bluuebunny/crossref_metadata_2025 huggingface dataset:
88. Efficacy of nirmatrelvir-ritonavir in high-risk trial participants with prior SARS-CoV-2 infection or vaccination: a pooled analysis
Authors: McLaughlin John M , Leister-Tebbe Heidi , Bao Weihang , Quercia Romina , Hammond Jennifer
Published: January 2025

Background

EPIC-HR, a trial conducted early-on in the COVID-19 pandemic, showed > 85% efficacy of oral nirmatrelvir-ritonavir (NMV/r) for preventing COVID-19 hospitalization and all-cause death in unvaccinated high-risk patients (≥ 1 risk factor for severe COVID-19). The applicability of these findings to current settings of high population-level immunity, however, are not well understood. We evaluated efficacy of NMV/r in a subset of high-risk trial participants with pre-existing SARS-CoV-2 immunity from either prior infection or vaccination.

Efficacy of NMR-r by outcome in high-risk EPIC-HR and EPIC-SR mITT patients with prior SARS-CoV-2 infection or vaccination (n=1600)

Methods

Efficacy of NMV/r received within 5 days of COVID-19 symptom onset was assessed vs placebo through 28 days against a range of pre-specified outcomes. Data were pooled from two Phase 2/3 RCT modified intention-to-treat populations: (1) high-risk EPIC-HR patients who were unvaccinated and SARS-CoV-2 seropositive at baseline, and (2) high-risk EPIC-SR patients who previously received COVID-19 vaccine.

Results

1600 participants were included, of whom 969 (60.6%) were high-risk and SARS-CoV-2 seropositive from EPIC-HR and 631 (39.4%) were high-risk and vaccinated against COVID-19 from EPIC-SR. Overall, 807/1600 (50.4%) received NMV/r and 793/1600 (49.6%) placebo. Compared to placebo, NMV/r reduced the risk of COVID-19 hospitalization and all-cause death by 73.7% (95% confidence interval: 21.4–91.3%; absolute rate reduction: 1.40% [0.33–2.47%; P=.010]), any COVID-19 medical visit by 65.0% (24.4–83.8%; P=.008), and having severe COVID-19 symptoms by 22.1% (0.66–38.9%; P=.044) and 46.6% (22.1–63.4%; P=.001) in the 2–6 and 7–28 days following treatment initiation, respectively (Table). Median time to sustained symptom alleviation was 2 days shorter (12 vs 14 days; P=.047) for those who received NMV/r vs placebo.

Conclusion

In a subset of RCT participants with pre-existing natural or vaccine-derived SARS-CoV-2 immunity, treatment with NMV/r significantly reduced the risk of COVID-19 hospitalization and all-cause death, with a number-needed-to-treat of 71. Treated patients also had fewer COVID-19-related medical encounters, lower risk of having severe COVID-19 symptoms, and shorter time to symptom alleviation. These data underscore the utility of NMV/r in high-risk patients with baseline SARS-CoV-2 immunity.

Disclosures

John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Heidi Leister-Tebbe, BSN, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds (Public Company) Weihang Bao, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Romina Quercia, M.D., Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Jennifer Hammond, PhD, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds (Public Company)
100. Genomic epidemiology of carbapenemase-producing Enterobacter species in Toronto, Canada, 2007-2021
Authors: Izydorczyk Conrad , Lee Robyn , Mataseje Laura , Golding George , Braukmann Tom , Carroll Amanda C , Katz Kevin , Kozak Robert , Jamal Alainna J , MacFadden Derek , Mazzulli Tony , Melano Roberto , Patel Samir , Poutanen Susan M , Richardson David , Waglechner Nicholas , McGeer Allison
Published: January 2025

Background

Identification of transmission networks of carbapenemase-producing organisms (CPO) is critical to identifying their reservoirs and limiting their spread. This study aimed to use whole-genome sequencing to identify genomic relationships between CP Enterobacter (CP-Ent) in Ontario, Canada over a 15-year period.

Methods

All CP-Ent cases identified by prospective population-based surveillance in the Toronto/Peel Region from first isolate in 2007 to 2021, from hospital sinks (2016-2019), and wastewater treatment plants and surface water sites (2015-2017) were included. CPO isolates were identified by phenotypic screening (ertapenem MIC > 1mg/L or meropenem disc diffusion diameter ≤ 25mm), confirmed as Enterobacter by MALDI-TOF MS and as positive for carbapenemase genes by PCR, and sequenced by Illumina. Genomics analysis utilized a custom pipeline combining Snippy, IQ-Tree, and ClonalFrameML.

Results

Overall, 182 isolates from 127 patients, 61 isolates from 40 sinks, and 155 isolates from 9 wastewater plants/surface water sites were available (Table 1). Thirty-one of 127 (24%) patients had > 1 sequenced isolate: in 29 patients all isolates were highly related (median SNV distance 3.5, range 0-13); one patient had two CP-Ent species ∼1.5 years apart, and one had 2 sequence types (STs) 86 days apart. Of 12 (30%) sinks with > 1 isolate, 5 had 2 STs recovered at different times (4 with different carbapenemases). Multiple species, STs, and carbapenemases were recovered from sewage trunks and surface water. Using a ≤ 20 SNV threshold between any one pair of isolates, 14 multi-patient putative clusters involving 39 patients were identified; 1 added cluster was identified and 4 expanded when the threshold was increased to 40 SNVs (Table 2). At the 40 SNV threshold, the median number of patients per cluster was 2 (range 2-9), and the median number of hospitals with at least one first identified patient in each cluster was 1.5 (range 1-4). In total, 35% (45/127) patients were part of a cluster.

