bluuebunny/crossref_metadata_2025_split huggingface dataset:
2768. In Vitro Antibiotic Susceptibility Pattern of Non-diphtheriae Corynebacterium Isolates 2012-2023, reference lab experience
Authors: Saleh Omar M Abu , Zein Said El , Rivera (O'Connor) Christina G , Stevens Ryan W W , Schuetz Audrey N , Fida Madiha 
Published: November 2023

Abstract

Background
Non-diphtheriae Corynebacterium spp. are important human pathogens responsible for a broad spectrum of clinical syndromes. Data on species-specific susceptibility patterns is limited. In this study we aim to study these susceptibility patterns over time and summarize the species-specific resistance profile that could be used by clinicians to guide therapeutic decisions.

Methods
We conducted a retrospective review of all the Non-diphtheriae Corynebacterium isolates that were submitted for antimicrobial susceptibility testing (AST) between January-2012 and February of 2023 to our reference lab.

Results
A total of 1925 Corynebacterium isolates were submitted for susceptibility testing over the study period. The most commonly identified species was C. striatum (35.6%) followed by C. amycolatum (24.4%). Figure-1 outlines the species distribution. Temporal analysis showed decreasing susceptibility rates over the study period from 47.5% to 20.6% for penicillin & from 50% to 7.6% for clindamycin.
Linezolid and vancomycin were universally active against all species (Table-1). Daptomycin non-susceptibility was reported in 25% of C. jeikeium isolates (MIC=2). High level resistance to daptomycin with MIC &gt;256 were noted in seven C. striatum and single C. amycolatum isolate. Doxycycline has the highest susceptibility rates among the tested oral agents after linezolid for the non-striatum species.
Significant variation in species-specific susceptibility pattern was noted and summarized in Table 1. C. striatum was associated with concerning resistance rates to beta-lactams, tetracyclines, trimethoprim-sulfamethoxazole & fluoroquinolones with limited reliable oral treatment options beside linezolid. C. kroppenstedtii (associated with granulomatous mastitis) showed high susceptibility rate to tetracyclines and trimethoprim-sulfamethoxazole despite prevalent penicillin resistance.

Conclusion
Non-diphtheriae Corynebacterium spp are commonly isolated from clinical specimens and are associated with various clinical syndromes. Significant variation in resistance profile exists between different species. Prevalent resistance among the most common species such as C. Striatum is associated with therapeutic challenges.

Disclosures
Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Audrey N. Schuetz, MD, Merck: Advisor/Consultant
2770. Investigating the Impact of Non-CTX-M Producing ESBL-E Bloodstream Infections on Patient Outcomes
Authors: Hareza Dariusz A , Simner Patricia J , Fiawoo Suiyini , Lee Jae Hyoung , Bergman Yehudit , Jacobs Emily B , Cosgrove Sara E , Tamma Pranita 
Published: November 2023

Abstract

Background
Studies investigating optimal treatment and patient outcomes for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) generally do not distinguish between ESBL genes in bloodstream infections (BSI). To address a key knowledge gap, we compare the clinical outcomes of patients with non-CTX-M and CTX-M-producing ESBL-E BSIs.

Methods
We collected 500 ceftriaxone-resistant Enterobacterales bloodstream isolates from patients in the Johns Hopkins Health System between 2018-2021. Broth microdilution confirmed antimicrobial susceptibilities, and whole genome sequencing identified ESBL genes. We used 1:3 propensity score matching (PSM) to compare the odds of 30-day mortality between patients infected with non-CTX-M and CTX-M ESBL-Es. Propensity scores were derived using seven variables: age, sex, severe immune compromise, Pitt bacteremia score ≥4, Charlson comorbidity index ≥5, adequate source control, and carbapenem use.

Results
ESBL genes were confirmed in 396 isolates, including 370 (93%) blaCTX-M genes and 26 (7%) non-blaCTX-M ESBL genes: blaSHV (13), blaOXY (8), blaVEB (5). Common species harboring blaCTX-M were: Escherichia coli (265), Klebsiella pneumoniae (88), K. oxytoca (5), and Enterobacter cloacae (5); and non-blaCTX-M were: K. pneumoniae (8), K. oxytoca (8), and Proteus mirabilis (5). After PSM, baseline patient characteristics were similar, and the aOR of 30-day mortality was 0.94 (95% CI 0.89-0.99) comparing patients with non-blaCTX-M and blaCTX-M isolates. In an exploratory analysis limited to patients with non-blaCTX-M isolates: 2 of 15 patients (13%) receiving meropenem and 6 of 11 (55%) not receiving meropenem died within 30 days (aOR=0.61; 95% CI 0.42-0.90).

