how individual and bundled quality measures for SBP associated with outcomes after multi-level adjustment for health-system, patient clinical factors and quality measures. Individual and bundled quality metrics were inpatient antibiotics within 48 hours, intravenous albumin, repeat paracentesis within 48 hours, recognition of SBP, and prophylactic antibiotics upon discharge. Among 4,330 patients with newly diagnosed SBP, in-hospital mortality was 15.5% and 12-month mortality was 56.6%. The incidence of Stage 1 AKI was 26.6%, 15.7% for Stage 2, and 22.8% for Stage 3. The cumulative incidence of recurrent SBP was 10.3%. Guideline-recommended albumin was the only individual metric associated with reduced in-hospital mortality (HR 0.73, 95%CI 0.59 - 0.91). Receipt of a higher number of metrics from the SBP bundle was associated with progressively lower 12-month post-discharge mortality: patients who received 3, 4, and 5 SBP bundle components had 20%, 38%, and 56% lower hazard of mortality, respectively, relative to those receiving 2 or fewer (all p<0.001). The SBP bundle was associated with lower incidence of Stage 3 versus Stage 0-2 AKI (OR 0.66, 95%CI 0.51-0.86). Prospective implementation of evidence-based SBP bundles may improve care outcomes and mortality in SBP.