Conclusion

CP-Ent in Ontario are diverse, but a significant minority of affected patients are part of genomically-defined clusters. Genomic clusters may reflect undetected transmission of CP-Ent in healthcare, exposure to water, or other as yet unidentified sources.

Disclosures

Allison McGeer, MD, AstraZeneca: Honoraria|GSK: Honoraria|Merck: Honoraria|Moderna: Honoraria|Novavax: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Honoraria|Seqirus: Grant/Research Support|Seqirus: Honoraria
157. Long-Acting Injectable HIV Treatment in Individuals with Adherence Challenges: Real-World Insights from Southern California
Authors: Hastie Elizabeth , Hill Lucas , Bamford laura , CS Martin Thomas
Published: January 2025

Background

Long-acting injectable antiretroviral therapy with cabotegravir and rilpivirine (LAI CAB/RPV) showed superiority over daily oral ART among persons with HIV (PWH) with adherence challenges in the LATITUDE study. This trial included conditional economic incentives (CEI) and compensation, which may limit generalizability. We aimed to assess real-world outcomes of LAI CAB/RPV among a similar population in a Ryan White funded primary care HIV clinic.

Methods

PWH with adherence challenges who initiated LAI CAB/RPV at the UCSD Owen Clinic were included. Adherence challenges were defined as at least one HIV viral load (VL) > 200 copies/mL in the previous 12-months, along with either poor response to oral ART (two HIV VLs > 200 copies/mL separated by ≥ 4-weeks in the prior 18-months despite being prescribed oral ART) or being lost to clinical follow-up (no contact with an HIV provider for ≥ 6-months and non-adherence to ART for ≥ 7-days). The primary outcome was discontinuation of LAI CAB/RPV or VL ≥ 200 copies/mL within 48-weeks of initiation. Secondary outcome was confirmed virologic failure with resistance-associated mutations (RAMs).

Results

63 PWH fulfilled the inclusion criteria: 71% male, 27% female and 2% non-binary, with a median age of 43 years. 46% were white, 16% black, and 38% Hispanic. 41% reported current or prior injection drug use, 40% had active substance use, and 57% had a psychiatric diagnosis. At LAI CAB/RPV initiation, 43% had a VL ≥ 50 copies/mL and 11% had a VL > 10,000 copies/ml. 14 (22%) participants, including all those with a detectable VL at baseline, were prescribed an additional ART for at least part of the 48-weeks. Of the 50 participants with virologic data to 48-weeks, 10 (20%) discontinued LAI CAB/RPV: 4 (8%) had virologic failure (VL ≥ 200 copies/mL) with RAMs and 6 (12%) discontinued for other reasons including participant preference and one participant death.

Conclusion

This observational, real-world study demonstrated that PWH with adherence challenges experienced similar outcomes to those in clinical trials with CEI (20% with VL ≥ 200 copies/mL or LAI CAB/RPV discontinuation vs 24.1% in LATITUDE at 48-weeks). Our study’s lower primary outcome rate may be due to a higher-risk population being referred to LATITUDE to take advantage of CEI and compensation.

Disclosures

Lucas Hill, PharmD, AAHIVP, ViiV Healthcare: Honoraria Thomas CS Martin, MD, Gilead Sciences: Grant/Research Support
305. Hospitalized Patients with Community-Acquired Pneumonia and Structural Lung Disease: A Multicenter Analysis
Authors: Doumat Geroge , Nielsen Daniel , Ratz David , Horowitz Jennifer , McLaughlin Elizabeth , Czilok Tawny , Malani Anurag , Osterholzer Danielle , Gupta Ashwin , Gandhi Tejal N , Petty Lindsay A , Saravolatz Louis , Flanders Scott A , Vaughn Valerie
Published: January 2025

Background

Patients with structural lung disease (SLD) are more susceptible to community-acquired pneumonia (CAP) and are at higher risk for resistant organisms. CAP studies often exclude patients with SLD making it difficult to determine when to treat patients empirically with broad-spectrum antibiotics (BSA). Here, we describe the epidemiology of CAP in inpatients with moderate to severe SLD.

Methods

Between 1/2017 and 12/2023, we analyzed data from inpatients with CAP in 68 Michigan hospitals. SLD was defined as documented moderate or severe chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, or interstitial lung disease. BSA use was defined as therapy covering methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas and was considered appropriate if recommended by IDSA/ATS CAP guidelines. General estimating equation models, adjusted for variables known to be associated with outcomes, were used to compare 30-day outcomes between SLD and non-SLD CAP inpatients. Logistic or Poisson models, as appropriate, were adjusted for variables known to be associated with the outcomes.

