bluuebunny/crossref_metadata_2025_split huggingface dataset:
2736. Real-world Effectiveness of Posaconazole Prophylaxis in Preventing Invasive Fungal Infections in Recipients of Allogeneic Stem Cell Transplantation
Authors: Álvarez-Ortega Carolina , Muñoz-Lombo Jenny Patricia , Rebellon-Sanchez David E , Llanos-Torres Julio , Rosso Fernando , Vélez Juan Diego , Moncada Pablo A 
Published: November 2023

Abstract

Background
Invasive fungal infections (IFIs) can cause high morbidity and mortality in immunocompromised patients. Posaconazole is a commonly used triazole antifungal agent for prophylaxis against IFIs in high-risk populations. However, the effectiveness of Posaconazole as antifungal prophylaxis in Allogeneic Stem Cell Transplantation (allo-SCT) in Latin-America has not been well described. The aim of this study is to describe the clinical experience with the use of Posaconazole as antifungal prophylaxis in allo-SCT in a high complexity medical center in Latin-America.

Methods
A retrospective descriptive study was conducted to evaluate the experience of using Fluconazole or Posaconazole as antifungal prophylaxis in patients undergoing Allogeneic Stem Cell Transplant at the Fundación Valle de Lili in Cali, Colombia between 2012 and 2020. (Figure 1). The primary outcome variable was the incidence of IFI in the first 100 days of prophylaxis.
Allogenic Stem Cell Transplant: Methods selection
A Retrospective descriptive study involving the selection of 194 patients who underwent Allogeneic Stem Cell Transplantation, of which 179 patients met the selection criteria for the study.

Results
This study analyzed 179 individuals with hematologic malignancies who received prophylaxis with either Posaconazole (n=164) or Fluconazole (n=15). The occurrence of IFI was lower in the Posaconazole group compared to the fluconazole group during the initial 100 days of prophylaxis (1.22% vs. 13.33%, p=0.03) (Figure 2). Aspergillus spp were the most frequent microorganisms observed in 3 cases (1.67%). The Number Needed to Treat (NNT) was 8.25, indicating that 8 patients treated with Posaconazole can prevent one IFI that would have occurred with Fluconazole treatment.
Comparative analysis of Posaconazole and Fluconazole as antifungal prophylaxis in Allogeneic Stem Cell Transplantation
Percentage of Invasive Fungal Infections found in Allogeneic Stem Cell Transplantation during the first 100 days post-transplantation in patients who received prophylaxis with Posaconazole or Fluconazole.

Conclusion
This study suggests that using Posaconazole as antifungal prophylaxis reduces the incidence of invasive fungal infections (IFI) in patients undergoing Allogenic Stem Cell Transplantation under real-world conditions and is a safe alternative to be used in low-income settings. Further clinical studies with larger sample sizes are required to confirm these findings.

Disclosures
All Authors: No reported disclosures
162. The Genotypic Antibiogram: Using Results of Gram-Negative Antimicrobial Resistance Genes Identified via Rapid Blood Culture Identification Tests to Optimize Treatment of Enterobacterales Bloodstream Infections
Authors: Sunagawa Shawnalyn , Tigh Jeremy E , Okada Ashlyn , Bergman Scott J , Van Schooneveld Trevor C , Chan Yolande , Fey Paul D , Ryder Jonathan H 
Published: November 2023

Abstract

Background
With the increasing incidence of infections from Enterobacterales resistant to commonly used antibiotics, rapid diagnostic tests, such as BioFire’s Blood Culture Identification 2 (BCID2) multiplex PCR panel, can be utilized to detect potential antimicrobial resistance more rapidly and help direct more appropriate empiric therapy. We describe the epidemiology of Enterobacterales bloodstream infection (BSI), associated antimicrobial resistance genes using BCID2, and subsequent susceptibility patterns at an academic medical center to develop a genotypic antibiogram.

Methods
We reviewed all positive BCID2 results at Nebraska Medical Center from 8/1/2021–11/1/2022. Only monomicrobial Enterobacterales BSI were included. Patient demographics, antimicrobial resistance markers, BCID2, culture, and susceptibility results were assessed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of blaCTX-M marker were compared to ceftriaxone susceptibility patterns.

Results
We reviewed 456 unique Enterobacterales isolates, of which 236 were from male patients (52%), 189 (41%) immunocompromised patients, and 342 (75%) community onset. The most common species identified were Escherichia coli (55%) and Klebsiella pneumoniae (17%). blaCTX-M was detected in 49 (11%) isolates, with 41 (84%) E. coli and 6 (12%) K. pneumoniae. blaKPC was detected in 2 isolates (1 K. oxytoca and 1 K. variicola), but no other carbapenemase genes were detected. blaCTX-M sensitivity and specificity for detection of ceftriaxone resistance was 83% and 100%, respectively. blaCTX-M PPV for ceftriaxone resistance was 100%, while the NPV of absent blaCTX-M for ceftriaxone susceptibility was 97%.

Conclusion
Locally, the majority of ceftriaxone-resistant E. coli and Klebsiella BSIs harbor blaCTX-M, while carbapenemases are rare. Utilization of rapid diagnostics can optimize antimicrobial therapy for Enterobacterales by creation of a genotypic antibiogram.

Disclosures
Scott J. Bergman, PharmD, bioMerieux, Inc.: Honoraria Trevor C. Van Schooneveld, MD, FSHEA, FACP, AN2 Therapeutics: Grant/Research Support|Biomeriuex: Advisor/Consultant|Biomeriuex: Grant/Research Support|Insmed: Grant/Research Support|Thermo-Fischer: Honoraria
2742. The Prevalence and Clinical Impact of Antibiotic Allergy Labels in Solid Organ Transplant Recipients
Authors: Nair Sashi , Bigliardi Paul , Fontana Lauren 
Published: November 2023

Abstract

Background
Antibiotic allergy labels (AAL), specifically Penicillin allergy labels (PAL) are reported in up to 20% of immunocompromised patients. However, up to 95% of reported PALs can be disproven by skin and provocation testing. Compared to first line beta-lactam antibiotics, alternative agents are associated with significant complications, such as drug resistance, C. diff infection, and failure of antibiotics. Knowledge regarding the impacts of AAL on the Solid Organ Transplant (SOT) population is evolving. However, the impact on 1-year outcomes is not known. Our primary objective for this study was to evaluate the impact of AAL, particularly PALs on patient outcomes in SOT.

Methods
We performed a retrospective review of adult SOT recipients who underwent a single kidney, liver, lung, heart, or pancreas (with or without a kidney transplant) transplant between 1/1/2012 and 1/1/2021. We subsequently identified recipients with at least 1 AAL at the time of transplant and collected clinical data,\ using our institutional database. Statistical analysis was performed with a Pearson’s chi-square test to assess association between categorical variables. Multivariate logistic regression was also performed on outcomes using significant variables from the univariate analysis.

Results
2373 SOT recipients were included, and their details are shown in Table 1.In our cohort, 331(13.6%) had a PAL and 572 (24.1%) had at least one AAL. Lung recipients had a significantly higher rate of PAL than other organ types. Recipients with a PAL were statistically more likely to have pretransplant COPD, ESRD, or obesity (Table 2). Furthermore, recipients with a PAL were more likely to have graft failure and C. diff, but not death within the first year after transplant (Table 2). The association between PAL and C. diff rates persisted even in a multivariate model.
Univariate and Multivariate Logistical Regression Analysis for SOT Recipients with a Penicillin Allergy Label

Conclusion
To our knowledge this is the largest study with the longest duration of follow up evaluating the prevalence and outcomes of AAL and PAL in SOT recipients. Specifically, we identified worse outcomes associated with PAL such as higher C. diff rates and graft failure. This study highlights the need to better understand the impact of AAL and to promote multidisciplinary interventions that aim to remove invalid AAL pre-transplant.

Disclosures
All Authors: No reported disclosures
2749. Impact of rapid carbapenemase identification on management of patients with carbapenem-resistant Enterobacterales infections
Authors: Burke Elysia , Dutcher Lauren , Hamilton Keith W , Degnan Kathleen , Glaser Laurel , Maguire Christina , Saw Stephen , Mersinger Katherine , Patel Sonal , Athans Vasilios , Binkley Shawn 
Published: November 2023

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) infections can lead to increased length of stay and mortality. Identification of the mechanism of resistance is vital to assist in antibiotic selection. In October 2021, our institution’s microbiology laboratory switched from the CARBA NP assay, which detects carbapenemase production, to the CARBA 5 assay, which detects and differentiates types of carbapenemases. The primary aim was to characterize the pattern of carbapenemases within our institution. The secondary aim was to identify whether the transition to the CARBA 5 assay impacted antibiotic management.

Methods
This was a quasi-experimental, pre-post study design, including adults with at least one isolate of carbapenemase-producing Enterobacterales (CPE) from October 2020 – October 2022. The CARBA 5 testing protocol began on October 27th, 2021. The pretest-posttest groups were assigned before and after this date, respectively. For patients with multiple CPE isolates, only the first isolate per patient was included. Patients who were deemed to be colonized (not treated) were not included in outcome analysis. Descriptive statistics were used to characterize demographics, distribution of carbapenemase type, and colonization. Time-to-appropriate therapy was defined as time to administration of the first antibiotic with known susceptibility. All time-based outcomes were measured from the time the culture resulted as carbapenem-resistant in the medical record.

Results
The pretest group had 49 patients, of which 22 were treated. The posttest group had 37 patients, of which 17 were treated. Distribution of carbapenemases and pathogens are listed in Table 1 and Table 2. The median time-to-appropriate therapy was 5.3 hours (IQR 3.2-23.9) in the pretest group versus 5.0 hours (IQR 3.3-10.7) in the posttest group. Of the patients treated, 6 (26.1%) patients experienced 30-day mortality in the pretest group versus 4 (22.2%) in the posttest group. Median time-to-discharge in the pretest group was 14.7 (IQR 7.6-19.2) days versus 9.6 days (IQR 5.7-15.3) in the posttest group.

Conclusion
The most common carbapenemase was KPC; the most common pathogen was Klebsiella pneumoniae. Time-to-appropriate therapy and time-to-discharge during the CARBA 5 test period were numerically lower.

Disclosures
Kathleen Degnan, MD, Gilead: Grant/Research Support Christina Maguire, PharmD, Viiv: Advisor/Consultant
2767. Impact of iron limitation on in vitro and in vivo activity of ceftazidime against A. baumannii
Authors: Eales Brianna , Smith James , Hudson Cole , Pouya Nazanin , Tam Vincent 
Published: November 2023

Abstract

Background
Acinetobacter baumannii (AB) is known to have high rates of multidrug resistance (MDR), new treatment options are critically needed to prevent further spread and mortality. Deferiprone (DFP), a metal chelator, has been shown to induce transient growth inhibition in previous studies, and this could be potentially exploited for therapeutic purposes. The objective of the study was to examine the impact of iron limitation on the in vitro and in vivo activity of ceftazidime against AB.

Methods
An MDR bloodstream isolate (AB14) recovered from a 50 years-old male patient was used. Ceftazidime (CAZ) minimal inhibitory concentration was determined by microbroth dilution in the presence of DFP. In vitro growth profiles were discerned by an automated process (BacterioScan 216Dx) tracking CFU/mL over time. Bacteria were started at a concentration of approximately 5.5 log CFU/mL in tryptic soy broth. The effect of DFP (1000μM) and CAZ (128μg/ml) on bacterial growth was studied either alone or in combination. A neutropenic pneumonia mouse model was used in which the animals were given two doses of cyclophosphamide and one dose of uranyl nitrate intraperitoneally prior to infection. For infection, anesthetized mice were inoculated with approximately 1 × 106 CFU (with and without DFP) via the trachea under laryngoscopic guidance. A humanized regimen consisting of three doses of CAZ over 8h was used to mimic a dose of 2g. Quantitative culture was used to ascertain the bacterial burden of lung tissue immediately and 8h post infection.

Results
MIC of CAZ was reduced from &gt; 256μg/mL to 64, 32, and 1μg/mL in the presence of 500, 1000, and 1500μM of DFP respectively. A combination of subinhibitory concentrations of CAZ and DFP resulted in minimal (&lt; 0.5 log CFU/mL) growth in 20h. The lung bacterial burden of the control groups increased ≥ 1 log CFU/g after 8h, whereas the combination group (CAZ + DFP) stayed comparable to baseline. Control groups compared to combination was statistically different p&lt; 0.05).

Conclusion
These results support that limiting iron has the potential to be a novel approach to treating MDR AB infections. Further research is warranted to broaden the scope to encompass additional clinical isolates, and to optimize the approach as a therapeutic solution.

Disclosures
All Authors: No reported disclosures
2769. Treatment of Hypermutator Pseudomonas aeruginosa Induces Multidrug Resistance but Can Be Targeted by Combination Therapy
Authors: Hall Kalen M , Wimley William C , Bojanowski Christine M , Pursell Zachary F , Morici Lisa 
Published: November 2023

Abstract

Background
Up to 60% of Pseudomonas aeruginosa (Pa) strains isolated from human chronic lung infections lack an active DNA mismatch repair (MMR) system, resulting in a hypermutator phenotype. Hypermutator Pa isolates are associated with enhanced multidrug resistance and treatment failure, and treatments targeting hypermutators are not available. Although hypermutation has been shown to catalyze drug resistance acquisition, it is unclear how treatment of hypermutator Pa influences the development of multidrug resistance.

Methods
Here, we performed in vitro adaptive evolution of hypermutator Pa under different antibiotic conditions to assess if treatment of hypermutator Pa induces multidrug resistance acquisition via repeated selection for specific resistance-conferring mutations. We serially exposed hypermutator Pa and wild type Pa to four different antibiotics representing three drug classes, and subsequently tested evolved lineages against a panel of six non-treatment antibiotics from varying classes.

Results
We observed that hypermutator Pa acquired levels of resistance above clinical breakpoints (defined by Clinical and Laboratory Standards Institute) to all antibiotics tested faster than wild type Pa. Antibiotic treatment of hypermutator Pa selectively induced multidrug resistance acquisition but was irrespective of drug class. Using whole genome sequencing of resistant lineages, we found that treatment-induced multidrug resistance acquisition was determined by shared mechanisms of resistance rather than shared cell target. We subsequently tested combination therapies requiring independent and exclusive mechanisms of resistance and found that combined aztreonam/colistin effectively eliminated multidrug resistance acquisition in hypermutator Pa. Currently, we are testing this combination therapy on 14 Pa isolates (with 4 hypermutator and 10 wild type) from cystic fibrosis patients.

Conclusion
Our results shed light on how hypermutator Pa may acquire multidrug resistance within the host and suggest that combination therapies that require independent mechanisms of resistance could potentially reduce emergence of multidrug resistance in hypermutator Pa, providing a viable therapeutic option.

Disclosures
Kalen M. Hall, B.S., B.A., Informuta: 1|Informuta: Ownership Interest|Informuta: Stocks/Bonds
2776. Decrease in ceftriaxone treatment failure rates for infections caused by inducible AmpC producing Enterobacterales associated with changes in laboratory susceptibility testing reporting
Authors: Khan Ayesha , Humphries Romney 
Published: November 2023

Abstract

Background
Due to the risk of AmpC induction and subsequent emergence of resistance on therapy, IDSA guidelines suggest avoiding ceftriaxone (CRO) for the treatment of E. cloacae, K. aerogenes or C. freundii (CEK group) but not for S. marcescens (SM), citing the lack of evidence. Many clinical laboratories still report CRO susceptibilities for these organisms. In January 2021, our institution stopped reporting CRO results for Enterobacterales with inducible AmpC enzymes. We compare rates of CRO treatment failure in the 2 years before and after this reporting change.

Methods
We retrospectively evaluated (with IRB approval) all hospitalized patients that were diagnosed with an invasive infection due to CRO-susceptible Serratia, Enterobacter, K. aerogenes, or C. freundii. Final therapy was defined as antibiotic the patient was on within 24h of culture finalization for at least a 72h course. The primary outcome assessed rates of CRO treatment failure- defined as clinical failure (clinical decompensation) or microbiological failure (repeat growth of same organism). The years 2019 and 2020 (lab reported CRO) were compared to 2021 and 2022 (lab did not report CRO).

