bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1491. Practice variations and clinical outcomes of Intravenous Aminoglycosides in Nontuberculous Mycobacterium infections at three tertiary hospitals in London, Ontario, Canada
Authors: Babaeer Esraa , Minuk Jeffrey , McCormack David , Mura Marco , Dhaliwal Inderdeep , Elsayed Sameer , Bondy Lise , Devlin Megan K , Shalhoub Sarah , Mohammadi Mahshid , Saeed Huma , Silverman Michael , Fuller Jeffrey , Almutawa Fatimah , Shahmirzadi Reza Rahimi 
Published: January 2025

Abstract

Background
The worldwide occurrence of nontuberculous Mycobacterium (NTM) infections is rising. In Canada, there is a continuing surge in infections caused by Mycobacterium avium complex (MAC). Treating NTM infections is challenging and requires multidrug regimens with antimicrobial susceptibilities to guide therapy.
Generally, aminoglycosides have moderate in-vitro activity against NTM isolates. However, the synergistic effect with other antimicrobials makes it an attractive choice for clinicians, especially in the management of severe or refractory cases. The recommended duration of intravenous aminoglycosides is debatable due to side effects and the need for therapeutic monitoring. Moreover, NTMs are becoming more resistant to aminoglycosides.
This study aims to assess clinical practice variations in aminoglycoside use among NTM infections in terms of duration and monitoring in London, Canada.
Patient Characteristics and Clinical Presentation

Methods
Retrospective study reviewing the characteristics of 30 patients diagnosed with NTM infection between January 1, 2019 and December 31, 2023 in three tertiary care hospitals in London, Ontario, Canada.Table 2:NTM Susceptibility Report

Results
Mean age at diagnosis was 60.8 years. Seventeen (57%) were male and 13 (43%) were female. The presentations included pulmonary NTM infections in 19 (63%) and skin and soft tissue infections in four (13%). Among all identified species, MAC was the most common.
Fifteen (50%) patients received IV aminoglycosides, with 7 (32%) having documented susceptibility to aminoglycosides. Duration of aminoglycoside use varied among patients, ranging from 2 to 24 weeks. Of the patients started on an IV aminoglycoside, 3 (20%) developed ototoxicity and 2 (13%) had acute kidney injury. Serum aminoglycoside levels were checked in 12 (80%), but only 7 patients (47%) had at least one audiology screen.
In terms of outcomes, 7 (23%) achieved clinical cure while 9 (30%) had refractory disease, 7 (78%) of which were pulmonary. Two (57%) of the cured patients and 2 (22%) of the refractory patients had received an aminoglycoside.
Aminoglycoside Use and Monitoring

Conclusion
Aminoglycoside use for the treatment of NTMs is variable among clinicians, mostly due to concerns for side effects and the need for consistent drug monitoring, which limits its implementation in outpatient settings.
Clinical Outcomes

Disclosures
Lise Bondy, Assistant Professor, Pfizer: Honoraria|Viiv: Advisor/Consultant Michael Silverman, MD, FRCP, FACP, AAHIVMed, Pfizer: Grant/Research Support
P-1494. Factors Associated with Intravenous Sodium Stibogluconate Treatment Failure in Mucocutaneous Leishmaniasis: A Case-Control Study in Cusco, Peru, 2012-2022
Authors: Arando-Torres Katherin , Perez-Castilla Jesus , Concha-Velasco Fátima 
Published: January 2025

Abstract

Background
Mucocutaneous leishmaniasis is a neglected infectious disease primarily affecting impoverished individuals across various regions worldwide. Untimely diagnosis and treatment often result in lasting physical and psychological consequences for patients, significantly impacting their quality of life. Currently, first-line pharmacotherapy consists of pentavalent antimonials, with a treatment failure rate of over 30%. We explored factors associated with intravenous sodium stibogluconate (Sb) treatment failure in mucocutaneous leishmaniasis.

Methods
This retrospective case-control study was conducted at Antonio Lorena Hospital in Cusco, Peru, from 2012 to 2022. Clinical records meeting the criteria of confirmed mucocutaneous leishmaniasis through smear, culture, PCR, or histopathology, with completion of a 30-day intravenous Sb treatment regimen, were analyzed. To calculate the sample size, proportions for independent cases and controls were used, with an Odds Ratio of 2. Moderate to severe disease was defined as more than two mucosal areas compromised with dyspnea. Cases were defined as individuals experiencing treatment failure after the initial 30-day antimonial cycle; whereas controls were those successfully cured after one 30-day antimonial cycle. Adjusted odds ratios were calculated using a logistic regression model. Ethics approval was obtained for the study.

Results
A total of 124 clinical records were included, with a 49.6% intravenous Sb treatment failure rate in mucocutaneous leishmaniasis after the 30-day treatment. Of these, 75.8% (94/124) were male, 53.2% (66/124) were farmers, 17.7% (22/124) had comorbidities, 69.4% (86/124) had more than 12 months of disease, and 66.1% (82/124) had moderate to severe disease. The intravenous Sb treatment failure was associated with disease duration over 12 months (OR: 5.77, 95% CI: 2.01-16.52, p=0.001), comorbidities (OR: 21.12, 95% CI: 3.89–114.89, p&lt; 0.001), and moderate-severe disease (OR: 2.63, 95% CI: 1.05–8.72, p=0.048).

Conclusion
Our case-control study suggests that intravenous Sb treatment failure is associated with disease duration over 12 months, comorbidities, and moderate to severe disease. However, further studies are needed to elucidate this association.

Disclosures
All Authors: No reported disclosures
P-1499. Patient Characteristics and Clinical Outcomes Associated with Meropenem/Vaborbactam Treatment in Carbapenem-Resistant Enterobacterales Pneumonia
Authors: Caniff Kaylee E , Judd Chloe , Eubank Taryn A , Garey Kevin W , Krekel Tamara , Kufel Wesley D , Andrade Justin A , Cerenzio John , Veve Michael , Rybak Michael J 
Published: January 2025

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) are a major public health threat due to increasing prevalence and limited effective treatment options. Meropenem/vaborbactam (M/V) is a beta-lactam/beta-lactamase inhibitor agent designed to treat CRE. There is a paucity of data related to patient characteristics and associated outcomes with the utilization of M/V in pneumonia due to CRE. The objective of this study was to describe real-world experience with M/V in this setting.

Methods
This is a retrospective, observational, multicenter, cross-sectional study of patients ≥ 18 years old who received M/V for ≥ 72 hours for clinically-diagnosed hospital-acquired (HAP) or ventilator-associated pneumonia (VAP) due to CRE between 6/2020-2/2024. The primary outcome was clinical success, defined as resolution or improvement in signs/symptoms of infection and without the need for additional therapy. The secondary outcomes included 30-day mortality, 30-day microbiologic recurrence, 30-day symptomatic recurrence and adverse drug reaction(s).

Results
Sixty-two patients were included from six U.S. medical centers. The mean age (standard deviation [SD]) was 58.2 (15.4) years; patients were predominantly male (71.0%) and Caucasian (58.1%). At time of culture collection, the mean (SD) APACHE II score was 22.1 (7.8) and most patients (78.0%) were admitted to the intensive care unit. Klebsiella pneumoniae was the predominant species isolated in culture (43.5%). Notably, 65.6% were diagnosed with VAP, 32.3% had a COVID-19-related hospitalization and 29.0% developed secondary bacteremia. Patients received a median (interquartile range [IQR]) of 7.2 (6.1-12.0) days of M/V, with 21.0% receiving systemic combination therapy. Clinical success was achieved in 69.4% of patients and 30-day mortality occurred in 33.9%. Microbiologic and symptomatic recurrence occurred in 11.2% and 8.1% of cases, respectively. One patient experienced Clostridioides difficile infection attributed to the use of M/V.

Conclusion
Our study demonstrates promising clinical success with the use of M/V for treatment of pneumonia. Larger, comparative studies are needed in this population to identify patient factors associated with clinical success and assess M/V’s efficacy compared to other available therapies.

