bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1421. A socioeconomic index of Brazilian municipalities correlates with dengue cases severity status but not with lethality
Authors: Lira Guilherme , Takahashi Marcelo , Ota Victor , Leitão Isabela 
Published: January 2025

Abstract

Background
Social determinants of health (SDOH) affect a wide range of health outcomes and risks. This includes differences in exposure and vulnerability to infectious diseases such as tuberculosis, COVID-19 and arboviral diseases. However, information on SDOH can be difficult to retrieve from medical records. We set out to explore how SDOH measured at populational level can affect natural history and lethality in dengue fever.
ORs from logistic regressions performed

Methods
We performed a retrospective, descriptive study of dengue fever cases in Brazil, using Ministry of Health openly available notification databases. We used GeoSES, a composite index that summarizes the main dimensions of the Brazilian socioeconomic context for research purposes, as a proxy for SDOH in given municipalities. Only laboratory confirmed cases were included. Outcomes considered were case classification (dengue without warning signs, dengue with warning signs or dengue with severity signs) and discharge or death by dengue. We performed logistic regressions of recognized risk factors alongside GeoSES as predictors for outcomes. R software version 4.3.1 was used for analysis. Code will be made public upon abstract acceptance.

Results
We analyzed 2,137,462 cases notified between January 2014 and December 2023. In the proportional odds logistic regression model for case classification, the GeoSES index was associated with case classification (OR = 2.87, 95% CI 2.77-2.98; p-value &lt; 0.0001), indicating an increased risk of dengue with warning signs or severity signs as the index increases. However, in the binomial logistic regression for discharge or death, the index showed no association (OR = 0.99, 95% CI 0.88-1.12; p-value = 0.98) with outcome, holding constant all other variables. Interestingly, peptic ulcer disease stood out as a protective factor against negative outcomes in dengue fever patients.

Conclusion
As a seasonal disease with a recent upsurge in Brazil, reevaluating risk factors for dengue infection and complication is an ever-present necessity. Here, we demonstrate that the GeoSES index is not a strong predictor of dengue fever mortality. This does not excuse policymakers from improving structural conditions, but allows for rational evaluation in epidemic scenarioes.

Disclosures
All Authors: No reported disclosures
P-1481. Short-Treatment with Ceftazidime-Avibactam for Carbapenemase-Producing Enterobacterales Bacteremia
Authors: Herrera Fabián , Leone María V , Torres Diego , Rojas Rocío , Bues Florencia , Carlos Jimena , Temporiti Elena , Querci Marcia , Nicola Federico , Relloso Silvia , Smayevsky Jorgelina , Bonvehi Pablo E 
Published: January 2025

Abstract

Background
Ceftazidime-avibactam (CA) and CA plus aztreonam (ATM) are the preferred treatment options for KPC and metallo-beta-lactamase (MBL) carbapenemase-producing Enterobacterales bacteremia (CPEB). However, data regarding short therapy are scarce.

Methods
Prospective observational cohort study performed in a university hospital in Argentina between August 2018 and February 2024. All adult patients with CPEB who received adequate empirical treatment with CA or CA+ATM, with a median duration of 7 days (IQR: 7-8), with clinical response and source control of infection were included. They were followed for 30 days to evaluate mortality.

Results
Twenty-two patients were included. They had a median age of 61 years (IQR: 49-70.5). The median APACHE II and Pitt scores were 18 (IQR: 13.25-24) and 2 (IQR: 1-4). Sixty-eight percent of the patients were immunocompromised, being hematological malignancies (45.45%), high-dose corticosteroids (40.9%) biological agents/anti-lymphocyte therapies (36.36%), and neutropenia (31.81%) the most frequent causes. Eighty-six percent had a clinical source of bacteremia; abdominal, central venous catheter, and urinary tract being the most common. Klebsiella spp. (72.72%) was the main etiological isolated microorganism, and the resistance mechanisms involved were KPC production (77.2%), MBL production (13.6%), and KPC+MBL production (9%). Recent colonization with KPC-CPE and MBL-CPE was detected in 68.1% and 9% of the patients. Septic shock at onset and intensive care unit requirement were 40.9% and 45.4% respectively. Empirical and definitive antibiotic therapy were combined in 66.6% and 9% of the patients. Thirty-day overall and infection-related mortality were 22.7% and 9%.

Conclusion
This data showed that short-course antibiotic treatment with CA or CA+ATM for patients with CPEB who had clinical response with source control of infection might be adequate.

Disclosures
Diego Torres, Medical Doctor, Gador: Honoraria|GSK: Advisor/Consultant|Khight Therapeutics: Honoraria|MSD: Honoraria
514. The Impact of Xeruborbactam on in vitro Activity of Cefiderocol against a Panel of Acinetobacter baumannii Enriched in Isolates with Reduced Cefiderocol Susceptibility
Authors: Hara Takafumi , Ishibashi Naoki , Miyagawa Dai , Onishi Motoyasu , Lomovskaya Olga , Yamano Yoshinori 
Published: January 2025

Abstract

Background
Cefiderocol (CFDC) is a siderophore cephalosporin with potent activity against resistant gram-negative bacteria. Recent SIDERO-WT surveillance studies demonstrated potent activity of CFDC against 5,225 isolates of Acinetobacter baumannii complex (ACB) (MIC50/90=0.12/1 µg/mL; 96% susceptible using CLSI breakpoint) including 2,810 carbapenem-resistant isolates (MIC50/90=0.25/2 µg/mL; 94% susceptible). CFDC MIC values were higher (MIC50/90=4/8 µg/mL) against metallo-β-lactamase (MBL) producers (N=25 including 21 NDM producers; 0.48% of total ACB) and isolates that produced PER or VEB β-lactamase (N=103; 1.98% of total ACB; MIC50/90=128/256 µg/mL). Xeruborbactam (XER) is a novel beta-lactamase inhibitor that inhibits multiple serine-type β-lactamases (SBLs) and MBLs. In this study, we evaluated the combination of CFDC and XER against a challenge panel of ACB enriched with CFDC-resistant isolates.
MIC50/90 of cefiderocol (CFDC) alone and in the presence of xeruborbactam (XER) against Acinetobacter baumannii

Methods
A challenge panel of 160 ACB isolates that included 59 PER- or VEB-producing and 22 NDM-producing isolates was used for this study. 144 (90%) and 136 (85%) isolates had CFDC MIC &gt; 1 µg/mL (FDA non-susceptible breakpoint) and &gt; 2 µg/mL (EUCAST non-susceptible PK/PD breakpoint), respectively. β-lactamases content was determined by PCR or whole genome sequencing. MICs were determined for CFDC alone and in combination with 1, 2 and 4 μg/mL of XER according to CLSI guidelines for CFDC using iron-depleted CAMHB.

Results
MIC50/MIC90 of CDFC alone and XER alone against 160 ACB were &gt; 32/ &gt; 32 and 16/ &gt; 16 μg/mL, respectively. The addition of xeruborbactam at all concentrations resulted in a reduction of CFDC MICs. For the subset of 59 highly CFDC-resistant PER or VEB producers, XER at ≥ 2 µg/mL reduced CFDC MIC50/90 from &gt; 32/ &gt; 32 to 0.25/1 µg/mL, which is similar to MIC50/90 values observed for CFDC alone for all ACB from recent surveillance studies. XER at 4 μg/mL reduced MIC50/90 of NDM producers from 32/ &gt; 32 μg/mL to 0.5/8 μg/mL.

Conclusion
Addition of XER significantly improved the activity of CFDC against isolates of ACB with elevated CFDC MICs.

