bluuebunny/crossref_metadata_2025_split huggingface dataset:
2758. Clinical Significance and Antifungal Susceptibility Profile of 103 Clinical Scedosporium Species Complex and Lomentospora prolificans Isolated from NIH Hospitalized Patients
Authors: Czech Mary , Stock Frida , Aneke Chioma , Lionakis Mihalis , Cuellar-Rodriguez Jennifer , Seyedmousavi Amir 
Published: November 2023

Abstract

Background
Members of the fungal genera Scedosporium species complex and Lomentospora have been increasingly recognized as emerging opportunists affecting immunocompromised patients. Reduced susceptibility to systemic antifungals is common, and optimal treatments are incompletely described.

Methods
103 clinical isolates from NIH, Bethesda, MD, were investigated. The identity of each isolate was confirmed at the species level via PCR-sequencing of internal transcribed spacer (ITS) of the ribosomal DNA (rDNA) region and the calmodulin gene. Antifungal susceptibility testing was conducted in accordance with the CLSI M38-A3 guidelines. Patient data were collected retrospectively.

Results
The frequency of Scedosporium species complex and Lomentospora prolificans isolates are detailed in Figure 1. In vitro susceptibility results of eight antifungals against all isolates are listed in Table 1. The novel antifungal olorofim showed the lowest MICs against all Scedosporium and L. prolificans, followed by micafungin. Among triazoles, voriconazole (VRC) showed lower MIC values against clinical members of Scedosporium. Amphotericin and posaconazole (POS) demonstrated species-specific and inter-species variable activity. Itraconazole, isavuconazole, and terbinafine had high MICs against Scedosporium and L. prolificans.
Clinical data were available for 90 isolates. 9 patients (28 isolates) had disease or infection (Table 2). All but one case occurred in immunocompromised hosts, and all patients were treated with a regimen that included VRC or POS. Five patients died. Three patients with chronic granulomatous disease were cured following hematopoietic cell transplant. 24 patients (62 isolates) had colonization, of which 58 isolates reflected respiratory colonization in patients with bronchiectasis.

Conclusion
Our data support that species-specific and inter-species differences exist in the distribution of antifungal susceptibility patterns among Scedosporium and L. prolificans. Our in vitro data suggest that olorofim may be a promising therapy for Scedosporium and L. prolificans. Our clinical data suggest that host status, in conjunction with effective antifungal therapy, is an important determinant in treatment outcomes.

Disclosures
All Authors: No reported disclosures
2763. Evaluating the Safety and Effectiveness of Long-term Antibiotic Suppression in Patients with Left Ventricular Assist Devices
Authors: Hamlin Kelsey D , Bookstaver P Brandon , Derrick Caroline , Teng Chengwen , Brown Jacob , Skweres Andrew , Mardis Andrew , Straw Laura , Justo Julie Ann , Ampadu James , Al-Hasan Majdi N , Sanasi Kamla , Winders Hana R 
Published: November 2023

Abstract

Background
The utilization of left ventricular assist devices (LVADs) as a bridge to transplantation or destination therapy for non-transplant candidates continues to rise. Unfortunately, infection remains one of the most common complication and lack of definitive source control often leads to the decision to initiate long-term antibiotic suppression. The purpose of this retrospective cohort study is to evaluate the long-term safety and effectiveness of antibiotic suppression following an LVAD-related or LVAD-specific infection.

Methods
Adults who underwent LVAD placement between August 2018 and September 2022 at Prisma Health Midlands and received antibiotic suppression for an LVAD-related or LVAD-specific infection were evaluated. Safety was evaluated as a composite endpoint of treatment emergent adverse events, and discontinuation of or decrease in dose due to tolerability concerns. Effectiveness was evaluated as the proportion of patients without a suppression emergent infection (SEI) within six months of antibiotic suppression initiation. Patients experiencing a SEI (failure) were compared to those without an SEI (success) at six months. Secondary outcomes included the proportion of patients experiencing early SEI within 90 days of antibiotic suppression initiation and evaluation of factors associated with success of antibiotic suppression at six months.