Conclusion
Mortality was slightly lower in patients with BSIs due to non-CTX-M-producing ESBL-Es compared to CTX-M-producing ESBL-Es. Similar to what has been observed with CTX-M-producing ESBL-Es, meropenem is protective against mortality in patients infected with non-CTX-M producing ESBL-Es, underscoring the importance of diagnostics to detect a comprehensive array of ESBL genes among diverse Enterobacterales.

Disclosures
Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant
2794. Assessing the impact of inappropriate antibiotic therapy on mortality among intensive care unit patients
Authors: Pereira Rogério , Silva Sinval Lins , Couto Braulio 
Published: November 2023

Abstract

Background
This study evaluates the potential association between inappropriate antibiotic therapy and adverse clinical outcomes in infected patients admitted to ICUs.

Methods
We analyzed data from infected patients admitted to a medical-surgical Intensive Care Unit (ICU) in Belo Horizonte, a city with a population of three million in Brazil. The data was collected between January 2020 and June 2021, and included patients with healthcare-associated and community-acquired infections. In order to determine the appropriateness of antibiotic therapy, cultures and susceptibility reports were utilized. Empiric antimicrobial therapy was classified as inappropriate if the isolated strain was resistant to all empirically administered antimicrobials, while it was considered adequate if the isolated strain was susceptible to at least one of the antimicrobials used empirically.

Results
A total of 470 patients who received antimicrobials in the ICU were included in the analysis, all of whom had a positive culture. Among them, 65 patients experienced a FAILURE of the antimicrobial regimen, resulting in an overall failure rate of 14%. The monthly rate of inappropriate antibiotic therapy showed significant heterogeneity during the study period, ranging from 100% success in March 2021 to a failure rate of 33% in June 2021 (Fig 1). The failure rate of antimicrobial regimen was found to be significantly higher in cases where the infection was caused by multidrug-resistant (MR) strains compared to multisensitive (MS) strains, as shown in Table 1. Failure of the antimicrobial regimen was a significant risk factor for patient death, regardless of whether the infection was caused by MS or MR strains (Tables 1 and Fig 2). Patients who died tended to receive more antimicrobials compared to those who were discharged, with an average of three antimicrobials prescribed for patients who progressed to death, while discharged patients received an average of two drugs.

Conclusion
Inappropriate antibiotic therapy in ICU patients is associated with increased mortality risk, regardless of the type of infection. Timely and appropriate antimicrobial therapy is crucial in the management of ICU infections to improve clinical outcomes.

Disclosures
All Authors: No reported disclosures
2796. A Decade of Rhodococcus spp. Infections: Microbiology, Antimicrobial Susceptibility, and Clinical Experience
Authors: Ranganath Nischal , Mendoza Maria Alejandra , Stevens Ryan W W , Wengenack Nancy , Shah Aditya 
Published: November 2023

Abstract

Background
Rhodococcus spp. are a zoonotic, Gram-positive coccobacilli that cause pulmonary and disseminated disease in immunocompromised patients. Rhodococcus infection is associated with high morbidity and mortality and treatment can be challenging due to intrinsic resistance to several antibiotics. There is limited data on antibiotic susceptibility patterns and clinical characteristics of infection in humans.

Methods
We retrospectively evaluated the microbiology and antibiotic susceptibility testing (AST) of Rhodococcus isolates submitted to our medical reference laboratory between June 2012 and 2022. Identification (ID) was performed by Sanger 16S rRNA gene sequencing or MALDI-TOF mass spectrometry. AST was performed by microbroth dilution. We also reviewed the clinical characteristics, management, and outcomes of patients managed at our local academic medical center.

Results
Over a 10-year period, 322 isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R equi/hoagii and R corynebacteriodes were the most frequently isolated species, with 19% of isolates only identified to genus level (Figure 1). 199 isolates were evaluated for AST, with high rates of resistance to cephalosporins and aminoglycosides. Optimal antibiotics based on AST included imipenem, vancomycin, linezolid, clarithromycin, and TMP-SMX. Discordance in susceptibility was noted between ciprofloxacin (62%) and moxifloxacin (94%) (Table 1). Ten clinical cases of Rhodococcus infection were identified. Eight patients were immunocompromised with 6 having pulmonary and 3 with extra-pulmonary disease. Significant variability in choice and duration of therapy was noted, but all patients had positive treatment response with minimal complications (Table 2).

