bluuebunny/crossref_metadata_2025 huggingface dataset:
2709. Breakthrough fungal infection after isavuconazole primary prophylaxis in patients with hematologic malignancy and hematopoietic stem cell transplant: Systematic Review
Authors: Ishida Keiko , Haraguchi Mizuki , Kimura Muneyoshi , Araoka Hideki , Reynolds John M , Raja Mohammed , Natori Yoichiro
Published: November 2023

Background

Isavuconazole (ISA) is a relatively newer triazole with a broad spectrum of anti-fungal activity and has been used for both treatment and prophylaxis of invasive fungal infections (IFIs) in patients with hematologic malignancy (HM) and hematopoietic stem cell transplant (HSCT) with a more favorable side-effect profile as compared to other agents. Widespread prophylactic use of mold-active agents has resulted in a decline in the incidence of IFIs, but breakthrough (bIFIs) has been reported previously. Thus, we performed a systematic review of HM and HSCT patients receiving ISA as primary prophylaxis to determine incidence and clinical characteristics of bIFI in this vulnerable population.

Methods

We conducted a comprehensive literature search with search term of ISA, prophylaxis and either HM and/or HSCT in several search engines (Embase, Scopus Web of Science, MEDLINE and CENTRAL). The database search strategy was developed by an academic health science librarian. We excluded patients who had ISA as treatment or secondary prophylaxis.

Results

With initial search, 630 unique articles were identified and after reviewing abstracts, we finally conducted a full-text review of 70 articles, of which 27 studies were included (Figure), of which 17 studies included more than or equal to 10 patients on ISA prophylaxis. Overall, ISA was well tolerated during primary prophylaxis. Of note, of the 17 studies, 717 patients received ISA as primary prophylaxis, out of which 58 patients (8.1%) developed bIFI with range of 0%-20% and occurred 13-138 days after initiation (Table). ISA levels were checked in 6 studies with a plasma level between 1.5-6.3 μg/mL. Out of 58 bIFI cases, 33 cases were identified including 6 Mucorales spp., 3 Fusarium spp., 8 Candida spp and 14 Aspergillus spp. Most commonly used regimen for treatment of bIFI was combination of Liposomal amphotericin B with Posaconazole. Overall mortality after bIFI was 0%-66.7%.

Conclusion

Our systematic review shows a high incidence of bIFI in patients with underlying HM or HSCT receiving ISA prophylaxis. Caution should be used in patients receiving long term prophylaxis with ISA. Further studies are needed to assess for risk factors that predispose to bIFI in patients receiving ISA prophylaxis.

Disclosures

John M. Reynolds, MLIS, Pfizer Inc: Stocks/Bonds
2710. Long Term Use of Contezolid in Lung Transplant Recipients Infected with Nocardia Species
Authors: Ju Chunrong
Published: November 2023

Background

Nocardia commonly infects lung transplant recipients (LTR). Current oral options for long-term therapy may result in intolerance or adverse events. Contezolid is a new oxazolidinone antibiotic with potential less toxicity than linezolid that was approved in China. This study describes the use of contezolid in the treatment of nocardiosis among LTR.

Methods

This retrospective study reviewed clinical data of adult LTR who were complicated with nocardiosis between January-2018 and December-2022 at the large transplant center China. Diagnosis of nocardiosis was confirmed by high resolution CT and cultures from representative samples. Nocardia spp. were identified by metagenomic next generation sequencing (mNGS). Drug susceptibility was determined by E-Test for TMP-SMX, Imipenem and Linezolid, and Kirby-Bauer for the others. Patients were followed in hospital and during home therapy for the whole duration of the treatment. Cure was defined by resolution of clinical symptoms, CT scan and culture negative BAL.

Results

During the study period 18 solid organ transplant patients infected with Nocardia spp. were identified. Among these patients 14 had pulmonary nocardiosis and 4 had disseminated diseases. A total of eight species of Nocardia were identified. Nocardia farcinica was the most common (5/8); 8 strains of Nocardia were resistant to ≥1 common antibiotics (Table 1). Linezolid was the only drug which maintained activity against all Nocardia spp. The initial treatment was a combination, usually with TMP-SMX, followed by a continuation regimen reduced to a single antibiotic according to susceptibility. The overall length of combined regimen was 18 days (range 14-25). Linezolid was used in 11 and contezolid in 9 patients, respectively. In 4 patients linezolid was switched to contezolid due to thrombocytopenia (4), anemia (1), and leucopenia (4). The median length of treatment in patients receiving contezolid was 110 days (range 90-210). Overall 16/18 patients were cured, including all patients who received contezolid. Patients’ characteristics, treatment and outcomes are displayed in Table 2.

Conclusion

Our study suggests that contezolid can be used in the long-term treatment of nocardiosis among lung transplant recipients.

Disclosures

All Authors: No reported disclosures
2714. Invasive Fungal Disease in Lung Transplant Recipients: Incidence, Risk Factors, and Outcomes
Authors: Kovac Victor , Goldberg Hilary J , Kim Andy J , Joyce Mary-Ruth M , Mallidi Hari R , Coppolino Antonio , Townsend Keri , Thaniyavarn Tany , Kennedy John C , Lee Stefi F , Durney Valerie , Liakos Alexis , Harris Courtney E , Little Jessica S , Sherman Amy C , Issa Nicolas C , Baden Lindsey R , Sharma Nirmal S , Woolley Ann E
Published: November 2023

Background

Invasive fungal disease (IFD) is common after lung transplant and is associated with increased morbidity and mortality. Antifungal prophylaxis is a common preventative strategy against IFD in lung transplant recipients (LTRs). We assessed the incidence of IFD in the first 3-years post-transplant, diagnosed by EORTC/MSG criteria, risk factors for developing IFD, and outcomes of LTRs stratified by development of IFD at a single center that does not use universal antifungal prophylaxis post-lung transplant.

Table 1

Preoperative and perioperative characteristics and clinical outcomes of lung transplant recipients stratified by invasive fungal disease (IFD) status

Methods

A single-center, retrospective study of lung transplant recipients between January 2017 and December 2019 was performed with 3-year follow-up. Donor and recipient preoperative characteristics, microbiologic and radiographic data, perioperative characteristics, and 1- and 3-year outcomes were adjudicated and analyzed.

Results

In this 3-year study period, 168 patients underwent lung transplant. 26 (15%) developed IFD; 23 (14%) were proven or probable, and 3 (1%) were possible [Table 1]. 21 (81%) had evidence of pulmonary infection and 17 (65%) were mold infections with Aspergillus being the predominant pathogen. 4 (15%) were Candida. 81% (21/26) of patients who developed IFD were recipients of bilateral lung transplants compared to 95% (135/142) of patients who did not develop IFD (p = 0.022). Other donor/recipient characteristics and 12-month outcomes between patients who did vs did not develop IFD were similar. 21% of patients (4/19) who developed IFD had developed antibody-mediated rejection (AMR) by three years post-transplant compared to only 4% of patients without IFD (5/112) (p = 0.025). The incidence of acute cellular rejection, chronic allograft rejection, and overall survival at three years were similar.

Conclusion

Despite the lack of universal antifungal prophylaxis in the first 90 days post-transplant, we observed a low incidence of IFD in LTRs at our center in this 3-year cohort. Other than receipt of a single vs bilateral lung transplant, there were no significant differences in preoperative or perioperative recipient characteristics. Other than an increased proportion of patients who had AMR, patients who developed IFD had similar overall outcomes to those who did not have IFD, including overall survival at 1, 2, and 3 years.

Disclosures

Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Astellas: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Fujifilm: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support
2720. Uninvited Guests in Tiny Tummies: An Assessment of Multidrug Resistant Organism Gut Colonization in Pediatric Transplant Patients
Authors: Parzen-Johnson Simon , Arshad Mehreen , Toia Jacquie , Sajwani Alima , Patel Sameer , Kremer Aspen N , Fishbein Joseph D
Published: November 2023

Background and Objectives

Immunocompromised patients infected with multi-drug resistant (MDR) bacteria are at higher risk of morbidity and mortality. Gut colonization with these strains can increase the risk of invasive infections with the same organism. However, the gut as a reservoir of MDR bacteria is critically understudied in this population. This study therefore aims to determine the prevalence of MDR bacterial gut colonization in pediatric transplant patients and identify associated clinical risk factors.

Methods

A prospective cohort study of pediatric transplant patients was performed at a quaternary medical facility. Patients were enrolled prior to transplant and stool samples were obtained pre-transplant, weekly for one month after transplant, and monthly for the following 5 months. Samples were selectively cultured for ceftriaxone-resistant gram-negative bacilli (CefR-GNB). Immunosuppressant, chemotherapeutic, and antibiotic use was tracked prior to transplant through one year following discharge. Patient demographics, central-line use, admission frequency, and documented infections were also tracked.

