bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1507. In Vitro Activity of Ceftazidime-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
Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/β-lactamase inhibitor combination approved to treat infections caused by Gram-negative organisms. Notably, CAZ-AVI has activity against Enterobacterales producing Class A, C, and D β-lactamases, but not Class B metallo-β-lactamases (MBLs). The in vitro activity of CAZ-AVI and comparator agents against clinical Enterobacterales isolates producing one or more β-lactamase collected as a part of the ATLAS global surveillance program (2018-2022) was evaluated.

Methods
89,316 isolates from 228 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), acquired AmpC, serine-carbapenemase, or MBL was identified among 17,348/18,798 isolates characterized. Against isolates producing ESBLs (51.1%), susceptibility to CAZ-AVI was similar if the isolate carried one ESBL (99.4%) or two ESBLs (98.4%). Against acquired AmpC-producing isolates (5.9%), CAZ-AVI susceptibility was similar if the isolates co-carried 0, 1, or 2 ESBLs (98.9%, 97.1%, and 100% susceptible, respectively). Against isolates carrying serine-carbapenemases (18.6%), CAZ-AVI activity was similar regardless of co-carriage of acquired AmpC and/or one or more ESBLs (95.5-100% susceptible). CAZ-AVI was not active against isolates that carried an MBL (16.6%), regardless of other enzyme carriage (0-2.9% susceptible).

Conclusion
These results highlight that the number of distinct β-lactamases have little association with susceptibility to CAZ-AVI, while the type of β-lactamase (MBL or non-MBL) has a greater association.

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-1523. Evaluation of Standardized Treatment Regimens for Patients with Documented Melioidosis Septicemia at Tertiary Care Hospital in Thailand
Authors: Pudpong Korawan , Gatechan Tipanong 
Published: January 2025

Abstract

Background
Burkholderia pseudomallei (B. pseudomallei), an environmental Gram-negative bacterium, is the causative agent of melioidosis in humans. Therefore, its biothreat potential, the U.S. Centers for Disease Control and Prevention designates it as a tier 1 select agent.
Melioidosis is predominantly a disease in subtropical and tropical regions. It is endemic in northern Australia and parts of Southeast Asia and the Indian subcontinent. Mostly, melioidosis (85%) results in acute infections from recent bacterial exposure. The majority of patients with acute melioidosis present with sepsis with or without pneumonia, or localized abscesses, regardless of the route of infection.
Currently, therapy consists of an intensive phase of a minimum of 10 days with intravenous ceftazidime or a carbapenem (meropenem or imipenem), with or without trimethoprim-sulfamethoxazole to prevent mortality followed by an eradication phase with oral antibiotics to prevent relapse.
In Thailand, still found the mortality rate was 40%.We have uncleared study clinical outcomes comparable to ceftazidime and carbapenems treatment in documented melioidosis septicemia.
This is the first study to evaluate the efficacy of ceftazidime compared to carbapenems in patients with documented melioidosis septicemia whose blood cultures confirmed B. pseudomallei and susceptible to both ceftazidime and carbapenems in Thailand.
Baseline characteristic (N=264)

Methods
A retrospective study was conducted at Sunprasitthiprasong hospital, Thailand from 2021-2023. Adult patients who were admitted had documented positive B. pseudomallei septicemia and received ceftazidime or carbapenem at least one dose. The exclusion criteria were incomplete chart summary. Significant level p-value≤0.05 (STATA version 16)
ceftazidime versus carbapenems in non-septic shock patients
p-value &lt; 0.001

Results
264 patients were included and reported B. pseudomallei septicemia susceptibility to ceftazidime and meropenem were 264 (100%) pathogens and imipenem/cilastatin 262 (99.24%) pathogens.
ceftazidime versus carbapenems in septic shock patients
p-value =0.034

Conclusion
Ceftazidime compared to carbapenems in the intensive phase for documented melioidosis septicemia trends higher survival rate in 14 days after confirming pathogens in non-severe patients. Furthermore, randomized controlled trials (RCTs) will prove clinical outcomes in documented melioidosis septicemia.
Factors associated with mortality

Disclosures
All Authors: No reported disclosures
P-1532. Surveillance of Eravacycline Against Clinical Pathogens, Including Resistant Isolates, Collected Worldwide from Multiple Infection Sites During 2018-2022
Authors: Hawser Stephen , Monti Federica , Siegert Sherry , Zappas Kristie , McLeod Sarah , Moussa Samir H 
Published: January 2025