Conclusion
This study demonstrates high rates of resistance among Rhodococcus isolates with need for accurate ID and AST to guide effective treatment of infection among immunocompromised patients.

Disclosures
Nancy Wengenack, PhD, Mayo Clinic Laboratories: Employee
2806. The Mechanism of β-Lactam Antibiotic Action: Structural Analysis of Mycobacterium abscessus l,d-Transpeptidases, d,d-Carboxypeptidase and penicillin-binding-proteins binding by imipenem, ceftaroline, and amoxicillin
Authors: Shin Eunjeong , Nantongo Mary , Dousa Khalid M , Bethel Christopher R , Taracila Magdalena A , Kreiswirth Barry N , Holland Steven M , Bonomo Robert A 
Published: November 2023

Abstract

Background
M. abscessus (Mab) is among the most clinically challenging pathogens. There are significant gaps remaining in mechanism of β-lactams action in Mab. β-Lactams preferentially inactivate one or multiple different L,D-Transpeptidases (LDTs) and penicillin-binding proteins (PBPs). Founded on our LDT binding data and in vitro synergistic efficacy of imipenem (IPM), ceftaroline (CFT), and amoxicillin (AMX) in Mab, this study aimed to identify binding affinities, conformational changes and the thermal stability of five LDTs and PBPs via β-lactam binding for further structure-activity relationship.

Methods
Binding affinity was measured by kinetic studies, MS analysis, or Bocillin-FL inhibition assay. We investigated changes in the secondary structure of five LDTs (LDT1-5), d,d-carboxypeptidase, PBPB, and PBP-lipo in response to bind of IPM, CFT, and AMX using circular dichroism (CD) spectroscopy in the far-UV region. To assess the thermal stability of these LDTs, we employed a Differential Scanning Fluorimetry (DSF) assay.

Results
CD analysis revealed a significant negative shift of LDT1, LDT2, and PBPB upon binding with either single or combination of imipenem (IPM) and ceftriaxone (CFT), particularly in the 210-220 nm range. Using DSF, IPM and CFT binding to LDTs, DDC and PBPB were found to alter the thermal stability of these protein enzymes. IPM induced a decrease in the melting temperature (Tm) in the range of 2.6-6.8 ˚C for LDTs and PBPB, while caused an increase in Tm for DDC. CFT caused decrease in Tm in the range of 1.4-3 ˚C for LDTs but increase in Tm for DDC and PBPB. In contrast, amoxicillin (AMX) only targeted DDC, PBPB, and PBP-lipo and caused changes in Tm. The magnitude of the change in Tm varied between combinations and single β-lactams. Although there was no evidence of a correlation between changes in protein stability upon ligand binding and ligand binding affinity, IPM with high binding affinity (lower value of Ki,app) resulted in larger decreases in Tm compared to CFT.

Conclusion
β-Lactam binding in single and combination leads to distinct structural changes of LDTs and PBPs, likely reflecting synergistic interactions between the two β-lactams. Further crystallography will be required to gain a better understanding of the induced structural changes.

Disclosures
Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support
2808. Evaluation of a Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide empiric therapy in pneumonia cases
Authors: Skoglund Erik , Banuelos Leslie , Farihi Destiny 
Published: November 2023

Abstract

Background
Empiric antibiotic selection must balance the need for prompt active coverage against the risk of antibiotic resistance pressure imposed by using broad agents. The guidance available from conventional antibiograms is limited in this setting as they provide no information about the relative frequency of pathogens for a given infectious syndrome. Weighted-Incidence Syndromic Combination Antibiograms (WISCAs) overcome this limitation. To better promote appropriate empiric antibiotic use at our institution, we sought to develop a WISCA depicting empiric activity of various regimens against previous cases of bacterial pneumonia.

Methods
Patients admitted between 2018-2022 were screened for respiratory cultures with positive bacterial growth and a discharge diagnosis code consistent with bacterial pneumonia. Patients were excluded if they lacked radiologic evidence or clinical symptoms. The first episode of pneumonia per admission was considered. Interpretations were determined using CLSI breakpoints, and assumptions were used to extrapolate the activity of agents for which no breakpoints or MICs were available. A case was considered susceptible to a given regimen if all cultures in that case were covered by at least one agent in the regimen. The expected performance of WISCA-directed empiric therapy was compared to the activity of actual empiric therapy received by a retrospective cohort of pneumonia patients.

Results
The WISCA was built using 674 respiratory cultures from 441 unique patient cases. The most common empiric agents received in the retrospective cohort were vancomycin (158, 77%), piperacillin-tazobactam (133, 65%), ceftriaxone (77, 38%), and meropenem (57, 28%). Among this cohort, 126 (61%) of patients received active empiric coverage against all case pathogens. According to the WISCA, the combination of piperacillin-tazobactam + levofloxacin provides active empiric coverage for 63% of cases, which is not significantly different than that achieved in the retrospective cohort while avoiding use of carbapenems or vancomycin.

Conclusion
Our findings suggest that WISCAs provide additional guidance for empiric antibiotic prescribing compared to conventional antibiograms alone.

Disclosures
All Authors: No reported disclosures
2813. Impact of a Recent Change in Tobramycin Breakpoints (CLSI) on the Proportion of Pseudomonas aeruginosa Clinical Isolates that are Multidrug-Resistant: CANWARD, 2016 to 2021
Authors: Walkty Andrew , Adam Heather , Baxter Melanie , Lagace-Wiens Philippe , Karlowsky James , Zhanel George 
Published: November 2023

Abstract

Background
Pseudomonas aeruginosa (PA) is an important nosocomial pathogen. In 2023, tobramycin (TM) susceptibility breakpoints for PA were lowered (from ≤4 to ≤1 µg/mL) by the Clinical and Laboratory Standards Institute (CLSI). The purpose of this study was to evaluate whether this change will result in an increase in the proportion of PA clinical isolates that are considered multidrug-resistant (MDR).

Methods
PA clinical isolates were obtained from patients evaluated at hospitals across Canada (January 2016 to December 2021) as part of an ongoing national surveillance study (CANWARD). Susceptibility testing was carried out using custom broth microdilution panels. MICs were interpreted using current (2023) CLSI breakpoints, with the exception of TM (interpreted using the 2022 and 2023 breakpoints). MDR PA were defined as isolates testing not susceptible at least three of the following: ceftazidime, ciprofloxacin, meropenem, piperacillin-tazobactam, and TM (assessed with both the 2022 and 2023 CLSI breakpoints).

Results
1649 PA isolates were included in this study. The proportion of isolates testing susceptible to TM using the 2022 (S ≤4 µg/mL) and 2023 (S ≤1 µg/mL) CLSI breakpoints were 93.6% and 84.8%, respectively. Overall, 21.6% (356/1649) and 22.7% (374/1649) of PA isolates were MDR, using the 2022 and 2023 CLSI breakpoints. Below, the in vitro activities of common antipseudomonal antimicrobials versus PA isolates from this study (all and MDR subset) are presented.

Conclusion
In this dataset, the proportion of MDR PA isolates was minimally altered by a recent change to the CLSI TM susceptibility breakpoints. A reduction in the proportion of PA isolates that were susceptible to TM using the new breakpoints was most pronounced for the MDR subset.

Disclosures
George Zhanel, PhD, Avir: Grant/Research Support|Iterum: Grant/Research Support|Merck: Grant/Research Support|Orimed: Grant/Research Support|Paladin Labs: Grant/Research Support|Pfizer: Grant/Research Support|Verity: Grant/Research Support|Zambon: Grant/Research Support
2814. The Impact of Novel Antibiotics on Curbing Antimicrobial Resistance and Infection Spread a Dynamic Modeling Study
Authors: Ambavane Apoorva , Litkiewicz Michal , Sardesai Aditya , Teloian Diana , Obi Engels N , Yang Joe 
Published: November 2023

Abstract

Background
Antimicrobial resistance (AMR) is a growing global concern. Novel antibiotics (ABXs) target resistant pathogens causing gram-negative (GN) bacterial infections. This study assesses the broader impact of novel ABX use on the US healthcare system, including preventing the onward spread of infections and reducing the level of high-threat AMR.

Methods
A stochastic dynamic transmission model was developed to simulate the interaction between infection transmissibility, bacterial resistance development, and multiple lines of ABX. Included infection types were intra-abdominal infections, urinary tract infections and hospital-acquired /ventilator-associated pneumonia. Included AMR types were carbapenem-resistant and ESBL-producing enterobacterales (CRE and ESBLE), and multi-drug resistant pseudomonas aeruginosa (MDRP). The model has compartments for non-infected, colonized, or infected patients, with a sensitive or resistant strain in a US hospital. Infected patients receive antibiotics resulting in infection clearance or use of an alternate ABX class. Sensitive pathogens gain resistance due to drug pressure or conversely could lose resistance. Ordinary differential equations were used to estimate compartment membership. The primary data source was the Premier healthcare database (172 hospitals, 2016-2020). The model examined the potential reduction in AMR levels and avoided hospital infections, by comparing two scenarios: targeted use of novel ABX for specific AMR types and the status quo with limited novel ABX use.

Results
When even novel ABXs are reserved as the 2nd or 3rd line of treatment, compared to the status quo, it could result in a ∼1.5% reduction in hospital infections and a change in CRE, ESBLE, and MDRP by −2.5%, −3.6%, and −2.1%, respectively, on an annual basis. The cumulative impact of novel ABXs over 5-10 years was much larger but subject to higher prediction uncertainty. The primary driver of results are infection clearance rates, risk of resistance gain on various ABX, and uptake of novel ABX.

Conclusion
Targeted use of novel ABXs for resistant pathogens could lead to improved, earlier infection clearance with most types of infections and pathogens, thereby reducing infection transmission and rise of high-threat AMR in the long-term.

Disclosures
Apoorva Ambavane, PhD, Merck & Co., Inc: Grant/Research Support Michal Litkiewicz, MSc, Merck & Co., Inc: Grant/Research Support Aditya Sardesai, MSc, CSL Seqirus: Advisor/Consultant|Merck & Co. Inc: Grant/Research Support|Merck & Co. Inc: Grant/Research Support Diana Teloian, MA, Merck & Co., Inc: Grant/Research Support Engels N. Obi, PhD, Merck & Co Inc: Employee Joe Yang, PhD, Merck & Co., Inc: Employee|Merck & Co., Inc: Stocks/Bonds
2815. Outcomes of Novel Antimicrobials Compared to Polymyxin B for treatment of infections due Carbapenem-Resistant Enterobacterales Infections
Authors: Zheng Tina , Kubin Christine J , Nelson Brian 
Published: November 2023

Abstract

Background
Carbapenem-resistant Gram-negative infections remain a serious threat due to their increasing incidence and high mortality rates. Since 2015, various antimicrobials with in vitro activity against carbapenem-resistant Enterobacterales (CRE) have been approved for use. There is limited evidence on the safety and efficacy of these novel antimicrobials compared to previous first-line agents, polymyxins, for treating CRE infections.

Methods
This was a retrospective cohort study that evaluated the clinical efficacy and safety of the novel antimicrobials compared to polymyxin B. Adult patients with a CRE infection treated with ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB), or polymyxin B (PMB) for at least 2 days between June 2013 to November 2022 were included. Patients receiving the novel agents (CZA+MVB) were compared to PMB. The primary outcome was 30-day mortality. Secondary outcomes included clinical and microbiological success, 90-day recurrence, development of resistance, frequency of acute kidney injury (AKI), and global success. Global success encompassed 30-day mortality, clinical and microbiological success, and 90-day recurrence.

Results
110 patients were included: 75 in the novel agents group (53 CZA, 22 MVB) and 35 in the PMB group. The median age was 59 years (IQR 45,70), simplified Pitt bacteremia score (qPITT) was 1 (IQR 1,2), and Charlson Comorbidity score was 4 (IQR 2,6). The most common organism was K. pneumoniae (62%) and the most common site of infection was respiratory (54%) followed by blood (22%). 30-day mortality did not differ between the novel agents compared to PMB (23% vs. 29%; p=0.665). Numerically higher clinical success occurred with the novel agents (72% vs. 54%; p=0.106) while microbiological success was similar (93% vs 91%; p=1.0). In the 18 patients who had follow up positive cultures, 3/9 (33%) developed resistance in the novel agents group compared to 7/9 (78%) in the PMB group. No differences were identified in 90-day recurrence and global success. Patients who received novel agents had less AKI compared to the novel agents (16% vs 54%; p&lt; 0.001).

Conclusion
Patients receiving CZA and MVB for CRE infections did not have differences in clinical and microbiological outcomes but had less AKI compared to patients receiving PMB.

Disclosures
All Authors: No reported disclosures