bluuebunny/crossref_metadata_2025 huggingface dataset:
2705. Predictors of Severe COVID-19 among Solid Organ Transplant Recipients
Authors: Gillcrist Marion , Waller Stephen , Taylor Ryan M , Bahr Nathan C , Cibrik Diane M , Shah Zubair , Montgomery Robert , Eid Albert
Published: November 2023

Background

While some studies have found worse COVID-19 outcomes among solid organ transplant (SOT) recipients, others found no difference when comorbidities and other risk factors for severe disease were accounted for. It remains unclear whether immunosuppressive medications increase the risk of progression to severe disease in SOT recipients.

Methods

We conducted a retrospective case-control study of SOT recipients diagnosed with COVID-19 at the University of Kansas Medical Center between January 1, 2020 and December 31, 2022. Severe COVID-19 was defined by hypoxia while the patient was on room air during a 21-day period after the COVID-19 diagnosis was established. We fit a logistic regression model with severe COVID-19 as the response variable and adjusted for prescription of mycophenolate, tacrolimus and prednisone and a set of covariates including age, sex, race, body mass index, hypertension, diabetes mellitus, prespecified time period of COVID-19 diagnosis during the pandemic, chronic heart disease, chronic lung disease, malignancy, end stage renal disease, cirrhosis, smoking, receipt of COVID-19 vaccine, and receipt of monoclonal antibodies.

Results

A total of 570 SOT recipients were diagnosed with COVID-19. Our cohort consisted of 458 kidney, 73 liver, 54 heart, 43 pancreas, and 8 lung recipients. The median patient age was 54 years, 59% were male, and 70% were white. Severe COVID-19 developed in 127/570 (22.3%) patients. A total of 58/570 (10.2%) patients died. A multivariable analysis showed that age (OR = 1.04; p < 0.01), race other than white (OR = 1.88; p = 0.02), chronic heart disease (OR = 1.91, p = 0.01), chronic lung disease (OR = 2.21; p = 0.02), lack of prior COVID-19 vaccination (OR = 2.09; p = 0.01), and not receiving treatment with monoclonal antibodies (OR = 3.82; p < 0.01) were associated with severe COVID-19. Being on treatment with mycophenolate, tacrolimus, or prednisone at the time of COVID-19 diagnosis was not associated with severe disease.

Conclusion

Patients receiving mycophenolate, tacrolimus, or prednisone at the time of COVID-19 diagnosis were not more likely to experience severe disease. Overall mortality in our SOT population was 10%.

Disclosures

All Authors: No reported disclosures
2717. Beware the bacteria: risk of bacterial infections persists more than 60 days post CAR-T
Authors: Mathur Poonam , Riedel David J , Bork Jacqueline T , Prakash Katya , Hardy Nancy , Baddley John W
Published: November 2023

Background

Immunosuppressive conditioning regimens for chimeric antigen receptor-modified T cells (CAR-T) and subsequent T cell dysfunction increase risk for infection. Prior studies of infection risk after CAR-T have found bacterial infections are most common in the first month, and viral infections are more frequently seen after 30 days. We evaluated longer-term infection outcomes, up to 180 days post CAR-T infusion.

Methods

We performed a retrospective chart review of 144 patients who received CAR-T infusion at our institution between March 2018 and March 2022. We collected data on demographics, type and timing of infections, onset and treatment of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or Cytokine Release Syndrome (CRS), and mortality up to 180 days after CAR-T infusion. We determined if ICANS, CRS, or treatment for either was associated with infections using Chi-square test.

Results

The mean age of patients in our cohort was 59 years. Most patients were male (65%), White (66%), and had not received a prior stem cell transplant (78%). Fifty-one (35%) patients had at least one infection during the study period (29% bacterial, 13% viral, 2% fungal). Mortality was 23% at 180 days. Most infections occurred within 60 days post CAR-T (Figure 1). Infections occurring between days 61 and 180 were mostly bacterial. In addition, ICANS ≥grade 3 and CRS ≥grade 2 occurred in 22 (15%) and 54 (38%) patients, respectively; both were significantly associated with bacterial infection (p< 0.05).