Abstract

Background
Eravacycline is a fully synthetic, fluorocycline antibiotic approved for the treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age in Europe, Singapore, China, Taiwan, Hong Kong, the US and the UK. The purpose of this study was to monitor the in vitro activity of eravacycline against isolates collected from a global surveillance study from 2018-2022. A total of 35,336 isolates were collected of which data for 23,127 isolates comprising Staphylococcus aureus (including methicillin-resistant S. aureus, MRSA), Enterococcus spp. (including vancomycin-resistant Enterococcus, VRE) and Streptococcus spp., Enterobacterales (C. freundii, E. cloacae, E. coli, K. oxytoca and K. pneumoniae) and non-fermenters are reported.

Methods
A total of 23,127 clinical isolates were collected during 2018-2022 from multiple infection sources, including, IAI, body fluids, blood, gastrointestinal, genitourinary and respiratory. The isolates were from Asia/Pacific (n=4,812), Europe (n=9,606) and North America (n=8,709). Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. For comparative purposes, isolate susceptibility for eravacycline and tigecycline was determined with both FDA and EUCAST breakpoints, where available.

Results
Summary MIC data for eravacycline and tigecycline as a selected comparator are shown in the Table. Susceptibility to eravacycline in all Gram-positive pathogens were greater than 90% for most species /phenotypes though was notably higher when EUCAST breakpoints were applied to the analysis. For Enterobacterales, eravacycline susceptibilities were consistently &gt;93% though MDR susceptibility was slightly lower (84.2% susceptible to eravacycline).

Conclusion
Eravacycline demonstrated sustained high activity rates against clinically important pathogens. Importantly, the MIC90 and susceptibilities did not change over time and were similar for the different geographical regions.

Disclosures
Sherry Siegert, PharmD, Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company)|Innoviva Specialty Therapeutics, Inc.: Employee Kristie Zappas, PharmD, Innoviva Specialty Therapeutics, Inc.: Employee Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company) Samir H. Moussa, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company)
P-1534. The Impact of Broad-spectrum Antimicrobials in Patients with Community-onset Pneumonia at Low Risk of Drug-resistant Pathogens: A Historical Cohort Study
Authors: Takazono Takahiro , Hosogaya Naoki , Saito Yoshiyuki , Takemura Masahiko , Iwanaga Naoki , Sakamoto Noriho , Hirayama Junichi , Ueno Rie , Mukae Hiroshi 
Published: January 2025

Abstract

Background
The administration of broad-spectrum antimicrobials has prevailed in the clinical management of community-onset pneumonia (COP). Growing evidence suggests that the use of unnecessary broad-spectrum antimicrobials for patients with COP leads to adverse events and poor outcomes. This study aims to understand the impact of broad-spectrum antipseudomonal β-lactam use on clinical outcomes and resource utilization in patients hospitalized for COP with a low risk for drug-resistant pathogens (DRPs).

Methods
This historical cohort study analyzed the hospital claims database in Japan from January to December 2018. The study includes patients aged 20 or older hospitalized with COP having intravenous antimicrobial therapy administration and excludes patients with a high risk for DRPs. Patients were selected into a broad-spectrum (antipseudomonal β-lactam therapy) and a narrow-spectrum (non-antipseudomonal β-lactam therapy) group based on the initial antimicrobial regimen. This study evaluates 30-day mortality as a primary outcome by inverse probability of treatment weighting (IPTW)and healthcare resource utilization as one of the secondary outcomes.

Results
A total of 15,617 patients met the inclusion criteria. This target population was divided into two groups: 2,627 patients in the broad-spectrum and 12,990 in the narrow-spectrum group. In the first group, the most commonly used antimicrobials were Piperacillin / Tazobactam (68%), and the 30-day mortality was 10.6 in contrast with 5.3% in the second group. Thus, the broad-spectrum group was associated with an increased 30-day mortality rate in contrast with the narrow-spectrum group after IPTW weighting (adjusted odds ratio 1.77, 95% confidence interval [1.52 to 2.06], &lt; 0.001). This trend was observed regardless of pneumonia severity. The average inpatient cost was $6,139 USD for the broad-spectrum group against $5,184 USD for the narrow-spectrum group, with respective length of stay (LOS) figures of 23.1 and 19.8 days.

Conclusion
This study shows that the initial use of antipseudomonal β-lactams for COP with a low risk for DRPs is associated with higher poor outcomes, including death and higher healthcare resource utilization. Judicious selection of initial antimicrobials is warranted in the management of COP.

Disclosures
Junichi Hirayama, n/a, bioMerieux Japan: employee of bioMerieux, salary Rie Ueno, MD., BioMérieux Japan Ltd.: Employee of BioMérieux Japan Ltd. Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi & Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees
P-1541. Antimicrobial susceptibility and antimicrobial synergy testing of human Streptococcus suis isolates in Thailand
Authors: Thipmontree Wilawan , Kajeekul Rattagan , Lewrod Athita , Kerdsin Anusak , Yongkiettrakul Suganya 
Published: January 2025

Abstract

Background
Streptococcus suis (S. suis) infection can cause serious infections with high morbidity and mortality. Both humans and pigs have reported emerging antimicrobial resistance. This study aims to investigate the antimicrobial susceptibility test (AST) and antimicrobial synergy testing in S. suis human isolates.Table 1.Clinical manifestations of 25 culture-confirmed S. suis infection cases who performed an antimicrobial synergy test.

Methods
We conducted a retrospective study of patients with culture-confirmed S. suis infection in Northeast Thailand. We analyzed the clinical manifestations, the AST and selected 23 isolates for determining the antimicrobial synergy effect via checkerboard microdilution.Table 2:Antimicrobial synergy testing by checkerboard microdilution in 23 S. suis human isolates.

Results
Between 2021 and 2023, we included 253 culture-confirmed S. suis patients; the mortality rate was 15%. A total of 194 patients underwent echocardiograms, and 95 (48.9%) patients had infective endocarditis. The prevalence of S. suis strain resistance to penicillin increased from 7.8% in 2021 to 31.9% in 2023. Additionally, the intermediate susceptibility of S. suis to CRO/CTX rose from 3.1% in 2021 to 9.9% in 2023. Moreover, in 2023, two isolates of S. suis showed resistance to CRO/CTX.
We performed antimicrobial synergy testing in response to the surge in antimicrobial resistance of S. suis infection. The AST of 23 isolates exhibited the following: susceptible to both penicillin and ceftriaxone/cefotaxime (CRO/CTX) (3); intermediately sensitive to penicillin but sensitivity to CRO/CTX (12); intermediately sensitive to both penicillin and CRO/CTX (1); resistance to penicillin but sensitive to CRO/CTX (5); and resistance to penicillin but intermediately sensitive to CRO/CTX (2).The combination of ampicillin and ceftriaxone demonstrated synergy in 34.8% (8/23) of cases, with 65.2% showing a partial synergism effect. Penicillin and ceftriaxone showed synergy in 21.7%, partial synergy in 69.6%, and indifference in 8.7%. Conversely, the results for ampicillin-gentamicin, penicillin-gentamicin, and ceftriaxone-gentamicin showed mostly indifference: 65.2%, 73.9%, and 78.3%, respectively.

Conclusion
S. suis infection is associated with high mortality rates and increased resistance to antimicrobials. A combination therapy comprising ceftriaxone and ampicillin may be the optimal and most effective treatment option.

Disclosures
All Authors: No reported disclosures
P-1542. Determining Pseudomonas aeruginosa antibiotic resistance by leveraging methylation risk scores
Authors: Gan Shuheng , Kim Jiwoong , Kim Juyeon , Clark Andrew E , Greenberg David E , Zhan Xiaowei 
Published: January 2025

Abstract

Background
The increasing prevalence of antibiotic-resistant bacteria poses a significant threat to global health, necessitating innovative approaches to predict and manage resistance. Traditional methods for detecting antibiotic resistance primarily rely on phenotypic assays or short-read sequencing techniques, which often overlook the intricate epigenetic modifications that can influence bacterial behavior and resistance mechanisms. One such modification, DNA methylation, has emerged as a critical regulator in bacterial gene expression and pathogenicity. The emergence of long-read sequencing technologies offers a unique opportunity to comprehensively map methylation patterns across bacterial genomes, potentially unveiling novel insights into the mechanisms underlying antibiotic resistance.

Methods
We systematically sequenced 133
Pseudomonas aeruginosa
bacterial isolates using Oxford nanopore technology and profiled their methylation characteristics.

Results
We detected 3.38 million common methylation sites (average methylation larger than 1%, occurred in more than 10% samples). By applying methylation association analysis, we discovered 10 methylated sites that are statistically associated with resistance to 12 antibiotics. Based on these results, we developed LASSO regression models using novel weighted methylation risk scores. We benchmarked MRSs using cross validation and observed MRS prediction models have high prediction performance for phenotypic resistance to 9 antibiotics across multiple drug classes.

Conclusion
In all, this work demonstrated that long-read derived methylation can serve as a powerful predictor of antibiotic resistance, potentially transforming the field of microbial resistance research.

Disclosures
David E. Greenberg, MD, Jannsen: DSMB member|Sarepta Therapeutics: Advisor/Consultant|Shionogi: Grant/Research Support
P-1543. Clinical Characteristics and Factors Associated with Acquisition of Gram-Negative Bacteria during Ceftazidime-avibactam Therapy
Authors: Chuang Chien , Kao Tzu-Chi , Chou Sheng-Hua , Juan Chih-Han , Ho Yu-Chien , Liu Szu-Yu , Lin Yi-Tsung 
Published: January 2025

Abstract

Background
Ceftazidime-avibactam (CZA) is recommended to treat infections caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa with difficult-to-treat resistance. The subsequent isolation of gram-negative bacteria (GNB) would cause superinfection or result in the change of antibiotics. However, the clinical characteristics and factors for acquisition of GNB during CZA treatment has not been reported.
Demographic and clinical characteristics of patients who acquired Gram-negative bacteria and those who did not acquire Gram-negative bacteria during ceftazidime-avibactam therapy

Methods
Adult patients treated with CZA ≥ 5 days were retrospectively enrolled at Taipei Veterans General Hospital (December 2019 to June 2021). We compared clinical features of patients who acquired GNB from clinical specimen 5 days after the use of CZA and those who did not acquire any GNB. Multivariate analysis was used to explore risk factors for acquisition of GNB during and 28-day mortality in patients who acquired GNB.
Distribution of acquisition of Gram-negative bacteria during ceftazidime-avibactam therapy

Results
A total of 321 patients receiving CZA for ≥ 5 days was analyzed, and 67.3% of them were infected with CRE. A total of 68 GNB were identified from the 55 patients (17.1%, 55/321). Elizabethkingia species (n=15) was the most common species, followed by Acinetobacter species (n=13) and Burkholderia cenocepacia (n=11). Diabetes mellitus [odds ratio (OR), 2.12; P=0.022], and use of mechanical ventilation (OR, 6.47; P=0.001) were the independent risk factors for acquisition of GNB in the multivariate analysis. In hospital mortality in patients who acquired GNB was higher than those who did not acquire any GNB during CZA treatment (58.2% versus 42.1%, P=0.029). More than half (63.6%, 35/55) of patients acquiring GNB were considered to have superinfection, and antibiotics were changed. Cerebrovascular disease [hazard ratio (HR), 3.27; P=0.009] and SOFA score at acquisition (HR, 1.22; P=0.001) were associated with increased 28-day mortality in patients who acquired GNB.

Conclusion
Elizabethkingia species, Acinetobacter species, and Burkholderia cenocepacia were the major GNB identified during CZA treatment, and patients who had diabetes mellitus and use of mechanical ventilation were at higher risk of acquisition of GNB. Patients who acquired GNB had higher in-hospital mortality rate. Cerebrovascular disease and disease severity were determinants of 28-day mortality.

