bluuebunny/crossref_metadata_2025 huggingface dataset:
388. Co-Testing: Increasing HIV Testing in Patients Undergoing Sexually Transmitted Infection Evaluation in a Large Integrated Healthcare Network
Authors: Seibert Allan M , Matheu Michelle M , Buckel Whitney , Moores Todd Tamara , MD Vines Caroline , Bledsoe Joseph , Balls Adam , Hellewell James , Smout Randall J , Lopansri Bert K , Stanfield Valoree K , Wormser Vanessa R , Gwiazdon Matt , Willis Park , Wallin Anthony , Hersh Adam , Patel Payal K , Webb Brandon J , Stenehjem Eddie
Published: January 2025

Background

Utah ranks last among states in the percentage (26.5%) of adults ever tested for Human Immunodeficiency Virus (HIV). We hypothesized that linking “co-testing” for HIV to evaluations for sexually transmitted infections (STIs) in Urgent Care (UC) and Emergency Departments (ED) would increase HIV screening. We implemented a multifaceted intervention in the UCs and EDs of our integrated health system and evaluated its impact on HIV co-testing.

Methods

The initiative included education and HIV test follow-up support along with an electronic medical record-embedded alert (Figure 1). The alert surfaced if gonorrhea (GC), chlamydia (CT), or other STI testing was ordered for patients ≥ 18 years with unknown HIV status and encouraged HIV testing if not already ordered. We sequentially implemented the initiative in 26 UC and 22 ED sites from April 2023 – December 2023. We used interrupted time series analysis to evaluate HIV co-testing rates among eligible GC/CT testing encounters in pre-implementation (April 1st, 2022 – March 31st, 2023) and post-implementation (April 1st, 2023 – March 31st, 2024) UC and ED cohorts. We compared the observed rate to the predicted counterfactual (had no intervention taken place). We also assessed co-testing by social determinants of health (SDOH) categories, alert volume, and system impact on HIV testing and diagnoses.

Results

During the 24-month study, there were 19,232 GC/CT test encounters: 5,730 UC/2,524 ED pre-implementation and 7,696 UC/3,282 ED post-implementation. In UC, the increase in the observed HIV GC/CT co-test rate vs the predicted was 14.5 percentage points (95% CI 9.08-20.06, p< 0.001) (Figure 2). In the ED, the increase in the observed HIV GC/CT co-test rate vs the predicted was 13.7 percentage points (95% CI 5.75-21.71, p< 0.001). HIV GC/CT co-testing varied by SDOH (Table 1). 4,704 alerts fired (54% UC/46% ED) and resulted in 730 HIV co-tests (225 UC/505 ED), representing a 15.5% engagement rate. Of these 730 alert-initiated HIV co-tests, 5 (0.7%) revealed new HIV diagnoses, representing 29% of all HIV diagnoses in UC and ED during the post-implementation period (Figure 3).

Conclusion

HIV co-testing in our UC and ED sites increased during a multifaceted initiative. New HIV diagnoses occurred in UC and ED as a result of HIV testing ordered via our alert.

Disclosures

Bert K. Lopansri, MD, D(ABMM), FIDSA, Cepheid: Grant/Research Support|Seegene: Advisor/Consultant
P-1053. Invasive Fusariosis: 5-Year Update from a Single-Center Experience in the Voriconazole Era
Authors: Kovac Victor , Baden Lindsey R , Woolley Ann E
Published: January 2025

Background

Invasive fusariosis is a rare but aggressive infection seen in immunocompromised patients that is often multidrug resistant. The optimal therapeutic approach in the presence of elevated MICs to standard antifungal treatment remains unknown and careful monitoring of local epidemiology of this infection is needed. We performed a retrospective review of invasive fusarium infections to help guide management at our center.

Methods

We identified all cases of invasive Fusarium infection between January 2019 and April 2024. We collected patient characteristics, including clinical presentation, therapy, and 12-week outcomes, as well as organism speciation and susceptibility testing.

Results

Seven patients were diagnosed with either proven (6, 86%) or probable (1, 14%) invasive fusariosis. The median age was 60 years and six (86%) patients were male. Four (57%) had hematologic malignancies, of which 3 (75%) received stem cell transplant, 1 (14%) idiopathic neutropenia, 1 (14%) severe burns, and 1 (14%) received solid organ transplant. Four (57%) had prolonged preceding neutropenia. Cutaneous lesions were the most common presentation (5, 71%). The four cases in neutropenic hosts had cutaneous lesions with presumed or confirmed disseminated disease involving the sinuses or lung. Three (43%) received combination therapy with voriconazole and terbinafine, 2 (29%) received posaconazole, 1 (14%) received amphotericin, and 1 (14%) received voriconazole. Fusarium solani complex was the most commonly isolated species (2, 29%). Species identification was not available in 3 cases. Susceptibility testing was available in 5 (71%) cases and MICs to voriconazole were ≥16 µg/mL and to terbinafine were ≥2. All 4 cases treated with voriconazole had elevated MICs and yet exhibited a partial (2, 50%) or complete clinical response (2, 50%) to treatment. 12-week survival was seen in 4 (57%) of cases, with one patient lost to follow-up.

Conclusion

Mortality to invasive fusariosis is high but remains similar at our center compared to the 2002-2014 period. Diagnosis remains challenging and tissue biopsy is critical. Despite elevated MICs, clinical responses to voriconazole with or without the addition of terbinafine are observed.

Disclosures

All Authors: No reported disclosures
P-1059. In vitro Activity of Gepotidacin against Klebsiella pneumoniae, Including Molecularly Characterized ESBL and Carbapenemase positive Subsets Causing Urinary Tract Infections in the United States (2019-2022)
Authors: Mendes Rodrigo E , Scullin Abigail , Kimbrough Hank , Hubler Cory , Kapoor Renuka , Torumkuney Didem , Ryan Arends S J
Published: January 2025

Background

Gepotidacin (GEP) is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial that inhibits bacterial DNA replication by a unique mechanism of action, distinct binding site, and provides well-balanced inhibition (for most uncomplicated urinary tract infection [uUTI] uropathogens and Neisseria gonorrhoeae) of two different type II topoisomerase enzymes. GEP recently completed two phase 3 trials for the treatment of uUTI. This study reports the activity of GEP and other oral antibacterials against K. pneumoniae, including molecularly characterized ESBL and carbapenemase producing isolates collected from UTI patients in the US.

Methods

A total of 2,001 K. pneumoniae were collected from 73 sites. CLSI methods were used for both susceptibility testing and MIC interpretation. Isolates with aztreonam, ceftazidime, ceftriaxone or meropenem MIC of ≥2 mg/L were subjected to genome sequencing, and screening of plasmid-mediated AmpC (pAmpC), ESBL, and carbapenemase genes.

Results

A total of 11.0% (220/2,001) K. pneumoniae were screened for β-lactamase genes (Table). Majority of these isolates carried blaCTX-M alone (78.2%; 172/220), and a small number carried combinations of blaCTX-M and ESBL variants of blaSHV (2.7%; 6/220), blaSHV alone (2.7%; 6/220), or pAmpC alone (2.3%; 5/220). Among screened isolates, 9.1% (20/220) carried carbapenemases. GEP had MIC50 and MIC90 of 4 mg/L and 8 mg/L, respectively, against isolates that did not meet the MIC criteria for screening of β-lactamases. Other oral agents showed susceptibilities of 92.8–99.5% against this group, except for nitrofurantoin (35.7%). GEP had an MIC90 of 32 mg/L against screened strains carrying ESBL and pAMPC, and an MIC90 of 16 mg/L against carbapenemase positive isolates. Other oral agents had limited activity (< 42%) against strains carrying ESBL and/or pAMPC.

Conclusion

GEP showed activity against UTI-causing K. pneumoniae in US medical centers, including against isolates carrying ESBL, pAmpC and/or carbapenemases. These data support further clinical development of GEP as a potential treatment option for uUTI caused by K. pneumoniae including when other oral treatment options have limited activity due to drug resistance.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company)
P-1060. In vitro Activity of Gepotidacin Tested Against Molecularly Characterized Escherichia coli Isolates Responsible for Urinary Tract Infections in the US (2019-2022)
Authors: Mendes Rodrigo E , Beekman Danielle , Scullin Abigail , Karr Maura , Kapoor Renuka , Torumkuney Didem , Ryan Arends S J
Published: January 2025

Background

Gepotidacin (GEP) is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial that inhibits bacterial DNA replication by a unique mechanism of action, distinct binding site and provides well-balanced inhibition (for most uncomplicated urinary tract infections [uUTI] uropathogens and Neisseria gonorrhoeae) of two different type II topoisomerase enzymes GEP completed two phase 3 trials for treatment of uUTI This study reports the activity of GEP and other oral antibacterials against E. coli (EC), including molecularly characterized isolates carrying ESBL and carbapenemase genes collected from UTI patients in the US.

Methods

3,995 EC collected from 52 US sites as part of the gepotidacin uropathogen global surveillance study were included (2019-2022). CLSI methods were used for susceptibility (S) testing and MIC interpretations. Isolates with aztreonam, ceftazidime, ceftriaxone or meropenem MIC of ≥2 mg/L were subjected to genome sequencing, and screening of β-lactamase genes and epidemiology typing (MLST, O:H, and fimH).

Results

A total of 86.2% (3,444/3,995) of EC did not meet the MIC criteria for molecular characterization (Table) and had GEP MIC50 and MIC90 values of 2 mg/L and 4 mg/L, respectively. Cefazolin (97.0%S), fosfomycin (FOS) (99.7%S), and nitrofurantoin (NIT) (98.7%S) had activity among oral comparator agents tested against this group. A total of 13.8% (551/3,995) of EC were screened for β-lactamase genes, and this group had GEP MIC50 and MIC90 values of 2 mg/L and 4 mg/L respectively. Other oral agents had limited activity, except for FOS (98.0%S) and NIT (92.7%S). In general, GEP retained activity with MIC50 and MIC90 values of 2 mg/L and 4 mg/L, respectively, against isolates carrying ESBL, AmpC and carbapenemase genes, and against clonal complex (CC) 131 and the resistant subset O25b:H4.

Conclusion

GEP showed generally consistent activity against UTI-causing EC in the US, including against isolates carrying ESBL, AmpC and/or carbapenemase genes. In addition, GEP had activity against the CC131 high-risk EC clone. These data support further clinical development of GEP as a potential treatment option for uUTI caused by EC including when other oral treatment options are limited due to drug resistance.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company)
P-1063. SCY-247: A Second-generation IV/Oral Triterpenoid Antifungal with Extensive Tissue Distribution and Pharmacokinetics, and Low Drug-Drug Interaction Potential
Authors: Wring Steve , Borroto-Esoda Katyna , Wiederhold Nathan P , Angulo David A
Published: January 2025

Background

SCY-247 is an IV/oral second-generation triterpenoid anti-fungal for systemic fungal infections including multidrug resistant pathogens. Here we present translational data for nonclinical pharmacokinetics (PK) including dose-related tissue disposition in a murine C. glabrata model and correlation to reductions in fungal burden. Further, in vitro CYP450 interactions were evaluated to assess potential for clinical drug-drug interactions (DDIs).

Methods

The PK of SCY-247 was determined in rats and dogs. Plasma and tissue exposures were compared to reductions in kidney and lung fungal burden in a model of invasive C. glabrata. Neutropenic mice were infected IV with C. glabrata (∼108 yeast cells/mouse) and sacrificed on Day +7. Potential for inhibiting or inducing CYP450 isoforms was assessed in vitro using methods supportive of an FDA Investigational New Drug (IND) Application.

Results

SCY-247 has low clearance (∼10% liver blood flow) with half-life ≥15 hours following oral and IV administration to rat and dog consistent with once-daily administration in humans. Volume of distribution is ∼3 L/kg supportive of extensive tissue distribution. Exposure increased on repeat administration. Solubility of oral SCY-247 as a salt is >30 mg/mL at gastric pH consistent with rapid dissolution in the stomach and rapid absorption - as demonstrated by an early Tmax (0.5-2hr) following oral administration. In a murine model of C. glabrata infection, SCY-247 demonstrated dose-related increases in exposure and corresponding reduction in fungal burden (right figure panel) with higher distribution in kidney and lung tissue compared to plasma (left figure panel). In vitro, SCY-247 did not induce human CYP450s 1A2, 2B6 or 3A4. The IC50 values for inhibition of human 2C9, 2C19 and 3A isoforms were >20 μM ( >10-fold higher than the anticipated clinical Cmax) supportive of low risk of DDI’s for these isoforms.

Conclusion

SCY-247 has demonstrated dose- and tissue-related exposure reductions in fungal burden, PK consistent with once daily dosing to humans and low risk for CYP450-related DDIs.

Disclosures

Steve Wring, PhD, SCYNEXIS, Inc.: Advisor/Consultant Katyna Borroto-Esoda, MS, Scynexis Inc: Advisor/Consultant Nathan P. Wiederhold, PharmD, BioMerieux: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mycovia: Grant/Research Support|Scynexis: Grant/Research Support|Sfunga: Grant/Research Support David A. Angulo, MD, SCYNEXIS, Inc.: Board Member|SCYNEXIS, Inc.: SCYNEXIS, INC Officer and Board Member, SCYNEXIS Patents|SCYNEXIS, Inc.: Stocks/Bonds (Public Company)
P-1083. Antimicrobial Activity of Aztreonam-Avibactam and Comparator Agents against a Large Collection of Stenotrophomonas maltophilia Isolates Collected in United States Medical Centers (2019-2023)
Authors: Sader Helio S , Doyle Timothy , Winkler Marisa , Ryan Arends S J , Castanheira Mariana
Published: January 2025

Background

The occurrence of S. maltophilia infections has increased continuously in the last few years. We evaluated the in vitro activities of aztreonam-avibactam (ATM-AVI) and comparators against a large collection of S. maltophilia clinical isolates.

Activity of aztreonam-avibactam and comparator agents stratified by infection type.

Methods

1,400 clinical isolates were consecutively collected from 62 United States (US) medical centers. Infection sites included pneumonia (n=1,020), bacteremia (n=117), skin and skin-structure infection (SSSI; n=124), and others (n=139). Isolates were susceptibility tested by CLSI M07 broth microdilution methods. ATM-AVI was tested with AVI at fixed 4 mg/L and a pharmacodynamic/pharmacokinetic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison.

Results

ATM-AVI inhibited 99.6% of isolates at ≤ 8 mg/L (MIC50/90, 2/4 mg/L) and demonstrated potent activity against isolates from all infection types (Table). ATM-AVI inhibited 99.7% of isolates from pneumonia and 100.0% of isolates from BSI at ≤ 8 mg/L and retained potent activity against isolates non-S to other agents commonly used to treat S. maltophilia infections. ATM-AVI was active (MIC ≤ 8 mg/L) against 100.0% of trimethoprim-sulfamethoxazole (TMP-SMX)-non-S isolates, 99.3% of isolates non-S to minocycline or levofloxacin, and 99.5% of isolates with tigecycline MIC > 2 mg/L. Moreover, ATM-AVI activity remained stable during the study period; the percentages inhibited at ≤ 8 mg/L varied from 100.0% in 2019 and 2020 to 99.3% in 2023. TMP-SMX (MIC50/90, ≤ 0.12/0.5 mg/L; 96.9% S) also showed good activity against S. maltophilia. Minocycline (MIC50/90, 0.5/2 mg/L) and levofloxacin (MIC50/90, 1/8 mg/L) were active against 89.2% and 78.9% of isolates according to the 2024 CLSI breakpoint criteria.

Conclusion

ATM-AVI exhibited potent activity and broad coverage against S. maltophilia from US hospitals and its activity was not adversely affected by resistance to other agents. Our results indicated that ATM-AVI may represent a valuable option to treat S. maltophilia infections, addressing a major unmet medical need.

Disclosures

Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support
P-1085. Characterization of Enterobacter cloacae and Citrobacter freundii Species Ccomplex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam-avibactam and Comparator Agents (2019-2023)
Authors: Sader Helio S , Doyle Timothy , Kimbrough Hank , Hubler Cory , Castanheira Mariana
Published: January 2025

Background

Aztreonam-avibactam (ATM-AVI) is under clinical development for treatment of Gram-negative infections, including those caused by metallo-β-lactamase (MBL) producers. We evaluated the activity of ATM-AVI and comparators against cephalosporin non-susceptible (S) E. cloacae (ECLC) and C. freundii species complex (CFC) from patients hospitalized in United States (US) medical centers.

Antimicrobial susceptibility of cephalosporin-non-susceptible E. cloacae and C. freundii species complex

Methods

A total of 43,235 Enterobacterales (1/patient) were collected via the INFORM Surveillance Program and susceptibility tested by broth microdilution in 2019-2023; among those, 5,106 (11.8%) were ECLC (n=3,732) or CFC (n=1,374). We evaluated the antimicrobial susceptibility and β-lactamase production of isolates ceftazidime-resistant (MIC ≥ 16 mg/L) or cefepime-non-S (MIC ≥ 2 mg/L). The collection includes 1,065 ECLC and 379 CFC. ATM-AVI was tested with AVI at fixed 4 mg/L and a PK/PD S breakpoint of ≤ 8 mg/L was applied for comparison. Comparator included ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), and cefiderocol (carbapenem-resistant [CB-R] isolates only), among others. All isolates (n=1,444) were characterized by whole genome sequencing.