Figure 1

Infections 180 days after CAR-T. *includes bacteremia, pneumonia, and skin and soft tissue infections.

Conclusion

This cohort analyzed long-term infection outcomes post CAR-T. Most infections occurred early after CAR-T, within 60 days, and ICANS and CRS were associated with bacterial infection. We found that infections still persisted late after CAR-T, between Days 61 and 180, and were predominately bacterial, rather than viral or fungal. The low rates of fungal infection throughout the study period may be due to our institution’s fungal prophylaxis protocol. Future analyses will elucidate risk factors for infections in the late CAR-T period.

Disclosures

David J. Riedel, MD, MPH , Gilead: Advisor/Consultant
2719. Oral Antibiotics for Treatment of Gram-Negative Bacteremia in Solid Organ Transplant Recipients: A Propensity Score Weighted Retrospective Observational Study
Authors: Nussbaum Eliezer Zachary , Koo Sophia , Kotton Camille N
Published: November 2023

Background

Treatment of gram-negative bloodstream infections (GNBI) with oral rather than intravenous (IV) antimicrobial agents can reduce length of stay, catheter associated complications and improve patient satisfaction. There is minimal data regarding this practice in solid organ transplant recipients (SOTR). We assessed the safety and efficacy of oral step-down therapy for treatment of uncomplicated GNBI in SOTR.

Methods

We identified all SOTR within the Massachusetts General and Brigham and Women’s Hospital systems from 2016-2021 with uncomplicated GNBI that were transitioned from IV to oral agents to complete treatment. We identified a second group of patients with uncomplicated GNBI who remained on IV antimicrobials for the entirety of treatment but had an infecting organism susceptible to at least a moderately bioavailable oral agent. We conducted a propensity score weighted retrospective study to compare outcomes of the oral and IV groups. Primary endpoints were mortality, recurrence of bacteremia and re-initiation of IV antibiotics within 30 days of treatment completion. Secondary endpoints included length of stay, C. difficile infection, treatment associated complications, and need for tunneled central venous access.

Results

120 GNBI from 107 patients met inclusion criteria in the oral group and 42 GNBI from 40 patients in the IV group. There was no statistically significant difference in mortality, bacteremia recurrence, or re-initiation of IV antibiotics between oral and IV groups. Compared with the IV group, patients transitioned to oral antibiotics had an average length of stay that was 1.97 days shorter (p=0.005, 95% CI -3.56, -0.39 days). Odds of developing C. difficile were 8.4 times higher in the IV group (p=0.015, 95% CI 1.5, 46.6) and the odds of developing other treatment associated complications were 6.4 times higher in the IV group (p=.002, 95% CI 1.9-20.9). 55% of patients in the IV group required placement of a tunneled central venous catheter. There was no difference in total duration of antibiotic treatment between groups.

Baseline Patient Characteristics

Infecting Species, Source of Infection and Antibiotic Therapy

Clinical Outcomes in Oral and IV Antibiotic Treatment Groups

Conclusion

Conversion from IV to oral therapy with moderate to highly bioavailable antimicrobials was effective and associated with fewer treatment related adverse events in SOTR with uncomplicated GNBI.

Disclosures

Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support
2722. Risk of Infectious Adverse Events of Venetoclax Therapy in the Treatment of Hematologic Malignancies: A Systematic Review and Bayesian Meta-Analysis of Randomized Controlled Trials
Authors: Prosty Connor , Katergi Khaled , Nguyen Alex , Luo Owen , Sorin Mark , Cherniak Vladimir , Sebag Michael , Demir Koray , McDonald Emily , Lee Todd C , Cheng Matthew
Published: November 2023

Background

Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia and chronic lymphocytic leukemia. Recent post-marketing studies on venetoclax suggested that it may predispose to opportunistic infections (OIs). We sought to systematically review the randomized controlled trial (RCT) evidence on venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia.

Methods

We systematically reviewed the RCTs comparing venetoclax therapy to active (i.e., a regimen with additional anti-cancer agents) or placebo controls in patients with hematologic malignancies, irrespective of treatment line. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis and we computed the probability of any increased risk in infectious or neutropenic complications (Risk Ratio [RR] >1). Subgroup analyses were conducted based on treatment line, use of an inactive comparator, malignancy type, and prophylaxis strategy. Additionally, we pooled the incidence rates of fatal OIs between venetoclax and comparator arms and compared them by univariate meta-regression.

Results

Seven RCTs were included comprising 2067 patients. In venetoclax versus comparator regimens there was a 81.1% probability of any increase in IAEs (RR=1.14, 95% Confidence Interval [95%CI]=0.76-1.66). The probabilities of venetoclax increasing the risk of grade 3-5 and fatal IAEs were 86.6% (RR=1.16, 95%CI=0.86-1.55) and 81.1% (RR=1.40, 95%CI=0.66-2.94), respectively. There was a 97.2% likelihood that venetoclax increased the risk of grade 3-5 neutropenia (RR=1.44, 95%CI=1.01-2.10). Venetoclax treatment did not increase the incidence of fatal OIs (P=0.55).

Conclusion

Our results suggest that venetoclax likely increases the risk of high-grade neutropenia and IAEs overall, but not fatal OIs. However, our analyses did not identify any specific IAEs that would benefit from routine anti-infective prophylaxis or pre-emptive testing.

Disclosures

Michael Sebag, MD, PhD, Amgen: Advisor/Consultant|BMS: Advisor/Consultant|Focus Therapeutics: Advisor/Consultant|Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|GEn1E lifesciences: Advisor/Consultant|GEn1E lifesciences: Stocks/Bonds|Kanvas Biosciences, Inc.: Board Member|Kanvas Biosciences, Inc.: Pending patents|Kanvas Biosciences, Inc.: Ownership Interest|Merck: Honoraria|nomic bio: Advisor/Consultant|nomic bio: Stocks/Bonds|Pfizer: Honoraria|Scynexis Inc.: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria
2725. Bacterial blood stream infections in Pediatric Liver Transplant Patients: Prevalence, Organisms and Risk factors. A Systematic review
Authors: Shieb Mohamad , Hasanain Rand , Arshad Zara , Nawaz Faisal A , Kashyap Rahul , Stern Eric J
Published: November 2023

Background

Bacterial blood stream infection (BSI) is a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient population. This systematic review aims at pooling global data from the leading transplant institutions to identify the overall prevalence and risk factors associated with bacterial BSI and the most common causative organisms.

Methods

A systematic review of PubMed and OVID databases was conducted for the past 20 years. Initial search from both databases had a yield of 252 unique articles which were reviewed independently by two authors. Data related to demographics, prevalence, organisms and risk factors were extracted from the articles and subsequently analysed. The systematic review was registered on PROSPERO (ID: CRD42023403206).

The PRISMA flow diagram visually summarises the screening process

Results

A total of 14 articles were included from the United States of America, France, Italy, Thailand, Japan, Spain and Korea. A total of 4215 liver transplants were included in the final analysis. The overall prevalence of BSI in pediatric liver transplant patients was 23.5% with the highest prevalence reported in Japan (39.5%) and lowest in the USA (18.7%). Mean age of the patients was 25 months and 54% were females. The most common organisms reported were Staphylococcus epidermidis at 22.8% followed by Enterococcus species (16.6%), Klebsiella species (11.9%) and Escherichia coli (11.4%). Among the risk factors studied, postoperative biliary complications, past medical history of biliary atresia and younger age were the risk factors most associated with BSI.

Prevalence of bloodstream infections (BSI) post pediatric liver transplant in included countries.

Bacterial organisms isolated in blood cultures in pediatric post liver transplant patient with a bloodstream infection.