Disclosures
Kaylee E. Caniff, PharmD, BCIDP, T2Biosystems: Honoraria Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support Tamara Krekel, PharmD, BCPS, BCIDP, Merck Inc: Honoraria Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker
515. Neurological Complications in Children Hospitalized for Influenza, 2010 to 2022, the Canadian Immunization Monitoring Program Active (IMPACT)
Authors: Vaugon Esther , Morris Shaun , Bettinger Julie A , Burton Catherine , Halperin Scott , Jadavji Taj , Kazmi Kescha , Modler Jacqueline , Sadarangani Manish , Papenburg Jesse 
Published: January 2025

Abstract

Background
Influenza-associated neurological complications are rare, but can cause significant morbidity and mortality. We aimed to estimate the proportion of children with neurological complications among those hospitalized for influenza and to identify associated risk factors. The secondary objective was to compare the risk of severe outcomes among children with neurological complications to that of those without.

Methods
Prospective active surveillance was conducted in 12 pediatric hospitals from the Immunization Monitoring Program, ACTive (IMPACT), representing &gt;90% of all tertiary pediatric beds in Canada. We included patients aged ≤ 16 years hospitalized for microbiologically confirmed influenza during the 2010-11 to 2021-22 influenza seasons. Regression analyses were used to calculate adjusted odds ratios (aORs) for factors associated with neurological complications (seizure, meningitis, encephalitis, myelitis, encephalopathy, radiculopathy, cerebral edema, hydrocephalus, or stroke). The risk of severe outcomes (intensive care unit admission, mechanical ventilation, or death) in children with neurological complications was compared to that of children without these complications using the Chi-square and Wilcoxon tests.

Results
Among the 9533 children hospitalized for influenza, 1228 (12.9%) had neurological complications. Children with neurological complications had longer hospitalization (6.3 days vs 4.5 days, p &lt; 0.001) and were at higher risk of intensive care unit admission (31.8% vs 14.1%, p &lt; 0.001), mechanical ventilation (20.5% vs 4.4%, p &lt; 0.001), and death (2.2% vs 0.3%, p &lt; 0.001). In a multivariable model adjusting for IMPACT site and influenza type, factors associated with neurological complications were: pre-existing neurological condition (aOR 4.19, 95% CI 3.61-4.86); age between 6 and 24 months (aOR 1.62, 95% CI 1.29-2.03) and age between 2 and 4 years (aOR 1.36, 95% CI 1.09-1.71).

Conclusion
More than one in ten children hospitalized for influenza developed neurological complications and these were associated with higher risk of severe outcomes. Risk factors identified for neurological complications were age between 6 months and 4 years and the presence of a pre-existing neurological condition.

Disclosures
Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK Canada: Advisor/Consultant|GSK Canada: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi Canada: Advisor/Consultant|Sanofi Canada: Honoraria Jesse Papenburg, MD, MSc, Merck: Honoraria|Merck: Site investigator, RCT
P-1506. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents against Pseudomonas aeruginosa Collected from Patients with Presumed Hospital- and Community-acquired Respiratory Tract Infections as a Part of the ATLAS Global Surveillance Program 2018-2022
Authors: Li Henry , Estabrook Mark , Stone Gregory , Sahm Daniel F 
Published: January 2025

Abstract

Background
The β-lactamase inhibitor, avibactam, has potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. This study evaluated the in vitro activity of ceftazidime-avibactam and comparators against respiratory tract infection (RTI)-associated Pseudomonas aeruginosa isolated from presumed community-acquired (CA; culture started &lt; 48 hours after hospital admission) and hospital-acquired (HA; culture started ≥48 hours post-admission) infections collected from 2018-2022.

Methods
13,186 isolates were collected from the lower respiratory tract of patients from 224 medical centers in 57 countries (excluding China and North America). Of these, 8,880 were HA and 4,306 were CA. MICs were determined using CLSI broth microdilution and interpreted using CLSI 2024 breakpoints. Isolates testing nonsusceptible (NS) to meropenem (MEM) were screened by PCR and Sanger sequencing for β-lactamase genes.

