bluuebunny/crossref_metadata_2025_split huggingface dataset:
968. Universal Newborn Testing for Congenital Cytomegalovirus (cCMV) Infection Comes of Age: Clinical Sensitivity of Screening Tests and Infant Outcomes in a cCMV Screening Study in Minnesota
Authors: Schleiss Mark R , Osterholm Erin , Hernandez-Alvarado Nelmary , Kruc Rebecca , Herd Hannah , Sidebottom Abbey , Licensed Genetic Sondra Rosendahl , Dollard Sheila , Lanzieri Tatiana 
Published: November 2023

Abstract

Background
Universal congenital cytomegalovirus (cCMV) screening is controversial. In 2023, we completed a study evaluating analytical and clinical sensitivity of dried blood spots (DBS) for detection of cCMV infection and disease. Analytical sensitivity is the ability of an assay to detect infection, while clinical sensitivity is an assay's ability to identify individuals with disease. The completion of this study coincided with implementation of new legislation making Minnesota the first state in the USA to mandate universal cCMV testing.

Methods
In six newborn nurseries in Minnesota, consented newborns were screened for cCMV, comparing PCR of saliva with PCR of the DBS obtained for routine newborn screening. Screen-positive infants had a confirmatory urine PCR, and a diagnostic clinical evaluation. Using international consensus criteria, we categorized cCMV cases as: moderate-to-severe; mildly symptomatic; asymptomatic with isolated sensorineural hearing loss (SNHL); or asymptomatic.

Results
From February 2016 - January 2023, among 23,644 newborns screened, 87 (3.7 per 1,000) were identified with cCMV. Analytical sensitivity of saliva was 93.1% (81); for DBS, it was 73.6% (64) by the UMN lab, and 77.0% (67) by the CDC lab. At birth, 67 (77%) infants were asymptomatic; 6 moderately-to-severely symptomatic (2 with SNHL); 10 mildly symptomatic; and 4 asymptomatic with isolated SNHL. 4 infants had delayed-onset SNHL (2 asymptomatic, 2 symptomatic). Among 20 infants with symptomatic cCMV at birth and/or SNHL, clinical sensitivity of saliva was 95% (19), and for DBS was 75% (15) in the UMN lab, and 85% (17) in the CDC lab.

Conclusion
This unselected screening study demonstrated a prevalence of 3.7/1000 of cCMV in Minnesota newborns. The enhancement in clinical sensitivity of DBS (over analytical sensitivity) to identify children with symptoms or sequelae suggests their usefulness for cCMV screening, though most identified infants will be asymptomatic. In parallel with this work, in the spring of 2023, Minnesota became the first state to screen all newborns for cCMV, using the newborn DBS. Continued evaluation of CMV DBS testing methods for reproducibility, efficiency, high-throughput capability and clinical correlation will be important as other states consider universal cCMV screening.

Disclosures
All Authors: No reported disclosures
970. Assessing the burden of Acinetobacter baumannii and Candida auris among ventilated patients in Maryland: A statewide period prevalence survey of two urgent threats
Authors: Harris Anthony , Pineles Lisa , Kristie Johnson J , O’Hara Lyndsay M , Smith Lauren Leigh , French Indira , Rubin Jamie , Perlmutter Rebecca , Heller Ashley , Klein Liore , Blythe David , Vaeth Elisabeth 
Published: November 2023

Abstract

Background
To date, only one statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the United States, and no statewide prevalence survey has been performed for Candida auris. We aimed to determine the prevalence of A. baumannii and C. auris among mechanically ventilated patients in Maryland.

Methods
The Maryland MDRO Prevention Collaborative performed a statewide point prevalence survey of mechanically ventilated patients admitted to acute care hospitals (ACH) and long-term care (LTC) facilities between March 7, 2023, and June 8, 2023. Surveillance cultures were obtained from all mechanically ventilated patients. Sputum, peri-anal, and arm/leg cultures were cultured for A. baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by PCR for C. auris.

Results
One hundred percent of all eligible healthcare facilities participated. 482 ventilated patients were included in the analysis. A. baumannii was cultured from at least one body site in 148/482 (31%) patients, CRAB was identified in 88/482 (18%) patients and C. auris in 31/470 (7%) patients. LTC patients were more likely to be colonized with A. baumannii (RR 7.7, 95% CI 5.1-11.5, p&lt; .0001), with CRAB (RR 5.5, 95% CI 3.4-8.9, p&lt; .0001) and C. auris (RR 2.0, CI 0.99-3.9, p=.05) compared to acute care hospital patients (Figure 1). Nine (29%) C. auris-positive patients were previously unknown to the Maryland Department of Health. Susceptibilities for A. baumannii are in Table 1.
Figure 1: Prevalence of A. baumannii, carbapenem-resistant A. baumannii, and C. auris stratified by type of facility. Figure 2. Resistance Mechanisms in Carbapenem-Resistant Isolates (N=88) Table 1: Antimicrobial Data: All patient A. baumannii isolates demonstrating antimicrobial susceptibility, N (% susceptible)

Conclusion
A. baumannii, CRAB and C. auris colonization are common among mechanically ventilated patients in both ACH and LTC facilities. Both pathogens were significantly more common in long-term care facilities than acute care facilities. Ventilated long-term care patients are an extremely high-risk population for emerging pathogens and surveillance and infection prevention efforts should be targeted to these facilities.

Disclosures
Anthony Harris, MD, MPH, Merck: Grant/Research Support|UpToDate: Infection Control Editor
178. Assessment of an IOTA (Intravenous to Oral Transition of Antimicrobial Therapy) in Gram Negative Bacteremias at a Community Teaching Hospital
Authors: Wilson Victoria , Gardner Sara R , Cady Beth 
Published: November 2023

Abstract

Background
Retrospective studies suggest that IV to oral therapy for gram-negative bacteremia has similar outcomes to IV regimens. The benefits of transitioning patients from IV to oral antibiotic therapy are well-recognized. The purpose of this study was to assess the percentage of patients (with a gram-negative bacteremia from a urinary source) who were transitioned from IV to oral antibiotics based on a pre-determined checklist.

Methods
This retrospective cohort study was performed at a 400-bed hospital from January 1, 2019 to May 31, 2022 . The primary objective was to assess the percentage of patients with a gram negative bacteremia (from a urinary source) who were eligible and switched from IV to oral antibiotics. Patients were included in the study if they were &gt; 18 years old, had a positive blood culture for E. coli or K. pneumoniae (with &gt; 1 susceptible oral antibiotic), had a monomicrobial infection from a urinary source, signs of clinical improvement, could tolerate oral medication, and had at least 24 hours of IV therapy.

Results
Sixty patients out of 200 (30%) with a gram negative bacteremia met the above eligibility criteria to be switched from IV to oral therapy. Sixty three percent (38/60) were switched to oral antibiotics for the completion of therapy. A majority of patients (95%) had E. coli bacteremia. Of the eligible patients, 70% (42/60) had received an ID consultation. Of those, 62% (26/42) were switched. Among the 18 eligible patients who did not receive an ID consult, 67% were switched to PO. Reasons for not switching (as determined from the EHR) for the 22 eligible patients include: 3 patients had pathogens resistant to fluoroquinolones, 8 had contraindications (unclear), 3 had concomitant infections, 7 had reasons unknown, and 1 patient denied oral antibiotics.

Conclusion
Most patients (63%) who met inclusion criteria derived by previous studies were switched from IV to oral antibiotics in the presence of monomicrobial E. coli or Klebsiella pneumoniae bacteremia from a urinary source with clinical improvement. There is an opportunity to educate providers to transition more patients from IV to oral antibiotics with a gram negative bacteremia.

Disclosures
All Authors: No reported disclosures
179. From Epidemiology of Community-onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-decision Algorithm in a Region with High Burden of Antimicrobial Resistance
Authors: Chotiprasitsakul Darunee , Trirattanapikul Akeatit , Namsiripongpun Warunyu , Chaihongsa Narong , Santanirand Pitak 
Published: November 2023

Abstract

Background
More antimicrobial-resistant (AMR) infections have emerged in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and factors associated with mortality, and develop the empirical antimicrobial treatment-decision algorithm.

Methods
A retrospective cohort study was conducted at a tertiary-care hospital. All positive blood cultures from adult patients at the emergency room and outpatient clinics were identified from 1 Aug 2021-15 Apr 2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were at first sensitive. Risk factors associated with AMR-BSI and factors associated with 30-day mortality were determined. The independent risk factors for AMR-BSI were placed into steps to create an empirical treatment-decision algorithm. C-statistics were calculated. The internal validation cohort was evaluated.