Results
Fifty-one patients received antibiotic suppressive therapy following an LVAD-related or LVAD-specific index infection. Patients were followed for a minimum of 6 months and an average 2.8 years. Treatment emergent adverse events occurred in 4 (7.8%) patients, with 2 events leading to antibiotic discontinuation. SEI occurred in 9 (17.6%) of patients at 6 months with the most common organisms being P. aeruginosa, S. aureus, and S. epidermidis. Early SEI was observed in 4 (7.8%) patients. Overall, SEI occurred in 28 patients (55%) at a median 341 days (IQR 157-502). Documented resistance to suppressive antibiotic was observed in 13 (25.4%) patients. Index infections with a gram-negative organism was significantly more common in those experiencing SEI (80% vs. 47%, p=0.031).

Conclusion
Antibiotic suppression following LVAD-associated infections is well-tolerated and successful in 82% of patients at 6 months.

Disclosures
Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Gilead Sciences: Advisor/Consultant|Shionogi: Advisor/Consultant|Vaxart: Stocks/Bonds
2777. Species Distribution and Antimicrobial Susceptibility of Enterobacter in Bacteremia of Korean Children, 2011-2022
Authors: Kang Da Yun , Kim Ye Eun , Choi Sung Hwan , Choi Eun Hwa , Yun Ki Wook 
Published: November 2023

Abstract

Background
Enterobacter is an increasingly important nosocomial pathogen due to the resistance to penicillin and cephalosporin mediated by a chromosomal (ampC) beta-lactamase. We aimed to identify the species distribution and antimicrobial susceptibility isolated from the blood of Korean children.

Methods
Demographic, clinical, and laboratory data were retrospectively reviewed from patients under 21 hospitalized for bacteremia at Seoul National University Children's Hospital during 2011-2022. A VITEK II automated was used for species identification and antimicrobial susceptibility testing, and the susceptibility was determined according to the Clinical and Laboratory Standards Institute guidelines.

Results
Bacteremia due to Enterobacter species was identified in 106 cases in a total of 102 patients. The proportion of patient’s age group was 33.0% in infants (&lt; 1 year old), 17.9% in toddlers (1-4 years old), 22.6% in children (5-11 years old), and 26.4% in adolescents (12-20 years old). Species were 70.8% of Enterobacter cloacae, 23.6% of K. aerogenes, 3.8% of Enterobacter asburiae, and each one (0.9%) of Enterobacter amnigenus and Enterobacter intermedius. Overall, non-susceptibility to piperacillin-tazobactam (PIP-TAZ), cefotaxime (CTX), cefepime, and carbapenem were 27.4%, 36.8%, 7.5%, and 4.7%, respectively. The most susceptible antibiotic was amikacin (99.1%). Multidrug resistance (MDR) was identified in 16.0% of isolates. Although statistically non-significant, the non-susceptibilities to PIP-TAZ and CTX increased from 16.7% and 8.3% in 2013 to 60.0% and 40.0%, respectively, in 2022. In addition, the proportion of E. cloacae has significantly increased (p for trend=0.034) from 66.7% in 2014 to 91.7% in 2020. K. aerogenes is significantly (p=0.002) more common in infants than E. cloacae, and E. cloacae (17.3%) showed more than twice as many MDR feature as K. aerogenes (8.0%), although not statistically significant.

Conclusion
Although Enterobacter species has been steadily detected as a cause of pediatric bacteremia, the rate of E. cloacae has been increasing recently. Considering antibiotic susceptibility data, cefepime alone or combination with a third-generation cephalosporin and amikacin might be reasonable empirical antibiotic therapy regimen.

Disclosures
All Authors: No reported disclosures
2780. Factors associated with Staphylococcus aureus susceptibility to two lytic bacteriophages; Comparison of phage host susceptibility using a reference set of S. aureus
Authors: Lee Shinwon , Lynch Stephanie , Zakour Nouri Ben , Coombs Geoffrey , Myung Heejoon , Iredell Jonathan 
Published: November 2023

Abstract

Background
Timely access is a major concern when considering phage therapy. Using susceptible phage is critical for the outcomes of phage therapy. For timely access to susceptible phages, identifying factors associated with phage susceptibility and building a reference set (RS) to compare host ranges is needed.

Methods
Phage K, which was a well-documented lytic S. aureus phage, and phage PBSA02, which was a new S. aureus phage from the Korean phage biobank, were used.
The efficiency of plating (EOP), the relative activity of phage against specific strain/host strain, and growth kinetics assays were used to determine phage susceptibility. The isolates with high lytic activity (HLA) were defined as susceptible (EOP &gt; 1%).
The phage PBSA02 and phage K susceptible groups were compared to the non-susceptible groups to determine the associating factors of phage susceptibility.

Results
We constructed a methicillin-resistant S. aureus (MRSA) RS using the Australian Group on Antimicrobial Resistance (AGAR) repository. We determined the predominant sequence types (ST) of MRSA in Australia in 2021; ST22 accounted for 90.1% of HA-MRSA and 5 STs for 67.9% of CA-MRSA (figure 1). Then, we randomly selected 39 AGAR MRSA isolates corresponding to each ST from each region in Australia (figure 1).
Phage PBSA02 exhibited HLA against 56.4% of the 39 RS isolates, while phage K exhibited HLA against 30.8%. Phage PBSA02 showed HLA against 100% of ST93 and ST30 isolates following ST1 (62.5%), ST22 (37.5%), ST5 (20%) and ST45 (16.7%); phage K showed HLA against 100% of ST30 and 62.5% of ST22 isolates but against none of the ST93 isolates.
Phage PBSA02 susceptibility correlated with the ST of MRSA isolates and ciprofloxacin susceptibility (table 1). Isolates from pneumonia/empyema tended to show phage PBSA02 susceptibility (table 1). Phage K susceptibility was also significantly associated with the ST (table 2).

Conclusion
Our study demonstrated that phage susceptibility was associated with the STs of MRSA, and the RS could be useful for a standardised comparison of the phage host range. Phage PBSA02 with broad susceptibility to the RS could be useful for phage therapy. Further work includes antibiotic synergy testing and resistance mechanism identification in these isolates.

Disclosures
All Authors: No reported disclosures
2799. Evaluating Resistance Patterns of LVAD-related Pseudomonas Infections
Authors: Russo Kelly A , Alexis Jeffrey , Hay Christine M , Lopa Samia H , Wang Lu , Alpizar-Rivas Rodolfo M 
Published: November 2023

Abstract

Background
Left ventricular assist devices (LVADs) provide a clear benefit to patients with end-stage heart failure. Despite this, device-related infections such as driveline infections, device pocket infections, and LVAD-related bloodstream infections occur in up to 39% of implanted patients. Pseudomonas aeruginosa is a common causative organism in LVAD-associated infections and frequently develops resistance, limiting treatment options. This study aims to analyze the relationships between the frequency of acquired resistance (AR) and single-agent antibiotic courses, as well as the frequency of AR and duration of antibiotic courses; and compare the likelihood of AR between different antibiotic classes.

Methods
This was a single-center retrospective cohort study involving all patients with LVAD-associated P. aeruginosa infections between 2011-2023. Patients treated with piperacillin-tazobactam, cefepime, ciprofloxacin, or meropenem, were included (n = 37). Each antibiotic course (n = 117) was associated with a pre- and post-antibiotic sensitivity. AR was defined as culture-proven, newly developed resistance to the utilized antibiotic after starting therapy.
The incidence and cumulative proportion of AR were estimated using Poisson regression and Kaplan-Meier curve analysis, respectively. A marginal proportional hazards model was used to analyze time to AR between different antibiotic groups.

Results
There was a significantly lower incidence of AR with cefepime [0.8 (95% CI 0.2-3.3) per 100 person-weeks] compared to piperacillin-tazobactam [3.6 (1.7, 8)], meropenem [7.6 (4.1, 14.5)], and ciprofloxacin [6.4 (3.4, 12.5)] (p=0.04). Similarly, the cumulative proportion of AR was significantly lower with cefepime as compared to other antibiotic classes (Figure 1). The hazard rate of AR was approximately 3.5 to 6.7 times higher with each antibiotic in comparison to cefepime (p = 0.02) (Table 1).Figure 1.Kaplan-Meyer curve demonstrating cumulative proportion of acquired resistance
Resistance occurs early and more frequently with piperacillin-tazobactam, meropenem, and ciprofloxacin, but less frequently and late with cefepime. The cumulative proportion of acquired resistance over time differed significantly across antibiotic types (p = 0.02).