Disclosures
All Authors: No reported disclosures
P-1581. Incidence of Cystitis and Vaginitis/Balanitis in US Veterans on Sodium/Glucose Cotransporter 2 Inhibitor Therapy for Diabetes
Authors: Lobo Zeena , Psevdos George 
Published: January 2025

Abstract

Background
Sodium glucose co-transporter 2 inhibitors (SGLT-2) are currently recommended for type 2 Diabetes, chronic kidney disease and atherosclerotic cardiovascular disease. Despite their known health benefits, a recent study within the Veterans Affairs (VA) Health care system found a relatively low rate of utilization for SGLT-2. Several studies have shown an association of SGLT-2 with increased risk for genital mycotic infections, cystitis and urosepsis. We evaluated the incidence of such infectious complications in US Veterans (VET)Table 1.Demographic Characteristics of the Cohort

Methods
Retrospective chart review of VET at Northport VA Medical Center who had received at least six months of SGLT-2 empagliflozin (EMP) for diabetes. VET who received EMP for heart failure only were excluded. The study years were 2018-2023. Demographic data, urinalysis, urine cultures, medical charts were reviewed for documentation of cystitis, clinical diagnosis of vaginitis/balanitis and need for hospitalization for urosepsisTable 2.Comparison of the two groups: infectious vs. no infectious complications

Results
400 VET were analyzed in the study period. The median age was 74.5 years. 78% were Caucasian, 15.5% black. 93% men. Table 1 shows the demographics of the cohort. There were 43 (10.75%) occasions of infectious complications: 32 (8%) cystitis (4 in women; one recurrent), 6 Balanitis, 5 fungal vaginitis (2 recurrent) . EMP was discontinued in all cases. 7/32 cystitis were clinical diagnoses without culture data. 6 cases of cystitis had more than 1 organism isolated. 2 VET were hospitalized due to urosepsis. There were no multidrug resistant organisms isolated (2 E. coli were resistant to ciprofloxacin) 1 case of balanitis in an HIV-infected man was cultured and grew Trichoderma atroviride. No cultures were obtained in cases of vaginitis. There were no differences in the two groups (infectious complications vs. noninfectious) in terms of age, HbA1c, BMI, GFR, duration of EMP treatment, use of insulin; However BPH was more common in the infectious group. See table 2. Table 3 lists the organisms isolated in urine cultures. No patient died from infectious complicationsTable 3.Organisms isolated in clinical specimens

Conclusion
The incidence of infectious complications in our diabetic VET due to EMP was overall low, with cystitis being at 8%, and observed more in men with prostatomegaly. E. coli was the most frequent isolate in urine cultures but no multidrug resistant organisms seen

Disclosures
All Authors: No reported disclosures
P-1588. Effect of Multiplex Polymerase Chain Reaction (PCR) versus Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MF) on Time to Optimal Therapy in Patients with Positive Blood Cultures
Authors: Baum Alexandria , Miller Jessica , Gavaghan Victoria , Argotsinger Jill 
Published: January 2025

Abstract

Background
Rapid diagnostic technology is an important tool that can be used to optimize antimicrobial therapy for patients with bloodstream infections Several technologies for rapid organism identification exist including matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and multiplex polymerase chain reaction (PCR). The primary objective is to compare time to optimal antimicrobial therapy with MALDI-TOF MS vs multiplex PCR rapid diagnostic systems for patients with positive blood cultures.

Methods
This multicenter, retrospective, cohort study included patients with a positive blood culture and identification via MALDI-TOF MS (June 1st – June 7th, 2021) compared to multiplex PCR (June 1st – June 7th, 2022). Patients were excluded if expired or discharged before organism identification, transferred from an outside hospital with a positive blood culture, if rapid diagnostics not performed, if identified pathogen had no defined optimal therapy per system guidelines or polymicrobial infection. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to effective therapy (TTET), length of stay, and clinical failure defined as recurrence of bacteremia within 30 days or in-hospital mortality.

Results
A total of 221 patients were included (MALDI-TOF MS = 117; multiplex PCR = 104). Utilization of multiplex PCR compared to MALDI-TOF MS significantly reduced overall TTOT (21.1 hours vs 41.1 hours, p &lt; 0.01). This significant reduction in TTOT with multiplex PCR was observed with gram-negative bacteremia (4 hours vs 37 hours, p &lt; 0.01) and gram-positive bacteremia (17.8 hours vs 41.1 hours, p &lt; 0.01) but was not statistically significant for blood cultures deemed contaminants (42 hours vs 43.5 hours, p=0.58). TTET was improved for multiplex PCR although not statistically significant (1.5 hours vs 7.5 hours, p=0.06). No differences were observed for clinical failure or hospital length of stay.

Conclusion
Multiplex PCR significantly decreased time to optimal antimicrobial therapy when compared to MALDI-TOF MS for patients with positive blood cultures.

Disclosures
All Authors: No reported disclosures