Results

Isolates were mainly from urinary tract (35.5%), pneumonia (23.6%), and bloodstream infection (BSI; 16.1%). The most common ESBLs were CTX-M type (99; 49.0% of ESBL producers), SHV type (95; 47.0%), and OXA type (80; 39.6%); ≥ 2 ESBLs were identified in 67 isolates (33.1%), mainly OXA-1/30 plus a CTX-M (64 isolates; 31.7%). A carbapenemase was identified in 55 of 64 (85.9%) CB-R isolates; including KPC type (40 isolates; 62.5% of CB-R) and NDM-1 (15; 23.4% of CB-R). ATM-AVI inhibited 99.9% of isolates at ≤ 8 mg/L and showed complete activity (100.0% inhibited at ≤ 8 mg/L) against ESBL producers and CB-R isolates, including NDM producers (Table). CAZ-AVI and MEM-VAB were active against 92.1-92.6% of ESBL producers and 70.3-71.9% of CB-R isolates. Cefiderocol was active against 83.9% of CB-R isolates but only 46.7% of NDM producers.

Conclusion

ATM-AVI was highly active against cephalosporin-non-S ECLC and CFC, including MBL producers. The activities of CAZ-AVI, MEM-VAB, and cefiderocol were compromised against CB-R isolates due to the high frequency of NDM producers.

Disclosures

All Authors: No reported disclosures
P-1095. Activity of Rezafungin against Clinical Isolates of Uncommon Species of Candida spp
Authors: Winkler Marisa , Rhomberg Paul , Klauer Abigail , Castanheira Mariana
Published: January 2025

Background

Rezafungin (RZF) is a long-acting echinocandin recently approved by the FDA to treat invasive candidiasis (IC) and candidemia. RZF CLSI breakpoints are available for Candida albicans, C. auris (CARS), C. dubliniensis (CDUB), C. glabrata, C. krusei, C. parapsilosis (CPRP), and C. tropicalis. However, RZF susceptibility results are scarce against other Candida spp. We evaluated in vitro activity of RZF, anidulafungin (AND), caspofungin (CAS), micafungin (MCF), fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB) against less common species of Candida spp. including CARS and CDUB.

Methods

We tested 590 (1/patient) less common Candida spp. isolates from IC infections as part of the SENTRY Program (Table 1). Isolates were collected from 2020-2022 in 80 hospitals including 31 in North America, 29 in Europe, 14 in Asia-Pacific, and 6 in Latin America. Isolates were identified by MALDI-TOF MS and/or sequencing and susceptibility testing was performed using the CLSI broth microdilution method. CLSI breakpoints or epidemiologic cutoff values were applied where available.

Results

RZF displayed similar activity to other echinocandins (within ±2-fold for MIC50/90 values) against all Candida spp. tested (Table 2). The lowest RZF MIC50/90 values were noted against C. kefyr (n=51, 0.03/0.06 mg/L) and C. pelliculosa (n=10, 0.015/0.03 mg/L). Higher RZF MIC50/90 values were noted for C. guilliermondii (CGU, n=33, 1/1 mg/L) and for isolates in the CPRP complex (C. orthopsilosis (CORT) n=49, 0.5/1 mg/L, C. metapsilosis (CMET) n=25, 0.12/0.5 mg/L). The same pattern was seen with other echinocandins against these Candida spp. RZF was active against 97.7% of CDUB and 95.4% of CARS isolates applying the CLSI breakpoints. There were three CARS isolates that were resistant to RZF with MICs of 1- >4 mg/L. Two of these were susceptible to CAS and one was resistant or non-wildtype to all echinocandins. For FLC 69.7% of CGU, 85.7% of CORT, 100% CMET, and only 10.8% of CARS isolates were susceptible.

Conclusion

RZF has potent in vitro activity against a large collection of less common Candida spp. as demonstrated by worldwide surveillance testing. The activity of RZF against these isolates was comparable to other echinocandins and generally better than FLC.

Disclosures

Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support
P-1106. Sulopenem is Efficacious in a Rabbit Model of Inhalational Anthrax
Authors: Puttagunta Sailaja , Aronin Steven I , Halasohoris Stephanie , Babyak Ashley , Spencer Jade , Gray Annette , Torres Marjorie , Klimko Christopher , Cote Christopher , Hourihan Mary , Meinig James
Published: January 2025

Background

Sulopenem (SUL) is a penem β-lactam antibiotic in development for the treatment of resistant bacterial infections. It is available as intravenous and oral prodrug formulations, and its activity aligns with the most urgent drug-resistant antimicrobial threats defined by the CDC. SUL possesses potent activity against Enterobacterales species that encode ESBLs or AmpC-type β-lactamases that confer resistance to 3rd generation cephalosporins. SUL has also demonstrated potent in vitro activity against numerous biothreat pathogens, including Bacillus anthracis at concentrations likely to be achieved after oral dosing in humans. B. anthracis is a CDC Tier 1 Select Agent, and remains of considerable concern for biodefense. The potential for mass casualties resulting from a biothreat incident combined with the risk of antibiotic resistance necessitates development of novel medical countermeasures (MCM) for B. anthracis. Orally administered SUL was previously shown to be protective in the murine model of inhalational anthrax and provided proof-of-concept to advance the drug into the well-established rabbit model.

Methods

Female New Zealand White rabbits were challenged with a lethal dose of B. anthracis Ames spores via the inhalational route. Post-exposure prophylaxis (PEP) was initiated at 24 ±1 h postchallenge with cohorts (N=6) of animals receiving vehicle (saline, SC), ciprofloxacin (CIP) 10 mg/kg, SC or SUL 10 mg/kg, SC. This dosing regimen was informed by pharmacokinetic models to establish a human-equivalent dose. Treatment was continued BID for 14 days. Clinical progression and survival were assessed up to 30 days postchallenge.

Results

The untreated saline control group demonstrated 100% lethality with a median time to death of 48 h. Both the SUL and CIP groups demonstrated 100% survival through study termination on day 30.

Conclusion

As a MCM for inhalational anthrax, SUL would provide considerable advantages as an addition to the slate of current standards of care. Combined with positive efficacy results in two preclinical models of inhalational anthrax and advantages offered by an orally available penem antibiotic, SUL remains a promising candidate for advanced development for treating B. anthracis.

Disclosures

Sailaja Puttagunta, MD, Iterum Therapeutics: Employee|Iterum Therapeutics: Employee|Iterum Therapeutics: Stocks/Bonds (Public Company)|Iterum Therapeutics: Stocks/Bonds (Public Company) Steven I. Aronin, MD, Iterum Therapeutics: Employee|Iterum Therapeutics: Employee|Iterum Therapeutics: Stocks/Bonds (Public Company)|Iterum Therapeutics: Stocks/Bonds (Public Company)
P-1134. Use of Respiratory Panel Polymerase Chain Reaction (RPP): Challenging Diagnostic Stewardship
Authors: Fernandez Marisol , Downey Rachel , Wesolowski Alec
Published: January 2025

Background

National diagnostic stewardship initiatives recommend against routine use of broad respiratory pathogen panels (RPP) for children with suspected respiratory viral illness. Use of RPP testing increased at our institution after 2020, likely related to the ongoing pandemic. Our antimicrobial stewardship team sought to meet in person with ordering services to improve diagnostic stewardship, reserving RPP for cases in which broad testing was likely to affect treatment. The aim of our study was to assess if the handshake stewardship initiative was enough to decrease the number of RPP ordered. A secondary aim was to evaluate the proportion of positive RPP tests that resulted in treatment change before and after the stewardship initiative.

Methods

This single-center, retrospective study included pediatric patients with RPP test in January to February 2023 (pre-intervention) and January to February 2024 (post-intervention). Stewardship interventions took place in June 2023. Of the ordering services included, only the emergency department (ED) and hospital service opted to meet in person. Cases were compared pre and post intervention for length of stay, race, underlying medical conditions, results of RPP, ordering service, and documented change in treatment plan based on the test results.

Results

172 and 290 RPP orders in the pre and post intervention groups were included. 101 (59%) tests were positive in the pre-intervention group compared to 136 (47%) in the post-intervention. Figure 1 shows the distribution of the ordering medical services. There was a significant decrease in RPP orders in the ED post intervention (p < 0.001) (fig 1). Among patients with a positive RPP there was a treatment change in 20 (20%) pre vs 36 (26%) post-intervention (p=0.298). Figure 2 shows distribution of pathogens among positive testing. The most common viral pathogen identified in both groups was rhinovirus/enterovirus.

Conclusion

In-person handshake stewardship has the potential to guide appropriate utilization of diagnostic tests. RPP testing did not result in changes in treatment for the majority of patients regardless of handshake stewardship guidance. Future work will include developing a diagnostic algorithm to refine selection of patients to be tested.

Disclosures

All Authors: No reported disclosures
P-1143. Etiology and resistance phenotypes of blood-culture proven neonatal sepsis from two large NICUs in Mexico: a multicenter three-year retrospective analysis
Authors: Garza-Castro Abraham P , Ballesteros-Suarez Ana , Concha-Mora Lindsay A , Prieto-Baca Ericka Paulina , Tamez-Rivera Oscar
Published: January 2025

Background

Neonatal sepsis is a significant cause of morbidity and mortality in newborns. Etiology depends on multiple factors, particularly regional epidemiology. Current international guidelines are based on data from developed countries, which may not reflect the situation of developing regions. Microbiological surveillance in Mexican NICUs is limited, which may lead to inappropriate antimicrobial use.

Methods

This is a retrospective multicenter study conducted in two NICUs from NL, Mexico (2021-2023). Clinical and microbiological data on ≤28-day newborns with blood culture-proven neonatal sepsis were collected. Neonatal sepsis was classified as early (≤3 days) and late onset ( >3 days). Descriptive statistical analyses were performed to assess microbiologic etiologies, as well as clinically-relevant resistance phenotypes (VITEK® 2).

Results

A total of 928 blood cultures from 775 patients were included. 49.0% were preterm. Mean gestational age was 35.2. Most episodes (66.9%) were classified as late-onset sepsis (Table 1). Staphylococcaceae were the most commonly identified family (48.6%). Coagulase-negative Staphylococci were the most common group (42.7%), being S. epidermidis the most common. Gram-negative bacilli were the second most common cause of neonatal sepsis (33.7 %), mostly due to K. pneumoniae (12.7%). Low prevalence of GBS was observed (3.0%). Fungal (4.1%) and enterococcal (5.2%) isolations were uncommon. The prevalence of ESBL-producing Enterobacterales were 39.4%; MRSA was 30.2% (Table 2). 4 cases (1.4%) of carbapenem-resistant Enterobacterales (CRE) and 2 cases (0.7%) of AmpC Enterobacterales were identified. Notably, 5 cases (10.4%) of vancomycin-resistant Enterococci (VRE) were identified.

Conclusion

The study reported clinical and microbiological data of blood culture-proven neonatal sepsis. In contrast with U.S. data, this study showed a lower prevalence of GBS and a significant presence of Gram-negative pathogens, alongside notable resistance profiles such as ESBL-producing Enterobacterales and VRE. Antimicrobial surveillance in developing regions is necessary in order to recognize the most common etiologies and develop treatment guidelines according to local epidemiology. VRE is a worldwide concern and should be closely monitored.

Disclosures

All Authors: No reported disclosures
P-1157. Clinical and Economic Outcome of Drugs Used in the Treatment of Pneumonia in Pediatric Population in a Tertiary Care Hospital in India-A Pharmacoeconomic Analysis
Authors: Joseph Jameskutty
Published: January 2025

Background

Antibiotic therapy expenses for treating pneumonia in hospitalized pediatric patients can substantially impact healthcare expenditures. We conducted a longitudinal study to investigate prescription appropriateness, predictors of treatment patterns, and key outcomes—readmission rates, length of hospital stay (LOS), and direct and indirect costs associated with diagnosing and treating community-acquired pneumonia in pediatric patients admitted to a tertiary care hospital in India.

Methods

We observed 180 children diagnosed with pneumonia and receiving antibiotic treatment upon admission to the pediatric inpatient department. We collected demographic data and prescription details, calculating direct and indirect costs. Multivariate regression analysis was employed to identify predictors of LOS and costs, while one-way ANOVA was utilized to assess cost disparities among treatment groups.

Results

Among all pneumonia admissions, mild-to-moderate cases accounted for 78.1% of cases; 66% (119 out of 180) of children had comorbid conditions alongside pneumonia. Beta-lactam antibiotics constituted the majority of prescriptions (54%), followed by aminoglycosides (20%) and macrolides (12%). Parenteral antibiotics were administered in 62.2% of cases, and switch therapy was performed in 45.5% (82) of cases. The median LOS was 3 days, with a cure rate of 95.5% (95% CI: 97-100%). Switch therapy was significantly associated with shorter LOS and substantially lower treatment costs. The average cost per pneumonia patient management was 14363 ± 782 INR ($172.26 ± 9).

Conclusion

Hospital management of pediatric pneumonia was more influenced by early discharge policies than by clinical variables.

Disclosures

All Authors: No reported disclosures
P-1173. NICU MRSA Surveillance: Implications of Retesting Versus Not Retesting MRSA-Colonized Infants
Authors: Green Julianne , Lovelace Tamika , Flynn Madelaine , Palavecino Elizabeth , Bischoff Werner
Published: January 2025

Background

Methicillin resistant Staphylococcus aureus (MRSA) colonization often precedes invasive infection; decolonization may prevent morbidity and mortality. MRSA surveillance protocols vary widely; at Brenner Children's Hospital (BCH), infants in the neonatal intensive care unit (NICU) undergo repeat testing after decolonization, allowing assessment of MRSA colonization/recolonization events and their relationship to invasive infection.

Methods

MRSA PCR of combined nasal/umbilical swabs from infants in the BCH NICU from 1/1/23 to 2/29/24 were performed on admission and weekly thereafter. Positive infants were decolonized with 5 days of bid intranasal mupirocin and one chlorhexidine gluconate bath (if age-eligible), then underwent repeat weekly testing along with their MRSA-negative counterparts. If/when decolonized infants subsequently tested negative by PCR, no further decolonization occurred unless/until the infant tested positive again (recolonization). Community onset (CO) colonization = a positive MRSA PCR on admission; hospital onset (HO) = at least one negative MRSA PCR prior to a positive.

Results

Of the 1061 infants admitted to the NICU, 93/1061 (9%) were MRSA PCR positive: 16/93 (17%) CO and 77/93 (83% HO), with 2.8 HO colonization events per 1,000 patient days. HO infants took an average of 5 weeks to become newly colonized; 58/77 (75%) were successfully decolonized but 36/58 (62%) of those became recolonized at least once. Long term NICU residents required multiple decolonization cycles- a maximum of 17 cycles for one infant hospitalized for 265 days. Three of four NICU MRSA bacteremia events occurred in HO infants; in each case colonization immediately preceded bacteremia.

Conclusion

Once colonized with MRSA, the majority of neonates underwent repeated decolonization/recolonization cycles. This brings into question the practice of continuous testing after initial decolonization. Events classified as recolonization may actually represent low level carriage in body sites not detected by surveillance, the inability of decolonization to fully eradicate MRSA, or detection of DNA fragments rather than viable organisms.

Disclosures

All Authors: No reported disclosures
P-1174. MBI-CLABSI Cluster in Pediatric Oncology Patients with Hematologic Malignancies Introduces New Barrier in Fluoroquinolone Prophylaxis
Authors: Jowers Karlye , Mason Matt , Gilman Margaret , Vodzak Jennifer
Published: January 2025

Background

Levofloxacin is preferred for prophylaxis during neutropenic periods in pediatric patients with high-risk acute myeloid and lymphoblastic leukemias (AML and ALL, respectively). The goal is to decrease risk of morbidity and mortality from bacteremia related to central venous lines (CVL) and chemotherapy-induced mucosal barrier injury (MBI), but antibacterial resistance may develop. Our institution observed an unexpected increase in MBI-central line associated bloodstream infections (MBI-CLABSI) in 2023, prompting a multidisciplinary review of the MBI-CLABSI cluster.

Methods

Retrospective chart review was performed to characterize a cluster of MBI-CLABSI events occurring in pediatric patients with AML or ALL from 2020-2023 at our 220-bed, urban/suburban, free-standing children’s hospital. Descriptive analysis of the 2023 cluster events was performed, including patient demographics, diagnosis, transplant status, pathogen and prophylactic drug data to identify commonalities and potential harm-reduction interventions.

Results

Rate of MBI-CLABSI were steady from 2020-2022 (0.24) and increased to 1.11 per 1,000 central line days in 2023 in patients with AML or ALL. Standard infection ratio of 3.69, p-value 0.0001. 85.7% (n=12/14) MBI-CLABI occurred in patients who had received prophylactic levofloxacin. Almost all organisms causing the MBI-CLABSIs were levofloxacin resistant (98%) and most (58%) were resistant to at least one additional antibiotic. Patients with multiple MBI-CLABSI events with a levofloxacin-resistant organism during the cluster year was not uncommon (66.7%; n=8/12)). . In this subset, patients continued to receive prophylactic levofloxacin despite having earlier infections caused by a levofloxacin-resistant pathogen.

Conclusion

Use of levofloxacin prophylaxis for neutropenia episodes in high-risk AML and ALL patients may increase the risk of MBI-CLABSI events with levofloxacin-resistant organisms, thus reducing the effectiveness of the prophylaxis goal to prevent serious bacterial infections and reduce harm. Further studies are needed to better delineate optimal use of prophylactic antibiotics by incorporating population-level antibiograms and patient-specific infection histories.