Results
Ceftazidime-avibactam was the most active agent tested against the CA population (92.3% susceptible, MIC90 of 8 µg/mL; Table). Against HA isolates, ceftazidime-avibactam was active against 88.6% (MIC90 of 16 µg/mL). Only amikacin was active against more HA isolates (89.4% susceptible; MIC90 32 µg/mL). Of isolates that were MEM-NS and metallo-β-lactamase (MBL)-negative, 81.0% of HA isolates and 79.5% of the CA isolates were susceptible.

Conclusion
The in vitro activity of ceftazidime-avibactam against CA and HA organisms infecting the lower respiratory tract indicates that it remains an important option for treating infections including those caused by MEM-NS organisms that do not carry an MBL.

Disclosures
Henry Li, MS in Biotechnology, Pfizer, Inc.: Advisor/Consultant Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1508. In Vitro Activity of Aztreonam-avibactam against Enterobacterales Isolates Producing Multiple β-lactamases Collected Globally as a Part of the ATLAS Global Surveillance Program from 2018-2022
Authors: Estabrook Mark , Li Henry , Stone Gregory , Perez Katherine , Sahm Daniel F 
Published: January 2025

Abstract

Background
Aztreonam-avibactam (ATM-AVI) is a β-lactam/β-lactamase inhibitor combination to treat infections caused by Gram-negative organisms, particularly those carrying metallo-β-lactamases (MBLs) and other β-lactamases. Aztreonam is stable to hydrolysis by MBLs and avibactam inhibits Class A, C, and some Class D enzymes. We examined ATM-AVI activity against Enterobacterales isolates producing one or more β-lactamase collected as a part of the ATLAS global surveillance program (2018-2022).

Methods
88,750 isolates from 227 medical centers in 57 countries (excluding mainland China, Canada, and the USA) were collected and tested for susceptibility using the broth microdilution method according to CLSI guidelines. Analysis was performed with CLSI 2024 breakpoints. Isolates testing with meropenem MIC values &gt;1 µg/mL or Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis isolates testing with ceftazidime and/or aztreonam MIC values &gt;2 µg/mL were screened for β-lactamase genes by PCR, which were sequenced when identified.

Results
One or more extended-spectrum β-lactamase (ESBL), serine-carbapenemase, MBL, or acquired AmpC was identified among 17,013/18,408 isolates characterized. Among isolates carrying one or two ESBLs (51.4%), 99.9-100% tested with ATM-AVI MICs ≤8 µg/mL (MIC90 values of 0.12 and 0.5 µg/mL, respectively). Among isolates with a serine-carbapenemase and one or more ESBL (18.3%), 99.9-100% tested with ATM-AVI MICs ≤8 µg/mL (MIC90 values of 0.5-1 µg/mL). MBL-positive isolates with or without serine-carbapenemases and/or ESBLs (13.7%) demonstrated MICs ≤8 µg/mL among 98.3-100% of isolates in each category (MIC90 values of 0.5-1 µg/mL). Isolates carrying acquired AmpC as well as any combination of additional β-lactamases (9%) tested with ATM-AVI MICs ≤8 µg/mL among 93.6-100% of each population (MIC90 values of 0.5-8 µg/mL).

Conclusion
ATM-AVI demonstrated potent in vitro activity against Enterobacterales isolates regardless of the number of β-lactamases carried. Slightly reduced potency was observed in populations that carried acquired AmpC. This may be expected as some variants of AmpC with extended-spectrum activity are known to increase ATM-AVI MICs.

Disclosures
Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Henry Li, MS in Biotechnology, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1510. In Vitro Activity of Ceftibuten-Avibactam and Comparator Agents Against Enterobacterales Collected Globally as Part of the ATLAS Surveillance Program, 2022 by Region
Authors: Estabrook Mark , Dickson Julie , Stone Gregory , Perez Katherine , Sahm Daniel F 
Published: January 2025

Abstract

Background
Ceftibuten is an orally administered third-generation cephalosporin in clinical development in combination with an oral prodrug of avibactam, an inhibitor of class A β-lactamases, including ESBLs and KPC, class C (AmpC) β-lactamases, and some class D (OXA-48) β-lactamases. This study evaluated the in vitro activity of ceftibuten-avibactam and comparators against Enterobacterales isolates collected globally as part of the 2022 Antimicrobial Testing Leadership and Surveillance (ATLAS) program, by region.

Methods
23,088 non-duplicate clinical Enterobacterales isolates were collected in 2022 from 217 medical centers in 56 countries. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2024 breakpoints. Ceftibuten was tested with a fixed concentration of 4 µg/mL avibactam.

Results
Ceftibuten-avibactam was active at ≤1 µg/mL against more isolates than were susceptible to any oral comparator agent (87.3-97.5%). Ceftibuten-avibactam also demonstrated the lowest MIC90 values, by region among the oral agents tested. Regional differences in the in vitro activity of ceftibuten-avibactam were observed with a lower MIC90 value against isolates collected in Europe, North America, the South Pacific, and the Middle East (0.12-0.25 µg/mL) as compared to Latin America, Asia, and Africa (0.5, 4, and 16 µg/mL, respectively). This phenomenon was also observed among oral comparator agents, with fewer isolates collected in Africa susceptible to cefixime (40.8%), cefpodoxime (42.5%), levofloxacin (48.7%), and trimethoprim-sulfamethoxazole (37.8%) than in any other region. A similar pattern was observed for the intravenously administered ceftazidime-avibactam, with 89.3% of isolates collected in Africa susceptible.

Conclusion
Based on these data, ceftibuten-avibactam demonstrates promise as a candidate for oral treatment of infections caused by Enterobacterales. Regional trends in antimicrobial resistance to a diverse range of agents warrant continued monitoring.

Disclosures
Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Julie Dickson, BS, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1511. In Vitro Activity of Gepotidacin Against Molecularly Characterized Neisseria gonorrhoeae Isolates Exhibiting Reduced Susceptibility to Antibacterial Agents, 2018-2021
Authors: Estabrook Mark , Kapoor Renuka , Torumkuney Didem , Li Henry , Sahm Daniel F 
Published: January 2025

Abstract

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 a well-balanced inhibition (for most uncomplicated urinary tract infection (uUTI) uropathogens and N. gonorrhoeae)) of two different Type II topoisomerase enzymes. We present the activity of GEP against molecularly characterized N. gonorrhoeae isolates collected from patients in Australia, India, and the United States from 2018-2021 as part of a GEP global gonococcal surveillance study.

Methods
N. gonorrhoeae isolates were tested for susceptibility to GEP and comparator agents by CLSI agar dilution method and analyzed using CLSI 2024 breakpoints. Isolates that met predefined selection criteria, which included GEP MIC values &gt;1 µg/mL or nonsusceptible or resistant (R) to select comparators, were characterized by whole genome sequencing.

Results
A total 711 N. gonorrhoeae isolates were collected and of these 341 (48%) were characterized. The GEP MICs for both populations of isolates ranged from ≤0.06 to 2 µg/mL; MIC90 of 1 µg/mL (Table 1). Of 324 ciprofloxacin-R isolates, 105 (32.4%) had a mutation of D86N in ParC; this mutation was associated with a GEP MIC90 of 2 µg/mL (range= 0.25-2 µg/mL). Isolates with this mutation also carried mutations in the quinolone-resistance determining region (QRDR) of GyrA as well as mutation(s) suggesting the upregulation of the MtrCDE efflux pump. When categorizing isolates by QRDR mutation, ParC D86N was the only mutation associated with a GEP MIC90 &gt;1 µg/mL. A myriad of resistance mechanisms relevant to penicillin, azithromycin, and tetracycline, were identified among the characterized isolates, against which GEP MIC90s ranged from 1-2 µg/mL (Table 2).

Conclusion
GEP demonstrated potent in vitro activity against N. gonorrhoeae isolates, including those that were not susceptible to comparator agents. GEP’s MIC90 value relative to all isolates, and those with other QRDR mutations in this study, was one dilution higher (2 versus 1 µg/mL) against isolates that carried ParC D86N, which is known to be important for GEP binding.

Disclosures
Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Henry Li, MS in Biotechnology, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant