bluuebunny/crossref_metadata_2025_split huggingface dataset:
2743. Pre-Transplant Human T-Lymphotropic Virus Screening In Allogeneic Hematopoietic Stem Cell Transplant Recipients At A Large Metropolitan Tertiary Referral Centre In Melbourne, Australia
Authors: Paykin Gabriel , Trevillyan Janine , Gador-Whyte Andrew , Garner Sarah E , Shuttleworth Peter , Trubiano Jason , Smibert Olivia 
Published: November 2023

Abstract

Background
Pre-transplant infectious diseases screening is an essential component of the pre-transplant workup. Many centres that offer allogeneic hematopoietic stem cell transplantation (HSCT) routinely screen for human T-lymphotropic virus (HTLV) in all recipients in the pre-transplant setting. The aim of this single centre retrospective chart review was to assess pre-transplant HTLV screening rates in allogeneic HSCT recipients at our institution in Melbourne, Australia and determine the prevalence of HTLV in this cohort.

Methods
Patients who received an allogeneic HSCT between 1st January 2018 and 31st December 2022 were identified from an institutional database. Patients who received a second HSCT during the study period were excluded from this analysis. Demographic and clinical data were extracted from electronic medical records. Descriptive analysis of the patient cohort was conducted. Data on the number and outcome of HTLV screening tests performed in this cohort between 1st January 2017 and 31st December 2022 were collated in order to determine the rate of pre-transplant HTLV screening and prevalence of HTLV in this cohort.

Results
Over the study period 116 patients received an allogeneic HSCT at our institution. Of these, 110 were included in this analysis. 67 (60.9%) were male and 43 (39.1%) were female. The mean age at time of transplant (D0) was 51.0 years. Eight (7.3%) patients received haploidentical transplants, 20 (18.2%) received matched unrelated donor transplants, 44 (40.0%) received sibling transplants and 38 (34.5%) received unrelated donor transplants. 158 pre-transplant HTLV screening tests were performed on included patients over the study period. 75 (68.2%) patients had one pre-transplant HTLV test, 25 (22.7%) had two pre-transplant HTLV tests, seven (6.4%) had three pre-transplant HTLV tests and three (2.7%) had four pre-transplant HTLV tests. All HTLV tests included in this analysis were non-reactive on enzyme immunoassay screening.

Conclusion
All patients included in this study had at least one pre-transplant HTLV screening test over the study period. There were no cases of HTLV detected in this cohort. Further research is required on the utility and cost effectiveness of routine pre-transplant HTLV screening in transplant recipients in non-endemic areas.

Disclosures
All Authors: No reported disclosures
2745. In-Vitro Activity of Cefiderocol Against Multidrug Resistant Strains of P. aeruginosa DTR, A. baumannii complex DTR, A. xylosoxidans MDR, S. maltophilia MDR & B. cepacia complex, by Iron-Depleted Broth Microdilution
Authors: Alexander Jose , Navas Daniel , Charles Angela 
Published: November 2023

Abstract

Background
The emergence of multidrug-resistant (MDR) & difficult-to-treat (DTR) non-fermenter (NF) organisms poses a critical challenge for antimicrobial therapy, threatening the efficacy of existing antimicrobial and contributing to an increasing worldwide mortality rate. MDR NFs are among the most challenging organisms isolated in the clinical laboratory. Cefiderocol (CFD), a novel siderophore cephalosporin, offers an interesting approach by exploiting the bacteria's iron-acquisition system and its intrinsic stability against multiple classes of β-lactamases. In this descriptive abstract, we present the in-vitro activity of cefiderocol against multiple strains of NF organisms.
Tab.1
Cefiderocol MIC distribtion for MDR non-fermenters. Dec. 2022 to April 2023

Methods
MIC values by iron-depleted broth microdilution (Liofilchem ComASP®) were collected and distributed by organism from December 2022 up to April 2023 at AdventHealth Orlando Microbiology Department. P. aeruginosa DTR (n=88), A. baumannii cpx DTR (n=38), A. xylosoxidans MDR (n=153), S. maltophilia MDR (n=84) & B. cepacia cpx (n=11). P. aeruginosa DTR is defined as an isolate intermediate (I) or resistant (R) to all tested antimicrobials except aminoglycosides. A. baumannii DTR as an isolate I or R to ampicillin/sulbactam and meropenem and one more active agent. A. xylosoxidans MDR as an isolate I or R to one agent in at least three active antimicrobial classes & S. maltophilia MDR as an isolate I or R to trimethoprim/sulfamethoxazole.