Results
In 2019-2020, 67 patients were hospitalized with bacteremia, endocarditis, pneumonia or urosepsis (25 by SM, 42 by CEK group). 15 (22.4%) were treated with CRO (6 SM, 9 CEK). 12 patients (80%) failed CRO therapy (5 SM, 7 CEK), of which 4 had a repeat organism cultured, with 1 documented CRO-resistant isolate (E. cloacae) after treatment. In 2021-2022, of the 77 patients with infections (34 by SM, 43 by CEK group), 2 (2.6%) were treated with CRO and both failed therapy (2 SM).Table 1.Summary of results. * CRO treatment failure rates based on number of patients who showed clinical or microbiology failure after being placed on CRO treatment

Conclusion
Our single-center evaluation suggests that laboratories not reporting CRO susceptibility results for Enterobacterales with inducible AmpC may decrease use of CRO for these organisms and decrease subsequent treatment failures. Larger multi-center studies are warranted. Contrary to the IDSA guidelines, SM infections had a similar risk of CRO treatment failure as infections by CEK organisms, despite the initial isolate’s susceptibility. We hypothesize that due to the complex mechanism of inducible AmpC resistance, most cases of CRO treatment failure are not accompanied with the repeat culturing of a CRO-resistant organism after therapy.

Disclosures
Romney Humphries, PhD, D(ABMM), M(ASCP), Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Ventorx: Advisor/Consultant
166. Impact of Pneumonia Panel Implementation with Stewardship Support on Antibiotic De-escalation in the ICU
Authors: Schooneveld Trevor C Van , Bergman Scott J , Lyden Elizabeth , Fey Paul , Miller Molly M , Kate Anderson Mary , Kashyap Akshay , Mantz Sara , Vetter Rachel , Wurtz Paul , Stohs Erica J 
Published: November 2023

Abstract

Background
Pneumonia is the most common indication for antibiotics in the ICU. Better diagnostic tools are needed to target therapy. We evaluated the impact of the BIOFIRE Pneumonia Panel (PNP) coupled with aggressive stewardship interventions in the ICU.

Methods
The PNP was implemented 5/2020 with interpretation guidance, provider education, and intermittent stewardship feedback. From 2/21 to 7/21 (Intervention) stewardship personnel reviewed all ICU PNP and provided structured feedback. We compared this group to patients with a respiratory tract culture in the ICU 9/19-2/20 (Control). We evaluated only first PNP/culture and excluded age &lt; 19 years and expired &lt; 24 hours after PNP/culture. Antibiotic use for 7 days after PNP/culture was compared between groups with time to de-escalation as the primary outcome. Times were measured from PNP/culture collection.

Results
A total of 313 intervention patients and 315 controls were compared with differences noted in ICU location and LOS, COVID detection, specimen type, and mortality (Table 1). PNP results were available 4 hours after collection and positive in 56.9% (culture positive 38.3%) with the most common pathogens detected being S. aureus (MSSA 61, MRSA 28), H. influnezae (32), respiratory viruses (30), and P. aeruginosa (24). Use of urine antigens and respiratory pathogen panel testing was less common in the Intervention group (Table 1) while stewardship interventions were more common (82% vs. 13%) and occurred 23 hours earlier (Table 2). Intervention period antibiotic de-escalation occurred 18 hours earlier (P&lt; 0.0001) and time to stopping anti-MRSA and anti-Pseudomonal therapy was shorter (absolute difference 13 hours, P=0.005 and 16 hours, P=0.060). Median antibiotic days were decreased (9 vs. 8, P=0.008) and days of vancomycin, metronidazole, azithromycin, and Anti-Pseudomonal therapy significantly decreased during the intervention.

Conclusion
PNP detected more pathogens and when coupled with an aggressive stewardship intervention resulted in faster pathogen detection, decreased urine antigen testing, faster de-escalation of antibiotics, and less antibiotic use. Clinical characteristics and outcomes were different between the groups which may be due to differences in the populations including the presence of COVID.

Disclosures
Trevor C. Van Schooneveld, MD, FSHEA, FACP, AN2 Therapeutics: Grant/Research Support|Biomeriuex: Advisor/Consultant|Biomeriuex: Grant/Research Support|Insmed: Grant/Research Support|Thermo-Fischer: Honoraria Scott J. Bergman, PharmD, bioMerieux, Inc.: Honoraria Erica J. Stohs, MD, MPH, bioMerieux: Grant/Research Support|Merck: Grant/Research Support