Results
A total of 1,151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Nonsusceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed based on the independent risk factors for AMR-BSI: the presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63; 95% CI 1.95-6.75; P&lt; 0.001), prior antimicrobial exposure within 90 days (aOR 1.94; 95% CI 1.08-3.50; P=0.03), and urinary source (aOR 1.79; 95% CI 1.06-3.01; P=0.03). The positive and negative predictive values were 53.3% (95% CI 45.4-61.1%) and 83.2% (95% CI 80.4-85.6%), respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39; 95% CI 1.20–1.62; P&lt; 0.001), solid malignancy (aHR 2.61; 95% CI 1.30–5.24; P=0.01), and urinary source (aHR 0.30; 95% CI 0.11–0.79; P=0.02).
Univariable analysis and multivariable analysis of risk factors for antimicrobial resistance
Proposed empirical antimicrobial treatment algorithm for patients with suspected community-onset bloodstream infections
Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and C-statistics of the algorithm in predicting antimicrobial resistant infection

Conclusion
One-fourth of community-onset BSI were antimicrobial-resistant, and almost one-third of Enterobacteriaceae were nonsusceptible to ceftriaxone. Treatment-decision algorithm based on the presence of MDROs within 90 days, prior antimicrobial use within 90 days, and the urinary source may reduce overly broad antimicrobial treatment.

Disclosures
All Authors: No reported disclosures
182. Piperacillin/tazobactam (P/T) versus meropenem (Mero) for treatment of extended-spectrum beta-lactamase (ESBL)-producing E.coli and K. pneumoniae bloodstream infections (BSIs)
Authors: Cox Alexandra L , Beardsley James R , Williamson John C , Stone Tyler J , DeWitt Michael E , Palavecino Elizabeth , Luther Vera , Taylor Alex D 
Published: November 2023

Abstract

Background
A recent study of Mero vs. P/T for the treatment of BSIs caused by ceftriaxone-resistant Enterobacterales, including ESBL-producing organisms, revealed discouraging outcomes for patients (pts) receiving P/T. The purpose of this study is to evaluate clinical outcomes in pts treated with P/T versus Mero for BSIs caused by ESBL-producing E. coli or K. pneumoniae.

Methods
This is a single health-system, retrospective, observational study. Adult inpatients with blood cultures positive for ESBL-producing E. coli or K. pneumoniae during 2016-2020 were identified by a report from an automated broth microdilution system. Pts with an isolate susceptible to both P/T and Mero who received either P/T or Mero within 24 hours of culture collection and for a duration of least 48 hours were included. Pts who had neutropenia, expired or transitioned to comfort care within 48 hours of study drug initiation, did not have source control by day 5, had a polymicrobial infection, or had a concurrent infection caused by another gram-negative organism were excluded. Pts were screened for eligibility and then randomly selected until a target of 25 pts meeting study criteria in the Mero and the P/T groups were included. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included length of hospital stay, clinical and microbiological resolution by day 5, and time to clinical and microbiological resolution.

Results
Forty-nine pts met study criteria and were included after one pt was excluded from P/T group due to a polymicrobial infection. Overall, the median age was 67 [53, 76], 29 (59%) pts were female, and 21 (43%) pts were admitted to an ICU at culture draw or within 24 hours. Forty-three of the 49 (88%) infections were caused by E.coli, and 38 (78%) infections originated from a urinary source. Results of the analysis are shown in table 1 and figures A-C.Table 1.Primary and Secondary OutcomesFigure:Boxplot A. Length of Stay, B. Time to Clinical Resolution, C. Time to Microbiological Resolution

Conclusion
In this real-world study of pts with ESBL-producing BSIs that were predominantly from a urinary source, pts treated with P/T and Mero had similar outcomes. These results demonstrate the need for additional randomized, controlled trials, in a variety of settings to further assess outcomes in this pt population.

Disclosures
Tyler J. Stone, PharmD, ViiV Healthcare: Employee
184. Implications of Enterococcus faecalis penicillin susceptibility in patients with bacteremia
Authors: Hedvat Jason , Gitman Melissa R , Nwoye Angella , Chen Li , Martin Colleen , Wang Mandie , Vasa Chirag , Cusumano Jaclyn A 
Published: November 2023

Abstract

Background
Enterococcus faecalis isolates with an elevated penicillin minimum inhibitory concentration (MIC) ≥ 4 mg/L have decreased in vitro ampicillin plus ceftriaxone bactericidal and synergistic activity, despite ampicillin susceptibility. This phenotype’s implication on patient outcomes and prevalence in the US is unknown due to limited penicillin susceptibility reporting.

