bluuebunny/crossref_metadata_2025_split huggingface dataset:
2823. In Vitro Efficacy of Minocycline on Clinical Gram Negative Bacterial Isolates
Authors: Saleh Omar M Abu , Crowley Patrick , Ranganath Nischal , Challener Douglas , Streck Nicholas 
Published: November 2023

Abstract

Background
Urinary tract infections (UTIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) have become increasingly challenging to manage due to the limited number of available effective oral agents. Minocycline, a second-generation tetracycline with a broad antimicrobial spectrum and reasonable urinary concentration, has recently gained attention as a potential treatment option for MDR-GNB UTIs. In this study, we aim to review the in vitro minocycline susceptibility against a wide spectrum of urinary GNB isolates performed at our reference lab.

Methods
We conducted a retrospective review of all minocycline susceptibility testing performed on urinary GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We stratified our results for different species based on phenotypic resistance profiles as well as known species-specific resistance association.

Results
During the study timeframe, we identified 28,388 GNB isolates that underwent minocycline susceptibility testing. Among the Escherichia coli (E.Coli) isolates resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibility was noted to be 78%, 46%, 76%, respectively (Fig 1). Among the Klebsiella pneumonia (KP) isolate resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibilities were 47%, 40%, and 53% respectively (Fig 1). Among the high risk Amp-C group Citrobacter freundii, Enterobacter Cloacae and Klebsiella aerogenes, minocycline susceptibility rate was noted to be 87%, 77%, and 89%, respectively (Fig 2). Finally, among the isolate group of non-fermenters including Achromobacter spp, Acinetobacter spp & Stenotrophomonas spp, susceptibility rates were noted to be 65%, 94%, and 100%, respectively (Fig 3).

Conclusion
Minocycline showed in vitro activity against many hard to treat GNB urinary isolates, including ceftriaxone and meropenem resistant E.coli & KP isolates. High-risk Amp-C producing GN species & some of the less common GN including Stenotrophomonas, Acinetobacter, and Achromobacter.

Disclosures
All Authors: No reported disclosures
2824. 3rd Generation Cephalosporin (3rd CEP) Use and Antibiotic Selection Appropriateness for Uncomplicated Febrile Urinary Tract Infections (UTI) in Children
Authors: Dantas Marina , Eckard Allison Ross , Williams Daniel C , Morrisette Taylor , Thacker Stephen A , Pudalov Natalie , Teufel Ronald J 
Published: November 2023

Abstract

Background
Concerns regarding antibiotic resistance have led many pediatricians to rely on 3rd CEP, namely ceftriaxone (CRO) and cefdinir (CDR), for UTI treatment. 3rd CEP use is a major risk factor for C. difficile infections and contribute to multidrug resistance. We sought to examine local prescribing patterns for uncomplicated febrile UTI in children to guide development of a standardized treatment pathway aimed at reducing unnecessary 3rd CEP use.

Methods
We conducted chart review of children aged 2 mo.-18 yrs treated at our institution for uncomplicated febrile UTI between Oct 2021 – Oct 2022. Subjects were identified by abnormal urine culture (UCx) regardless of colony-forming units (CFU) and included if they met a priori definition. Antibiotic selections were evaluated relative to urinalysis (UA), UCx, and bacterial susceptibilities to assess appropriateness of treatment. This project was certified by our institutional review board as quality improvement.

Results
61 subjects were included (85% female; 3.8 yrs median age; 70%, 16%, 13% treated in ED only, ED/inpatient, inpatient only, respectively). CRO or CDR were most frequently given as initial in-house treatment (ED or inpatient) (Fig 1). 53% of subjects received ≥1 dose of CRO or CDR (ED, inpatient or discharge prescription). 31% of subjects (68% in ED only) were identified as misdiagnosed with UTI (e.g., bacterial growth below CFU threshold or suggestive of contaminant). Providers relied on urine test strips rather than UA/microscopy in 38% of cases misdiagnosed UTIs. Of those with confirmed UTI, E. coli was most common pathogen (81%) followed by other Gram-negative bacteria (14%); susceptibilities were reported in 97% (Fig 2). Initial antibiotic selection was deemed inappropriate in 68% (Fig 3); 39% received CRO/CDR unnecessarily. ≥5 white blood cells per high-power field was most associated with a confirmed UTI (P=0.004).

Conclusion
Inappropriate 3rd CEP use and antibiotic overuse in general were prevalent in our study. The biggest drivers were UA underutilization contributing to UTI misdiagnosis and failure to use UCx to de-escalate antibiotics. Our findings serve as a foundation from which to build a standardized treatment pathway for uncomplicated febrile UTIs that will improve antibiotic stewardship and reduce 3rd CEP use.

Disclosures
Taylor Morrisette, PharmD, MPH, AbbVie: Advisor/Consultant|Basilea: Advisor/Consultant Ronald J. Teufel, II, MD, MSCR, Enanta Pharmaceaticals: Grant/Research Support|Health Resources and Servises Administration: Grant/Research Support|Moderna: Grant/Research Support|National Institute of Health: Grant/Research Support
171. Gram-Positive Blood Culture Contamination Rates: A Comparative Assessment Between Verigene® and Conventional Method
Authors: Almaghlouth Nouf K , Motwani Reena , Guevara Roberto , Khalique Umara , Alrahamneh Hebah , Attia Mohamed , Alrahamneh Osaid A , Allokka Mohamed , Alrahamneh Zaid , Alfarargy Arwa Y , Anyiam Felix 
Published: November 2023

Abstract

Background
The estimated cost of treatment for septicemia among hospitalized patients is $15.4 billion. Approximately 20%-50% of all positive blood cultures were likely false positives. The rates of the reported contaminations in the literature range from 0.6%-12.5%. The false positive report of bacteremia has significantly impacted overall healthcare by increasing mortality rates, prolonging hospital stays, and expanding the cost of care. The use of Verigene® offers polymerase chain reaction (PCR) amplification in &lt; 5 minutes. In our study, we examine the Verigene®, compared to the standard blood culture by the Vitek-2®, to assess for detecting Gram-positive blood contamination (GPBC).

Methods
Blood cultures were collected from patients with sepsis in four hospitals in El Paso, Texas (1/1/2018-5/30/2022). Samples were run through Verigene®. Simultaneously, all specimens were cultured using the conventional method and then incubated for five days. Gram stain used for positive samples. Speciation and antimicrobial susceptibility using Vitek-2®. GPBC in Vitek-2® was identified when one set of two grows microorganisms, universally known as skin flora, without clinical sepsis within 48hr. GPBC in Verigene® was identified when it recognized any skin flora without clinical sepsis within 24hr. The analysis was made using McNemar’s Chi-square test. An observation was statistically significant if the p-value was ≤0.05.

Results
A total of 816 Gram-positive results were obtained. The prevalence of GPBC based on the traditional technique was 98.65% and 64.25% based on the Verigene®. Staphylococcus epidermidis was the most detected at 52%, followed by Staphylococcus aureus at 26%. The sensitivity of the Verigene® for GPBC detection was 64.22%, and the specificity was 33.33%.Figure 1.Frequency of Gram-positive Microorganisms DetectionFigure 2.Sensitivity and Specificity of Verigene® in Identification of Contamination in Gram-positive Blood CultureTable 1.Sensitivity and Specificity of Verigene® in Identification of Contamination in Gram-positive Blood Culture

Conclusion
The use of Verigene® alone in identifying GPBC is insufficient. Despite the higher sensitivity in detecting microorganisms compared to Vitek-2®, this should be paired with clinical judgment and conventional methods. The ability to recognize GPBC by Verigene® was affected by the lack of clinical evidence to exclude sepsis in the first 24hr. This study is the first to evaluate Verigene® for identifying GPBC. Further interventions should be introduced, i.e., reporting titer by PCR on any detection.

Disclosures
All Authors: No reported disclosures
2845. Two Times versus Four Times Daily Cephalexin Dosing for the Treatment of Uncomplicated Urinary Tract Infection in Females
Authors: Yetsko Aidan , Eid Kristen , Draper Heather , Jameson Andrew , Dumkow Lisa E 
Published: November 2023

Abstract

Background
The current IDSA treatment guidelines recommend beta-lactam antibiotics as an alternative, rather than first-line agents, for the treatment of uncomplicated UTI (uUTI). Changing susceptibilities over the past decade, however, have resulted in the need to rely on oral cephalosporins for uUTI. Cephalexin is a commonly prescribed oral first-generation cephalosporin with excellent bioavailability and urinary penetration; however, little data exist to support optimal dosing for uUTI, with pharmacokinetic data supporting twice daily dosing, but common drug databases recommending four times daily dosing.

Methods
This retrospective, multicenter, cohort study included adult female patients treated at Trinity Health Michigan ambulatory sites who received cephalexin for symptomatic uUTI with cefazolin-susceptible urine cultures between February 1, 2020, and August 31, 2022. The primary objective was to compare uUTI treatment failure between patients treated with cephalexin 500 mg twice daily (BID Tx) versus 500 mg four times daily (QID Tx) in the outpatient setting. Treatment failure was defined as the combined endpoint of continued symptoms or necessitation of new therapy while on the initially prescribed 5-7 day course of treatment or recurrent UTI within 30 days of initial therapy. Secondary outcomes included reported adverse events within 7 days of treatment and occurrence of C. difficile within 30 days of treatment. Pregnancy, diagnosis of pyelonephritis or complicated UTI, presence of urinary catheter, history of recurrent UTI, receipt of IV antibiotics, or urine culture not susceptible to cefazolin resulted in exclusion.

Results
A total of 261 patients were included (BID Tx, n= 173; QID Tx, n= 88). There was no difference in treatment failure observed between groups (BID Tx 12.7% vs QID Tx 17%, p=0.343), including failure while on therapy (BID Tx 2.3% vs QID Tx 5.7%, p=0.438) or recurrence within 30 days (BID Tx 10.4% vs QID Tx 11.3%, p=0.438). No differences in reported adverse events (BID Tx 4.6% vs QID Tx 5.7%, p=0.103) or C. difficile within 30 days of treatment (BID Tx 0% vs QID Tx 0%, p=1.0) were observed between groups.

Conclusion
Reduced frequency, 500 mg twice daily, cephalexin is as effective as more frequent, four times daily, dosing for uUTI and may improve patient adherence.

Disclosures
All Authors: No reported disclosures
196. Does Cefepime Provide an Advantage over Ceftriaxone in the Treatment of Bloodstream Infections due to Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, and Proteus spp. if CTX-M is not Detected by Rapid Molecular Testing?
Authors: Lynn Hammer Katie , Hamm Alyssa , Welch Stephanie N , Smith Jordan R , Ann Medaris Leigh , Boger Michael S , Boger Michael S , Williamson Julie E 
Published: November 2023

Abstract

Background
The BIOFIRE® Blood Culture Identification 2 (BCID2) Panel (bioMérieux) allows for rapid detection of pathogens and antibiotic resistance genes in bloodstream infections (BSIs), including CTX-M, an Extended Spectrum Beta-Lactamase. Atrium Health’s treatment algorithm recommends cefepime (FEP) over ceftriaxone (CRO) for BSI due to non-CTX-M Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, or Proteus spp. in critically ill patients. It is unclear if use of FEP improves outcomes over CRO in this setting.

Methods
This was a multisite, retrospective cohort study of adults with BSI due to E. coli, K. pneumoniae group, K. oxytoca, and Proteus spp. without CTX-M detected by BCID2 from April 4, 2022 – February 12, 2023. The primary outcome was a composite of in-hospital mortality and length of stay (LOS) more than 14 days in patients who received FEP vs CRO. Secondary outcomes included in-hospital mortality, hospital LOS, intensive care unit (ICU) LOS, rates of mechanical ventilation, and rates of CRO and FEP resistance.

Results
Three hundred patients were enrolled: 150 in each group. Patients in the FEP group were more severely ill at baseline by ICU status and PITT bacteremia score and were less likely to have a urinary source of BSI (Table 1). The composite primary outcome of in-hospital mortality or extended LOS occurred in 54/150 (36%) in the FEP group vs 24/150 (16%) in the CRO group; (p &lt; 0.001). In-hospital mortality, hospital LOS, rates of mechanical ventilation and CRO resistance were higher in the FEP 5/158 (3%) vs. 2/150 (1%) in the CRO group. ICU LOS, in-hospital mortality and rates of FEP resistance were similar (Figures 1 and 2). Of note, of the 7/308 isolates with CRO resistance there was no in-hospital mortality or extended LOS in the CRO group and 5/7 were Proteus spp. There was no FEP resistance.Table 1.Select Baseline Characteristics

Conclusion
Though CRO resistance was relatively low, it was most common among Proteus spp. Treatment with FEP was not associated with improved clinical or microbiological outcomes overall compared to CRO. These results highlight potential overuse of FEP in BSIs due to E.coli, K. pneumoniae group, or K. oxytoca and may have implications on the selection of empiric therapy.

Disclosures
All Authors: No reported disclosures
218. Development of a Simple Score for Diagnosis Melioidosis
Authors: Khaejawat Kanjana , Panichote Anupol , Meesing Atibordee 
Published: November 2023

Abstract

Background
Melioidosis is a common gram-negative bacterial infection in northeastern Thailand. Patients with melioidosis infections often experience severe conditions and high mortality rates. This study aims to develop a clinical prediction model to estimate the risk of melioidosis septicemia.

Methods
This retrospective case-control study included patients with positive hemoculture for Burkholderia pseudomallei (BP) and other gram-negative bacteria (Escherichia coli, and Klebsiella pneumoniae) admitted to Srinagarind Hospital between January 2015 and December 2020. Logistic regression analyses were used to determine the calculation of a score for diagnosing melioidosis infection.

Results
A total of 426 patients with positive hemoculture were included: 132 patients for BP and 294 patients for other gram-negative bacteria. The clinical prediction model for diagnosing melioidosis utilized seven variables: age ≥ 60 years (-2 points), male gender (3 points), duration of symptom onset to hospitalization ≥ 7 days (5 points), occupation as a farmer (3 points), presence of diabetes mellitus (2 points), presence of cancer (-5 points), and platelet count (x 109/L) (200-399.9: 1 point, ≥400: 3 points). The model demonstrated good discrimination (area under the curve: 0.89; 95% CI: 0.86-0.93) and acceptable calibration (Hosmer and Lemeshow goodness of fit test: P-value of 0.252). A cut-off point of the melioidosis score ≥ 5 points (maximum score = 16 and minimum score = -7) resulted in an accuracy of 84.3% (95%CI 80.5-87.6), a sensitivity of 78.8%, and a specificity of 86.7%.

Conclusion
The melioidosis score exhibited high performance and clinical utility in predicting melioidosis infection.

Disclosures
All Authors: No reported disclosures
248. Evaluation of Continuous versus Intermittent Infusion of Nafcillin in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia
Authors: Williamson Julie E , Wood Sarah , Carlson Travis J , Jaffa Rupal K , Boger Michael S , Boger Michael S 
Published: November 2023

Abstract

Background
Anti-Staphylococcal penicillins (ASPCN) are first-line agents in the treatment of methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B), and continuous infusion (CI) of oxacillin was associated with higher rates of 30-day microbiological cure versus intermittent (II) in infective endocarditis. Nafcillin (NAF) is the formulary ASPCN at Atrium Health (AH) and is variably ordered as CI or II. The purpose of this study is to compare NAF infusion strategies and related outcomes in the treatment of MSSA-B.

Methods
This was a retrospective, observational, multisite study at 15 sites in the Greater Charlotte, NC Region of AH. Hospitalized adults with MSSA-B who received NAF from 1/1/2020 – 3/31/2022 were included. The primary outcome was receipt of CI vs II NAF. Secondary outcomes included time to microbiological cure (TTMIC), in-hospital 30-day all-cause mortality, hospital length of stay (LOS), and rates of adverse drug events (ADE) - acute kidney injury (serum creatinine increase at least 1.5 times baseline), transaminitis (aspartate aminotransferase / alanine transaminase ≥ 5 times the upper limit of normal), hypokalemia (potassium of ≤ 2.9 mmol/L), and allergic reaction. TTMIC, in-hospital mortality, LOS, and ADEs were also evaluated in a cohort of patients in the ICU within 48 hours of NAF start.

Results
A total of 166 patients were included: 99 (59.6%) in the CI group and 67 (40.4%) in the II group. Thirteen patients in the II group were eventually changed to CI, but their results were analyzed in the II group. TTMIC was not significantly different between the CI and II group (5 vs 4 days, respectively p = 0.56), with similar time to receipt of NAF in both groups (Figure 1). In-hospital mortality, hospital LOS, and rates of ADE also did not differ between groups (Figure 1). Forty-seven patients were included in the ICU cohort: 29 in the CI group and 18 in the II group. Trends observed in the ICU cohort were similar to those observed in the larger population (Figure 2).Table 1.Selected Baseline Characteristics
Figure 1
Figure 2

Conclusion
In a small, unmatched, observational cohort of patients with MSSA-B, outcomes were not different based on NAF administration route. This suggests that administration strategy should be determined based on patient specific factors, such as available lines and patient convenience.

Disclosures
All Authors: No reported disclosures
253. Detecting Vancomycin-Resistant Enterococcus (VRE) Gut Colonization in Medical Intensive Care Unit (MICU) Patients: Comparing Culture and Metagenomics
Authors: Bassis Christine , Sansom Sarah E , Schoeny Michael , Thotapalli Lahari , Fukuda Christine , Dangana Thelma E , Pirani Ali , Snitkin Evan , Young Vincent B , Hayden Mary K 
Published: November 2023

Abstract

Background
Investigation of the colonization dynamics of vancomycin resistant Enterococcus faecium (VRE) depends on reliable detection methods. In this study we investigated if metagenomic sequencing enhances our understanding of VRE gut colonization in addition to selective culture.

Methods
We performed metagenomic sequence analysis on 48 stool and rectal swab samples from 15 medical intensive care unit (MICU) patients with dynamic VRE colonization patterns by selective culture. After metagenomic sequences were quality-filtered, trimmed and human sequences were removed, the antimicrobial resistance (AMR) genes were identified using AMR++ v3.0 and the AMR database MEGARes v3.0.

Results
Microbial sequencing depth varied between samples due to low total DNA and varied percentage of human DNA (median: 68.6%; IQR: 55.9-90.5%). We obtained a median of 1.4 million microbial sequence reads/sample (IQR: 0.6 - 6.0 million). Vancomycin resistance gene cluster sequences (Van-type genes) were detected in the metagenomes of 14 samples. There was agreement between VRE-status as by selective culture and detection of Van-type gene sequence in 33/48 samples. 12 samples that were VRE positive by culture did not have Van-type genes detected in the metagenome, possibly due to lower microbial sequencing depth (median: 1 million sequences/sample; IQR: 0.6 - 4.6 million) compared to samples with Van-type genes detected (median: 10.9 million reads/sample; IQR: 1.6 - 29.7 million).
Three VRE culture-negative samples had Van-type genes detected. 2 of these contained the same Van-type genes found in other samples from the same subject, suggesting that they represent actual VRE colonization. In another patient, 2 VRE culture-positive samples collected 15 days apart had the same 11 VanA-type gene sequences, suggesting the same VRE strain was present in both samples.

Conclusion
Metagenomic detection of VRE was influenced by microbial sequencing depth, which is related to total sequencing depth and percentage of host reads. Greater sequencing depth may improve sensitivity of metagenomics to detect resistant organisms. Longitudinal analysis of antimicrobial resistance gene sequences from metagenomes has the potential to provide insight on colonization dynamics.

Disclosures
Vincent B. Young, MD, PhD, ASM: Senior Editor for mSphere Journal|Debiopharm: Consultant|mSphere: Senior Editor|Vendanta Biosciences: Consultant
254. Genomic diversity of Gram-negative Bacilli from Bloodstream Infections in Hospitalized Children
Authors: Blumenthal Jennifer , Conwill Arolyn , McGann Patrick , Sandora Thomas J , Lieberman Tami , Priebe Gregory P 
Published: November 2023

Abstract

Background
Gram-negative bloodstream infection (BSI) in hospitalized children is associated with significant morbidity and mortality. It is unclear whether bacterial clonality of isolates during BSI in a unique patient is associated with clinical characteristics such as immunocompromise. We hypothesized that genomic diversity of BSI isolates would be higher in immunocompromised patients due to mucosal barrier injury and therefore larger translocation bottleneck.

Methods
We prospectively enrolled patients with a central venous catheter who were hospitalized at Boston Children’s Hospital and had a positive blood culture that grew E. coli, Klebsiella spp., or Pseudomonas aeruginosa. An aliquot from the blood culture bottle was plated on agar, and at least 24 colonies were picked randomly and subjected to whole-genome sequencing (WGS). Patient-specific reference genomes were constructed using long-read sequencing of at least 1 isolate on the PacBio platform. All isolates were sequenced using Illumina (MiSeq or NextSeq). Single nucleotide variant (SNV) calls were made using the WideVariant pipeline (github). Clinical characteristics were obtained retrospectively from the electronic medical record. We defined immunocompromise as neutropenia (ANC&lt; 500) on the day of BSI or prior solid organ or stem cell transplant. The proportion of BSI episodes with clonal blood isolates (defined as 0 SNV) was compared between immunocompromised and non-immunocompromised patients using Fisher’s exact test.

Results
We enrolled 34 patients (median age 2.33 years, IQR 0.8-3.8 years), 25 having BSI from Enterobacterales (11 E. coli, 14 Klebsiella spp.) and 9 from Pseudomonas aeruginosa. Immunocompromised patients had a significantly higher proportion of Enterobacterales BSI episodes with clonal isolates compared with non-immunocompromised patients [13/18 (72%) vs. 1/7 (14%) respectively, P=0.021). This was not seen with Pseudomonas BSI, which had clonal isolates in 3/5 (60%) vs. 2/4 (50%) respectively (P=1).

Conclusion
Contrary to our hypothesis, immunocompromised patients were more likely to have clonal Enterobacterales BSI isolates compared with non-immunocompromised patients, perhaps due to lower host pressures for bacterial population diversification in immunocompromised patients.

Disclosures
Arolyn Conwill, PhD, Day Zero Diagnostics: current employee|Day Zero Diagnostics: Stocks/Bonds