Results
The average, mode, median and range MIC (µg/mL) were calculated for each organism. P. aeruginosa DTR: 3.55, 0.25, 0.5, 0.06-128; A. baumannii DTR: 7.66, 0.5, 0.5, 0.12-128; A. xylosoxidans MDR: 3.66, 0.25, 0.25, 0.06-128; S. maltophilia MDR 0.37, 0.25, 0.25, 0.06-2; B. cepacia cpx: 11.77, 0.06, 0.06, 0.06-128.

Conclusion
Using the P. aeruginosa susceptible CLSI BP (&lt; =4 µg/mL) as a reference for P. aeruginosa DTR, A. xylosoxidans MDR & B. cepacia cpx, 96.6%, 97.39% & 90.9% respectively have an MIC value in the susceptible BP. 76.3% of A. baumannii DTR have an MIC &lt; =4 µg/mL (susceptible BP) and 97.6% of S. maltophilia MDR have a susceptible CLSI BP &lt; =1 µg/mL. Although clinical outcome data is needed, cefiderocol demonstrated a significant potency against the most resistant NF strains and may represent a significant therapeutic option for difficult to treat isolates.

Disclosures
Jose Alexander, MD, D(ABMM), FCCM, CIC, SM/MB(ASCP), BCMAS, Shionogi: Advisor/Consultant|Shionogi: Honoraria
2746. Assessment of in vitro synergy between Piperacillin-Tazobactam-Meropenem and Imipenem-Meropenem against OXA-48 Producing Klebsiella pneumoniae Using Time-Kill Assays
Authors: Demir Mervenur , Aslan Abdullah Tarik , Seren Tanrıverdi Elif , Otlu Barış , Akova Murat , Paterson David , Harris Patrick N A , Hazırolan Gülşen 
Published: November 2023

Abstract

Background
Although double carbapenem regimens have reliable synergy against carbapenemase-producing Klebsiella pneumoniae (CP-Kp), the capacity of piperacillin-tazobactam (TZP) to provide synergistic activity with meropenem (MEM) is uncertain.

Methods
We used time-kill assays to evaluate synergy between TZP and MEM and imipenem (IMI)-MEM against non-clonal clinical CP-Kp isolates (tested by pulse-field gel electrophoresis). Five major carbapenemase genes (blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48 family) were tested by an in-house PCR. The antibiotic concentrations used in the assays were determined in two ways. First, the concentrations were selected to reflect those achievable in vivo in critically ill patients using optimal dosing strategies, i.e., 16/4 mg/L for TZP, 8 mg/L for MEM, 4 mg/L for IMI. Second, for organisms in which the MEM MIC was &lt; 8 mg/L and IMI MIC was &lt; 4 mg/L, the time-kill assays were performed using concentrations of carbapenems relative to the isolate’s MIC. Synergy was defined as a ≥ 2-log10-CFU/ml reductions at 24 h of exposure to the antibiotic combination compared with the single most active antibiotic, with the number of surviving organisms in the presence of the combination at &gt; 2 log10 CFU/ml below the starting inoculum.

Results
17 OXA-48- and 3 NDM-1-producing Kp isolates were included. The combinations of TZP-MEM and IMI-MEM were synergistic against 41.2% (7/17) and 52.9% (9/17) of OXA-48 producers, respectively (Table 1, 2). The synergy between TZP and MEM (85.7%, 6/7) was relatively higher than that of IMI and MEM (71.4%, 5/7) for isolates with low MEM MIC (0.5-2 mg/L). However, the synergy was lower in TZP-MEM combination (10%, 1/10) compared to IMI-MEM combination (40%, 4/10) among isolates with MEM MIC ≥ 16 mg/L. The TZP and MEM combination was bactericidal, demonstrating a ≥ 4 log10 CFU/mL reduction at 24 h, among 35.3% (6/17) of all OXA-48 producers and 71.4% (5/7) of OXA-48 producers with low MEM MIC. In contrast, the bactericidal synergy between IMI and MEM was shown among 29.4% (5/17) of all OXA-48 producers and 28.6% (2/7) of OXA-48 producers with low MEM MIC.
There was no synergy against NDM producers for both combinations.

Conclusion
TZP-MEM combination seems to be more reliable than double-carbapenem regimens for OXA-48-producing Kp with low MEM MIC.

Disclosures
David Paterson, AMR Action Fund: Board Member|Entasis: Board Member|Merck: Board Member|Pfizer: Board Member|QPex: Board Member|Venatorx: Board Member Patrick N A Harris, PhD, DTMH, MRCP, FRACP, FRCPA, Merck: Advisor/Consultant|Opgen: Advisor/Consultant|Sandoz: Advisor/Consultant
163. Can Machine Learning Guide Antibiotic Initiation for Lower Respiratory Tract Infections?
Authors: Tang Sarah , Chang Daniel , Zhi Chin De , Piotr Chlebicki Maciej , Jasmine Chung Shimin , Wei Lee Lai , Lee Winnie , Yvonne Zhou Peijun , Kwa Andrea 
Published: November 2023

Abstract

Background
Accurate diagnosis of acute bacterial lower respiratory tract infections (LRTI) is often elusive. The lack of diagnostic gold standard, exacerbated by overlapping syndrome with non-infective/non-bacterial respiratory conditions, have contributed to antibiotic over-prescribing. This in turn drives drug resistance, healthcare costs and patient morbidity. We explored feasibility of developing a
classification model to identify instances where antibiotics should be initiated or withheld when bacterial LRTI is suspected.

Methods
All inpatients in Singapore General Hospital during Y2019-2020 and had ICD-10 codes for LRTI or mimicking conditions were included. Only cases with ICD-10 codes for LRTI and manually assessed to be true by the hospital antimicrobial stewardship unit (ASU) were labelled as ground truth “Yes” (i.e., antibiotics should be initiated). Cases with ICD-10 codes for other conditions were labelled as ground truth “No” (i.e., antibiotics could be withheld). Patient information (e.g., clinical notes, radiology reports, vital signs) were extracted from our hospital’s electronic data repository. Gradient boosting algorithm was applied for model building and evaluated on a 20% held-out test set. A sub-analysis on incorrect classification was also performed.

Results
There were a total of 24,399 episodes. After exclusion by ASU review and under-sampling, the ground truth “yes” and “no” groups had 2,887 and 4,888 cases respectively. The model achieved a good performance of 80% accuracy, 83% sensitivity and 79% specificity, corresponding to an AUC of 0.89. Chest imaging findings, procalcitonin, c-reactive protein, cough, neutrophil count and oxygen saturation at start of episode were the 5 most important features. Incorrect classifications had lower confidence scores, and were more likely to occur among those with severe illness or radiological reports that were not suggestive of LRTI.

Conclusion
We developed a machine learning model to support decision-making on antibiotic initiation for suspected bacterial LRTI. Further work is needed to optimise this model and evaluate its impact in clinical practice.

Disclosures
All Authors: No reported disclosures
2759. Cefiderocol vs Best Available Therapy for the Treatment of Carbapenem- Resistant Acinetobacter baumannii
Authors: Daisey Gabrielle N , Vyas Nikunj M 
Published: November 2023

Abstract

Background
Cefiderocol has been evaluated as a treatment of carbapenem-resistant gram negative infections. However robust data for the optimal approach to treat carbapenem-resistant Acinetobacter baumannii (CRAB) is lacking. The purpose of this study was to evaluate the efficacy of cefiderocol vs best available therapy (BAT) for the treatment CRAB infections.

Methods
This IRB-approved retrospective observational review was conducted at a three-hospital community health system between June, 2020 to February, 2021. Hospitalized patients were included if they were ≥18 years old and received ≥24 hours of targeted antibiotics for CRAB. Patients were excluded if they were considered to be colonized or were pregnant. Patients in the cefiderocol group were matched with patients in BAT group based on age and source of infection in a 1:3 ratio. The primary endpoint of this study was to assess all-cause inpatient mortality (ACIM) at the end of therapy. The secondary endpoint included clinical cure (CC) at the end of therapy. A subgroup analysis was performed for patients treated with cefiderocol monotherapy, cefiderocol combination therapy, and combination BAT to determine differences in ACIM and CC.

Results
A total of 60 patients were included in the primary analysis; 15 receiving cefiderocol and 45 receiving BAT. There was no difference in patient age, race, and diagnosis between both groups. Patients in the BAT group had a shorter length of stay vs cefiderocol group (14 vs 19 days. P=0.05). Ampicillin/sulbactam (86.7% vs 57.8%, P=0.06) and minocycline (86.7% vs 22.2%, P=0.0001) non-susceptible CRAB isolates were more common in the cefiderocol group vs BAT group (as seen in Figure 1). No differences were seen in ACIM (27% vs 18%, P=0.47) and CC (53% vs 60%, P=1.0) between both groups. The subgroup analysis revealed cefiderocol combination therapy had a decreased number of patients with ACIM and had favorable CC outcomes compared to cefiderocol monotherapy and combination BAT (as seen in Figure 2).
Comparison of Susceptibility Patterns
All Cause Inpatient Mortality and Clinical Cure in Subgroup Analysis of Monotherapy vs Combination Therapy

Conclusion
Cefiderocol seems to be a viable option for treatment of CRAB infections. No differences were seen in ACIM and CC between cefiderocol and BAT. Cefiderocol combination therapy seems to be a preferred therapeutic option for CRAB infections.

Disclosures
All Authors: No reported disclosures
2778. Retrospective evaluation of effectiveness of Flomoxef for infections due to extended-spectrum β-lactamase-producing Enterobacterales
Authors: Koizumi Ryuji , Hayakawa Kayoko , Hamada Yukihiro , Mezaki Kazuhisa , Ohmagari Norio 
Published: November 2023

Abstract

Background
Flomoxef (FMOX), an oxacephem, is resistant to hydrolysis by extended-spectrum β-lactamase (ESBL), and is expected to serve as a carbapenem-sparing therapy for infections caused by ESBL-producing Enterobacterales (ESBLPE). FMOX has been approved and used in Japan for the treatment of ESBLPE infections; however, data on its effectiveness and optimal dosing are limited.

Methods
This retrospective observational study was conducted at the National Center for Global Health and Medicine. We reviewed the medical records of patients with ESBLPE infections treated with FMOX for &gt; 48 h, from 2019 to 2021. The time above the minimum inhibitory concentration (MIC) (TAM) of ESBLPE was calculated using the MIC value of FMOX for ESBLPE and the simulated FMOX concentration. Creatinine Clearance (CrCl) was calculated using the Cockcroft-Gault equation. Clinical effectiveness was defined as improvement in symptoms compared with baseline after FMOX treatment, as judged by infectious disease specialists. Microbiological effectiveness was defined as reduction of urine ESBLPE bacterial load to≤10^3 CFU/ml for urinary tract infections (UTI), or disappearance of ESBLPE for non-UTI.

Results
Fourteen patients were included in the study: 11 patients had ESBL-producing E. coli as the causative organism and nine patients had UTI. Bacteremia accounted for 35.7% of all patients. The median age of the study cohort was 81 years (interquartile range [IQR], 67.75 – 91). Nine of the patients were female.
FMOX doses varied according to the CrCl category (Table). TAM was 100% in all but one case (CrCl 48.9 mL/min, MIC of FMOX=0.5 mg/L, FMOX 1g q 12h, TAM=88.9%). Of the 13 cases for which clinical effectiveness could be assessed, FMOX was effective in nine of ten (90%) UTIs and one of three (33.3%) non-UTIs.
Microbiological effectiveness was evaluated in only two cases (UTI and pneumonia, respectively), and FMOX was microbiologically effective in both.
Characteristics of patients who received FMOX against infection caused by ESBL-producing Enterobacterales (n = 14)

Conclusion
FMOX was a clinically effective treatment for the majority of UTIs caused by ESBLPE.
For non-UTI patients, the rate of clinical effectiveness was low despite the high TAM.
FMOX is a potential carbapenem-sparing therapy for UTIs caused by ESBLPE.

Disclosures
All Authors: No reported disclosures
2783. Evaluation of Appropriate Antibiotic Prescribing Following Modification of Culture & Susceptibility Cascade for High Risk AmpC-Producing Gram-Negative Bacteria
Authors: Lim Andy , McSweeney Terrence D , Thwe Phyu , Chang Mei , Bao Hongkai , Lee Philip J , Guo Yi 
Published: November 2023

Abstract

Background
Updated cascade reporting of antimicrobial susceptibility (CRAS) for high-risk AmpC-producing Gram-negative organisms was implemented by the antimicrobial stewardship (ASP) and microbiology teams in June 2022 based on recent IDSA guidance. The CRAS focuses on highlighting weak inducers and poor substrate antibiotics such as cefepime and meropenem for AmpC-producing organisms: H. alvei, E. cloacae, C. freundii, K. aerogenes, and Y. enterocolitica (HECK-Yes).

Methods
A retrospective, observational, quasi-experimental study was conducted comparing the appropriateness of antimicrobials prescribed for infections with HECK-Yes organisms between pre-implementation period (July 2021-April 2022) and post-implementation period (July 2022-April 2023). Patients &gt;18 years old with a positive blood or respiratory culture with any HECK-Yes organisms were included. The primary outcome of the study was the frequency of patients on appropriate antibiotics within 24 hours of final susceptibility report. Secondary outcomes included time to appropriate antibiotic order and administration, clinical success, microbiological failure, mortality, and reinfection/readmission within 30 days.

Results
Fifty patients were included in the pre- and post-implementation groups. Baseline characteristics were similar between the two groups (Table 1). A relative increase of 38.7% was observed in the appropriateness of antibiotics within 24 hours of final culture & susceptibility report (pre: 62% vs. post: 86%, p = 0.01). No significant difference was observed between the two groups in time to appropriate antibiotic order (pre: 4.8 hours vs. post: 3.3 hours, p = 0.37) or administration (pre: 5.9 hours vs. post: 8.0 hours, p = 0.53). There was a trend towards a lower 30-day mortality rate in the post-implementation group (pre: 24% vs. post: 14%, p = 0.10). No significant difference was observed for clinical success, microbiological failure, and reinfection/readmission within 30 days (Table 2).

Conclusion
Updating CRAS effectively increased the frequency of appropriate antibiotic prescribing for the treatment of HECK-Yes infections. The collaborative efforts of ASP and microbiology teams optimized antimicrobial prescribing for infections with HECK-Yes organisms at our institution.

Disclosures
All Authors: No reported disclosures
169. Positive blood culture after emergency department discharge of patients from a cancer center. Epidemiology, clinical features, and outcome
Authors: Alatorre Fernandez Pamela , Cardona Ortiz Alex , Islas-Muñoz Beda , Volkow-Fernández Patricia , Cornejo Juarez Patricia , Velazquez Acosta Consuelo 
Published: November 2023

Abstract

Background
Cancer patients frequently go to the emergency room (ER) because of fever. Within the approach, blood cultures are taken, and they are often discharged if their clinical condition is stable. The objective of the study is to know the epidemiology, clinical characteristics, and outcome of patients with positive blood cultures after discharge from the emergency department.

Methods
Between 2021 and 2022, 178 blood cultures taken in the ER were positive for infection. Of these, 93 cases (38%) corresponded to outpatients who were included. Demographic, clinical, and microbiological data were collected. A bivariate analysis comparing the cohort vs. patients that were admitted (controls) from the ER in the same period was done.

Results
Most frequent oncological diagnosis was breast cancer (21.5%), lymphoma (18.3%), and cervical cancer (11.8%). Forty-nine (53%) had recently been diagnosed with cancer, 52 (55.9%) had received chemotherapy, and 15 (16.1%) had received antibiotics within the previous month. The most frequent reasons for consultation were febrile syndrome (28%), fever after CVC manipulation (20.4%), and fever with urinary symptoms (12%). Antibiotics were prescribed on discharge from the emergency department in 57 patients (61.3%), being adequate in 36.9% of the cases. The isolate was considered to be pathogenic in 84 cases, mainly due to Gram-negative bacilli (n=58, 69%). 72 (77.4%) attended reassessment (due to telephone contact or persistence of symptoms), and 56 (60.2%) were hospitalized. The most frequent bloodstream infections were secondary (n=45, 48.4%) and catheter-related (n=33, 35.5%). Three patients died, and only in one case was it secondary to an infection, compared to 23.5% in the admitted group. The bivariate analysis is reported in Table 1.

Conclusion
Mortality in discharged patients was low (3%); Close monitoring of positive blood cultures, patient follow-up, and identification of risk factors for adverse outcomes, such as neutropenia, inflammatory response syndrome with high C-reactive protein or Procalcitonin, uncontrolled foci of infection, recent hospitalization, or antibiotic treatment should be considered for admission in this high risk population.

Disclosures
All Authors: No reported disclosures
2819. Clinical Outcomes of Fosfomycin Treatment in E. coli vs. Non-E. coli Enterobacterales Urinary Tract Infection
Authors: Traugott Kristi , Lee Grace , Groff Lindsey , Aguilar Samantha 
Published: November 2023

Abstract

Background
Oral fosfomycin tromethamine is considered a first-line agent for the treatment of uncomplicated acute cystitis in women according to the national Infectious Disease Society of America (IDSA) guideline. However, non-E. coli Enterobacterales urinary tract infection (UTI) pathogens exhibit higher minimum inhibitory concentrations (MICs) for fosfomycin and limited data exist to determine whether treatment outcomes are comparable to patients being treated with fosfomycin for E.coli UTIs. The objective of this study is to compare the clinical outcomes of patients being treated with fosfomycin who have E. coli UTIs compared to non-E. coli Enterobacterales UTIs.

Methods
This was a retrospective noninferiority study of adult inpatients with a UTI who received a fosfomycin inpatient from July 15, 2020 to March 15, 2023. The primary outcome was incidence of treatment failure within 30 days of start of fosfomycin, defined by retreatment for UTI; UTI related- hospitalization, urgent care visits, and/or ambulatory visits; subsequent positive blood culture; and/or infection related mortality. One-sided test for noninferiority was used with a 20% margin. Multivaraible logistic regression analyses were conducted adjusting for age/sex, UTI severity, and prior UTIs.

Results
A total of 77 patients were included; 45 with E. coli UTIs and 32 with non-E. coli Enterobacterales UTIs. The majority of the patients were female (80.5%), with a median age of 67 years (IQR, 61-69), Hispanic/Latino (50.6%), had chronic kidney disease (33%), and diabetes mellitus (35%), and were admitted to a non-ICU floor (79%). The overall incidence of treatment failure was 19.5% (90% CI 12.9%-27.7%); 15.6% in those with E. coli vs. 25% in those with non-E. coli Enterobacterales UTIs (p=0.385; absolute difference 9.4%; 90% CI -7.3% to 26.2%), not meeting the criteria for non-inferiority. In multivariable analysis, E. coli vs. non-E. coli Enterobacterales UTIs did not associate with treatment failure (adjusted odds ratio, 0.66; 95% CI 0.193-2.25; p=0.505).

Conclusion
Fosfomycin treatment for non-E. coli Enterobacterales UTIs did not meet non-inferiority criteria when compared to patients with E. coli UTIs. Further studies with larger sample sizes are required.

Disclosures
All Authors: No reported disclosures