bluuebunny/crossref_metadata_2025 huggingface dataset:
2846. Microbiological Characteristics of the Patients with Acute Pyelonephritis who experienced Urinary Tract Infections within prior to 1 year
Authors: Yoon Choseok , Kim Jeoungyeon , Jang Wooyoung , Go Ji Won , Kim Jinnam , Lee Yangsoon , Kim Bongyoung
Published: November 2023

Background

Approximately 15% of patients with acute pyelonephritis (APN) experience another urinary tract infection (UTI) within 1 year in South Korea. The purpose of this study is to examine the microbiological characteristics of patients with APN who experienced UTIs within prior to 1 year.

Methods

A retrospective cohort study was performed in a tertiary-care hospital in South Korea from July 2019 to December 2021. All female patients who were diagnosed with community acquired APN at admission were recruited. Patients who had prolonged hospitalization period due to medical problems that were not associated with APN treatment were excluded. We regarded recurrent group as the cases which have history of UTI within 1 year. Types of causative organism, major antibiotic resistance of E.coli isolated from patients' urine or blood, and the genetic characteristics of E.coli were compared between recurrent group and non-recurrent group.

Results

A total of 285 APN patients were finally included in this study, of which 41 (14.4%) were belong to recurrent group. E.coli was the most common causative pathogens in both groups, but the proportions of some pathogens, such as Klebsiella pneumonia (17.1 vs. 4.7%, P=0.007) and Pseudomonas aeruginosa (5.7 vs. 0.5%, P=0.014) were higher in the recurrent group than the non-recurrent group. There were no significant differences between the two groups in the proportions of antibiotic resistances to E.coli, such as amikacin (0 vs. 1.2%, P=0.597), cefotaxime (25.0 vs. 22.5%, P=0.788), and fluoroquinolone (20.8 vs. 28.9%, P=0.409), etc. The most prevalent β-lactamase and PMQR determinant were CTX-M-1G (44.4 vs 60.0%, P=0.308) and aac(6’)-lb-cr (50.0 vs 36.2%, P=0.303), respectively, and the predominant clone was ST131 (22.2 vs 17.8%, P=0.744) in both groups. However, there were no significant differences in the proportions of phylogenic groups, resistance genes, and virulence factors between the two groups.

Conclusion

E.coli was the most common causative pathogens in both groups, but the proportion of pathogens except E.coli was higher in the recurrent group than the non-recurrent group. There were no significant differences between the two groups in the proportions of antibiotic resistances to E.coli, phylogenic groups, resistance genes, and virulence factors.

Disclosures

All Authors: No reported disclosures
2848. Risk factors for recurrence of community-onset urinary tract infections caused by extended spectrum cephalosporin-resistant Enterobacterales
Authors: Zhang Helen L , Perez Reinaldo , Krishnan Jay , Lautenbach Ebbing , Anderson Deverick J
Published: November 2023

Background

Extended spectrum cephalosporin-resistant Enterobacterales (ESCR-E) are increasingly implicated in community-onset urinary tract infections (UTIs). In this study, we assessed risk factors for recurrence among patients with community-onset UTI caused by ESCR-E.

Methods

This retrospective cohort study included adult patients evaluated April 2018 – December 2021 in the Duke University Health System with community-onset ESCR-E UTI, defined as (1) ESCR-E in a urine culture obtained in an outpatient clinic, emergency department, or within 48 hours of hospital admission; (2) ≥10 leukocytes per high-power field on urine microscopy or urine dipstick positive for leukocyte esterase; and (3) new antibiotic administration or prescription. ESCR-E UTI recurrence was assessed 14 to 180 days after completion of antibiotic treatment for the index UTI. Patients were right censored at end of follow up period or upon death. Univariate Cox proportional hazards regression was performed to evaluate the relationships between candidate risk factors and time to recurrence.

Results

1428 patients were included; 207 (14.5%) experienced recurrence. In unadjusted analyses, risk factors for recurrent ESCR-E UTI included diabetes mellitus (hazard ratio [HR] = 1.4, 95% confidence interval [CI]: 1.1 to 1.9, p = 0.01), chronic renal insufficiency (HR = 1.6, 95% CI: 1.2 to 2.1, p < 0.001), neurogenic bladder (HR = 2.1, 95% CI: 1.4 to 2.9, p < 0.001), previous UTI diagnosis within one year (HR = 2.6, 95% CI: 1.9 to 3.5, p < 0.001), fluoroquinolone non-susceptibility (HR = 1.6, 95% CI: 1.2 to 2.2, p = 0.004), and trimethoprim-sulfamethoxazole non-susceptibility (HR = 1.3, 95% CI: 1.0 to 1.8, p = 0.045). Patients with ESCR Klebsiella pneumoniae UTI had a 53% greater hazard of recurrence compared to patients with ESCR E. coli UTI (HR = 1.5, 95% CI: 1.1 to 2.1, p = 0.008).

Conclusion

ESCR-E UTI recurrence was common, and several clinical and microbiologic characteristics were associated with recurrence. Patients with these characteristics should receive particular consideration for aggressive UTI risk factor modification and other non-antibiotic prevention strategies. Future studies should evaluate strategies to reduce the risk of recurrence among patients with ESCR-E UTI.