Cefepime had a statistically significantly lower hazard of AR when compared to the rest of the antibiotic groups as a whole, and when compared individually, had a significantly lower hazard than ciprofloxacin and meropenem.

Conclusion
This study suggests a lower incidence of AR for LVAD-associated P. aeruginosa infection treated with cefepime. AR also seems to develop later in patients treated with cefepime. There is a 3.5-6.7-fold increase in the risk of acquiring resistance with other antibiotics compared to cefepime.

Disclosures
Jeffrey Alexis, MD, Abbott: Grant/Research Support
2816. Comparative Effectiveness of Meropenem/Vaborbactam vs. Ceftazidime/Avibactam among Adults Hospitalized with an Infectious Syndrome in the US, 2019-2021
Authors: Zilberberg Marya D , Nathanson Brian H , Redell Mark , Sulham Kate , Shorr Andrew 
Published: November 2023

Abstract

Background
Increasing rates of antimicrobial resistance have complicated the treatment of severe infections. Designated an “urgent threat” by the CDC, carbapenem-resistant Enterobacterales (CRE) lead to excess morbidity and mortality in multiple syndromes. Although several novel agents exist with activity against CRE, little data compares outcomes between them.

Methods
To explore comparative effectiveness of meropenem/vaborbactam (MEV) vs. ceftazidime/avibactam (CZA), we conducted a multicenter retrospective cohort study within the Premier Healthcare Database, 2019-2021. We included all adult hospitalized patients who either were 1) admitted with or 2) during hospitalization had sepsis, a urinary tract (UTI), a complicated intraabdominal (cIAI) infection, or pneumonia. All syndromes were defined based on previously published administrative algorithms. We employed descriptive statistics to compare patients receiving MEV to those receiving CZA along demographic and clinical characteristics. We applied multiple regression models to adjust for confounding in the outcomes.

Results
Among 1,989,765 patients who met enrollment criteria, 455 received MEV and 2,320 CZA. Compared to those on CZA, MEV patients were more likely to be Hispanic, more likely to suffer from diabetes and liver disease, but less likely to have chronic pulmonary disease (Table). They were more commonly seen in hospitals in the South and less so in teaching institutions. More MEV than CZA patients required dialysis sometime during hospitalization. Pneumonia as the index infection was less prevalent in the MEV than in the CZA group. In multivariable regression models adjusting for multiple confounders, patients on MEV had lower mortality and a reduced risk for ICU admission. We further observed a trend towards MEV-treated (vs. CZA-treated) patients having a shorter ICU length of stay (LOS) post-infection onset and a lower risk for incident C. difficile infection (Table).
Table

Conclusion
In this cohort of hospitalized patients treated with either MEV or CZA for their infectious syndrome, MEV was associated with lower adjusted mortality and ICU admission, and a trend toward a reduction in incident CDI and ICU LOS post-infection onset compared to CZA.

Disclosures
Marya D. Zilberberg, MD, MPH, Melinta Therapeutics: Grant/Research Support|Merck: Grant/Research Support|scPharmaceuticals: Advisor/Consultant|scPharmaceuticals: Grant/Research Support Brian H. Nathanson, Ph.D., Merck & Co., Inc: Advisor/Consultant Mark Redell, PharmD, Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Stocks/Bonds|Melinta Therapeutics: Stocks/Bonds Kate Sulham, MPH, Melinta Therapeutics: Advisor/Consultant
2817. Outcomes of Timely vs. Delayed Meropenem/Vaborbactam Treatment of Infections with CRE among Adults Hospitalized in the US, 2019-2021
Authors: Zilberberg Marya D , Nathanson Brian H , Redell Mark , Sulham Kate , Shorr Andrew 
Published: November 2023

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) represent an urgent threat. Mortality rates associated with this pathogen approach 80%. Timely treatment of serious infections, even with highly resistant organisms, among hospitalized patients improves the chances of survival. We explored whether meropenem/vaborbactam (MEV) conforms to this observation.

Methods
We conducted a multicenter retrospective cohort study in ∼300 hospitals reporting microbiology data within the Premier Healthcare Database, 2019-2021, to explore the effect of timely (MEV-T) vs. delayed (MEV-D) CRE treatment. We included all adult hospitalized patients who either upon admission or during hospitalization had sepsis, a UTI, a cIAI, or pneumonia, and had at least one corresponding culture positive for CRE. Treatment was MEV-T if instituted within 2 days of obtaining the index culture. All other was considered MEV-D.

Results
Among 1,513 patients with CRE, 87 (5.8%) received MEV. Among those treated with MEV, 29 (33.3%) were treated in a timely manner. At baseline, MEV-T patients were directionally sicker than those in the MEV-D group, as evidenced by a higher prevalence of DNR on admission and a higher mean Charlson Comorbidity score (Table). Similarly, MEV-T patients were slightly more likely to require admission to an intensive care unit and mechanical ventilation. Although not statistically different, hospital mortality trended lower with MEV-T relative to MEV-D. Rates of incident C. difficile infection (CDI) and acute kidney injury (AKI) were lower with MEV-T (Table). Mean post-infection hospital length of stay (14.0+/-10.3 vs. 25.4+/-25.0 days, P=0.021) and hospital costs ($85,776+/-$81,454 vs. $149,506+/-163,748, P=0.052) were lower with timely MEV therapy.
Table

Conclusion
Despite being more severely ill, the group treated with timely initiation of MEV for CRE resulted in a significantly lower incidence of CDI and AKI. The post-infection LOS and hospital costs were also lower in the MEV-T group. Hospital mortality trended lower in the MEV-T group. Despite the small sample size, these differences suggest that timely administration of MEV may improve select significant clinical outcomes.

Disclosures
Marya D. Zilberberg, MD, MPH, Melinta Therapeutics: Grant/Research Support|Merck: Grant/Research Support|scPharmaceuticals: Advisor/Consultant|scPharmaceuticals: Grant/Research Support Brian H. Nathanson, Ph.D., Merck & Co., Inc: Advisor/Consultant Mark Redell, PharmD, Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Stocks/Bonds|Melinta Therapeutics: Stocks/Bonds Kate Sulham, MPH, Melinta Therapeutics: Advisor/Consultant
2820. Clinical Outcomes in Patients Who Receive a One-Time Aminoglycoside Dose for ESBL Enterobacterales or Pseudomonas aeruginosa cystitis
Authors: Bouwman Kelsey , George Melissa 
Published: November 2023

Abstract

Background
Extended spectrum beta lactamase (ESBL) Enterobacterales and Pseudomonas aeruginosa can be highly resistant organisms resulting in prolonged hospitalizations or the requirement of outpatient parenteral antibiotics. The Infectious Disease Society of America recommends a single dose of an aminoglycoside for uncomplicated cystitis caused by ESBL Enterobacterales and difficult to treat Pseudomonas aeruginosa. However, there is very little recent clinical evidence to support this recommendation. At our institution, we extrapolate this data to complicated cystitis and recommend a one-time aminoglycoside dose following about 3 days of effective therapy to help facilitate completion of antibiotic therapy and/or discharge. The objective of this study was to evaluate the safety and efficacy of a single-dose aminoglycoside for cystitis caused by ESBL Enterobacterales or Pseudomonas aeruginosa.

Methods
This was a multicenter, retrospective, cohort study. Adult patients treated for cystitis with ESBL Enterobacterales or Pseudomonas aeruginosa from January 2020 to December 2022 were identified for analysis, and data was obtained from electronic health records. Patients who received ≥ 3 days of standard of care were compared to patients who received a one-time dose of an aminoglycoside with or without a short course of effective therapy before. The primary outcome of this study was rate of relapse, and secondary outcomes included readmission rates, length of stay, and safety.

Results
A total of 66 patients were included in the study, with 33 patients in each study arm. The study populations were comparable except there were more males and complicated cystitis patients in the standard of care group. There was no difference found in the rate of relapse. The length of stay was significantly different between the two groups (4.5 ± 4.4 days in the aminoglycoside group vs 14.1 ± 10.1 days in the standard of care group, p &lt; 0.0001). No difference was found between the groups for readmission or safety.

Conclusion
A one-time dose of an aminoglycoside did not increase risk of relapse and was associated with shorter length of stay when used to treat cystitis caused by ESBL Enterobacterales or Pseudomonas aeruginosa.

Disclosures
All Authors: No reported disclosures