Disclosures
Takafumi Hara, MSc, SHIONOGI & CO., LTD.: Employee Naoki Ishibashi, MD, SHIONOGI & CO., LTD.: Employee Dai Miyagawa, n/a, SHIONOGI & CO., LTD.: Employee Motoyasu Onishi, PhD, Shionogi & Co., Ltd.: Employee Olga Lomovskaya, PhD, Qpex Biopharma Inc.: Board Member|SHIONOGI & CO., LTD.: Employee Yoshinori Yamano, PhD, Shionogi & Co., Ltd.: Employee
P-1495. Antibiotic and Phage Susceptibility of Pseudomonas aeruginosa Clinical Isolates From Phage Therapy Patients
Authors: Lee Justin J , Dorozko Sergei Elber , Shields Ryan K , Haidar Ghady , Van Tyne Daria 
Published: January 2025

Abstract

Background
Antibiotic resistance is a rising issue, with the World Health Organization predicting that by 2025, around 10 million deaths annually will be caused by resistant infections. Phage therapy is an alternative form of treatment for multidrug-resistant bacterial infections in which bacterial viruses, called bacteriophages, are used to combat the infection. Before phage therapy can be delivered at the bedside, clinical bacterial isolates from the patient are collected and screened for susceptibility in the laboratory to identify candidate phages that can infect and kill the bacteria causing the infection. Many phages have been isolated from wastewater and assembled into libraries without detailed knowledge of their host range or an understanding of which phages are the best performers.

Methods
Using 40 patient-derived P. aeruginosa clinical isolates collected from 21 phage therapy candidate patients at the University of Pittsburgh Medical Center in the years 2022 and 2023, we investigated the host range of 25 phages in a P. aeruginosa screening library. We also screened the isolates against 11 antibiotics currently used to treat P. aeruginosa infections.

Results
We identified correlations in phage susceptibility profiles both within and between patients’ isolates, finding that a three phage cocktail could target 100% of the isolates. We also examined the antimicrobial susceptibility profiles of the 40 isolates and found that 67.5% of isolates are multidrug resistant.

Conclusion
With this research, we hope to develop methods for identifying candidate phages more quickly, speeding up the process of phage susceptibility testing, and aiding in the assembly of highly active phage cocktails, which may result in increased accessibility of phage therapy to a more diverse patient base.

Disclosures
Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cystic Fibrosis Foundation: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support|PeerView Institute for Medical Education: Honoraria|PRIME: Honoraria|Regeneron: Grant/Research Support
P-1503. Dual β-Lactam Approach for Treatment of Mycobacterium abscessus Infections in Adults – Results in 19 Patients
Authors: Kalyatanda Gautam , Dousa Khalid M , Lyons Hannah , Mardourian Markos , Rhodes Jackson , Iakovidis Alexandria , El-Helou Guy , Wilson Brigid , Daley Charles L , Holland Steven M , Kreiswirth Barry N , Nguyen David C , Shin Eunjeong , Kurz Sebastian G , Johnson John L , Bonomo Robert A 
Published: January 2025

Abstract

Background
The prevalence of Mycobacterium abscessus (Mab) infection is rising, with immunocompromised individuals being especially susceptible. While treatment success for the subspecies abscessus has been as low as 33%, recent studies and case reports suggest potential efficacy of select dual β-lactam (Dβ). This study evaluated the efficacy and tolerability of select Dβ in treating MDR-Mab infections, guided by in-vitro susceptibility results.

Methods
We reviewed the treatment of 19 adults with Mab infection at the University of Florida Hospital, Gainesville, who underwent Dβ synergy testing between January 2019 and March 2023. Medical histories, laboratory results, and clinical outcomes were reviewed. We summarized patient and infection characteristics and compared the time from diagnosis to Dβs initiation across outcomes

Results
Of the 19 patients (mean age: 54 years; 68% females), 11 (58%) had undergone solid organ transplantation or had cancer, and 6 (32%) were on immunosuppressants for autoimmune diseases. Pulmonary infections predominated (68%), with 47% of isolates were macrolide resistant. 11 patients (58%) were due to subspecies abscessus. The Dβs most frequently used for treatment were imipenem combined with either amoxicillin (31%) or ceftaroline (26%). Successful clinical cure or stable culture conversion with ongoing treatment was observed in 9 (47%) cases. 4 patients died during treatment. We observed a trend towards shorter times before initiation of Dβ treatment among patients who were cured. Time to initiation of Dβ therapy exceeded 90 days in 3 of 4 patients who died. Eighteen of 19 patients tolerated dual β-lactams therapy well. Among the 5 who discontinued treatment, the multi-drug regimen, not specifically the dual β-lactams, was the likely cause