Disclosures

All Authors: No reported disclosures
174. Impact of Ceftaroline Duration after Bacteremia Clearance When Used in Combination Therapy for Persistent or High-grade MRSA Bacteremia
Authors: Cabanilla M Gabriela , Atallah Liana , Bernauer Michael , Briski Matthew , Koury Jason , Thompson Cecilia , Rodriguez Chelsea , Jakeman Bernadette , Byrd Thomas
Published: November 2023

Background

Methicillin resistant Staphylococcus aureus (MRSA) bacteremia is a clinically relevant syndrome with high mortality. Combination therapy with beta-lactam antibiotics has been employed in persistent MRSA bacteremia with reported clinical success. Ceftaroline is a beta-lactam antibiotic with activity against MRSA, which has been commonly used in combination therapy for this indication. However, adequate ceftaroline duration after bacteremia clearance continues to be elucidated. Thus, we aimed to evaluate clinical outcomes of patients receiving short vs. long duration of ceftaroline after persistent or high-grade bacteremia clearance.

Methods

This was a single-center, retrospective cohort study conducted from January 1, 2014, to June 30, 2021. Patients were included if ≥18 years of age, with high grade or persistent MRSA bacteremia, who received combination therapy with ceftaroline. The primary outcome was 30-day mortality. Secondary outcomes included hospital length of stay, time to bacteremia clearance, antibiotic-related adverse events and microbiological relapse.

Results

A total of 32 patients were included (mean age: 51.5 years; 71.9% white; 61.3% male). 96.9% had high-grade MRSA bacteremia and 68.8% had persistent bacteremia. The most common bacteremia source was bone and joint infections (28.1%). 56.3% of patients received ceftaroline in combination with vancomycin; mean duration was 8 days. Multivariable analysis showed increasing the duration of combination therapy after bacteremia clearance was not associated with a lower risk of 30-day mortality after controlling for Charlson comorbidity index and Pitt bacteremia scores (OR 0.75, 95% CI 0.94-2.45; p=0.07). Similarly, no association was observed with microbiological relapse (OR 1.03, 95% CI 0.92-1.16; p=0.73), antibiotic-related adverse event (OR 0.97, 95% CI 0.78-1.10; p=0.75), time to bacteremia clearance (p=0.88) or hospital length of stay (p=0.06).

Conclusion

Longer durations of ceftaroline in combination therapy after bacteremia clearance was not associated with lower rates of 30-day mortality, microbiological relapse, or higher rates of antibiotic-related adverse events. Larger studies are needed to determine the appropriate duration of combination therapy.

Disclosures

Cecilia Thompson, PhD, D(ABMM), MLS (ASCP), Roche Diagnostics: Honoraria
176. Impact of Rapid Blood Culture Identification Panel on Antibiotic Treatment and Clinical Outcomes in Bloodstream Infections, Particularly Those Associated with Multidrug-resistant Microorganisms
Authors: Yun Bae Ji , Bae Jiyeon , So Min-Kyung , Jung Choi Hee , Lee Miae
Published: November 2023

Background

The FilmArray Blood Culture Identification (BCID) panel (BioFire Diagnostics, USA) can detect 19 bacteria, five Candida spp., and three antimicrobial resistance determinants (mecA, vanA/B, and bla-KPC). This study evaluated the impact of BCID on the time to effective antibiotic administration and clinical outcomes in bloodstream infections, particularly carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant enterococci (VRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia.

Methods

The clinical outcomes and time to effective antibiotic administration for bloodstream infections were retrospectively compared between patients who had undergone BCID testing and conventional culture method (control group). Further, we compared the 30-day mortality and time to effective antibiotic administration between BCID and conventional methods in CRE, CRAB, and VRE bacteremia.

Results

We compared 144 and 214 patients who had undergone BCID testing and the conventional culture method, respectively. The median time until the administration of effective antibiotics (3 h for both BCID and conventional culture, P = 0.789), appropriate antibiotics (BCID: 37 h vs. conventional culture: 44 h, P = 0.727), and 30-day mortality (BCID: 9.7% vs. conventional culture: 10.7%, P = 0.755) did not differ significantly between the groups. Multivariable analysis revealed that BCID was not associated with 30-day mortality after adjusting for Pitt bacteremia and Charlson comorbidity index (adjusted OR: 0.833, CI: 0.398–1.743) (Table 1).

BCID did not reduce the risk of 30-day mortality in any subgroup: patients with ICU stay, hematologic department admissions, hospital-acquired infections, gram-positive and gram-negative bacteremia. Time to effective antibiotic administration was significantly reduced on using BCID in patients with CRE and VRE bacteremia, while no difference was observed in patients with CRAB bacteremia (Table 2).

Conclusion

BCID did not improve the clinical outcomes of overall bloodstream infections. However, it contributed to the early administration of effective antibiotics in patients with CRE and VRE bacteremia. BCID may be useful in selected patients in whom infection with multidrug-resistant microorganism is suspected.

Disclosures

All Authors: No reported disclosures
177. Infectious Diseases Consultation Associated with Decreased Mortality in Gram-Negative Bacteremia
Authors: Bruning Rebecca , Runyon Kyler , Burgess Donna R , Cotner Sarah , Olney Katie B , VanHoose Jeremy , El Haddad Hanine , Burgess David
Published: November 2023

Background

Bloodstream infections (BSIs) are major causes of morbidity and mortality for which prior analyses and validated scoring tools have attempted to stratify risk. This study investigated institutional and epidemiologic predictors of mortality with Gram-negative BSIs to better identify targeted antimicrobial stewardship efforts to improve outcomes.

Methods

All patients with aerobic, monomicrobial, Gram-negative BSIs admitted and discharged from our academic medical institution between July 2022 and March 2023 were included. Data collected included patient demographics, microbiological data, clinical management, length of stay, ID consultation, and clinical outcomes (in-hospital or hospice mortality). Univariate and multivariable logistic regression models were performed to identify variables that were primary drivers for inpatient mortality.

Results

Overall, 259 patients (83.7% Caucasian, 49% male, mean age 53.7 yrs) were identified. The most common organisms were E. coli (37.8%), K. pneumoniae (11.2%), P. aeruginosa (10.0%), S. marcescens (8.5%), and E. cloacae (6.2%). The majority (65.3%) were community acquired infections with 41.7% in the ICU, and 46.7% received an infectious diseases consult. The overall mortality was 14.7% with the highest mortality due to P. aeruginosa (34.6%) followed by S. marcescens (27.3%), K. pneumoniae (13.8%), E. cloacae (12.5%), and E. coli (8.2%). Overall mortality was significantly associated with several parameters in a univariate analysis (Table 1). In multivariable regression analysis hospital-acquired infection (0=0.002), cancer (p=0.012), qPitt > 2 (p< 0.001), SBP< 100 or vasopressor use at 72-96 hrs after positive blood culture (p=0.017) was associated with increased risk of mortality. The only parameter to reduce mortality within the multivariable regression analysis, by more than two-fold, was ID consultation (p=0.022).

Parameters Associated with Mortality in Univariate Analysis

Conclusion

The only factor found to significantly reduce mortality was formal ID consultation. ID consultation should be considered part of routine care for all patients with Gram-negative bacteremia.

Disclosures

Katie B. Olney, PharmD, BCIDP, The Society of Infectious Diseases Pharmacists (SIDP): Grant/Research Support
190. Meta-analysis of Impact of Follow-up Blood Cultures on Mortality in Patients with Gram-negative Bacteremia
Authors: Eljaaly Khalid
Published: November 2023

Background

It is not clear if follow-up blood cultures are beneficial in patients with Gram-negative bacteremia. It may improve clinical outcomes but have some drawbacks such as the possibility of inaccurate positive findings and extending the length of hospital stay and duration of antibiotic therapy. The aim of this meta-analysis was to evaluate the impact of follow-up blood cultures on mortality in patients with Gram-negative bacteremia.

Methods

PubMed and EMBASE databases were searched from inception to Jan 2023 for randomized controlled trials or observational studies comparing the mortality in patients with Gram-negative bacteremia who had follow-up blood cultures obtained versus those without these cultures. We estimated odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models and assessed for heterogeneity (I2).

Results

A total of six observational studies were included, while no randomized controlled trials were identified. The total number of patients was 4,631. One study used 28-day mortality, two studies used 30-day mortality, and three studies used in-hospital mortality. Follow-up blood cultures were associated with significantly lower odds of mortality ((OR, 0.6; 95%CI, 0.5-0.7; I2, 0%). No publication bias or heterogeneity was observed.

Conclusion

The use of follow-up blood cultures in patients with Gram-negative bacteremia was associated with lower mortality. Randomized controlled trials are needed. Currently, follow-up blood cultures should be obtained for at least the high-risk patients with Gram-negative bacteremia.

Disclosures

Khalid Eljaaly, PharmD, MS, BCPS, BCIDP, FCCP, Reckitt Benckiser Healthcare International Ltd, UK: Member of the Global Respiratory Infection Partnership, supported by unrestricted educational grant from Reckitt Benckiser Healthcare Ltd
191. When Staph Is Not Solo: Polymicrobial Methicillin-Resistant Staphylococcus aureus Bloodstream Infections
Authors: Escalona Angelica , Hayashi Emi , Evans Michelle , van Bakel Harm , Dupper Amy C , Alburquerque Bremy , McBride Russell B , Altman Deena
Published: November 2023

Background

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a serious public health concern. At times, MRSA is isolated from the blood along with other pathogens, the significance and the consequences of which are not well described. This study aims to outline the clinical characteristics and outcomes of those with polymicrobial MRSA BSI compared with those with monomicrobial MRSA BSI.

Methods

We conducted a retrospective case-control study of those with and without polymicrobial MRSA BSI from 2014 to 2022 at a single quaternary care center in New York. Risk factors and outcomes for polymicrobial MRSA BSI were assessed using logistic regression analyses in SAS.

Results

Of 646 patients with MRSA BSI during the study period, 48 (7.4%) had polymicrobial MRSA BSI. In the univariate analysis, the presence of urinary device (p = 0.0174), and gastrointestinal device (p = 0.0287) were significantly associated with polymicrobial BSI. Polymicrobial BSI was associated with ICU admission after BSI (p = 0.0184). Mortality did not differ. Gram-positive Enterococcus sp. (22%) was the most common co-pathogen of MRSA in polymicrobial BSI.

Conclusion

While polymicrobial BSI remains relatively infrequent, risk factors for development may include devices in the genitourinary and gastrointestinal systems. Those who develop polymicrobial MRSA BSI may be at higher risk of being admitted to the ICU, signifying increased morbidity during hospital stay. Further studies are needed to evaluate the impact of polymicrobial MRSA BSI to elucidate the interplay between pathogens and the impact on infected hosts.

Disclosures

All Authors: No reported disclosures
194. Carbapenem Resistance Gene Detection in Positive Blood Cultures Reveals Emergence of NDM-Harboring Organisms and Associated Morbidity and Mortality
Authors: Haghamad Aya , Lemon Jamie , Duong Scott , Juretschko Stefan , Streva Vincent
Published: November 2023

Background

Blood stream infections caused by organisms harboring carbapenemase genes are a significant cause of morbidity and mortality. The prevalence of carbapenemase producing organisms (CPO) has been increasing for several years, with the majority of isolates originating in healthcare settings and containing one of the five most prevalent carbapenemase genes (KPC, OXA-48-like, NDM, VIM, IMP). Management of patients with CPO is particularly challenging and knowledge of the specific carbapenemase gene harbored by these organisms is informative for proper selection of antimicrobial therapy.