Disclosures

All Authors: No reported disclosures
423. Mirror Mirror on the Wall Who is Driving all the Invasive GAS After All - The Utah Experience
Authors: McMillion Benjamin , Pershing Nicole L , Crandall Hillary , Hersh Adam , Ampofo Krow , Olson Jared , Oakeson Kelly F , Wagner Jennifer M , Nielsen Shannon , Dickey Mandy , Huynh Kelly , Pavia Andrew T , Blaschke Anne J
Published: January 2025

Background

Streptococcus pyogenes (GAS) is a common cause of non-invasive mucosal infections as well as rare life-threatening invasive disease. At the onset of the COVID-19 pandemic there was a decline in invasive GAS (iGAS) disease, followed by an increase in the fall of 2022 with the rise of emm12. Data on the association of circulating non-invasive and invasive emm-types are limited. We sought to characterize and compare emm-types of pharyngeal GAS to iGAS before and after the emergence of COVID-19.Figure 1:Positive GAS pharyngeal culture, PCH ED and iGAS cases by Quarter, Utah Q1 2018 - Q1 2023

Methods

We retrospectively identified both pharyngeal and invasive GAS isolates obtained at Primary Children’s Hospital (Salt Lake City, Utah) from 2018-2023 using our GAS isolate database. Pharyngeal isolates were obtained primarily from our emergency department, while iGAS isolates were from hospitalized patients. Isolates underwent whole genome sequencing for emm typing, virulence factor identification, and phylogenetic analysis. We compared pharyngeal and invasive isolates for emm-type distribution over time and the presence of known virulence genes.Figure 2:Invasive and Pharyngeal emm-type Percentages, by Year, Utah 2018-2023

Results

From 1/2018 to 4/2023, we identified ∼650 pharyngeal GAS isolates, of which a random subsample of 306 were sequenced; 286 yielded sequences suitable for analysis. We identified 145 iGAS cases; all were sequenced. We observed a marked decrease in pharyngeal GAS from Q2 2020 through Q3 2022, followed by a steep increase which paralleled iGAS (Figure 1). The distribution of emm-types causing iGAS mirrored that of non-invasive pharyngeal isolates over time (Figure 2). Post-pandemic, emm12 and emm1 dominated both pharyngeal and invasive isolates. Comparing virulence genes between pharyngeal and iGAS isolates showed sfbl/prtF1 were strongly associated with invasive disease in emm12 and emm59 (OR: 5.0, 95% CI [2.2-11]) while the presence of sic was strongly associated with invasive disease in emm1 (OR: 16.2, 95% CI [5.6-45.9]).

Conclusion

After a marked decrease in GAS infections in children during the COVID-19 pandemic in Utah, there was a rebound of disease. Molecular analysis revealed invasive emm-types mirrored trends in pharyngeal isolates. Virulence genes sfbl/prtF1 and sic were associated with invasive disease in emm12 and emm1 respectively. Further analysis of evolutionary relatedness and virulence determinants is ongoing.

Disclosures

Krow Ampofo, MBChB, Merck: Grant/Research Support Andrew T. Pavia, MD, GSK/Haleon: Advisor/Consultant|Sanofi: Advisor/Consultant Anne J. Blaschke, MD, PhD, BioFire Diagnostics/Biomerieux: I have IP owned by the U. of Utah licensed to BioFire and receive royalties.|Merck & Co: Advisor/Consultant
P-1212. Enterovirus D68 (EV-D68) Incidence and Spectrum of Illness among Children 0-2 years in a U.S. Community-based Birth Cohort in Cincinnati, OH during 2017-2020
Authors: Teoh Zheyi , Midgley Claire , Quigley Christina M , Conrey Shannon C , Cline Allison R , Ostrow Amy , White Brendon , McMorrow Meredith L , Payne Daniel C , Morrow Ardythe L , Staat Mary A
Published: January 2025

Background

The community burden and epidemiology of non-medically attended enterovirus-D68 (EV-D68) is unknown, as prior studies focus on EV-D68-associated asthma exacerbation, pneumonia, or acute flaccid myelitis (AFM) which occurs biennially. We describe EV-D68 incidence and spectrum of illness among children 0-2 years in Cincinnati, OH during 2017-2020.

Demographic and molecular characteristics of enterovirus D68 (EV-D68) infections (n=46) in PREVAIL, 2017-2020

Methods

The PREVAIL cohort is a community-based, longitudinal birth cohort of healthy mother-infant pairs with children observed from birth to 2 years of age. Nasal swabs were collected weekly from children and tested using the PCR-based Luminex Respiratory Pathogen Panel. Swabs positive for rhinovirus/enterovirus (RV/EV) between July-December, during which the typical U.S. enterovirus season occurs, were then tested for EV-D68 by RT-PCR. Weekly text surveys and chart abstraction identified symptoms and medically attended visits. Acute respiratory illness (ARI) was defined as the presence of cough or fever within 7 days of virus detection.

Symptomatology of enterovirus D68 (EV-D68) infections (n=46), by medical attendance

Results

The PREVAIL Cohort enrolled 245 mother-infant pairs who submitted 13,781 infant nasal swabs during 04/2017-07/2020. A total of 1,424 swabs positive for RV/EV between July-December were further tested for EV-D68. Forty-six EV-D68 infections were detected, all occurring between 08/2018-11/2018; no detections occurred in 2017, 2019, or 2020. Estimated annual incidence of EV-D68 was 0.78/100 child-weeks (95%CI: 0.57-1.04) for 2018. Median age at EV-D68 infection was 7.5 months (Table 1). Of the 46 infections, 21 (46%) met ARI criteria; the remaining 25 (54%) were considered asymptomatic. Overall, cough (39%), nasal congestion (35%) or fever (26%) were the most prevalent symptoms, while diarrhea (9%) or vomiting (4%) were infrequent (Figure 1). Seven (15%) EV-D68 infections were medically attended, with 3 evaluated in an emergency department. No hospitalizations and no cases of pneumonia or AFM occurred.

Conclusion

In our community cohort of healthy children aged < 2 years, less than half of EV-D68 infections met ARI criteria (46%), and 15% were medically attended; none required hospitalization. Prospective multi-year cohort studies in all ages would be valuable for understanding the full spectrum of symptoms, and burden of EV-D68.

Disclosures

Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
P-1213. Optimizing the synergy between Aztreonam & Avibactam for NDM plus OXA48 producing Carbapenem resistant Klebsiella pneumoniae infections: an innovative infusion method
Authors: Soman Rajeev , Gandhi Aashna , Kedare Noopur , Joe Geethu , Patil Saiprasad , Pednekar Amullya , Barkate Hanmant
Published: January 2025

Background

Ceftazidime-avibactam (CAZ AVI) along with aztreonam (ATM) is used off-label for NDM+OXA48 producing carbapenem resistant Klebsiella pneumoniae (CR Kp). If the level of AVI is maintained at 2.5 μg/ml, it protects ATM from OXA48 & allows it to act against such CR Kp. In such a situation the MIC to ATM has been found in a published report to be 2 μg/ml.

Table shows the measured protein bound drug levels. Estimated free drug levels are shown in brackets.

Methods

We used CAZ AVI (CAZ 2 grams and AVI 0.5 gram) infusion over 3 hours & ATM 2 grams infusion over the 2nd half an hour as shown in figure 1, in 5 patients infected with NDM+OXA48 CR Kp, as a proof-of-concept PK study. The rationale of starting the ATM infusion after the CAZ AVI infusion is begun is to allow AVI levels to build up & prevent inactivation of ATM by ESBL & OXA48. The administration of ATM over half an hour, rather than by a more prolonged infusion, may ensure a relatively high initial level of ATM, which is expected to remain for a considerable time owing to its long half life.

Infusion strategy for Ceftazidime-Avibactam (CAZ-AVI) & Aztreonam (ATM)

Results

After measurement of protein bound levels, free AVI (fAVI) & free ATM (fATM) levels were estimated from the known extent of protein binding. As shown in table 1, all levels of estimated fAVI were above 2.5 mcg/ml. The estimated levels of fATM, at 5 hours after beginning the infusion were at or above 15.6 mcg/ml, with a mean of 45.6 mcg/ml & range of 15.6 to 98.2 mcg/ml. Hence time above 4 times the assumed ATM MIC of 2 mcg/ml, for more than 50% of the dosing interval was easily achieved in all the patients.

Conclusion

Thus, the PK/PD index obtained is higher than that needed for optimal killing & can suppress resistance which may be useful from the perspective of antimicrobial stewardship.

Disclosures

Rajeev Soman, MBBS, MD (General Medicine), FIDSA, Astellas: Honoraria|Biomeriux: Honoraria|Cipla: Honoraria|Emcure: Honoraria|Gilead: Honoraria|Glenmark: Honoraria|Gufic: Honoraria|Intas: Honoraria|MSD: Honoraria|Mylan: Honoraria|Pfizer: Honoraria Saiprasad Patil, Global Medical Affairs, Glenmark Pharmaceuticals Limited: Employee Amullya Pednekar, Global Medical Affairs, Glenmark Pharmaceuticals Limited: Employee Hanmant Barkate, Global Medical Affairs, Glenmark Pharmaceuticals Limited: Employee
P-1215. Evaluation of Vancomycin AUC/MIC Ratio in Indian Patients with Enterococcal Infections: Impact on Clinical Outcomes and Nephrotoxicity
Authors: Sebastian Albin , Raju Jomel , Tom Maria
Published: January 2025

Background

Vancomycin is commonly used to treat enterococcal infections, but its optimal dosage remains uncertain in Indian patient populations. This study aimed to investigate the relationship between vancomycin AUC/MIC ratio and clinical outcomes, as well as nephrotoxicity, in Indian patients with documented enterococcal infections. Understanding this relationship is crucial for optimizing treatment strategies and improving patient outcomes in this context.

Methods

Data were collected retrospectively from medical records of 71 patients who received vancomycin with therapeutic drug monitoring at a single center in India between April 2015 and March 2022. Vancomycin AUC0–24 was calculated using a Bayesian technique, while MIC was determined using the VITEK 2 automated microbiology system. The AUC0–24/MIC ratio was computed for the initial 72 hours of therapy. Statistical analysis was conducted to assess the association between vancomycin AUC/MIC ratio and clinical outcomes, as well as nephrotoxicity.

Results

The cohort comprised 71 participants meeting the inclusion criteria. Results indicated that a vancomycin AUC/MIC of ≥400 mg·h/L exhibited significant differences in clinical response (aHR: 0.49, 95% CI: 0.21–0.98; p = 0.044) and microbiological response (aHR: 0.41, 95% CI: 0.17–1.08; p = 0.039) compared to AUC/MIC < 400 mg·h/L. However, patients with AUC/MIC ≥400 mg·h/L had a higher incidence of nephrotoxicity compared to those with AUC/MIC < 400 mg·h/L (aHR: 3.41, 95% CI: 1.11–15.83; p = 0.033). Elevated vancomycin concentrations may lead to declining renal function. Moreover, declining renal function could result from factors such as failure to resolve the infection focus or co-administration of other antibiotics, potentially leading to higher AUC/MIC ratios. The study identified a target vancomycin AUC/MIC of ≥400 mg·h/L, suggesting its optimality for monitoring the treatment of enterococcal infections in the Indian context.

Conclusion

In Indian patients with enterococcal infections, a vancomycin AUC/MIC of ≥400 mg·h/L is associated with improved clinical and microbiological responses but may increase the risk of nephrotoxicity. Therefore, careful monitoring of vancomycin dosage and renal function is essential to optimize treatment outcomes in this population.

Disclosures

All Authors: No reported disclosures