Methods
This was a retrospective cohort study of adult patients with E. faecalis bacteremia between August 20, 2018 and May 13, 2021 from the Mount Sinai Health System in New York City. Patients were excluded if they were discharged or deceased within 48 hours of index blood culture, did not receive active definitive therapy, or the blood culture was determined to be contamination. The primary outcome was differences in 30-day and 90-day mortality based on the penicillin MIC and the secondary outcome was microbiological relapse. Multivariable logistic regression was used to identify risk factors for 90-day mortality. Corresponding blood isolates were tested for penicillin susceptibility by broth microdilution in accordance with CLSI.

Results
A total of 124 patients were included, with 27% having an elevated penicillin MIC ≥ 4 mg/L. Differences in baseline characteristics (Table 1) as well as source of infection and treatments received (Table 2) were similar between groups. Endocarditis infected 18.5% of patients and was less common in cases with an elevated penicillin MIC. Thirty-day and 90-day mortality, and microbiological relapse were higher in cases with an elevated penicillin MIC (14.4% vs. 20.6%, p=0.58; 20% vs. 26.5%, p=0.59; and 4.4% vs. 8.8%, p=0.39, respectively). Pitt bacteremia score and prior ceftriaxone usage had a higher odds of 90-day mortality (OR 1.2 [95% CI 1.03-1.4], p=0.02; OR 2.8 [95% CI 1.02-7.9], p=0.04, respectively), whereas definitive treatment with an aminopenicillin compared to piperacillin/tazobactam was protective of 90-day mortality (OR 0.21 [95% CI 0.05-0.93], p=0.04).

Conclusion
E. faecalis with an elevated penicillin MIC ≥ 4 mg/L is present in over a quarter of patients across New York City. Larger studies are warranted to determine the impact on patient outcomes. E. faecalis bacteremia treatment with piperacillin/tazobactam may be associated higher mortality.

Disclosures
Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant
185. Pseudomonas aeruginosa (PA) Bacteremia and Patient Outcome during COVID-19 Pandemic
Authors: Vivekanandan Renuga , Witherspoon Kelsey , Destache Christopher J 
Published: November 2023

Abstract

Background
Pseudomonas aeruginosa (PA) bloodstream infection is associated with poor clinical outcomes. The purpose of this study was to evaluate treatment efficacy and patient outcomes from different antimicrobials used for treating PA bacteremia during 2020-2022.

Methods
This was a retrospective review of 2020-2022 hospitalized patients with PA bacteremias at our health system. Hospitalized patients from January 2020 - July 2022 with culture-positive PA were identified. Data collected included demographics, hospitalization and drug treatment length, SARS-CoV-2 infection, and need for vasopressors. Antibiotics used to treat PA, including dose, interval, and MIC data were evaluated. Finally, admission APACHE II score and hospital mortality were collected. Data were analyzed by SPSS. Data are presented as mean ± SD or percentage. Apriori significance was p ≤ 0.05.

Results
A total of 111 PA bacteremias occurred in 2020-2022, 65% of patients were male. Mean (± SD) age was 68 ± 13 years and weight were 88.2 ± 25 kg. Hospitalization length and duration of antibiotic therapy averaged 12 ± 13 days and 7.1 ± 5.9 days, respectively. Majority were treated with piperacillin-tazobactam (45%) or cefepime (44%). Median cefepime MIC was 2.0 (range 0.5-8). Thirty-seven (33%) PA-infected patients expired. Significantly more 7 of 17 (41%) cefepime patients died receiving 4G/d (1Gq6h) compared to 1 (9%) of 11 receiving 6G/d (2Gq8h), p&lt; 0.001. Significant correlation between mortality and ICU status or mechanical ventilation (p&lt; 0.001), respectively. No correlation between mortality and renal failure, SARS-CoV-2 co-infection, or vasopressor use. APACHE II score was significantly higher for expired patients (survived 13.9 ± 5.7 compared to 22 ± 8.3 in expired group, p&lt; 0.001).

Conclusion
ICU status and mechanical ventilation significant reduced survival. Cefepime 4G/d resulted in significantly higher mortality.

Disclosures
Christopher J. Destache, Pharm. D., BioMerieux, Inc: Advisor/Consultant
186. The Role of Repeated Blood Cultures in Hematologic Malignancy Patients with Neutropenic Fever due to Gram-Negative Bacterial Bloodstream Infections
Authors: Dhanaraj Nitya , Foppiano Palacios Carlo 
Published: November 2023

Abstract

Background
Several observational studies and a recent meta-analysis suggest there is a mortality benefit associated with acquiring repeat blood cultures for gram-negative bacterial bloodstream infections (GNBSI). However, limited data are available among patients with febrile neutropenia. We sought to evaluate the utility of obtaining follow-up blood cultures (FUBC) in GNBSI among neutropenic hematological malignancy patients.

Methods
A retrospective chart review was conducted to identify all patients with a hematologic malignancy admitted with a diagnosis of neutropenic fever due to gram-negative rod bacteremia (GNRB) from 2018-2021 at a large urban academic medical center. We collected demographics, cancer diagnosis and treatment data, microbiology and antibiotic information, and death at discharge, 30 days, and 90 days. Descriptive statistics and chi-square tests were used.

Results
A total of 47 episodes of GNBSI among 43 patients were included. Mean age was 57 years, 61% were male, 49% were White, and 14% were Latino. Most patients had AML (47%), and most common chemotherapy regimen was R-CHOP (19%). 32% of GNRB were due to K. pneumoniae, in the setting of long-term central venous catheter (53%), and from a gastrointestinal source (49%). FUBC were collected among most patients (87%), but only two patients (5%) had positive FUBC. ESBL resistance profiles were uncommon (6%), and most were treated with beta-lactams (55%). Patients who died at discharge were less likely to have FUBC collected (p&lt; 0.001). We also found an association between acquiring FUBC and mortality at 30 (p=0.01) and 90 days (p=0.02). However, there was no association between having a positive FUBC and mortality at discharge (p=0.47), 30 days (p=0.93), and 90 days (p=1.00).

Conclusion
Among patients with neutropenic fever found to have GNBSI, acquiring repeat blood cultures was associated with decreased mortality. Due to their immunocompromised status, patients with neutropenic fever and GNRB should have repeat blood cultures collected.

Disclosures
All Authors: No reported disclosures
199. Fast Detection of Ceftazidime-avibactam-resistant Enterobacterales with VITEK-MSTM Incorporating a Direct-on-target Microdroplet Growth Assay
Authors: haung Shenglei , qin Chengfeng , Pu Bingchun , Zhou Chunmei , ma Yan , Wang Beili , Pan Baishen , Hu Bijie , Guo Wei 
Published: November 2023

Abstract

Background
The direct-on-target microdroplet growth assay (DOT-MGA) was evaluated for its ability to rapidly detect ceftazidime-avibactam resistant Enterobacterales.

Methods
In this study, 47 non-duplicate CRE isolates were used to determine unequivocally the performance of ceftazidime-avibatam resistance detection of 7 organisms found in clinical isolates. The isolates were incubated for 3 to 6 h in the presence and absence of 8 µg/mL ceftazidime-avibatam in the broth applied as microdroplets directly on to the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) target spots. Following the incubation period, broth was separated from the microbes by pipette. MALDI-TOF MS was employed to evaluate the growth of isolates in each spot and to identify the microbes simultaneously. The micro-broth dilution method, recommended by EUCAST was used as a reference method. A PCR-based assay was carried out to evaluate the carbapenem resistance mechanisms by screening for the presence of various β-lactamase-encoding genes.

Results
It was found that a 3 h incubation time was insufficient for MS to identify isolates. At this time-point, the identification of valid results of the growth control was only 25.0%. Therefore, the study of 3 h incubation times was not continued. For ceftazidime-avibactam-resistant Enterobacter strains, 83.7% of growth controls were successfully detected after the 4 h-time-point of incubation when the sensitivity and specificity of drug resistance detection were both 100%. Following incubation for 5 h, the rate of growth controls, sensitivity and specificity were 98.0%, 100% and 100%. When the incubation was extended to 6 h, the rate of growth controls, sensitivity and specificity reached an ideal 100%.

Conclusion
The VITEK MS-based DOT-MGA is a fast, convenient and accurate in detecting Enterobacterales that is resistant to ceftazidime-avibatam within 5 to 6 h. The assay can also determine the resistance status of an isolate and the potential novel resistant mechanisms involved.

Disclosures
All Authors: No reported disclosures