Methods

We conducted a retrospective multicenter study of hospitalized patients with blood cultures positive for CPO from January 2021 to present. We used blood culture PCR results to identify the most common carbapenemase genes associated with blood stream infections in our hospital system. Additionally, we evaluated these patients for clinical outcomes including length of hospital stay and mortality.

Results

A total of 61 CPO positive blood cultures from 10 hospitals were included in our study. There was an increase in CPO from 2021 (13 CPO) to 2022 (38 CPO). This increase is maintained year to date in 2023 (9 CPO in Q1) and was primarily driven by the emergence of NDM harboring CPOs in 2022 (19 cultures) continuing into 2023 (5 cultures in Q1). The predominant CPO isolated was Klebsiella pneumoniae (40/61, 66%). We observed an increasing trend across the study years in both length of hospital stay (18 days for 2021, 21 days for 2022, 35 days for 2023) and patient mortality (46% for 2021, 54% for 2022, 60% for 2023), though overall clinical outcomes were poor.

Conclusion

Our results suggest that the landscape of CPOs is evolving in the New York City area. Timely reporting and differentiation of carbapenem resistance genes is important to inform changes in antimicrobial therapy. Despite appropriate clinical intervention, mortality rates appear to be increasing for patients with CPO bloodstream infections, likely due to the emergence of NDM-harboring CPOs in 2022.

Disclosures

All Authors: No reported disclosures
200. Comparison of Clinical Outcomes among Patients Treated with Ceftriaxone 2 Grams versus 1 Gram Daily for Gram-Negative Bacteremia
Authors: Huynh-Phan Ricky , Zidaru Andrei , Phe Kady
Published: November 2023

Background

Ceftriaxone (CRO) is commonly utilized for the treatment of Gram-negative infections. However, there are limited data on the appropriate dose of CRO for the treatment of Gram-negative bacteremia. This study aimed to assess the clinical outcomes of CRO 2 grams versus 1 gram daily for Gram-negative bacteremia.

Methods

This was a retrospective, single-center study of patients with Gram-negative bacteremia that received CRO for ≥ 72 hours or over 50% of treatment duration as definitive treatment. Patients were excluded if they had polymicrobial bacteremia, had bacteremia with a Gram-negative organism that was resistant to CRO, or received empiric antibiotics other than CRO for ≥ 72 hours. Definitive treatment was defined as antibiotic utilized after the antibiotic susceptibility report was available to the clinician. Treatment failure was defined as antibiotic escalation due to clinical worsening at any time during CRO therapy. The primary endpoint for this study was 30-day hospital mortality. Secondary endpoints were treatment failure, readmission rates, and adverse reactions.

Results

Of 127 patients included, 57% received CRO 2 grams and 43% received 1 gram. The mean APACHE-II score did not differ between the 2 grams and 1 gram groups (13.8 ± 5.97 versus 12.5 ± 5.61, respectively; p = 0.238). Hypoalbuminemia was present in 21% of patients in the 2 grams group compared to 20% in the 1 gram group (p = 1.00). The most common Gram-negative bacteria isolated were Escherichia coli and Klebsiella species in 68% and 24% of patients, respectively. Hospital mortality in the entire cohort was 4% (n = 127). Patients receiving 2 grams had a numerically higher 30-day hospital mortality rate (7% versus 0%; p = 0.069). Patients receiving 2 grams also had numerically higher rates of treatment failure (15% versus 5%; p = 0.094). Readmission due to infection did not differ between groups (8% versus 5%; p = 0.731). Overall, ceftriaxone was well tolerated in both groups with no reported adverse reactions.

Conclusion

There was no significant difference in hospital mortality among patients treated with ceftriaxone 2 grams versus 1 gram for Gram-negative bacteremia.

Disclosures

All Authors: No reported disclosures
202. Association of Neutrophil - Lymphocyte Ratio with Bacteremia and In-Hospital Mortality in Sepsis Patients: A Retrospective Multicenter Study
Authors: Isha Shahin , Jonna Sadhana , Raavi Lekhya , Jenkins Anna , Hanson Abby J , Satashia Parthkumar , Yarrarapu Siva Naga S , Govero Austin , Harrison Michael F , Baig Hassan Z , Caples Sean M , Grek Ami A , Vizzini Michael R , Khan Syed A , Heise Katherine , Sekiguchi Hiroshi , Cantrell Warren , Smith Jeffrey D , Gnanapandithan Karthik , Thompson Kristine M , Graham Charles G , Cowdell Jed C , Murawska Baptista Aleksandra , Shapiro Anna B , Bhattacharyya Anirban , Chaudhary Sanjay , Kiley Sean , Guru Pramod K , Libertin Claudia , Moreno Franco Pablo , Sanghavi Devang K
Published: November 2023

Background

Early diagnosis, prognostication, and treatment initiation are the cornerstones of sepsis management. There remains an immense interest in exploring the diagnostic and prognostic roles of neutrophil-lymphocyte ratio (NLR) in the sepsis population.

Methods

We performed a retrospective multi-center observational study including patients admitted to different Mayo Clinic sites with a diagnosis of sepsis between October 2018 and August 2022. Patients were excluded if they were aged < 18 years, lacked research authorization, or had missing Neutrophil or Lymphocyte count at admission. Data were collected from an existing sepsis database and Mayo Data Explorer (MDE). Categorical variables were summarized as percentages and continuous variables were summarized as medians. Chi-square test for significance, independent sample t-test, and multivariate Cox Proportional Hazard models were performed on IBM SPSS Statistics v28.0.

Results

Our study cohort consisted of 13968 patients, of which the majority were males (55.9%), Caucasian (91.6%), and non-Hispanic or Latino (94.3%). The median age of the cohort was 71 (60, 80) years, and the median BMI was 27.7 (23.4, 33.3) kg/m2.