Conclusion
Treatment with Dβ-containing regimens was associated with higher cure rates in this cohort of severely ill, immunocompromised patients. Earlier treatment correlated with better outcomes. Given the poor response to current treatment regimens and the initial promising results of Dβ therapy, clinical trials are planned. Finally, the chosen Dβs may not fully represent the optimal selection due to patient-driven preferences, possibly underscoring a conservative rather than optimal treatment outcome.

Disclosures
All Authors: No reported disclosures
P-1504. Propensity-Matched Comparison of Early vs. Late Antibiotic Therapy in Stenotrophomonas maltophilia Pneumonia: A Five-Hospital Study
Authors: May Elizabeth , Coyne Ashlan Kunz 
Published: January 2025

Abstract

Background
Stenotrophomonas maltophilia is a leading drug-resistant nosocomial pathogen worldwide. First-line antibiotic therapy for S. maltophilia is not a routine part of empiric antibiotic coverage. This study aimed to evaluate clinical outcomes of patients receiving early versus late antibiotic therapy for S. maltophilia pneumonia (PNA).Table 1.Baseline and Clinical Course Characteristics
aData are presented as “number (%)” or “median (interquartile range)”, as appropriate.
Abbreviations: BMI, body mass index; CrCL, creatinine clearance; LTAC, long-term acute care; NH/LTC, nursing home/long-term care.

Methods
A retrospective, observational study was conducted at five hospitals within University of Kentucky HealthCare. Patients treated for S. maltophilia PNA between 1/1/2014 and 12/31/2023 receiving sulfamethoxazole/trimethoprim, minocycline or levofloxacin with reported in-vitro susceptibility were included. Patient and bacterial characteristics, all-cause mortality, and desirability of outcome ranking (DOOR) at 30 days were compared between patients receiving early (≤48 hours of culture collection) versus late ( &gt;48 hours of culture collection) therapy (Table 1). Propensity-score matching (PSM) was used to adjust confounding. Subgroup and sensitivity analyses were used to verify the robustness of results.Table 2.Desirability of Outcome Ranking (DOOR)

Results
Median age of patients was 64 years (interquartile range [IQR] 52-71 years). The median Charlson Comorbidity Index and SOFA score were 4 (IQR 2-6) and 4 (2-7). At the time of index culture collection, 219/430 (50.9%) patients were in the intensive care unit, and 142/430 (33%) patients were on mechanical ventilation. Overall mortality at 30 days was 103/430 (24%). DOOR distribution of outcomes is shown in Figure 1. A randomly selected patient with early antibiotic administration had a 69% (95% CI 56%-79%, p&lt; 0.001) likelihood of a better outcome as compared to a randomly selected patient receiving late antibiotic therapy.Figure 1.DOOR Analysis of All Patients with S. maltophilia Pneumonia Receiving Early vs. Late Antibiotic Therapy

Conclusion
S. maltophilia PNA is associated with poor outcomes, especially in patients receiving therapy with in-vitro activity &gt;48 hours from index culture collection.

Disclosures
All Authors: No reported disclosures
P-1509. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2018-2022
Authors: Estabrook Mark , Dickson Julie , Stone Gregory , Perez Katherine , Sahm Daniel F 
Published: January 2025

Abstract

Background
The spread of antimicrobial resistance among clinically isolated Enterobacterales (Eba) is a threat to public health. Aztreonam (ATM) is a monobactam stable against hydrolysis by metallo-β-lactamases (MBLs) and avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases. ATM-AVI is being developed for use against infections caused by drug-resistant Eba, especially those co-producing MBLs and other β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2018-2022 from pediatric and adult patients as part of the ATLAS global surveillance program.

Methods
87621 Eba isolates were collected from patients in 226 medical centers in 57 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2024 breakpoints. PCR and sequencing were used to identify β-lactamase genes among all isolates testing with meropenem MIC &gt;1 µg/mL, and a randomly sampled subset of approximately 80% of Escherichia coli, Klebsiella spp. and Proteus mirabilis testing with ATM or ceftazidime MIC &gt;1 µg/mL.

Results
MIC90 values for ATM-AVI of 0.12 µg/mL (pediatric isolates) and 0.25 µg/mL (adult isolates) were observed. Against all Eba isolates, ≤8 µg/mL of ATM-AVI inhibited 99.9% of both pediatric and adult isolates, whereas only 66.3% (pediatric) and 71.4% (adult) of these isolates were susceptible to ATM alone (table). Among isolates that screened positive for an MBL, MIC90 values for ATM-AVI were 0.5 µg/mL (pediatric) and 2 µg/mL (adult) and ATM-AVI inhibited 100% (pediatric) and 98.6% (adult) at concentrations ≤8 µg/ml. In contrast, only 14.5% (pediatric) and 17.2% (adult) of MBL-positive isolates were susceptible to ATM without AVI.

Conclusion
Based on MIC90 values, ATM-AVI demonstrated potent in vitro activity against Eba isolated both from pediatric and adult patients. Avibactam’s ability to potentiate aztreonam against MBL-positive Enterobacterales isolates warrants its continued development.

Disclosures
Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Julie Dickson, BS, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1518. Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam and Comparators Against Clinical MDR and DTR non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa Stratified by Patient Age and Hospital Ward: SMART United States 2020-2022
Authors: Wise Mark G , Andrew DeRyke C , Esterly John , Bauer Karri A A , Siddiqui Fakhar , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2025

Abstract

Background
Hospital ward and patient age are factors that can guide in the selection of empiric therapy. Imipenem/relebactam (IMR) is a combination of imipenem with the β-lactamase inhibitor relebactam, an inhibitor of class A and C β-lactamases. Ceftolozane/tazobactam (C/T) combines ceftolozane, an anti-pseudomonal cephalosporin, with tazobactam. We evaluated the activity of IMR, C/T and comparators against isolates of non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa that were collected in the United States as part of the SMART surveillance program from 2020 to 2022 with data stratified by hospital ward (ICU versus general wards), and by patient age (&lt; 60 and ≥60 years old).

Methods
In 2020-2022, 26 clinical labs in the US each collected up to 250 consecutive Gram-negative pathogens per year. MICs were determined using CLSI broth microdilution and interpreted with 2024 CLSI breakpoints. Multi-drug resistance (MDR) was defined as resistance to ≥3 sentinel agents (amikacin, aztreonam, cefepime, ceftazidime [Enterobacterales only], colistin, imipenem, levofloxacin, and piperacillin/tazobactam). Difficult-to-treat resistance (DTR) was defined as non-susceptibility to all β-lactams (including aztreonam, ceftazidime, cefepime, imipenem, meropenem, piperacillin-tazobactam), and fluoroquinolones (levofloxacin).

Results
Susceptibility to commonly used β-lactams was lower among isolates from ICU patients compared to those in non-ICU wards, but no clear pattern was linked to patient age. Against the NME, IMR was among the most active agents inhibiting &gt;98% of the isolates in all strata (Table). Meropenem, ceftazidime/avibactam and amikacin also inhibited &gt;98% of the isolates. IMR retained activity against the MDR NME, as &gt;96.9% of the isolates were susceptible. Against P. aeruginosa, C/T was the first or second (after amikacin) most active agent versus isolates in all strata, with &gt;95% susceptible. C/T remained active against ≥77% of MDR and ≥72% of DTR isolates, 7-30 percentage points higher than ceftazidime/avibactam.

Conclusion
IMR is an important treatment option for patients with infections caused by NME, while C/T is an excellent choice against P. aeruginosa, regardless of patient age or treatment in the ICU.

Disclosures
Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant