bluuebunny/crossref_metadata_2025 huggingface dataset:
P-953. Infection prevention certificate exam performance: ChatGPT 4 vs ChatGPT 3.5
Authors: Saravanakumar Saujanya , Dorairajan Sureshkumar , Naveen Jenifer , Shobana S
Published: January 2025

Background

In recent times, AI models were utilized to evaluate competitive examinations such as the US medical licensing examination and clinical case conferences. However, there was limited data on their evaluation in infection control certificate examinations, known for their inclusion of complex questions. In this study, we aimed to assess the performances of ChatGPT-4 and ChatGPT-3.5 models in handling infection control certification examinations, providing insights into their efficacy in infection prevention.

Methods

This cross-sectional study, conducted by an infectious disease (ID) physician, involved an ENT resident, an ID physician assistant, and a Pharm D student. Questions were sourced from the International infection control certification examination and underwent complexity validation and answer approval by international infection prevention professionals. Each model, ChatGPT-4 and ChatGPT-3.5, received questions separately, and their answers were cross-checked with validated responses by the team. Statistical analysis employed the Chi-square test to assess performance differences. Data were collected in an excel sheet for subsequent analysis.

Results

In the evaluation of 96 infection control examination questions, ChatGPT-4 outperformed ChatGPT-3.5, achieving an accuracy of 82.3% (79 out of 96 questions answered correctly) compared to ChatGPT-3.5's accuracy of 65.6% (63 out of 96) as shown in table -1 below. Statistical analysis using a Chi-square test confirmed a significant difference between the two models (p < 0.05), highlighting the advancements in ChatGPT-4's capabilities. ChatGPT-4 excelled in contextual comprehension, while ChatGPT-3.5 struggled with adaptability in managing complex queries.

Conclusion

In this study, ChatGPT-4's accuracy of 82.3% exceeded that of ChatGPT-3.5, which achieved 65.6%. Future research should compare other AI models and analyse each question for contextual understanding to enhance AI models performance in infection prevention.

Disclosures

All Authors: No reported disclosures
374. Early Discontinuation of Empiric Antibiotics for Febrile Neutropenia in Pediatric Allogeneic Haploidentical Hematopoietic Cell Transplant Recipients
Authors: Castejon Ramirez Sandra , Ferrolino Jose Amadeo A , Allison Kim J , Merritt Pamela , Peterson Megan , Cole Amanda , Davis Amber , Gowen Ashleigh , Tang Li , Luo Guangjin , Dallas Ronald H , Wattier Rachel L , Hijano Diego R , Maron Gabriela
Published: January 2025

Background

Febrile neutropenia (FN) occurs in 80-90% of haploidentical hematopoietic cell transplants (haplo-HCT), but most patients do not have documented infections. Empiric antibiotics are frequently continued until neutrophil recovery, even when there is no evidence of infection. Shorter antibiotic courses to decrease antibiotic exposure have been studied in adult HCT recipients and have demonstrated safety compared to conventional management. In 2017 we implemented a strategy to discontinue antibiotics at ≤ 72 h in stable haplo-HCT patients with FN and no evidence of infection. In this study, we evaluate the implementation and outcomes of this practice.Figure 1.A. Mean antibiotic-free days across the study period. B. Individual antibiotic-free days in EAD and LAD

Methods

This single-center retrospective cohort included patients < 24 years old who underwent haplo-HCT from 2010 to 2022 with ≥ 1 episode of FN and no documented infection. They were classified by time period as follows: late antibiotic discontinuation (LAD) vs. early antibiotic discontinuation < 72 h (EAD). The primary outcome was antibiotic-free days. The secondary outcomes were subsequent breakthrough bloodstream infection (BSI), intensive care unit (ICU) admission, septic shock, mortality, and practice fidelity (adherence) and sustainability.Figure 2.Fidelity to implemented practice across time

Results

We included 230 patients (117 in LAD, 113 in EAD). No differences in age, sex, or race were observed. A higher proportion of patients received myeloablative conditioning regimens in LAD (p < 0.01, Table 1). There were more antibiotic-free days after EAD implementation (Figure 1), but no differences in the incidence of breakthrough bloodstream infections (EAD: 6.1%, LAD: 5.1%, p= 0.81) or other adverse clinical outcomes. There was no infection-related mortality in either group (Table 1). The fidelity (adherence) to recommended practice of discontinuing antibiotics ≤72 hours was 61.6%, with increase over time (Figure 2).

Conclusion

Implementation of EAD strategy for FN in haplo-HCT patients led to an increase in antibiotic-free days during the first 30 days post-HCT. Adverse clinical outcomes were infrequent in both groups and did not significantly increase after EAD. Prospective multicenter studies are required to evaluate the safety of EAD strategies.

Disclosures

Diego R. Hijano, MD, MSc, FDA: Grant/Research Support|Merck: Grant/Research Support|National Institute of Health: Grant/Research Support Gabriela Maron, MD, MS, Astellas Inc: Grant/Research Support|NIH: Grant/Research Support|SymBio Pharma: Advisor/Consultant|SymBio Pharma: Grant/Research Support
P-997. Congenital Cytomegalovirus and Hearing Loss and Response to Treatment with Valganciclovir
Authors: Mark Salzman B , Lin Lisa C
Published: January 2025

Background

Congenital cytomegalovirus (CMV) occurs in about 1 in 200 babies and is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children in the United States. Approximately 50% of children with SNHL secondary to CMV have progression of their hearing loss. Data on the effectiveness of valganciclovir in the treatment of infants with congenital CMV with isolated hearing loss at birth is limited.

Methods

All newborns who did not pass their newborn hearing screening at birth between 2019-2023 were included and tested for CMV by a nucleic acid test from saliva and if positive confirmed from urine. All infants with CMV detected in urine had a Brainstem Auditory Evoked Response (BAER) test by 2-3 weeks of life and if hearing loss was confirmed, offered treatment with valganciclovir for 6 months. Infants who only had CMV detected in the saliva were not included.

Results

204,680 newborns received hearing screens between 2019-2023. 7147 (3.5%) did not pass their hearing screening. 509 (7.1%) had hearing loss confirmed on BAER testing. 46 of the 7147 infants who did not pass their initial hearing screen had CMV detected in saliva and 17 of those had CMV detected in urine. 5 patients never received a urine test and were lost to follow-up. Among 17 cases with confirmed congenital CMV, 9 had confirmed hearing loss, 7 had normal hearing, and one lost to follow-up. 12 of the 17 cases were treated with valganciclovir, 8 with confirmed hearing loss, 3 with normal hearing, and one unknown. Among the 8 treated with hearing loss, 3 had progression of hearing loss, one improved, one was unchanged, and 3 lost to follow-up. Among the 7 with congenital CMV and normal hearing at birth, 3 were treated with valganciclovir and 2 remain with normal hearing with one to be determined. Among the 4 not treated, 3 remain with normal hearing and one was lost to follow-up.

Among the 6638 with normal hearing on follow-up, 7-13 had congenital CMV (1 in 511-948). Among the 509 with confirmed hearing loss, there were 9 (1.8%) who had congenital CMV.

Conclusion

Congenital CMV was found in only 1.8% of newborns with hearing loss and about 0.15% of newborns without hearing loss. Treatment with valganciclovir did not appear to be beneficial in preventing the progression of hearing loss in some newborns but the numbers were too small to reach a conclusion.

Disclosures

All Authors: No reported disclosures
P-999. Novel diagnostic tools to enhance early detection of congenital Chagas disease
Authors: Nolan Melissa , Lic Stanley Rodriguez , Katie Lynn M , Meyer Madeleine M , Lee Chris , Campbell Berry
Published: January 2025

Background

Chagas disease (CD), Trypanosoma cruzi infection, is a neglected vector-borne disease endemic in Latin America for which < 1% of cases have been treated. WHO estimates that ∼9,000 infected neonatal cases occur annually via vertical transmission—US CDC estimates up to ∼300 incident neonatal cases annually. Maternal and neonatal misdiagnosis are principally attributed to the paucity of accurate diagnostic tools for this complex chronic parasitic infection, with current guidelines requiring confirmation testing at >9 months of age—a significant barrier for vulnerable populations already experiencing healthcare access limitations.

Methods

A maternal-infant CD program was established in Sonsonate, El Salvador through a collaboration between flagship universities and the Ministry of Health. Employing machine learning methods, we developed a histology-based parasite image recognition application to aid in triaging of at-risk cases. Second, we developed an innovative diagnostic workflow integrating Bayesian statistics and novel digital PCR methods to validate a new diagnostic tool for enhanced disease detection among mothers-infants.

Results

Since March 2022, a 6% seropositivity was noted among parturition women. Maternal CD status was significantly associated with pregnancy complications and neonatal complications (Apgar < 9 at 1 min and at 5 mins, NICU admission, et al). A customized convolutional neural network design employed on bifurcated Giemsa-stained blood smears revealed >90% parasite detection accuracy. Lastly, McNemar’s statistic found significantly increased diagnostic capacity between our novel dPCR approach vs conventional qPCR. Specifically, dPCR was 2.74 times more likely to detect parasitic DNA in maternal blood than qPCR; 9.5 times more likely in placental tissue; 4.5 times more likely in cord tissue.

Conclusion

Congenital transmission is a growing international clinical concern. Our preliminary results provide compelling evidence for both the need of novel diagnostics and support for incorporation of study-developed cutting-edge diagnostics to aid in timely clinical management of congenital CD.

Disclosures

All Authors: No reported disclosures
P-1045. Decreasing Frequency of Invasive Aspergillus due to Aspergillus terreus Coinciding with the Introduction of Anti-Mold Azole Prophylaxis: A 30 Year Study of Invasive Aspergillosis at a Tertiary Cancer Center
Authors: Dagher Hiba , Hachem Ray Y , Haddad Andrea , Jiang Ying , Kontoyiannis Dimitrios P , Shrestha Jishna , Sherchan Robin , Lamie Peter , Makhoul Jennifer , Chaftari Patrick , Chaftari Anne-Marie , Raad Issam I
Published: January 2025

Background

Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in patients with haematological malignancy (HM) patients and hematopoietic stem cell transplant (HSCT) recipients. A. terreus is well known to be more resistant to amphotericin B regimens and is associated with worse outcomes as compared to non-terreus Aspergillus species. After the first introduction of effective anti-mold azole in May 24,2002, there has been limited data showing the change in in etiology of culture documented IA. We retrospectively reviewed all HM and HSCT patients with a positive culture of Aspergillosis who were treated for either definite or probable IA over the past three decades (1993-2023).

Methods

We compared baseline characteristics, antifungal prophylaxis and treatment between patients infected with A. terreus and those infected with non-terreus Aspergillus between July 1993 and July 2023 with a follow up period of 12 weeks. We examined the rate of A. terreus across the 3 decades 1993 – 2003, 2004 – 2013, and 2014-2023.

Results

A total of 699 patients with culture -documented IA were analyzed, 537 with A. non-terreus species and 162 with A. terreus. Type of underlying malignancy (HM and HSCT), neutropenia as well as GVHD were similar in both groups. Anti-mold prophylaxis was similar in both groups. After the introduction of anti-mold azoles, the rate of A. terreus decreased significantly from 35.9 % between 1993-2003 to 11.2% between 2004-2013 (p< 0.0001) and from 35.9% between 1993-2003 to 16.7% between 2014-2023 (p< 0.0001). ICU stay and mechanical ventilation were more common among patients with A. terreus (p=0.002). All-cause mortality at 6 weeks and at 12 weeks was significantly higher in patients with A. terreus (p< 0.01). Similarly, IA-associated 6 weeks mortality was significantly higher among patients with A. terreus (43 % vs 29%, p< 0.01).

Conclusion

The rate of IA due to A. terreus decreased significantly with the introduction of anti-mold azoles. However, IA caused by A. terreus continues to have poor prognosis in HM patients.

Disclosures

Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant
P-1050. A Decade of Pneumocystis jirovecii Pneumonia: a Single-Center Retrospective Analysis in Both HIV and Non-HIV Populations
Authors: Oliveira Susana Ramos , Bacelar Clara , Azeredo Constança , Gonçalves Maria João , Duarte Frederico , Pena Eduarda , de Abreu Ricardo Correia , Jordão Sofia
Published: January 2025

Background

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic disease, commonly occurring in individuals with human immunodeficiency virus (HIV) or immunodepression. This study analyzes PJP cases in our local setting, detailing the epidemiological and clinical characteristics, as well as prognosis, and underlying diseases.

Methods

Retrospective analysis of adult inpatient PJP cases (2014-2023). Diagnosis was presumptive (epidemiological, clinical, and imaging findings), or confirmed microbiologically. Statistical analysis utilized the chi-square test.

Results

Forty-two patients were identified: 66% male, median age of 47.5 years [25-83]. Seventy-four percent were HIV positive, with a median CD4+ count of 35 [1-347]. All had detectable HIV viral load, except one (suppressed for years, but with a new diagnosis of neoplasm). Non-HIV patients (26%) underlying diseases included hematological (n=6) or solid-organ malignancies (n=1), autoimmune diseases under corticosteroid therapy (n=2), pulmonary interstitial disease (n=1), and granulomatous systemic disease under investigation (n=1). Eighty-six percent had peripheral lymphopenia at diagnosis, and only one patient was receiving regular prophylaxis. The incidence of non-HIV patients significantly increased in the latter 5 years (5.5% vs 42%, p=0.008). Diagnosis was confirmed by positive direct antibody fluorescence staining in half of the patients. No molecular biology techniques or B-D-glucan assays were available. Seventeen (40%) patients required admission to level II or III units, of which 23% required invasive mechanical ventilation and 35% high-flow oxygen. Treatment included cotrimoxazole (n=40) and atovaquone (n=2). One-third of patients had cytomegalovirus reactivation, requiring antiviral therapy. Non-HIV patient mortality was significantly higher than HIV patients (45% vs 13%, p=0.023). Fifteen percent of survivors were readmitted within 30 days.

Conclusion

The epidemiology of PJP is evolving, with a noticeable increase in non-HIV cases, which are associated with significantly higher mortality despite appropriate treatment. Authors emphasize the importance of identifying new risk groups for chemoprophylaxis to improve prognosis.

Disclosures

All Authors: No reported disclosures
P-1054. BTK drives neutrophil activation for sterilizing antifungal immunity
Authors: Zarakas Marissa Agathonia , Desai Jigar , Wishart Andrew , Cunha Cristina , Carvalho Agostinho , Hohl Tobias M , Lionakis Michail S
Published: January 2025

Background

Bruton’s tyrosine kinase (BTK) is a critical component of B-cell receptor signaling and regulates B-cell proliferation and survival. Ibrutinib is an irreversible inhibitor of BTK and is successfully used in treatment of various B-cell malignancies. However, it has been associated with increased risk for invasive aspergillosis (IA).

Model of BTK-dependent responses promoting neutrophil activation in response to Aspergillus fumigatus.

Methods

To shed light in the susceptibility of ibrutinib-treated patients, we studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, BTKi-treated patients, and X-linked agammaglobulinemia patients.

Results

In response to fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcγR-dependent manner, leading to oxidative burst. BTK inhibition selectively impaired neutrophils’ capacity to damage Aspergillus hyphae, release primary granules and induce oxidative burst by impeding the activation of NADPH oxidase subunit p40phox and GTPase RAC2. Similarly, we found impaired neutrophil function in Aspergillus-infected, neutrophil-specific Btk deficient mice, whereas neutrophil recruitment and survival were spared. These defects were partially mitigated by GM-CSF via enhancing p47phox activation, supporting a role for GM-CSF use in susceptible patients. The presence of the BTK rs5951308 (T >C; E24G) in donors of allogeneic hematopoietic transplant recipients was independently associated with increased risk of IA.

Conclusion

Our data uncover a previously unappreciated role for BTK in fungal immune surveillance against Aspergillus fumigatus.

Disclosures

All Authors: No reported disclosures
P-1062. In vitro Activity of Gepotidacin and Comparator Agents against a Collection of K. pneumoniae Urine Isolates from the United States During 2019-2022
Authors: Ryan Arends S J , Kapoor Renuka , Torumkuney Didem , Mendes Rodrigo E
Published: January 2025

Background

Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a unique mechanism of action, a distinct binding site and provides well-balanced inhibition (for most uUTI uropathogens) of two different type II topoisomerase enzymes. This study reports on the in vitro activity of gepotidacin and other oral antibiotics tested against contemporary Klebsiella pneumoniae clinical isolates collected from patients with urinary tract infections (UTI) in the United States as part of a gepotidacin global uropathogen surveillance study.

Methods

A total of 2,001 K. pneumoniae isolates were collected during 2019-2022 from 73 medical centres located in the United States. All isolates were tested for susceptibility by CLSI methods at a central laboratory (Element Iowa City). MIC results for comparator agents were interpreted per CLSI guidelines. MIC results for oral antibiotics approved for the treatment of uncomplicated UTI. Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) subsets were interpreted per CLSI criteria.

Results

Gepotidacin (MIC50/90, 4/16 mg/L) displayed activity against 2,001 K. pneumoniae isolates (Table), with 94.9% of all observed gepotidacin MICs ≤ 16 mg/L. Susceptibility rates of oral comparators tested were ≤ 90.0% for amoxicillin-clavulanic acid (90.0%, MIC50/90, 2/8 mg/L), ciprofloxacin (86.3%, MIC50/90, 0.015/0.5 mg/L), levofloxacin (88.3%, MIC50/90, 0.06/1 mg/L), nitrofurantoin (34.0%, MIC50/90, 64/ > 128 mg/L), and trimethoprim-sulfamethoxazole (84.7%, MIC50/90, ≤ 0.12/ > 4 mg/L) (Table). Gepotidacin remained active against the 11.0% and 6.8% of K. pneumoniae isolates that displayed ESBL and MDR phenotypes, respectively, with observed MIC50/90 values of 8/32 mg/L for both.

Conclusion

Gepotidacin demonstrated potent in vitro activity against contemporary K. pneumoniae, including ESBL-producing and MDR isolates. Almost all oral comparator agents reported against US K. pneumoniae UTI isolates had susceptibility rates between 80-90% while the observed nitrofurantoin susceptibility rates were 34.0%, respectively.

Disclosures

Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1068. Inhibitory Effect of EDTA on Metallo β-Lactamase Producing Gram-Negative Pathogens Recovered from Cancer Patients with Bloodstream Infections
Authors: Raad Issam I , Rosenblatt Joel , Truong Y Lan , Gerges Bahgat Z , Jiang Ying
Published: January 2025

Background

The spread of metallo β-lactamase (Mβ-L) producing Gram negative pathogens is an important worldwide medical problem. It presents the broadest-spectrum β-lactam resistance of all carbapenemase-producing organisms leaving few remaining treatment options. Previously, adding EDTA, a potent metallo-chelator, was shown to restore activity for antibiotic combinations against Mβ-L pathogens isolated from patients with urinary tract and bronchial infections. In this study, we evaluated in vitro efficacy of EDTA alone and in combination with different β-lactam/β-lactamase inhibitors against Mβ-L isolates recovered from cancer patients with bloodstream infections (BSIs).

Methods

: EDTA over its concentration range was tested alone and in combination with cefepime (FEP)/Avibactam (AVI), and FEP/Tazobactam (TAZ) against ten Mβ-L blood clinical isolates {E.coli (n=6), K. oxytoca (n=2), P. aeruginosa (n=1), and E. cloacae (n=1)}. CLSI approved broth microdilution methods were used to measure MIC. MIC50, MIC90, MIC ranges, and susceptibility rate calculations were made according to CLSI 2022. The provisional breakpoints susceptibilities of FEP/AVI, FEP/AVI/EDTA are ≤8/4 while the provisional breakpoints for FEP/TAZ, and FEP/TAZ /EDTA are =≤2/4. Statistically, significant differences were determined using Fisher’s exact test (P≤0.05 is considered significant).

Results

Table 1. presents MIC50, MIC90, MIC ranges, susceptibility rates, and P values comparing EDTA with different concentrations alone and in combination with a range of FEP/AVI, and FEP/TAZ dilutions against ten Mβ-L bloodstream isolates.

Conclusion

EDTA alone at 100 mg/L, and 300 mg/L concentrations inhibited 100% of Mβ-L blood isolates, while 10 mg/L, and 50 mg/L inhibited 10%, and 90% of tested isolates respectively. The combination of 10 mg/L EDTA with FEP/AVI, and FEP/TAZ, synergistically improved the susceptibility rates from only10% (without EDTA) to 100% (at only10 mg/L EDTA). The differences in MICs, and susceptibility rates between the triple and double combinations were highly significant (P < 0.0001). Further studies are needed to show the synergy against a larger number of Mβ-L Gram negative BSI pathogens as well as to clinically verify these benefits.

Disclosures

All Authors: No reported disclosures
P-1072. Evaluation of the Spontaneous Mutation Frequencies of SPR719 Alone and in Combination with Other Agents Used to Treat Mycobacterium avium Complex Pulmonary Disease
Authors: Pillar Chris , Walser Olivia , DeLaet Naomi , Leer Zach , Thwaites Mary , Hufnagel David A , Cotroneo Nicole , Critchley Ian A , Hamed Kamal
Published: January 2025

Background

SPR720 (fobrepodacin), a novel oral benzimidazole prodrug that inhibits the ATPase activity of mycobacterial DNA gyrase B, is being developed for treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD). SPR719, the active moiety of SPR720, has previously demonstrated antimycobacterial activity against nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), the most common causative agent of NTM-PD.

Methods

In this study, the spontaneous mutation frequencies (SMFs) of MAC ATCC 700898 (macrolide-susceptible) and a clinical macrolide-resistant MAC isolate (MMX 9461) were evaluated in the presence of SPR719 alone, standard-of-care antimycobacterial agents (clarithromycin, ethambutol, and rifampin) alone, and for SPR719 in combination with these agents. The minimal inhibitory concentrations (MICs) for SPR719 and comparators against the NTM were determined by agar dilution. SMFs were determined by plating a high inoculum (108-109 colony forming units) on selective agar prepared at 2-, 4-, and 8-fold the MIC for SPR719, and at 4-fold the MIC for comparator agents. SMFs were also determined for SPR719 in combination with antimycobacterial agents where SPR719 was evaluated at 2-fold the MIC and a paired agent was evaluated at 4-fold the MIC. Putative mutants were patched from selection plates onto agar containing the selection drug, and susceptibility was then evaluated by broth microdilution alongside the parent isolate.

Results

All concentrations of SPR719 alone and in combination with other agents prevented growth of both isolates, resulting in low SMFs for SPR719 (< 2.21 × 10-9 and < 7.14 × 10-11). In contrast, mutants were readily selected with rifampin (SMF of 2.55 × 10-8 and 1.99 × 10-8) and clarithromycin (SMF of 1.16 × 10-8), and these mutants exhibited elevated MIC values ≥ 4-fold the MIC of the parent by broth microdilution. Colonies emerged during selection with ethambutol but were unstable and did not grow when patched onto ethambutol-containing agar.

Conclusion

The low propensity for the development of resistance against the novel agent SPR719 alone and in combination with other agents is important because emergence of resistance is a clinical concern in the setting of prolonged combination therapy for NTM-PD.

Disclosures

Nicole Cotroneo, B.S., Spero: Advisor/Consultant Ian A. Critchley, PhD, Spero: Employee Kamal Hamed, MD, MPH, Spero: Employee
P-1078. Gentamicin-releasing polydopamine catheter coating to prevent urinary catheter-related infections
Authors: Su Gillian , Karp Hannah , Schulz Michael , Rao Jayasimha , Nowak Elizabeth , Sriranganathan Nammalwar
Published: January 2025

Background

Catheter-associated urinary infections (CAUTIs) are among the most common healthcare-associated infections in the United States. The risk of CAUTI corresponds to the duration of catheterization; prolonged catheter uses impacts patient morbidity, mortality, and healthcare costs. Pseudomonas aeruginosa is a leading cause of CAUTI and is particularly adept at forming surface-associated biofilms that are difficult to treat. In the present study, we developed a catheter coating using polydopamine (PD) to embed gentamicin on the surface.

Bacterial Viability of PAO1 when exposed to PD-gentamicin coating

Colony-forming unit (CFU) count of PAO1 exposed to concentration series of PD-only and PD-Gent well plate coating.

Methods

Coating synthesis: PD-antibacterial coating was synthesized using dopamine hydrochloride salt and antibiotic drugs (i.e., gentamicin) in an alkaline buffer in the presence of polyvinyl chloride (PVC) tubing. A similar procedure was used for the well-plate study using 150 µL of solution per well, followed by heating at 60 °C.

Biofilm Quantification: PAO1 was added to a 96-well plate or tubes and incubated statically for 24 h. Biofilms were stained with 0.1% crystal violet, solubilized with 33% glacial acetic acid, and measured at OD590 nm.

Cell viability: Colony forming units were measured using 10-fold serial dilutions on TSA agar.

Biofilm formation of PAO1 after incubation with PD-gentamicin coating in PVC tubes

PAO1 biofilm concentration changes with changing the PD to gentamicin ratio during coating synthesis.

Results

PD-gentamicin coated tubes and 96-well plates showed elimination of PAO1 viability at PD concentrations of 0.25 mg/mL and above but had little bactericidal effect at lower concentrations (Fig. 1). There was no reduction in viability in PAO1 exposed to PD or gentamicin alone. PAO1 biofilm was reduced in the median PD-gentamicin concentrations 0.1-0.5 mg/mL, but this effect was lost at the extremes of concentration (Fig. 2).

Conclusion

The PD-gentamicin coating eliminated PAO1 viability and reduced biofilm at PD concentration 0.25 mg/mL. Similar results were observed in 96-well plates and PVC tubes, suggesting versatility in the adherence of the coating material. Additional studies are needed to assess the duration of these effects over time.

Disclosures

All Authors: No reported disclosures
P-1080. Aztreonam-Avibactam Activity Against Gram-negative Bacteria Isolated from Patients with Pneumonia from Europe, Asia, and Latin America (2021–2023)
Authors: Sader Helio S , Kimbrough Hank , Arends S J Ryan , Winkler Marisa , Mendes Rodrigo E , Castanheira Mariana
Published: January 2025

Background

Aztreonam-avibactam (ATM-AVI) is under development to treat Gram-negative (GN) infections. We evaluated the antimicrobial susceptibility of GN bacilli causing pneumonia

Activity of β-lactamase inhibitor combinations

Methods

7,560 organisms were consecutively collected (1/patient) from patients with pneumonia in 59 medical centres located in Western Europe (W-EU; 10 countries; 24 centres; 3,977 isolates), Eastern Europe (E-EU; 9 countries; 15 centres; 1,617 isolates), the Asia-Pacific region (APAC; 7 countries; 12 centres; 1,238 isolates), and Latin America (LATAM; 6 countries; 8 centres; 728 isolates). Isolates were susceptibility tested by broth microdilution. Cefiderocol was only tested against carbapenem-resistant Enterobacterales (CRE). CLSI breakpoints were applied. An ATM-AVI PK/PD susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. CREs were screened for carbapenemase-encoding genes by whole genome sequencing.

Results

ATM-AVI inhibited >99.9% of Enterobacterales (ENT) at ≤8 mg/L (MIC50/90, 0.06/0.25 mg/L) and showed consistent activity across regions (Table). Only 2 ENT had an ATM-AVI MIC >8 mg/L, an E. cloacae (Italy) and a K. pneumoniae (Taiwan). CRE rates ranged from 1.3% (W-EU) to 20.5% (LATAM). Multidrug-resistance (MDR; non-S to ≥3 classes) rates varied from 20.2% (W-EU) to 47.2% (LATAM). ATM-AVI retained potent activity against CRE (MIC50/90, 0.25/0.5 mg/L; 99.7% inhibited at ≤8 mg/L) and MDR ENT (MIC50/90, 0.12/0.5 mg/L; 99.9% inhibited at ≤8 mg/L). Cefiderocol was active against 95.8% of CRE. Ceftazidime-avibactam (CAZ-AVI; 61.7% S), meropenem-vaborbactam (MEM-VAB; 52.8%S), and imipenem-relebactam (IMI-REL; 44.5% S) showed limited activity against CRE and S rates varied greatly among regions. A metallo-β-lactamase was identified in 35.8% of CREs, varying from 23.8% in LATAM to 60.3% in APAC. IMI-REL (95.3% S), CAZ-AVI (94.7% S), and ceftolozane-tazobactam (TOL-TAZ; 93.3% S) were the most active agents against P. aeruginosa; whereas ATM-AVI inhibited 79.5% of isolates at ≤8 mg/L and 76.1% were piperacillin-tazobactam (PIP-TAZ)-S. ATM-AVI inhibited 98.9% of S. maltophilia isolates (n=440) at ≤8 mg/L.

Conclusion

ATM-AVI was the most active compound against CRE and S. maltophilia isolated from patients with pneumonia.

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 Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1088. Safety Study of Rifaquizinone in Dogs Following Intra-articular Administration
Authors: Wang Huan , Cheng Qin , Ke Weijian , Ma Zhenkun
Published: January 2025

Background

Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of prosthetic joint infections (PJIs). RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. This study sought to investigate the safety/tolerability of RFQ following intra-articular (IA) administration in Beagle dogs.

Methods

Forty Beagle dogs (20/sex) were randomly assigned to 4 groups (5/sex/group) to receive 0, 1, 2.5, and 5 mg/kg/day RFQ in 5% (w/v) glucose once daily for 14 days by IA administration into the right knee joint. All the dogs had a 14-day recovery period to assess the reversibility, persistence, or delayed occurrence of adverse effects. Blood and synovial fluid samples were collected and concentrations of RFQ in each matrix were determined by liquid chromatography tandem mass spectrometry.

Results

No test article-related adverse effects in body weight, food consumption, temperature, clinical pathology, or organ weight were observed in any of the study groups. In 2.5 and 5 mg/kg/day groups, lameness, swelling and ulceration of right knee joint during treatment were observed. The 5 mg/kg group dosing was terminated prematurely due to marked arthritis on right knee joint. The no observed adverse effect level (NOAEL) was 1 mg/kg/day. At this dose level the steady state of RFQ concentrations in synovial fluid was achieved in 4 days and maintained until Day 14 (Figure 1). The mean RFQ concentrations on Day 14 in synovial fluids for male and female dogs were 35,900 and 19,200 ng/mL, respectively, as compared to the plasma Cmax 411 and 303 ng/mL for male and female dogs, respectively. Plasma toxicokinetics (TK) analysis indicated no apparent sex differences in systemic exposure at any dose level.

Conclusion

The NOAEL of RFQ in dogs was 1 mg/kg/day via IA administration. The synovial fluid concentration at this dose level exceeded minimum biofilm bactericidal concentration inhibit 90% bacterial growth (MBBC90) levels for both S. aures and S. epidermidis. IA administration of RFQ is a promising option for the treatment of PJIs.

Disclosures

Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Qin Cheng, Master, TenNor Therapeutics (Suzhou) Ltd: Employee Weijian Ke, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee
P-1096. Activity of Ibrexafungerp and Comparator Antifungals Tested against Candida and Aspergillus Isolates Collected from Invasive Infections in a Global Surveillance Program in 2023
Authors: Winkler Marisa , Rhomberg Paul , Klauer Abigail , Edeker Samuel , Min Sharon , Castanheira Mariana
Published: January 2025

Background

Ibrexafungerp (IBX) is a novel triterpenoid antifungal agent that was approved by the U.S. FDA for the treatment of vulvovaginal candidiasis (VVC) in 2021. Further studies are ongoing to assess the efficacy of IBX for the treatment of invasive candidiasis (IC) and other refractory fungal infections, including aspergillosis. CLSI, EUCAST, or FDA clinical breakpoints or epidemiological cutoff values are not yet defined for IBX against fungi. We evaluated the activity of IBX and comparator agents against clinical isolates from IC and invasive aspergillosis infections collected from a global surveillance program in 2023.

MIC50/90 (mg/L) for ibrexafungerp (IBX) and comparator agents against 5 most common Candida spp., C. auris, and 3 most common Aspergillus spp. in 2023 SENTRY Antifungal Surveillance Program

Methods

A total of 1120 Candida spp. and 204 Aspergillus spp. isolates consecutively collected as part of the SENTRY Program were evaluated. Isolates were recovered from 11 medical centers in North America, 18 in Europe, 7 in Asia-Pacific, and 5 in Latin America. Identification was performed by MALDI-TOF MS and/or sequencing and susceptibility testing was performed using the CLSI broth microdilution method for IBX, anidulafungin (AND), micafungin (MFG), fluconazole (FLC), itraconazole (ITC), and voriconazole (VRC).

Results

Table 1 displays MIC50/90 results for the 5 most common Candida spp., C. auris, and the 3 most common Aspergillus spp. The IBX MIC50/90 results were low against all organisms including organisms of critical concern like C. auris. Among Candida species, IBX had similar or higher MIC50/90 to AND except for C. parapsilosis where IBX MIC50/90 values were 4- to 8-fold lower. MFG was more potent (4- to 16-fold) against most Candida spp. except for C. parapsilosis where IBX had 2-to 4- fold lower MIC50/90 and C. auris where IBX was similar to MFG. Notably, the highest MIC result observed for IBX against C. auris was 1 mg/L. MIC50/90 values for IBX were also 8- to > 256-fold lower than azoles against Aspergillus spp. but higher (2- to ≥ 16-fold) than MFG or AND.

Conclusion

IBX has good activity against the predominant Candida and Aspergillus species from a worldwide contemporary collection. This agent may represent an oral option for the management of difficult-to-treat invasive fungal pathogens such as C. glabrata, C. auris, and Aspergillus spp. from diverse infection sources in addition to its current indication for VVC.

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 Sharon Min, MS, GSK: Employee
P-1098. Clinical outcomes in four patients with refractory Coccidioidal meningitis treated with olorofim
Authors: Yousefzadeh Michelle , Goodman-Meza David , Allyn Paul R
Published: January 2025

Background

Coccidioidal meningitis (CM) remains a highly morbid condition. Olorofim is a novel agent that inhibits the fungal dihydroorotate dehydrogenase enzyme and has potent in vitro activity against Coccidioidomycosis.

Demographics of patients at the time of olorofim initiation with description of prior treatments.

Methods

We performed a retrospective case series of 4 patients with refractory CM treated with olorofim between 2020 and 2024 comparing outcomes assessed by symptoms, brain imaging, and Mycosis Study Group (MSG) score.

Change in Symptoms, MRI Brain Imaging, MSG Score, and CSF Parameters after Olorofim Initiation. Abbreviations: CF, Coccidiodes complement fixation; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging, MSG, Mycosis Study Group (MSG).

Results

At baseline, mean age was 53 (range 41-66), mean time since diagnosis 950 days (range 378-1591), mean MSG score 5.8 (range 3-11), and mean azoles failed 3.25 (range 2-4). Follow-up occurred at variable intervals for a total duration of 332-985 days on therapy. In early follow-up, symptoms were improved in 3 patients and stable in 1; available imaging was improved in 2 patients and stable in 1; mean MSG score was 4.75, decreased in 1 patient, unchanged in 1, and increased but low in 2. In late follow-up, symptoms were improved in 3 patients and stable in 1; available imaging was improved in 1 patient and stable in 1; mean MSG score was 2.7, decreased in 2 patients, unchanged in 1, and increased in 1. Patient 3 developed significant transaminitis requiring dose reduction at day 91 with subsequent relapse (MSG score 14) but was eventually stabilized on combination therapy with fluconazole.

Cerebral spinal fluid (CSF) complement fixation, glucose, protein and white blood cell count (WBC) graphed over time on antifungal treatment. Time 0 represents initiation of olorofim.

Conclusion

At last follow-up, 2 patients were doing well with improvement or stability in all domains, 1 patient died of unrelated causes, and 1 patient had late treatment failure after prolonged stability for 2.5 years. Olorofim may be an effective alternative treatment for patients with refractory CM.

Mycosis Study Group (MSG) scores plotted over time. The plot excludes an MSG score of 14 for patient 3 shortly after Early follow-up period during a temporary hold on olorofim administration due to medication induced transaminitis.

Disclosures

All Authors: No reported disclosures
415. Optimizing Blood Culture Utilization in Solid Organ Transplant Recipients: A Diagnostic Stewardship Approach
Authors: Steinbrink Julie M , Mehdiratta Nitin , Pena Heather E , Welsby Ian , Seidelman Jessica , Carugati Manuela
Published: January 2025

Background

Diagnostic stewardship of blood culture utilization is paramount to mitigate the risks associated with excessive culturing, including increased contamination rates and inappropriate antimicrobial administration. Although blood culture algorithms have been studied previously, there is insufficient data on their application specifically in solid organ transplant recipients. This study aims to retrospectively apply a blood culture algorithm (initially developed for a non-immunocompromised population) to assess its effectiveness in this immunosuppressed population.

Figure 1. Algorithm used by clinical providers to determine if blood cultures are appropriate or inappropriate

Methods

We conducted a retrospective review of adult solid organ transplant recipients with a blood culture event (BCE) occurring between February 2022 to January 2024 at a single academic medical center. A BCE was defined as the collection of at least one blood culture set for a specific clinical indication. During this time a blood culture algorithm (Figure 1) was implemented across 12 units in the hospital. Patient charts were manually reviewed to categorize BCEs as appropriate (the algorithm agreed with obtaining a blood culture), inappropriate (if the algorithm suggested to not draw a blood culture), or lacking documentation.

Results

Among 824 BCEs recorded in adult solid organ transplant recipients (Figure 2), 669 (81.2%) were deemed appropriate, 118 (14.3%) were inappropriate, and 37 (5.5%) lacked sufficient documentation. Adjudication of 388 BCEs with available data was performed and revealed 350 (90.2%) negative cultures, 25 (6.4%) true positives, and 13 (3.4%) contaminants (Figure 3). Within the subset of inappropriate BCEs (n=118), 113 (95.8%) yielded negative cultures, while 5 (4.2%) were contaminants; no true positives were identified.

Conclusion

The retrospective application of the blood culture algorithm did not reveal any missed true positive bacteremias in solid organ transplant recipients. Although this study is limited in scope, it provides initial evidence supporting the cautious application of the algorithm in this population. As a next step, we will adjudciate the remaining 436 BCE in the dataset. Further investigation is warranted to validate these findings and optimize diagnostic stewardship strategies for improved patient outcomes.