Results

Overall, 40 patients have been enrolled with 26 patients having completed the one-year follow-up period. The 26 patients included 11 stem-cell, 5 heart, 7 kidney, and 3 liver transplants. Eleven (42.3%) patients had at least one stool culture with CefR-GNB, and 7 (26.9%) had multiple positive stool cultures. There was no significant association between hospitalizations (P = 0.57), synthetic devices (P = 0.91), median days of gram-negative active antibiotics (P = 0.74), chemotherapeutics (P = 0.64), immunosuppressants (P = 0.43) in the pre-transplant period and risk of colonization with CefR-GNB. One patient developed an invasive infection with a resistant gram-negative organism during the study period.

Conclusion

Pediatric transplant patients have high rates of colonization with resistant gram-negative bacilli in their stool. In our small sample size, there was no association seen between prior medication use, admissions, or synthetic devices in place and risk of colonization with resistant organisms. Multi-center studies need to be conducted to assess these risks further.

Disclosures

All Authors: No reported disclosures
2750. Pseudomonas aeruginosa infections treated with cefiderocol: associations of site of infection and time to first dose with outcomes in PROVE (Retrospective Cefiderocol Chart Review) Study
Authors: Marcella Stephen , Cai Bin , Friedman Bruce , Verardi Stefano , Gozalo Laurence , Slover Christine M
Published: November 2023

Background

Gram-negative (GN) bacterial resistance is a major global health problem. Cefiderocol (CFDC) is active against Pseudomonas aeruginosa (PA). PROVE is an international, retrospective study of CFDC use in Gram-negative infections (GNI). This analysis examines outcomes by infection site and time of first CFDC dose from culture for patients with PA as of March 2023.

Methods

Eligible patients received ≥ 72 hours of CFDC as used in routine clinical practice and had a PA culture attributed to the use of CFDC. Patient characteristics, clinical course severity, and treatment patterns were assessed. Associations of infection site, carbapenem resistance (CR), CFDC susceptibility, and time of first (index) culture sample to first CFDC dose were examined with clinical cure and all-cause mortality (ACM) at 30 days. Clinical cure at the end of treatment was defined as resolution or improvement in infection signs and symptoms without evidence of later relapse.

Results

253 patients were treated with CFDC at 39 sites in the US and Europe for a primary PA infection; 30.8% were polymicrobial with other GN pathogens (Table 1). The median age was 57 years, interquartile range (IQR) 45-65; 70% were male. The most frequent comorbidities were diabetes (34.0%) and chronic pulmonary disease (20.2%). CFDC was given in an ICU setting in 72.3% with 48.6% requiring mechanical ventilation.

The most common sites of infection were respiratory (n=166, 65.6%) of which 22 (15.3%) had secondary bacteremia (Table 1). Most (90.3%) were CR. The median time from a positive culture to start of CFDC was 5 days (IQR 3-8).

Clinical cure was 63.6% and 30-day ACM was 22.5% (Table 1). Clinical cure was comparable in respiratory with and without secondary bacteremia (63.2% and 68.2%, respectively) and was lowest in patients with skin structure infections with bacteremia (40.0%). CFDC started 3-4 days after culture had the greatest cure rate (70.8%); those started later (5-7 days) had the lowest (59.2%). 30-day ACM was also greatest for patients treated later ( > 7 days after index culture) (28.1%) and for salvage after prior treatment failure (26.7%) (Table 2).

Conclusion

CFDC for PA is used in complex patients, most with respiratory disease. The trend of better outcomes with earlier use from culture warrants additional study.

Disclosures

Stephen Marcella, MD, MPH, Shionogi, Inc: contracting work for Shionogi, Inc Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Bruce Friedman, MD, Shionogi: Honoraria Stefano Verardi, MD, Shionogi B.V.: Employee Laurence Gozalo, PhD, Shionogi, Inc: Analyst Christine M. Slover, PharmD, Shionogi,INC: Employee
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

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

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

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 (< 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

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 > 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

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

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

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

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 < 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
2831. Efficacy and Safety of Gepotidacin for Uncomplicated Urinary Tract Infection: Pooled Subgroup Analyses of the EAGLE-2 and EAGLE-3 Randomized Phase 3 Trials
Authors: Hooton Thomas M , Perry Caroline R , Janmohamed Salim , Sheets Amanda , Dennison Jeremy , Millns Helen , Jarvis Emily , Huang Chun
Published: November 2023

Background

Two large Phase 3 trials showed that gepotidacin, a first-in-class oral triazaacenaphthylene bactericidal antibiotic, was efficacious in treating uncomplicated urinary tract infection (uUTI) in females and had an acceptable safety profile consistent with prior gepotidacin trials. We now present a pooled analysis of the EAGLE-2 and EAGLE-3 trials to evaluate gepotidacin efficacy and safety in patient subgroups.

Methods

Data were pooled from EAGLE-2 and EAGLE-3, near identical global, Phase 3, randomized, double-blind, double-dummy, active-controlled non-inferiority trials comparing oral gepotidacin (1500mg) to nitrofurantoin (100mg), both twice daily for 5 days. Females aged ≥ 12 years with ≥ 2 uUTI symptoms were eligible. Therapeutic success (combined clinical and microbiological success) was determined at the test-of-cure visit (Day 10–13) for patient subgroups – age, geographic region, history of recurrent uUTI, diabetes, and renal function. Efficacy subgroup analyses were conducted in the pooled microbiological intent-to-treat population of patients with baseline uropathogens (≥ 105 CFU/mL) susceptible to nitrofurantoin (micro-ITT NTF-S) and were adjusted for study. Pooled adverse event (AE) data for the overall population are presented.

Results

Both studies stopped early for efficacy (per independent data monitoring committee review). Among 1201 patients in the pooled micro-ITT NTF-S population, mean age was 51.5 years; 54% were aged > 50 years (Table 1). Across subgroups, differences in therapeutic success numerically favored gepotidacin vs nitrofurantoin (Table 2). Treatment differences were higher for > 50 years vs other age groups and for mild renal impairment vs normal renal function, and were similar within other subgroups. AEs were reported in 35% (gepotidacin) and 23% (nitrofurantoin) of patients (Table 3); most were mild to moderate and gastrointestinal in nature. There were few serious AEs.

Conclusion

Gepotidacin generally demonstrated consistent therapeutic efficacy in patient subgroups, including patients aged > 50 years and those with a history of recurrent uUTI (subgroups at higher risk of treatment failure). There were no new or concerning safety signals. Gepotidacin has potential as a novel oral treatment for uUTI in key patient subgroups.

Disclosures

Thomas M. Hooton, MD, GSK: Advisor/Consultant Caroline R. Perry, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Chun Huang, PhD, GSK: Employee and shareholder
2833. Multi-drug resistance of Escherichia coli from outpatient uncomplicated urinary tract infections in a large U.S. integrated health care organization
Authors: Ku Jennifer H , Bruxvoort Katia J , Salas Suzanne B , Varley Cara D , Casey Joan A , Raphael Eva , Robinson Sarah , Nachman Keeve , Lewin Bruno , Contreras Richard , Wei Rong , Pomichowski Magdalena , Takhar Harpreet , Tartof Sara Y
Published: November 2023

Background

Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multi-drug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision-making.

Methods

We evaluated UPEC resistance over time and by care setting (in-person vs. virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021.

Results

We included 174,185 individuals who had ≥1 UPEC uUTI (233,974 isolates), who were 92% female, and 46% Hispanic with a mean age 52 years (standard deviation 20). Overall, UPEC MDR decreased during the study period (13 to 12%) (Figure 1) both in virtual and in-person settings (p-for trend < 0.001). Resistance to penicillins overall (29%), co-resistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving penicillins and TMP-SMX plus ≥1 antibiotic class were common (10%) (Figure 2). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time, and by care setting.

Figure 2. Antibiotic resistance patterns of outpatient uncomplicated Escherichia coli urinary tract events, Kaiser Permanente Southern California, 2016 – 2021. Abbreviations: PNC = penicillin; FLQ = fluoroquinolone; TMP-SMX = sulfamethoxazole and trimethoprim; AGS = aminoglycoside; NFT = nitrofurantoin; CSP = cephalosporin

Conclusion

We observed a slight decrease in both class-specific AMR and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX, and consistent over time and by care setting. Virtual healthcare may expand access to UTI care without increased risk for MDR and the need for setting-specific antibiograms.

Disclosures

Jennifer H. Ku, PhD MPH, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Sara Y. Tartof, PhD MPH, Genentech: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Grant/Research Support|SPERO: Grant/Research Support
2836. Prostate Abscess due to Staphylococcus aureus: a Retrospective Case Series
Authors: Pellis Zachary , Mudroch Steven , Spivack Stephanie
Published: November 2023

Background

Most cases of prostate abscess are due to gram-negative enteric bacteria, but there are increasing reports of Staphylococcus aureus as a causative pathogen. Due to being an uncommon diagnosis, there are no current guidelines for the evaluation and treatment of S. aureus prostate abscesses. We examined the epidemiology and management of prostatic abscess due to S. aureus at an academic, urban tertiary center.

Methods

In this retrospective analysis, we identified patients with diagnosis of prostate abscess and concomitant culture with S. aureus who were aged 18 years or older and hospitalized at Temple University Hospital between 2016 and 2022. Cases were identified if they had both (1) a diagnosis code consistent with prostate abscess; and (2) positive blood, urine, or abscess cultures with S. aureus. Each case was reviewed to verify clinical or imaging criteria for diagnosis. Data regarding risk factors, interventions, and outcomes were compiled in REDCap, a de-identified electronic database for data management.

Results

We identified 18 patients who met inclusion criteria, with median [IQR] age of 50 years [40-70]. Computed tomography was used in all cases for identifying an abscess. The most common risk factors were intravenous drug use (IVDU) 55.6% [10/18] and diabetes 50% [9/18]. Culture positivity was 100% [6/6] for abscess fluid, 61.1% [11/18] for urine, and 56.3% [9/16] for blood. Of these, methicillin resistance was detected in 72.2% [13/18] of cases. Computed tomography was used in all cases for identifying an abscess. 61.1% [11/18] of patients underwent procedural interventions for treatment. Infectious Diseases consultation resulted in a change in management in 92.8% [13/14] of cases, with a median length of antibiotic administration of 42 days. 66.7% [6/9] of the bacteremic patients had additional infectious complications such as endocarditis or osteomyelitis.

Conclusion

Prostate abscess due to S. aureus should be considered in patients presenting with lower urinary tract symptoms and a history of injection drug use or diabetes. Evaluation should include imaging and cultures, particularly from blood. Treatment involves prolonged antibiotics and urology consultation for consideration of procedural intervention.

Disclosures

All Authors: No reported disclosures
172. Impact of a quality improvement re-training program on the blood culture volume, yield and contamination rates; experience from South India
Authors: Rabbani Amaanulla Kaamil Zubair , Ananthanarayanan Rajalakshmi , Asok Geetha Karthik , Rahim Mulla Rukhsar Abdur , Muhammed Niyas Vettakkara Kandy , Nair Ashalatha , Jomes Jeffrey , Hussain Febeena
Published: November 2023

Background

Blood cultures help to detect causative agents in bacteremia and are important for targeted therapy. Adequate blood culture volume is considered as 8-10ml in each bottle and at least 2 aerobic and 2 anaerobic blood culture bottles are recommended. Inadequate blood culture fills are common and may affect yield.

Figure 1

Methods

The study was done in our healthcare facility-KIMSHEALTH, Trivandrum, India. Pre-intervention period was between May 2021 and June 2021; post-intervention was between May 2022 and June 2022. The intervention was through plan/do/study/act (PDSA) cycles and included multiple training sessions to the phlebotomy team regarding adequate fill volume which is 8-10 ml in each blood culture bottle. Training for maintaining asepsis during collection was reinforced. All blood culture samples received in the hospital microbiology laboratory during the above period were included in this study and compared between the pre-intervention and post-intervention period. Pediatric blood culture samples were excluded.

Results

Blood culture samples studied during pre and post intervention period were 1428 and 1716 respectively. In the pre-intervention phase adequate fill volume was noted in 30.81% bottles (figure 1), while in the post intervention adequate fill volume was noted in 68.06% bottles (p < 0.01). Blood culture contamination rate was 3.01% in the pre-intervention period which improved to 2% in the post-intervention period and the difference was significant (p< 0.01). Blood culture yield of a pathogenic organism did not show significant difference after the intervention (11.2% in pre-intervention group Vs 11.45% in post intervention group).

Conclusion

In this study, an improvement was noted in the blood culture fills by 38% and contamination rate reduced by 1%. Though there was no significant increase in blood culture yield with intervention, the reduction in contamination was noted which will reduce unnecessary antibiotic initiation.

Disclosures

All Authors: No reported disclosures