Conclusion

Bacterial BSI post pediatric liver transplantation occurs with high prevalence. Further studies need to be conducted to better define risk factors for BSI and determine the best empirical antibiotic management for BSI in this population as the distribution of organisms varies greatly from otherwise healthy pediatric patients.

Disclosures

All Authors: No reported disclosures
2727. Risk factors and clinical outcomes of tuberculosis among hematopoietic stem cell transplant recipients in endemic country: A single-center, case-control study
Authors: Tanchotikul Kamolchanok , Lohawatcharagul Tuntanut , Jutivorakool Kamonwan , Bunworasate Udomsak , Vanichanan Jakapat
Published: November 2023

Background

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis following reactivation from latent infection. Immunocompromised individuals, including hematopoietic stem cell transplant (HSCT) recipient, are at risk for active TB which can lead to poor outcomes. Currently, the epidemiological data and risk factors related to TB infection among HSCT recipients especially in endemic country are still limited.

Methods

A matched single-center, case-control study was conducted in King Chulalongkorn Memorial Hospital. Cases were defined as HSCT recipients who were diagnosed proven or probable active TB between January 2008 to December 2020. For each case, 5 controls were matched by gender, age (±5 years), and type of transplant. Risk factor associated with TB was determined using multivariate cox regression.

Results

During the study period, a total of 570 patients underwent HSCT. Eleven patients were diagnosed with active TB represented incidence of 1.93%. Pulmonary involvement was the most common presentation (64%) followed by pleura (18 %), pleuropulmonary (9%) and pericardium (9%). Active TB was diagnosed at median duration of 3.76 months (1.33-22.88) after HSCT. Overall median duration for treatment was 6 months (IQR, 1.2-11.5). Autologous HSCT recipients mostly received rifampin-based regimen while allogeneic HSCT recipients received quinolone-containing regimen. Eight patients (73%) were cured, while another 3 (27%) patients died. There was no significant difference in mortality and primary disease relapse between case and control group. In multivariate analysis, previous TB contact or infection (OR 5.852 95%CI 1.268-27.011) and invasive aspergillosis (OR 6.113 95%CI 1.467-25.475) were associated with active TB in HSCT recipient.

Conclusion

Incidence and mortality of TB among HSCT recipients were higher compared to general population. Active TB was diagnosed shortly after HSCT and previous TB exposure was a significant risk factor. These findings may suggest reactivation of latent TB is the main pathogenesis of this patient population in endemic country.

Disclosures

All Authors: No reported disclosures
2728. Bronchial Cultures at Time of Transplant Affect Anastomotic Outcomes in Lung Transplant Recipients
Authors: Veisblatt Jesse , Altneu Eric , Kashem M Abul , Toyoda Yoshiya , Axelrod Peter , Mishkin Aaron D
Published: November 2023

Background

Anastomotic complications after lung transplant cause significant morbidity and mortality. Estimates of complication prevalence in lung transplant recipients range from 5-20%. Many factors are hypothesized to contribute to airway complications, including the presence of bacteria and fungi at time of transplant. Our aim was to examine the contribution of airway cultures at the time of transplant to airway complications.

Methods

We performed a retrospective analysis of lung transplant recipients who developed bronchial complications at a single, tertiary care center between January 1, 2016 and March 31, 2020. We identified 68 cases with anastomotic complications during this time period, then compared this cohort to 131 cases without bronchial complications. Primary outcomes were airway complications at 30 and 90 days. Please refer to the attached tables for variables of interest.

Results

Of 199 total study participants, 68 (34%) were found to have airway complications. Overall, the most common bacterial isolate was Staphylococcus aureus (72 MSSA and 17 MRSA). The most common fungal isolate was Candida albicans (87). When examining the patients with airway complications, MRSA isolates at time of transplant showed a statistically significant increase in airway complications (p=0.03, OR=3). An increase in airway complications was not seen for patients with other positive bacterial or fungal cultures at 30 days or 90 days.

Microbiological Risk Factors for Airway Complications

Patient Demographics and Characteristics

Conclusion

MRSA isolates at time of transplant correlated to increased 30 day and 90 day bronchial complications. This study helps confirm the importance of monitoring airway cultures at the time of transplant. A multi-center study with a larger sample size may be needed to further delineate contributions of specific microorganisms, surgical techniques, as well as perioperative and prophylactic antimicrobials on bronchial complications.

Disclosures

Aaron D. Mishkin, MD, Pfizer: Grant/Research Support|Takeda: Advisor/Consultant
2734. Evaluation of Empiric Antimicrobial Therapy for End-Stage Liver Disease Patients at an Academic Medical Center
Authors: Kim Annie , Kaip Emily A , Quan David , Doernberg Sarah B , Jariwala Ripal
Published: November 2023

Background

Patients with end-stage liver disease (ESLD) are prone to decompensation secondary to infections, with an increasing prevalence of multidrug-resistant organisms (MDROs). These patients often receive broad-spectrum antimicrobials prior to transplant, pre-disposing them to resistant pathogens. Our study assessed institutional guideline adherence, antimicrobial prescribing, and the incidence of MDROs in this population.

Methods

This IRB-approved, retrospective chart review included pre-transplant inpatients with ESLD on the adult liver transplant service who received antimicrobials between 1/1/20 and 10/30/20. Patients were excluded if they started antimicrobials post-transplant or transferred from another institution on parenteral antimicrobials. Per institutional guidelines for empiric antimicrobials in suspected infection in ESLD, patients were categorized into three infectious risk categories: Floor/Non-High-Risk (F-NHR), Floor/High-Risk (F-HR), and ICU or MELD greater than 35 (ICU/M35). Antimicrobial prescribing in each group was evaluated for guideline adherence and microbiology data. Results were analyzed using descriptive statistics.

Results

We included 92 patients: 28 F-NHR, 50 F-HR, and 14 ICU/M35. Table 1 summarizes baseline characteristics. The frequency of guideline adherence for the F-NHR, F-HR, ICU/M35 groups, respectively, was 11 (39%), 4 (8%), and 4 (29%) patients. For the F-NHR group, ceftriaxone (CRO) was most prescribed (n=17, 61%). For the F-HR group, 18 (36%) received CRO; 16 (32%) received vancomycin and piperacillin-tazobactam. In the ICU/M35 group, 13 patients (93%) received meropenem plus linezolid, and 11 (79%) also received caspofungin.

No methicillin-resistant Staphylococcus aureus or carbapenem-resistant Enterobacterales were isolated. Two patients (14%) in the ICU/M35 group experienced C. difficile infection within 30 days of antimicrobial initiation.Table 1.Baseline characteristics among guideline cohorts

Conclusion

Our study showcases opportunities to optimize internal ESLD antimicrobial protocols and curtail unnecessary antimicrobial exposure. Study limitations include a small cohort at a single center. Future directions include data dissemination and protocol updates.

Disclosures

David Quan, PharmD, Mallinckrodt Pharmaceuticals: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea: Clinical events committee/adjudication committee participation|F2G: Grant/Research Support|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clinical events committee/adjudication committee participation
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

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

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

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

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

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 > 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 (< 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< 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

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

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

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 < 19 years and expired < 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< 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
2786. Characterizing Ertapenem Neurotoxicity: A Systematic Review
Authors: Mitaka Hayato , Jain Rupali , Rakita Robert M , Pottinger Paul S
Published: November 2023

Background

Ertapenem is frequently used to treat ESBL-producing Enterobacterales infections. Although ertapenem has the highest incidence of delirium reported among antibiotics evaluated in a pharmacovigilance study of the FDA adverse event reporting system, little is known about clinical characteristics of its neurotoxicity. In this systematic review, we synthesize the existing literature on ertapenem neurotoxicity, focusing on comorbidities, clinical manifestations, and outcomes.