Disclosures

Jessica Seidelman, MD, MPH, 3M: Expert Testimony
P-1102. Real-World Effectiveness of Dalbavancin for Invasive Gram-Positive Bacterial Infections
Authors: Crocker Jake , Derrick Caroline , Justo Julie Ann , Brandon Bookstaver P , Yunusa Ismaeel , Jones Bruce M , White Bryan , Sassine Joseph , Belk Madeline , Pizzuti Morgan
Published: January 2025

Background

Emerging data suggest dalbavancin (DAL) may be used in complicated infections including bacteremia, prosthetic joints, osteomyelitis, and endovascular infections. The purpose of this study was to evaluate the real-world effectiveness of DAL for the treatment of invasive gram-positive infections (GPIs).

Methods

This multicenter, retrospective cohort study included adult patients receiving DAL for treatment of confirmed/presumed invasive GPI between February 2021 and December 2023. Invasive infections included those requiring ≥ 4 weeks of therapy. Patients were excluded if they received DAL for chronic suppression. The intention to treat (ITT) population included patients who received ≥ 1 DAL dose; the per protocol (PP) population received ≥ 2 doses within 7 days of expected administration dates. The primary outcome was clinical failure in the PP group at 90 days post-treatment. Secondary outcomes were logistical failures, clinical failures, and treatment-emergent adverse events in the ITT group at 90 days post-treatment.

Results

The ITT population included 150 patients (mean age 50.2 years, 65% male, 35% obese, 41% illicit drug use); the PP population included 107 patients. The most common infectious syndrome was osteomyelitis (63.3%, 95/150); the most common pathogens were MRSA (38%, 57/150) and MSSA (37%, 44/150). The most common dosing regimen was 1500 mg on day 1, followed by 1500 mg on day 8 (90%, 96/150). Among the PP population with follow-up, 22% (19/87) experienced clinical failure at 90 days post-treatment. No factors were significantly associated with clinical failure. Logistical failure occurred in 17% (26/150). Results of univariate regression analyses showed receipt of first dose at an infusion center vs. inpatient setting significantly increased logistical failure (OR 4.53, 95% CI 1.62 – 16.17; P = 0.008) while blood-based infectious syndromes significantly decreased logistical failure (OR 0.26, 95% CI 0.06 – 0.82; P = 0.038). Receipt of vancomycin within 6 weeks of DAL significantly increased risk of acute kidney injury (OR 4.12, 95% CI 1.20 – 14.68; P = 0.024).

Conclusion

Dalbavancin is a safe and effective treatment option for invasive GPIs; however there are modifiable risk factors associated with secondary outcomes of logistical failure and toxicity.

Disclosures

Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Shionogi: Advisor/Consultant Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Ferring: Honoraria|Innoviva: Honoraria|Paratek: Honoraria Bryan White, PharmD, BCPS, BCIDP, Melinta: Advisor/Consultant|Shionogi: Grant/Research Support Joseph Sassine, MD, Ansun BioPharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|Community Infusion Solutions: Grant/Research Support|F2G: Grant/Research Support|Shionogi: Grant/Research Support
P-1119. The role of Carbapenemase gene detection and synergy testing in invasive infections caused by Carbapenem resistant Enterobacterales in the pediatric population at a quaternary hospital in South India
Authors: Deshpande Sanjay , Iyer Ranganathan
Published: January 2025

Background

The incidence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections in children is increasing globally. However, there are limited studies that address clinical, microbiological profiles, molecular and synergy testing of these CRE infections, in this population. Our study was aimed at studying the clinical profile, microbiological and molecular diagnoses, and synergy testing of CRE bacteremia in children admitted to the intensive care unit (ICU).

Methods

Medical records of children admitted to the ICU with CRE bacteraemia over a year were reviewed. Their clinical background, microbiological diagnoses, molecular profile, antibiotic resistance patterns, synergy testing, and clinical outcomes were analyzed. Carbapenemase genes were detected using Gene X pert (Cepheid) and synergy testing was carried out on those isolates with New Delhi Metalloproteinase (NDM). NDM-1 or NDM + Oxacillinase (OXA) OXA-48 genes. The results were expressed as fractional inhibitory concentration index (FICI) and the same was correlated with treatment using Ceftazidime- Avibactam+/- Aztreonam.

Results

98 children with blood stream infections (40 in neonatal ICU and 58 pediatric ICU) were identified. K. pneumoniae accounted for a majority of BSI’s (n-34 in neonatal ICU and n- 47 in pediatric ICU) with most of them expressing the NDM gene (50%). The overall Colistin resistance across both ICU’s was (MIC > 2 ug ml) was 0.03%. Synergy to Ceftazidime-Avibactam- Aztreonam could be demonstrated in a majority of CREs which were NDM / NDM+OXA-48 producers (82.3% K. pneumoniae in neonatal ICU and 90% in pediatric ICU). Eight neonates (20%) and seventeen children (29%) succumbed due to other comorbidities, all of whom had NDM Klebsiella pneumoniae bacteraemia (n-17, 100%).

Conclusion

NDM producing Klebsiella pneumoniae remains the commonest identified BSI in neonatal and paediatric patients in the intensive care and was isolated in all children with adverse outcomes. Infection control, antimicrobial stewardship protocols and Carbapenemase gene detection with targeted synergy and directed therapy is recommended for favorable clinical outcomes of BSI’s in the critically ill children.

Disclosures

All Authors: No reported disclosures