Results

Of 51,953 patients with CAP across 68 hospitals, 18.2% (n=9,447) had documented SLD. Compared to patients without SLD, patients with SLD were sicker at baseline (see Table 1 for details) and, despite lacking traditional risk factors, were more often found to have MRSA (1.4% vs. 0.8%, p< 0.01) or Pseudomonas aeruginosa (4.7% vs. 1.7% p< 0.01) in their respiratory cultures (Table 2). While 42.2% of patients with SLD (vs. 35.5% without SLD) received broad-spectrum antibiotics, only 16.1% (vs. 10% without SLD) of such therapy was recommended by guidelines. Compared to patients without SLD, those with SLD had higher odds of mortality (aOR=1.31, p< 0.01 ) and hospital readmission (aOR = 1.19, p< 0.01; Table 3).

Conclusion

Patients with CAP and underlying SLD had more severe disease and experienced worse clinical outcomes. Though they were more likely to grow MRSA or Pseudomonas than patients without SLD, patients with SLD were far more likely to have non-guideline concordant empiric BSA use. New models may be needed to identify the risk of resistant pathogens in SLD and support better selection of empiric therapy.

Disclosures

Elizabeth McLaughlin, MS, RN, Blue Cross Blue Shield of Michigan: Salary 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
Authors: Lee Jaehoon T , Lee Imchang , Lee Ki-Byung , Soon Lee Seung
Published: January 2025

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-819. Epidemiology of Serratia marcescens Bloodstream Infections in a Hospital System in the Southeast U.S
Authors: Niravath Marilyn , Axell-House Dierdre B
Published: January 2025

Background

Serratia marcescens (Sm) is an environmental gram-negative bacilli that can cause a variety of serious human infections. Sm is frequently attributed as a hospital acquired infection. However, there is not extensive documentation as to the common etiologies of Serratia bloodstream infections (BSI), frequency of antibiotic resistance, and risk factors for recurrent infection or mortality.

Methods

We conducted a retrospective chart review of a cohort of patients (pts) ≥ 18 years old with Serratia marcescens BSI from 5/2016 to 10/2022 at our hospital system. Sm BSI was defined as ≥ 1 blood culture positive for Sm. Multidrug resistance was defined according to Centers for Disease Control (CDC) criteria. Patients were assessed for outcomes of recurrence of bacteremia (positive blood culture with same isolate within 3 months of clearance) and 30-day mortality.

Results

A total of 243 patients had Sm BSI during the study period. The most frequent etiology was central line-associated BSI (38%) followed by skin and soft tissue infection (12%). The majority (96%) of isolates were not multidrug resistant. Most patients had a repeat blood culture (67%), and of these patients, 15% had recurrence of bacteremia. A total of 44 patients (18%) died within 30 days. Echocardiogram was performed in 60% of our patients, with 7 patients diagnosed as having endocarditis or device endocarditis. Current active or history of injection drug use occurred in 7.5% of patients.

Conclusion

Our retrospective study demonstrates a low burden of antibiotic resistance in Sm at our hospital system. Similar to prior studies, CLABSI is a frequent cause of Sm BSI, and foreign materials/devices are common in patients with Sm BSI. Our patient population has a lower rate of IVDU compared to other studies of Sm BSI, and endocarditis is not common. Further analysis is needed to evaluate treatment regimens and other risk factors for recurrent BSI and mortality.

Disclosures

All Authors: No reported disclosures
P-826. Impact of Antimicrobial Stewardship Prospective Audit on the Treatment of Staphylococcus aureus Bloodstream Infections
Authors: Kim Eunice , Chapin Ryan W , McCoy Christopher
Published: January 2025

Background

Staphylococcus aureus (SA) is a serious cause of bloodstream infection (BSI) associated with significant morbidity and mortality. Empiric treatment of Gram-positive cocci (GPC) BSIs varies across institutions. Vancomycin, compared to beta-lactams for the treatment of MSSA, is associated with longer durations of bacteremia and higher relapse rates. At our center, a lack of rapid phenotypic diagnostics technology (RPDT) limits prompt optimization. A pre- and post- implementation analysis was performed to assess the impact of a guideline driven stewardship pharmacist intervention on GPC BSI treatment.

Methods

Patients with GPCs in blood cultures were identified using a third-party pharmacovigilance platform. Patients were included for if they grew SA in at least 1 blood culture bottle and excluded if they had polymicrobial infections or if they were placed on comfort measures before antimicrobial therapy was tailored. The primary endpoint was time to optimal therapy, defined as the narrowest effective therapy. Secondary endpoints included time to Infectious Diseases (ID) consultation after GPC identification, duration of BSI, and rate of stepdown to oral antimicrobials for patients with uncomplicated BSI.

Results

From June 2023 to April 2024, 136 patients were identified. Eighty-one patients were included in the pre-guideline group (before December of 2023), and 55 patients were included in the prospective review. Baseline demographics were similar between the two groups (table 1). Patients receiving optimal therapy within 24 hours was 70.9% in the pre-guideline group and 75% in the post-guideline group. Step-down to oral therapy occurred in 66.7% and 23.5% patients, respectively.

Conclusion

We found implementation of a SA BSI guideline with steward follow up did not significantly alter time to empiric therapy, ID consults, or number of patients on tailored therapy within 24h of susceptibilities. Since most patients in our analysis received an infectious diseases consult, fewer opportunities for independent stewardship intervention existed. RPTD may play a potential role to decrease time to optimal therapy at our institution, results will be shared to support the onboarding of this stewardship tool.

Disclosures

All Authors: No reported disclosures
P-829. Determination of novel clinical phenotypes among sepsis patients from an Indian sepsis registry
Authors: Edathadathil Fabia , Gutajhr Georg , Dipu T S , Singh Sanjeev
Published: January 2025

Background

Sepsis is a dysregulated host immune response with heterogenous clinical presentation reflected in its high dimensional data and with distinct epidemiological profile endemic to LMICs such as India. The study aims to identify and estimate the prevalence of clinical phenotypes from retrospective data of sepsis patients from a South Indian registry.

Characteristics of the identified clusters and outcomes

Methods

The registry enrolled all adult patients admitted through the emergency department with a presumed diagnosis of sepsis following Surviving Sepsis Guidelines(SSG) criteria(Edathadathil F, 2022)1. Following Ordering points to identify the clustering structure(OPTICS) assessment, k-means clustering was identified and employed as unsupervised clustering method for deriving clusters. The association of focus of infection and outcomes among the clusters was assessed. The identified Indian clusters were compared to the phenotypic clusters derived by Seymour et al using distance matching2(Seymour et al, 2019).

Distribution of focus of infection and causative pthogens among the clusters

Results

Of the 1009 patients enrolled in the registry, four clusters were identified with Cluster 1 exhibiting the highest prevalence and comprising 389 patients (39%), followed by Cluster 3 (254, 25%), Cluster 4 (225, 22.3%), and Cluster 2 (141, 14%). Age(p=0.024) and gender(p=0.04) significantly differed among the four clusters with septic shock (p< 0.001) and inhospital mortality (p< 0.001) significantly higher in Cluster 3 (septic shock at 19%, in hospital mortality at 32%)(Table 1). Among focus of infection, the prevalence of pneumonia (p=0.018), SSI(p=0.011) and bacteremia(p=0.004) significantly differed among the clusters (Fig 1). The proportion of bacteremia(29%) and pneumonia(28%) were observed to be significantly high in cluster 2. UTI(139, 38%) and SSI (57, 15%) were found to be significantly high in cluster 1. Pseudomonas (p=0.008) and staphylococcus aureus (p=0.02) were observed to be significantly different among the clusters. Clusters 1,2,3 and 4 exhibited close association to the gamma, beta, alpha and delta clusters respectively among the phenotypes derived by Seymour et al.

Conclusion

Our study has been one of the pioneer initiative in demonstrating inherent subgroups among sepsis patients within an Indian cohort data that significantly differed in outcomes and epidemiology.

Disclosures

All Authors: No reported disclosures
P-852. Not High Enough? Treatment Outcome Comparing High Dose Daptomycin vs. Linezolid in VRE Bacteremia: Implications of Daptomycin PD Target
Authors: Hwang Liang-En , Chuang Yu-Chung , Chen Yee-Chun , Wang Jann-Tay , Chang Shan-Chwen
Published: January 2025

Background

The best treatment for vancomycin-resistant enterococcus (VRE) bloodstream infection (BSI) remains controversial. In 2020, the CLSI revised the daptomycin breakpoints for E. faecium and recommended a high-dose daptomycin of 8-12 mg/kg/day. However, the effectiveness of high-dose daptomycin versus linezolid remains unanswered. The most effective PD parameter for daptomycin’s effectiveness is the free drug area under the curve to minimum inhibitory concentration ratio (fAUC/MIC). This study compares the clinical outcomes of VRE BSI between patients treated with linezolid and daptomycin within recommended dose. Additionally, we examined whether achieving the fAUC/MIC target influences the outcomes between these two groups.Figure 1.Flow diagram illustrating the selection of patients for the study.

Methods

An observational cohort study was conducted within National Taiwan University Hospital and its branches. From January 2010 to December 2021, patients treated with more than 8 mg/kg of daptomycin or linezolid for VRE BSI were included. The estimated fAUC was calculated, and the fAUC/MIC target was chosen based on the MIC determined using broth microdilution. The primary outcome was in-hospital mortality.Table 1.Demographics, clinical characteristics and univariable logistic regression analysis of mortality among patients with VRE BSI

Results

There were 1425 VRE BSI episodes, and 795 met inclusion criteria. The mean age was 67.7 years (SD 14.6), with 57.5% males. The mortality was 59.3%. Of 625 daptomycin-treated patients, 528 had estimated fAUC/MIC available. 114 had estimated fAUC/MIC above target. Mortality was 49.1% for daptomycin-treated patients with the PD above target, 66.2% for those below it, and 44.1% for linezolid-treated patients. Multivariable logistic regression showed Charlson comorbidity index (aOR 1.90, P=0.05), platelet count (aOR 0.96, P< 0.001), and Pitt bacteremia score (aOR 1.31, P< 0.001) to be associated with mortality. Daptomycin below PD target was associated with worse outcome than linezolid (aOR 2.52, P< 0.001), while daptomycin above PD target was not (aOR 1.00, P=0.99).Figure 2.Comparison of Kaplan–Meier survival curves between daptomycin and linezolid in patients with VRE BSI

Conclusion

Our findings suggest that daptomycin, even within the recommended dosage range, leads to poorer outcomes when it does not reach the estimated PD target compared to linezolid in treating VRE BSI. However, the outcomes are comparable with linezolid when PD target is reached.Table 2.Multivariate logistic regression analysis of the factors associated with in-hospital mortality (N=695)

Disclosures

All Authors: No reported disclosures
P-855. Epidemiology and Clinical Pattern of Bacteremia in a Referral Hospital in Nicaragua: a Three Year Cohort Study
Authors: Solís-Altamirano Anielka , Colomer-Sánchez Karina , Gavarrete-Rivas Kevin , Porras-Cortés Guillermo D
Published: January 2025

Background

In recent years, some institutions have described changes in the epidemiological, microbiological, and clinical profiles of bacteremias. The Dr. Fernando Vélez Paiz Hospital (HFVP) is a teaching and referral hospital in Nicaragua, which opened its services 5 years ago. The aim of this study is to describe and analyze the epidemiological, microbiological, and clinical characteristics as well as risk factors for mortality of patients with bacteremia.Table 1.Medical History in Patients with Bacteremia

Methods

This is a bidirectional, observational, analytical cohort study. Conducted with 467 patients from the Internal Medicine, Surgery, Orthopedics, Burn Unit, and Intensive Care Unit services of the HFVP who presented bacteremia between January 2021 to December 2023. After filtering the data, the patients included for analysis were 374. Different variables were analyzed, and mortality was analyzed with some factors including SOFA, NEWS2, and Pitt scores.Table 2.Microbiology of Bacteremia in Hospital Dr. Fernando Vélez Paiz

Results

The mean age of the patients was 50.2 ± 19.9 years, and 63.7% had a comorbidity. The most frequent comorbidities were hypertension (54%), diabetes (45.1%), and chronic kidney disease (15.7%). Most of the patients were from the surgery (31.8%), internal medicine (31.8%), and intensive care unit (28.6%) departments. In the medical history were relevant factors: use of antibiotics in the last 30 days (47.3%), surgery in the last 3 months (40.1%), presence or history of central vascular catheter (38.8%) (Table 1). The most common sites of infection that were documented were respiratory (29.9%), intra-abdominal (27.8%), and urinary (22.5%). At the time of bacteremia, patients had a mean of leukocytes/mm3 of 15,590 ± 9,540, C-reactive protein (mg/L) of 123.0 ± 65.8, and procalcitonin (ng/mL) of 16.6 ± 19.2. The most frequent bacteria were E. coli (17.1%), S. aureus (12.8%), and A. baumannii (9.1%) (Table 2). 62.6% of Gram-negative were multidrug-resistant. Factors associated with mortality were recent steroid use, associated chronic disease, and multidrug-resistance (Table 3). SOFA, NEWS2, and Pitt scores correlated with the probability of survival (Figure 1).Table 3.Risk Factors for Mortality in Patients with Bacteremia.

Conclusion

This is the first study to characterize bacteremias in Nicaragua, finding independent risk factors for mortality and validating severity scales to predict probability of survival.Figure 1.ROC Curve for SOFA, NEWS2, and PITT Score for Mortality Prediction in Patients with Bacteremia

Disclosures

All Authors: No reported disclosures
P-856. Beta Lactams as Oral Step Down Therapy in the Treatment of Uncomplicated Gram Negative Bacteremia: A Systematic Review and Meta Analysis
Authors: Dore Michael , Duffy Ryan , Huang Lily , Caputo Laura , Cantrell Sarah , Glasgo Blair
Published: January 2025

Background

Gram-negative bacteremia (GNB) treatment is initially intravenous but is often transitioned to oral antibiotics once stable. This decision is based on culture sensitivity, antibiotic bioavailability, and antibiotic side effect profile. Historically, fluoroquinolones (FQ) or trimethoprim-sulfamethoxazole (TMP-SMX) are selected over beta-lactams (BL) due to concerns about pharmacokinetics and bioavailability. In 2019, a systematic review and meta-analysis compared the use of BL for step-down therapy vs FQ and TMP-SMX was inconclusive, and the implementation of BL has not been widely adopted. Since then, several moderate-sized studies have evaluated this question but are limited by sample size. We performed a systematic review with meta-analysis evaluating BL in the treatment of uncomplicated GNB.Figure 1:30 Day Mortality

Forest plot illustrating the 30 day mortality comparison between beta lactams and FQ/TMP-SMX

Methods

The MEDLINE, Embase, and Web of Science databases were searched from inception to August 2023 for published articles related to bacteremia, BL antibiotics, and FQ or TMP-SMX antibiotics. Inclusion criteria included adults aged 18 years or older with uncomplicated GNB treated with IV antibiotics initially and transitioned to appropriate oral antibiotics based on sensitivity testing. Uncomplicated infections were defined as having definitive source control within 48 hours.Figure 2:Antibiotic Failure Rate

Forest plot illustrating the antibiotic failure rate between beta lactams and FQ/TMP-SMX

Results

The search yielded a total of 5029 citations. 1598 were removed as duplicates. 3431 titles and abstracts were screened with 3411 excluded. 20 full texts were retrieved and evaluated for eligibility; 13 were excluded and 7 were reviewed. A total of 7306 patients were included in the study with twice as many as the FQ/TMP-SMX vs BL group (4879 vs 2407). The average age (69 vs 71), percent male (51 vs 52%), percent urinary source (75 vs 77%), duration of IV antibiotics (4.2 vs 4.6), Pitt bacteremia score (1.1 vs 1.4) and Charleston comorbid index (2 v 2.2) were similar in each group. There was no statistical difference between the 30-day mortality -0.01 (95% CI -1.31 to 1.28) or antibiotic failure: 0.06 (95% CI -0.42 to 0.53)

Conclusion

BL are non-inferior to FQ or TMP-SMX as oral step-down therapy in the treatment of uncomplicated GNB . The individual decision to use a FQ, TMP-SMX or BL should be based on the patients' comorbid conditions, potential drug-drug interactions, cost, and potential for adverse events.

Disclosures

All Authors: No reported disclosures
P-868. Evaluating the Clinical Impact of Rapid Diagnostic Testing on Antimicrobial Stewardship Interventions
Authors: Huynh-Phan Ricky , Le Kevin , Lasco Todd M , Zidaru Andrei , Tam Vincent , Phe Kady
Published: January 2025

Background

The management of bloodstream infections (BSIs) may be improved with rapid diagnostic identification. The updated Biofire FilmArray blood culture identification (BCID) 2 panel is able to detect extended-spectrum beta-lactamase and additional carbapenemase encoding genes amongst other resistance markers, allowing for earlier antimicrobial stewardship interventions. The purpose of this study was to evaluate the time to optimal antimicrobial therapy.

Methods

This was a single-center retrospective chart review of patients before and after the implementation of the updated BCID panel (BCID1 vs. BCID2, respectively). Adult patients were eligible for inclusion if they had a positive blood culture with an accompanying BCID panel result. Patients were excluded if they received concomitant treatment for an unrelated infection or had monomicrobial BSI with Staphylococcus species. The primary endpoint was time to initiation of optimal antimicrobial therapy from index blood culture, defined as pathogen and resistance gene directed therapy per hospital treatment algorithm. Secondary endpoints included time to active antimicrobial therapy, defined as empiric therapy shown to be active against index isolate(s) with an antimicrobial susceptibility report, and 30-day mortality.

Results

Overall, 143 patients were included in the BCID1 group and 175 patients in the BCID2 group. Time to optimal antimicrobial therapy was shorter in the BCID2 group compared to the BCID1 group (17.1 hours vs. 29.3 hours; p < 0.05). Time to active therapy was shorter in the BCID2 group compared to the BCID1 group (3.1 hours vs. 5.9 hours; p=0.03). Thirty-day mortality rate was lower in the BCID2 group compared to the BCID1 group (9.7% vs. 20.9%; p < 0.05).

Conclusion

Time to optimal and active antimicrobial therapy were significantly shorter after the implementation of the BCID2 panel. Furthermore, 30-day mortality was lower, indicating that optimized therapy per local hospital treatment algorithms may improve outcomes.

Disclosures

All Authors: No reported disclosures
P-876. Factors Influencing Outcome in Patients Admitted with Melioidosis- A Single Centre Retrospective Study
Authors: Desai Raghavendra P , Ramachandra Koushik , Vidyalakshmi K , Srinivas Samyuktha
Published: January 2025

Background

Melioidosis is largely under-reported in the Indian subcontinent. This region is believed to account for 44% of total cases, with an estimated annual incidence of 52,500 cases. This retrospective study of 50 patients aimed at determining association between factors like diabetes mellitus, hypertension, existing heart disease, lung disease, liver disease, alcohol abuse, immunosuppression, symptoms at admission to the hospital, and time from symptom onset to isolation of the bacterium, on in-hospital mortality, development of acute kidney injury (AKI), need for renal replacement therapy (RRT), intensive care unit (ICU) stay and recurrence.

Objectives

To study the risk factors influencing in-hospital mortality in patients admitted with melioidosis. To study the association between risk factors identified and developemenet of Acute Kidney Injury, the need for Renal Replacement Therapy, ICU stay and recurrence of the disease.

Methods

Study setting: Teaching hospitals affiliated with Kasturba Medical College, Mangalore

Study design: Retrospective Cross Sectional Study

Inclusion Criteria: Patients admitted and diagnosed with Melioidosis, Age >18 years

Exclusion Criteria: Pre-existing kidney disease

Results

Data analysis showed that diabetes, hypertension, pre-existing heart disease, lung disease, liver disease, alcohol abuse, immunosuppression, symptom complex, time from symptom onset to isolation of organism, and development of AKI had no significant associations with in-hospital mortality. Hypertension, pre-existing heart disease, hyponatremia, and advanced age was noted to have statistically significant associations with development of AKI. Hypertension, pre-existing heart disease, and advanced age was noted have statistically significant associations with need for RRT. Pre-existing heart disease, and longer ICU stay had statistically significant associations with recurrence of the disease. Further analysis, with respect to geographic influences is ongoing.

Conclusion

In patients with Melioidosis, hypertension, pre-existing cardiac disease, hyponatremia, and advanced age were noted to have significant association with development of AKI while pre-existing cardiac disease and longer ICU stay were associated with recurrence.

Disclosures

All Authors: No reported disclosures
P-882. Comparison of Epidemiology, Risk factors, Antimicrobial susceptibility and Outcome of Anaerobic Bacteremia: 2011-2013 and 2020- 2022
Authors: Palanivetpillai Sivanthini , Lee Mao-Cheng , Naidu Prenilla
Published: January 2025

Background

Anaerobes are again entering the spotlight as patients become more complex and antimicrobial resistances continue to mount as a result of their widespread use. The aim of our study was to compare the incidence, risk factors and susceptibility patterns of anaerobic bacteremia during 1st Jan 2011-31st Dec 2013 (period 1) and 1st Jan 2020-31st Dec 2022 (period 2) in community hospitals and acute care centres in Edmonton and the North Zone in Alberta.

The percentages of anaerobic organisms isolated in 2011-2013 and 2020-2022

Methods

  • Microbiologic data extracted from laboratory information system

• Demographic and clinical data extracted from the EMR system

• Blood cultures were incubated on the BD BACTEC 9240™ system or the BD BACTEC™ FX Blood Culture System

• Organism identification was performed by Vitek® 2 ANC ID card, traditional phenotypic methods, Vitek® MALDI-TOF and, failing these, genomic sequencing

• Susceptibility testing by E-test; interpretation as per CLSI or EUCAST guidelines

The percentages of susceptible Bacteroides species to different antimicrobials in 2011-2013 and 2020-2022

Results

Period 1:

319 anaerobic bacteremia were identified. 247 were included in the study after exclusion of repeat positives (within the first 2 weeks of the first positive culture) and contamination. Total number of isolates were 279 and susceptibilities were available on 252 during this period.

Period 2:

830 anaerobic bacteremia were identified. 467 anaerobic bacteremia were included in the study after exclusion of repeat positives and contamination. The total number of isolates were 539 and susceptibilities were available on 417 isolates during this study period.

The total number of anaerobic bacteremia almost doubled from 82 cases per year to 156 cases per year during the study decade. The majority were monomicrobial bacteremia (71% and 85%) with the gastrointestinal tract identified as the commonest source. The most common isolated anaerobe was Bacteroides species. Metronidazole susceptibilities for all anaerobes were above 90%. The crude 30-day mortality rates were 22.7% and 25.8% in period 1 and 2 respectively.

Conclusion

The total number of anaerobic bacteremia increased significantly in the 9-year interval. No significant changes in metronidazole susceptibility were observed between both periods of time.

Disclosures

All Authors: No reported disclosures
P-905. Post One-year Outcomes for Corticosteroid Use in Non-HIV Cryptococcal Meningoencephalitis
Authors: Chang Bickey , Anjum Seher , Joseph Snow , Hammoud Dima A , Williamson Peter
Published: January 2025

Background

Cryptococcal meningoencephalitis (CM) is a major cause of mortality in HIV/AIDS, transplant recipients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) has been noted to have a favorable response to corticosteroids although long-term responses have not been studied.

Methods

In addition to standard antifungal therapy, 15 patients admitted with CM/PIIRS from 2015-2020 were treated with standard pulse – taper corticosteroid therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/d, tapered based on clinical and radiological response. One patient was excluded from the study due to death from an unrelated cause within 6 months of diagnosis. Comprehensive neurocognitive testing and MRI brain scans were performed one year after diagnosis to assess clinical status.

Results

80% of patients were male, median age 51 years. Median time from antifungal treatment to steroid initiation was 6 weeks. Eleven of 14 patients were neuropsychologically evaluated using performance-based neurocognitive tests. A one-sample T- test showed that the cohort obtained significantly lower scores in memory, learning, language, and information processing/psychomotor speed test in comparison to a normative sample. Also, the mean memory, learning, psychomotor, and information processing speed scores were in the low average range. These findings suggest very mild cognitive deficits in this cohort one year post diagnosis. With the exception of one patient whose MRI brain showed worsened findings at the one-year mark due to a neuro-inflammatory flare, radiological findings suggested stability or improvement for the remaining 13 patients. CSF cultures remained negative.

Conclusion

Neurocognitive testing performed in a small cohort of previously healthy patients with CM-PIIRS showed an absence of moderate or major neurocognitive deficits one year post diagnosis with minimal adverse effects and no reoccurrence of infection. Brain MRI findings were also stable or improved for the majority.

Disclosures

All Authors: No reported disclosures
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
Authors: Linsao Ma Jean Capulong , Bornales Dante P , Solante Rontgene M , Edrada Edna
Published: January 2025

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 >31 days ( >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-919. Epidemiology of Cerebral Sinovenous Thrombosis in Children with Acute Bacterial Intracranial Infection: a Single-Institution Retrospective Study
Authors: Mehta Nehali , Swami Sanjeev K , Halverson Mark , Loerinc Leah , Gambrah-Lyles Claudia , McGuire Jennifer
Published: January 2025

Background

Cerebral sinovenous thrombosis (CSVT) is a known complication of acute bacterial intracranial infection. The objective of this study is to determine the annual proportion of, risk factors for, and outcomes in children with CSVT secondary to acute bacterial intracranial infection.Figure 1:Annual proportion of CSVT in children with acute bacterial intracranial infection between Jan 1, 2015 and December 31, 2022

Methods

Retrospective single-center cohort study of children age 1-18 years hospitalized at a tertiary care children’s hospital for acute bacterial intracranial infection between 01/01/2015 and 02/01/2023. Cases were identified by discharge ICD codes for “meningitis,” “meningoencephalitis,” “subdural empyema,” “epidural abscess,” and “brain abscess.” Medical charts were manually screened to ascertain the diagnosis and to abstract relevant clinical data. Multivariate models were built to examine risk factors for CSVT.

Results

One hundred and three patients were included. Median age was 10.2 [5.9,12.7] years. 31/103 (30%) had CSVT. Annual proportion of CSVT did not vary; however, the total number of cases of intracranial infection rose during the study period. Patients with CSVT were no different from those without CSVT by demographics, vaccination status, neurologic signs or symptoms at presentation, or causative organisms. Non-pneumococcal streptococcus species were the most common causative organisms, found in 37/103 (36%) children. Need for neurosurgical intervention (aOR=11.6, p=0.027), need for ENT intervention (aOR=6.1, p=0.013), temporal location of infection (aOR=7.9, p=0.004), and concurrent mastoiditis (aOR=29.5, p=0.004) were associated with CSVT. The sigmoid sinus (55%, 17/31), transverse sinus (42%, 13/31), jugular vein (45%, 14/31), and superior sagittal sinus (45%, 14/31) were the most common locations for CSVT. Two patients (6%) had venous infarction; one (3%) had venous hemorrhage. A higher proportion of children with CSVT had behavioral concerns (p=0.020) and learning concerns (p=0.025) than children without CSVT.

Conclusion

CSVT is common in acute bacterial intracranial infection. Consider empiric surveillance in children with acute bacterial intracranial infection with mastoiditis, temporal location of infection, and/or those who require surgical intervention. Outcomes in this population should be further explored.

Disclosures

All Authors: No reported disclosures
P-922. Intracranial Pressure Phenotypes and Mortality Among People Treated for HIV-Related Cryptococcal Meningitis in Uganda
Authors: Schwartz Elizabeth L , Liu Minda , Kagimu Enock , Nuwagira Edwin , Tugume Lillian , Ssebambulidde Kenneth , Turyasingura Isaac , Kasozi Derrick , Kigozi Enos , Okurut Samuel , Musubire Abdu kisekka , Skipper Caleb , Abassi Mahsa , Fieberg Ann , Muzoora Conrad , Meya David , Boulware David R
Published: January 2025

Background

Cryptococcal meningitis is a leading cause of mortality among people living with HIV, especially among those with advanced HIV disease in Sub-Saharan Africa. Cryptococcosis causes an estimated 19% of HIV-related deaths worldwide. Elevated intracranial pressure (ICP, ≥ 200 mmH2O) is a common complication of cryptococcal meningitis. The causes, phenotypes, and clinical implications of persistently elevated ICP following treatment for cryptococcal meningitis are not well understood, but control of ICP has a survival benefit.

Methods

We prospectively enrolled adults with HIV and cryptococcal meningitis in Kampala and Mbarara, Uganda from 2013 to 2023. Cerebrospinal fluid (CSF) opening pressure (OP) was recorded for each diagnostic and therapeutic lumbar puncture performed during hospitalization. We used the highest OP value in each follow-up time frame (days 2-4, 5-9, 10-16) to categorize participants into distinct ICP phenotypes. We assessed 2-week survival across ICP phenotypes.

Results

We enrolled 1443 participants with cryptococcal meningitis. Analysis of CSF OP revealed five distinct ICP phenotypes (Figure 1). First, 35% of participants had normalizing ICP defined as ICP ≥ 200 mmH2O at diagnosis, followed by ≥ 1 instance of ICP < 200 mmH2O with no subsequent increase. Second, 28% had persistently normal ICP with all OP values < 200 mmH2O. Third, 19% had persistently elevated ICP with all OP values ≥ 200 mmH2O. Fourth, 10% had delayed elevation in ICP defined as normal ICP at diagnosis, followed by ≥ 1 elevated ICP and no subsequent documented normalization. Fifth, 8% had fluctuating ICP that did not fit any other phenotype definition. Among these groups, 2-week mortality varied from 9% to 25% (Table 1). The normalizing, persistently elevated, and persistently normal phenotypes were associated with the poorest prognosis (log-rank test p < 0.001).

Conclusion

This study highlights the heterogeneity of ICP phenotype patterns in cryptococcal meningitis. Further research is needed to investigate the underlying mechanisms and risk factors associated with these ICP phenotype groups and better anticipate clinical management needs.

Disclosures

All Authors: No reported disclosures