Methods

We searched PubMed and EMBASE for all peer-reviewed articles from inception through April 2023 using the following search terms: "ertapenem" AND ("Neurotoxicity" OR "Encephalopathy" OR "Seizures" OR “status epilepticus” OR "Convulsions" OR "Delirium" OR "Psychosis" OR "Hallucinations" OR “altered mental status” OR coma OR stupor OR obtundation). Studies were included if they described ertapenem specifically and reported clinical data related to neurologic adverse events.

Results

A total of 651 articles were identified through the initial database search and subsequent manual search. After removing duplicated items and screening based on title and abstract, 43 articles were assessed for eligibility. Finally, 30 studies with 114 patients were included in our data analysis. Of the 114 cases found, the mean age was 73, and 67% were male. The most common clinical signs and symptoms were seizures (69%), altered mental status/delirium/cognitive impairment (27%), and hallucinations (18%). The most common electroencephalogram (EEG) finding was slow waves, observed in 59%. Median time to onset was 4 days (IQR, 3–7 days) after starting ertapenem. Complete resolution of the symptoms was observed in 84% after discontinuation of ertapenem. Median time to recovery was 6.5 days (IQR, 3–8 days). Urinary tract infection was the most common indication for ertapenem use (49%). Renal dysfunction and predisposing central nervous system condition were noted in 70% and 32% of the patients, respectively.

Conclusion

This systematic review summarizes the current evidence and clinical characteristics of ertapenem neurotoxicity. Our study underscores the need for raising awareness among clinicians and a large observational study to accurately assess the true incidence, risk factors, and outcomes.

Disclosures

All Authors: No reported disclosures
167. Duration of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares PCR Positivity while Receiving Highly Active Anti-Staphylococcal Drugs
Authors: Wu Maximillian S , Kufel Wesley D , Riddell Scott W , Steele Jeff , Asiago-Reddy Elizabeth
Published: November 2023

Background

A growing body of evidence has demonstrated a close association between nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) and its invasive presence systemically. Thus, several hospitals have implemented MRSA nares PCR screening for all patients initiating treatment active against MRSA for various infections to help de-escalate an anti-MRSA antibiotic in the event of a negative result. However, little is known about the effects of anti-MRSA systemic agents on MRSA nasal colonization, potentially affecting the use of MRSA PCR as an effective screening tool if not conducted immediately upon hospital admission.

Methods

Adult Upstate University Hospital patients ≥ 18 years of age with an initial positive MRSA nares PCR result were considered for inclusion, starting from September 2022. Eligible patients were individuals who had a positive MRSA nares PCR performed within 36 hours of their initial dose of a systemic anti-MRSA antibiotic. Positive MRSA nares cultures were also considered if PCRs were initially indeterminate. Anti-MRSA antibiotics included vancomycin, daptomycin, linezolid, ceftaroline, and clindamycin. Patients who were received these agents for a duration of 48-96 hours were consented for their participation. If consented, a follow-up MRSA nares swab and PCR were collected at a goal timepoint of 72 hours post initiation of anti-MRSA antibiotics (sample collection ranged from 48-96 hours post initiation). MRSA colonization was reassessed with a repeat nares PCR and reflex to culture for indeterminate results if applicable.

Results

As of April 21st, 2023, 61 follow-up MRSA nares samples were collected from eligible participants. Follow-up samples were collected an average of 66.51 hours after their first dose of anti-MRSA drugs (IQR = 11.47). Of these follow-up samples, 56/61 (91.80%) resulted as a positive MRSA nares PCR or culture result.

Conclusion

Our interim results demonstrated that MRSA colonization in the nares via PCR generally persists even after 48-96 hours of continuous systemic administration of anti-MRSA antibiotics. These findings suggest that MRSA nares swabs can still be used after anti-MRSA antibiotic administration, increasing its utility as a screening tool.

Disclosures

Wesley D. Kufel, Pharm.D., BCPS, BCIDP, AAHIVP, Merck & Co.: Grant/Research Support Elizabeth Asiago-Reddy, MD, Glaxo-Smith-Kline: Grant/Research Support|Pfizer: Grant/Research Support