Among all sepsis patients, 6.0% had a positive blood culture and the most common organisms were E. coli (26.5%), Klebsiella sp. (15.6%), Streptococcus sp. (12.8%) and Staphylococcus aureus (9.9%). 13131 patients (94.1%) survived the hospital stay and 837 (5.9%) did not. There was no difference in mortality based on blood culture positivity status (6.0% vs 6.6%, p=0.41).

However, the median NLR was higher among patients with a positive blood culture (16.4 vs. 12.1, p< 0.001) and among non-survivors (14.3 vs 12.2, p< 0.001). NLR did not significantly vary based on the type of organism growing in the blood culture. A multivariate model revealed NLR as an independent predictor of mortality (HR 1.003, 95% CI: 1.000-1.006, p=0.029) after adjusting for comorbidities, baseline clinical and laboratory variables. (Tables 1 & 2)

Conclusion

Our retrospective multicentric study showed that the Neutrophil-Lymphocyte ratio at admission was higher among bacteremic sepsis patients and non-survivors. Further prospective studies are needed to explore its diagnostic and prognostic utility.

Disclosures

All Authors: No reported disclosures
204. Clinical and Epidemiologic Review of Capnocytophaga Infections Identified at a Public Health Reference Laboratory – California, 2005 – 2021
Authors: Kelly Emily , Campagna Rebecca , Vugia Duc , Fritz Curtis L
Published: November 2023

Background

Capnocytophaga spp. are bacteria commonly found in the mouths of dogs and cats, which can infect people through bites or other contact with saliva. This study describes the epidemiology and clinical features of patients from whom Capnocytophaga spp. were isolated from clinical specimens at the California State Microbial Diseases Laboratory (MDL) over a 17-year period.

Methods

All MDL reports of Capnocytophaga spp. isolated from human patients between 2005 and 2021, including specimen submission forms and accompanying medical records, were reviewed. Data from these records were used to identify patients in datasets of statewide hospital patient discharge (PD) and emergency department (ED) admissions when possible. Clinical and other information in the PD and ED databases were used to confirm and supplement information from laboratory records.

Results

Capnocytophaga spp. were isolated in 48 specimens from 47 patients. The median age of patients was 68 years (range 12 to 88 years), and 57% were male. C. canimorsus represented 83% of the Capnocytophaga spp. identified. Capnocytophaga spp. were most frequently isolated from blood (88%), followed by cerebrospinal fluid (4%) and synovial fluid (4%). The most common case presentation was sepsis (45%), followed by skin and soft tissue infection (13%). Records for 45% of patients indicated at least one comorbidity associated with immunosuppression, including current malignancy (19%), diabetes mellitus (17%), alcohol use disorder (6%), and history of splenectomy (6%). Six records (13%) reported an animal bite (five dog bites, one cat bite).

Conclusion

This study documented Capnocytophaga spp. infection causing rare, severe disease in older and immunocompromised persons, often without report of an animal bite. This vulnerable group should be made aware of the risk of Capnocytophaga spp. infection from contact with cats and dogs and counseled to seek prompt medical care for any signs of infection, even if no known bite occurred.

Disclosures

All Authors: No reported disclosures
206. Prevalence of liver abscess in patients with Klebsiella pneumoniae bacteremia during a 5-year experience in a tertiary hospital in Thailand
Authors: Kiatkangwanchon Natthapol , Fujitnirun Chris
Published: November 2023

Background

The incidence of liver abscess in Thailand has increased in number nowadays.

K. pneumoniae is the most common cause of pyogenic liver abscess in the recent large series. Liver abscess can be a complication of K. pneumoniae bacteremic patients. We aimed to study the prevalence of liver abscess in patients with K. pneumoniae bacteremia and the comparison in clinical and laboratory characteristics of patients with K. pneumoniae between a group with liver abscess and the other without liver abscess.

Methods

This is a retrospective study; data were collected in Bhumibol Adulyadej Hospital among patients who were diagnosed with K. pneumoniae bacteremia between January 2014 – December 2019 and compared the difference in clinical and laboratory characteristics of patients between a group with liver abscess and the other without liver abscess.

Results

Of All 758 patients with K. pneumoniae bacteremia, 335 (44.19%) patients were done abdominal imaging, and 37 (4.9%) patients were found with liver abscess. The mean age was 65 years old, and most were male. Comorbidities were present in almost half of the patients including diabetes (118 patients, 35.22%), previous hepatobiliary surgery (21, 6.26%), and history of cancer (70, 20.90%). The other demographic data are shown in Table 1. Patients with liver abscess had diabetes (54.1% vs 29.3%, p-value = 0.082) and fever (91.89% vs 76.84%, p-value = 0.056) more than patients without abscess, however only 29.7% of patients with liver abscess had abdominal pain. Elevated transaminases above 2 times the upper limit of normal range are more frequent among patients with liver abscess than patients without abscess, for AST; 54.1%vs 35.30% (p-value = 0.026) and ALT; 40.5% vs 25.20% (p-value = 0.048). Clinical and laboratory characteristics are shown in Table 2.Table 1:Demographic data of patients with K. pneumoniae bacteremiaTable 2:Clinical and laboratory characteristics of patients with K. pneumoniae bacteremia

Conclusion

The prevalence of liver abscess in patients with K. pneumoniae bacteremia is 37 from 758 (4.9%). Liver abscess should be suspected in K. pneumoniae bacteremic patients who have elevated transaminases above 2 times the upper limit of normal range regardless of abdominal pain.

Disclosures

All Authors: No reported disclosures
227. Staphylococcus aureus bacteremia: back to normal
Authors: Pedromingo Kus Miguel Sebastian , Cristina Antolí Ana , Iglesias Núñez Nuria
Published: November 2023

Background

Staphylococcus aureus bacteremia (SAB) source is often unclear. One of the most common origins of SAB is cutaneous wounds and intravascular catheter-related bloodstream infection (CRBSI). Moreover, as our study group previously described, abscess formation and SAB following intramuscular injections are rare but possible complications from vaccines/inoculations. After an initial period of heightened SAB due to COVID-19 vaccines, we noticed a reversal of this circumstance.

Methods

In this case series, we present a cohort of 100 patients with SAB from January 1, 2021 through April 24, 2023, attended in our Institution (Hospital Nuestra Señora de Sonsoles, Ávila, Spain). We identified the SAB association with previous events, and the change in the recent paradigm of its genesis.

Results

During the study period, 100 SAB were identified. 85/100 patients were COVID-19 vaccinated. 64% were male and the rest were female. We identified the source of SAB in 90% of cases: in 12% (12/100) it clearly was a previously recent intramuscular vaccine (12/85 vaccinated patients; 14.1% of all COVID-19 vaccinated subjects). All-inclusive, the emergence of SAB was represented as follows: 24% from CRBSI, 23% from skin and soft tissue infections (SSTI), 11% - urinary tract infections (UTI), 10% - respiratory tract infections (RTI), 5% - endovascular reservoirs, 3% from postoperative complications in trauma surgery; septic mouth and bacterial parotiditis were responsible for one case (1% each). Finally, we were not able to identify 10% of the bacteremic fount. Overall, 54 patients died - 54% (46 deaths directly related to the SAB – 85.2%).

Conclusion

SAB always implies an outstanding risk due to its potential complications. Although we previously found an increased incidence of SAB related to COVID-19 vaccines, common causes such as CRBSI and SSTI, are now restored as usual sources. Nevertheless, mortality remains still high amongst our patients.

Disclosures

All Authors: No reported disclosures
245. Comparing Enterococcus faecalis and Enterococcus faecium Bloodstream Infections’ Severity and Mortality
Authors: Varghese Shawn , Sanders James , Monogue Marguerite , Yen Christina
Published: November 2023

Background

Enterococcus species commonly cause bloodstream infections (BSIs) with E. faecium infections considered especially worrisome due to association with vancomycin resistance via expression of the vanA gene. However, it is unclear if there is an association with E. faecium’s drug resistance potential and increased morbidity or mortality. Here we aimed to assess the severity of disease and mortality of patients with E. faecalis versus E. faecium BSIs, including subgroup analysis of vancomycin resistant E. faecium (VRE).

Methods

We conducted a retrospective, observational cohort study at a large urban academic center. Adult patients admitted from January 2018 to October 2022 with either E. faecalis or E. faecium BSI were included. Variables collected, determined a priori, included history of previous antibiotic use, malignancy, transplant status, and bacteremia source. Outcome variables of interest were ICU stay, length of stay, and mortality.

Results

There was a total of 182 total cases of E. faecalis and E. faecium BSI, 123 and 65, respectively, including 6 cases with both species (Table 1). Patients with E. faecium had higher median Pitt bacteremia scores (2 [IQR 0-4] versus 1 [IQR 0-3], p = 0.02) and longer median length of stay (30 [IQR 12-51] versus 15 [IQR 8-27], p < 0.001). There was statistically higher all-cause mortality at time of data collection in the E. faecium (60% vs 41%, p = 0.01) and VRE cohorts compared with E. faecalis (63% vs. 41%, p = 0.02). Kaplan-Meier curve (Figure 1) demonstrates decreased survival in the E. faecium cohort compared to E. faecalis within the first 100 days after bacteremia (HR 1.84, p = 0.01). Of note, a difference in 90-day all cause mortality was only statistically different in the entire E. faecium cohort when compared to the E. faecalis cohort. (45% vs 29%, p = 0.04), in contrast to the VRE cohort (43% vs 29%, p = 0.12).

E. faecalis vs E. faecium results

Comparison of select variables

E. faecalis vs vancomycin resistant E. faecium results

Comparison of select variables

Conclusion

E. faecium BSIs appear associated with longer, more clinically severe hospital courses and significantly increased mortality, specifically 90-day mortality when compared to E. faecalis BSIs. Future inquiries should assess the extent to which E. faecium serves as an index versus driver of poor clinical outcomes and strategies to mitigate the associated mortality.

Disclosures

James Sanders, PhD, PharmD, Merck & Co., Inc.: Grant/Research Support|Shionogi Inc.: Grant/Research Support
246. A Retrospective Cohort Study Comparing Two Versus Three Blood Culture Sets in People Who Inject Drugs
Authors: Wang Aprilgate , Shih Michael C , Radosta Stella , Mushatt David
Published: November 2023

Background

The current standard of drawing two versus three sets of blood cultures lacks adequate guidance. Because people who inject drugs (PWID) are at higher risk for bacteremia and life-threatening illness, risk-benefit analysis become especially unclear.

Methods

We conducted a retrospective cohort study of PWID who had blood cultures drawn between 2017 and 2022 at a single multihospital system. Data was extracted and analyzed to determine (a) the rates of bacteremia for two versus three sets of blood cultures, (b) rates of false positive (contaminants) for two versus three sets of blood cultures, and (c) the downstream effects from contaminant growths. Exclusion criteria were blood cultures obtained greater than four hours apart, blood cultures obtained after antibiotic administration, and subsequent blood cultures obtained during the same hospitalization.

Results

998 PWID patients with 2278 sets of blood cultures were analyzed. There were 1618 cases with two blood culture sets and 660 cases with three. Potential benefit of adding a third blood culture set, indicated by 1 out of 3 containing pathogenic growth, was seen in 30 (4.5%) cases. However, only 13 (2.0%) cases showed true benefit, as 17 (2.6%) involved known inadequately treated infections or the same pathogen on another culture. The number needed to treat (NNT) was 51. By adding a third blood culture set, the relative risk of a contaminant increased by 39.7%; the number needed to harm (NNH) was 36. There were statistically more contaminants in three blood culture sets (65, 9.8%) than for two (114, 7.1%) (p<0.00001). Out of 179 culture sets with only contaminants, 115 (64.2%) were analyzed for complications, which included 7 (6.14%) hospital readmissions, average 3.4 (SD 1.9) extra days of admission for 9 patients, average 1.3 (SD 1.2) extra blood cultures, total 13 (11.9%) extra microbial speciations, and average 2.3 (SD 1.9) days of unnecessary antibiotic administration for 27 patients.

Conclusion

Benefits of a third blood culture set do not universally outweigh risks for contaminant growth for PWID. A third blood culture set should be considered in specific clinical scenarios (i.e., inadequately treated endocarditis and osteomyelitis).

Disclosures

All Authors: No reported disclosures
264. Resident Macrophages of the Amnion: Characterization and Response to Ascending Bacterial Pathogens
Authors: Fandozzi Eva , Smith Caroline , Megli Christina
Published: November 2023

Background

The primary organ of pregnancy, the placenta, exists as a maternal-fetal barrier and displays remarkable immunoactivity. This barrier is effective against multiple pathogens, yet, the underlying mechanisms of immune regulation and pathogen defense of this barrier are not well understood. The inner layer of the fetal membrane, the amnion, has been proposed to be a significant barrier to infection. The amnion has been reported to contain CD14+ cells, but the immune activity and localization of these cells are poorly characterized. As a monocyte marker, these CD14+ cells may be endemic to the amnion and involved in antimicrobial defenses.

Methods

We isolate macrophages from amnion explants of fetal membranes collected at cesarean section in the absence of labor and infection using a StemSep Human CD14+ Selection Kit. These cells are characterized using flow cytometry and FACS. In addition, mCherry labeled L. monocytogenes (LM) or CFSE labeled S. agalactiae (GBS) were used to infect intact explants and infectivity was quantified by colony forming units. Immunofluorescence staining was used to localize CD14. Bacteria colonization with CD14 was visualized in infected tissue explants. CD86 and CD163 were used as M1 and M2 markers respectively. Imaging was performed using the STELLARIS confocal microscope.

Results

CD14+ cells exist in healthy amniotic tissue explants and localize to the mesenchymal layer. Amnion CD14+ cells also co-localize with CD86 and without CD163 suggesting a distinct phenotype from other placental macrophages (Hoffbauer cells and PAMM subsets). Amnion explants have decreased growth of LM and GBS in comparison to chorion and chorionic villi. LM and GBS co-localized with CD14+ cells in the amnion.

CD14+ macrophages are present in healthy amnion explants

Immunofluorescence staining of healthy human amnion. CD14 (green) positive cells localize to the mesenchymal layer of the amnion. Nuclei and cytoplasmic actin are stained with DAPI (blue) and phalloidin (red) respectively.

GBS localizes to the mesenchymal layer of the amnion

Immunofluorescence staining of healthy human amnion. GBS (green) localizes to the mesenchymal layer of the amnion. Nuclei and cytoplasmic actin are stained with DAPI (blue) and phalloidin (red) respectively.

Conclusion

We present the novel finding of resident macrophages in the amnion and demonstrate the presence of amnion macrophages in the absence of infection. In addition, we demonstrate that these macrophages express CD86 and co-localize with bacteria that can be vertically transmitted during pregnancy, including LM and GBS. Further characterization of the regulation of these cells may provide insight into the immunomodulatory function of the fetal membrane.

Disclosures

All Authors: No reported disclosures
269. Reference Data of Biochemical and Hematology Parameters in Juvenile and Adult Owl Monkeys (Aotus nancymaae) for Biomedical Research
Authors: Carlos Gaspar Juan , Moeller Tyler , Buchta Jessica , Nieto Monica , Espinoza Nereyda , Castillo Rosa , Nunez Rosa
Published: November 2023

Background

Non-human primates (NHP), including New World monkeys (NWM), are used in varied fields of biomedical research encompassing infectious disease, behavioral sciences and drug and vaccine development. In these studies, normal reference values for biochemical and hematological parameters are often needed for comparison with experimental results. These blood parameters are useful guides in reaching a diagnosis, estimating the prognosis of the disease and monitoring the progress of treatment. Although there are various reports of biochemical and hematologic parameters in Old World monkeys, the range of reference values often differs between NHP species. Despite the importance of NWMs such as Aotus nancymaae in biomedical research, few studies have examined these values and with a limited number of animals only. A. nancymaae is widely used for research and often used to study the principal types of human malaria (P. falciparum and P. vivax). These primates have also been used to study leishmaniasis, schistosomiasis, tuberculosis and various types of enteric infections. Furthermore, in recent years oral challenge models have been developed in A. nancymaae for Campylobacter jejuni, Shigella flexneri, and Enterotoxigenic Escherichia coli (ETEC). However, there is no updated data on biochemical and hematological parameters for A. nancymaae. Therefore, the aim of this study was to provide complete and accurate reference intervals of biochemical and hematological values to assess the health status indices of A. nancymaae housed in a vivarium prior to their use.

Methods

To characterize these parameters, a total of 1250 blood samples (1003 from juvenile and 247 from adult monkeys) were analyzed between 2007 to 2022. A total of 14 biochemical and 20 hematology parameters were measured.

Results

A significant change was observed in the values of alkaline phosphatase (ALP), potassium (K+), glucose (GLU), blood urea nitrogen (BUN), creatinine (CRE), hemoglobin (HGB) and lymphocyte (LYM) in relation to sex and age.

Conclusion

In conclusion, this work establishes a comprehensive and systematic reference of serum biochemical and hematological parameters for A. nancymaae based on a large cohort which can be used to inform and guide future studies utilizing this animal model.

Disclosures

All Authors: No reported disclosures
314. Using CRISPR/Cas9 to dissect the regions of MLL/AF9 that are critical for myeloid immortalization
Authors: Yvanovich Emma , Timmer Kyle , Mansour Michael , Sykes David B
Published: November 2023

Background

High volumes of neutrophils are required for the successful granulocyte transfusion. Our goal is to expand neutrophil progenitors ex vivo to provide white blood cell transfusions of sufficient cell number. Creating a conditionally immortalized granulocyte-monocyte progenitor (GMP) would allow for exploration into the infinite expansion of GMPs to make a large volume of neutrophils.

The MLL/AF9 fusion oncoprotein is associated with mixed lineage leukemia (MLL), a form of acute myeloid leukemia (AML). MLL1 is a large gene with multiple binding sites associated with the development of MLL when broken and bound to a fusion parnter like AF9, highly efficient at causing MLL. We would like to understand whether certain regions of the gene might provide the capacity for ex vivo expansion without resulting in leukemia.

Methods

To determine the most relevant portion of the MLL/AF9 gene, we conducted a "walkdown" with a custom CRISPR/Cas9 gRNA library to identify elements crucial for immortalization. The Cas9 and gRNAs will be delivered by lentiviral transduction. This walkdown employs a custom gRNA library with guides targeting each base pair along the ∼6000bp coding region. Transduction of MLL/AF9 dependent human leukemia cell lines THP1 and MOLM13 will be performed to identify those gRNA that target essential regions of MLL/AF9 in this drop-out screening approach.

Results

Pilot experiments have been conducted to increase transduction efficiency for MLL/AF9 dependent cells. Transduction efficiency was maximized at 4 viral particles per cell in a 96 well plate (Figure 1). A larger scale walkdown pilot was conducted to maximize the amount of gDNA collected for PCR amplification. Sequencing of the PCR product will identify cells with essential areas knocked out (Figure 2).

Figure 1

GFP positivity in transduced MLL/AF9 cells in differing plate sizes displayed in two formats.

Figure 2

Predicted results of the walkdown experiment sequencing analysis.

Conclusion

The association of the MLL/AF9 fusion oncogene with myeloid lineage leukemia offers a natural mechanism through which to study GMP immortalization. Specific areas of the coding region can be identified by conducted a "walkdown" experiment with CRISPR/Cas9 gRNA library to knock out each base pair of the oncogene. Regions of the gene can be identified as essential to survival when cells with these areas knocked out die off. Manipulation of these essential areas can be used for further study in the immortalization of GMPs.

Disclosures

Michael Mansour, MD, PhD, Thermofisher: Grant/Research Support
317. Implementing lifestyle medicine innovations for preventing and reversing chronic diseases in HIV care at a Federally Qualified Healthcare Center
Authors: Anand Rahul , Prabhu Shagun S , Ingram Valerie R , Pevar Elena , Brown Orett
Published: November 2023

Background

Patients living with HIV are a vulnerable population, with high burden of chronic diseases and challenging social determinants of health. Many receive care in Ryan White grant funded multidisciplinary clinics in the community providing an opportunity to reimagine care delivery using innovative practices like shared medical appointments (SMAs). We designed and implemented lifestyle medicine (LM) interventions using interprofessional teams including one of the first described SMA programs for patients with HIV. Our pilot describes an iterative patient-centered model transferable and scalable to other HIV clinics or FQHCs for delivering lifestyle medicine to patients with HIV and other chronic infections.

Learning objectives of oral presentation

Learning objectives

Shared medical appointments recruitment flyer

Recruitment flyer

Methods

We piloted LM interventions both in individual patient care and via SMAs using interprofessional teams (physician, nutritionist, case managers). SMAs were 90 minutes long, designed to include 5-15 patients conducted monthly focusing on one pillar of LM at each event (nutrition,activity,sleep,stress,relationships,substance use). A whole health questionnaire was completed at the initial session, and American College of Lifestyle Medicine (ACLM) self-assessment on various pillars of lifestyle completed each session. Participants created a goal at the end of each session, and shared progress and key takeaways on return. Session guides were created for each session.

Lifestyle assessment page 1 of 2

Lifestyle assessment page 2 of 2

Results

Serial assessments at SMAs demonstrated tangible and sustained changes in various pillars of LM. Patient feedback indicated high patient and provider satisfaction; patients found group visits “grounding” in their lives. Disclosing HIV status to other patients was not considered a barrier by any attendees. Other key lessons learned include the benefit of social support for patients, ease of conducting repeated assessments of the six pillars of LM using ACLM form, benefit of creating session detailed guides for future iterations and scalability, and the importance of signing up an adequate number of patients for financial sustainability.

Lifestyle medicine shared medical appointments outcomes graphic

SMA Outcomes

Pre vs post program assessment data details for consenting patients

Pre vs Post program assessment data

Conclusion

Our pilot provides an iterative patient-centered model of SMAs easily transferable and scalable to other practices for delivering lifestyle medicine care to impact chronic diseases affecting patients with HIV and other vulnerable populations.

Disclosures

Rahul Anand, MD MBA MSCI, Paratek pharmaceuticals: Stocks/Bonds