bluuebunny/crossref_metadata_2025_split huggingface dataset:
159. Antibiotic and diagnostic stewardship surrounding pre-operative testing in patients undergoing cardiac surgery
Authors: Winkler Marisa , Huang Joanne , Starr Jessica , Paras Molly L , Letourneau Alyssa R , Hooper David , Shenoy Erica S 
Published: December 2022

Abstract

Background
Despite national guidelines from the US Preventative Services Task Force and the Infectious Diseases Society of America that recommend against screening for asymptomatic bacteriuria (ASB, defined as &gt; 105 CFU of an organism) in most circumstances, pre-operative screening urine culture (UCx) continues. Detection and treatment of ASB leads to antibiotic exposure and risk of antibiotic-associated adverse events like drug reactions, Clostridioides difficile infection (CDI), and colonization by drug-resistant organisms. We describe the implementation of eliminating pre-operative screening for ASB in patients undergoing cardiac surgery. Figure 1Pre-operative checklist for cardiac surgery prior to intervention

Methods
This was a pre-post study of practice change involving removing ASB screening as part of the pre-cardiac surgery checklist (Figure 1). The pre-intervention period was 08/18/21 – 11/17/21, the post intervention period was 12/1/21 – 3/1/22. We identified all patients who underwent a cardiac arterial bypass graft procedure with or without vein harvesting. We reviewed pre-operative UCx, test indication, antibiotic administration pre-operatively due to culture growth, and post-operative CDI and CAUTI within 30 days post procedure identified through routine infection prevention and control surveillance.

Results
Pre-intervention, 117/128 (91.4%) patients undergoing cardiac surgery had a UCx collected. Of the UCx, 100% were ordered as part of the pre-operative checklist and not for symptoms. Five patients pre-intervention had ASB detected. Four patients received antibiotics to treat ASB. A fifth patient received antibiotics for bacteriuria which did not meet ASB count threshold. Post-intervention, 15/123 had a UCx (12.3%). Of these, 12/15 were ordered as part of the pre-operative checklist (80%), and the remaining three had symptoms documented. Post-intervention, one patient had ASB detected and did not receive antibiotics. Pre- and post-intervention there were 2 cases of CDI (2/128, 1.6% and 2/123, 1.6%, respectively). There were no CAUTIs either pre- or post-intervention.

Conclusion
Standard pre-operative UCx is known to be a low-value test and is not recommended by national guidelines. In this single-center diagnostic stewardship intervention, screening was reduced by 87.2%. There was no change in infectious outcomes.

Disclosures
All Authors: No reported disclosures.
184. Impact of the BioFire® FilmArray® Blood Culture Identification 2 Panel on Antimicrobial Treatment of Enterobacterales Blood Stream Infections
Authors: Logan Ashley , Beardsley James , Taylor Alex D , Williamson John C , Palavecino Elizabeth , Luther Vera , Ohl Christopher , Stone Tyler 
Published: December 2022

Abstract

Background
The BioFire® FilmArray® Blood Culture Identification 2 (BCID2) panel is a rapid diagnostic tool that uses multiplex polymerase chain reaction technology to identify 43 different genetic targets. BCID2 detects 13 additional targets, including 7 resistance markers, not detected by the original BCID panel. For this reason, our institution changed panels from BCID to BCID2 in August 2020. The purpose of this study was to assess the time to antibiotic change for Enterobacterales bloodstream infections before and after switch to BCID2.

Methods
This was a retrospective, observational, before-and-after study conducted at an 885-bed academic medical center. Adult patients with blood cultures positive for E. coli or K. pneumoniae (EC/KP) who received broad spectrum beta-lactam therapy were included. Patients with a polymicrobial or concurrent infection, hemodynamic instability, lack of source control by day 5, or death within 72 hours (hrs) of cultures being collected were excluded. The primary outcome was time to antibiotic change in the BCID group compared to the BCID2 group. Secondary outcomes included time to de-escalation or escalation and the number of opportunities for de-escalation or escalation.

Results
88 patients were included, 55 in the BCID-group and 33 in the BCID2-group. Baseline characteristics are reported in Table 1. Median time to first antibiotic change was 65.3 hrs in the BCID-group vs 69.6 hrs in the BCID2-group (p=0.53). Times to first de-escalation and escalation and number of opportunities for de-escalation and escalation are presented in Table 2. Proportion of missed de-escalation opportunities based on panel results was greater in the BCID2 group (63.6% vs 0%, p&lt; 0.05).

Conclusion
Opportunities to make timely antibiotic modifications with the use of the BCID2 panel exist for EC/KP blood stream infections. While no difference in time to first antibiotic change was present between groups, this highlights the importance of having an active stewardship team member available to respond to rapid diagnostic test results.

Disclosures
All Authors: No reported disclosures.
210. Neutropenia and Associated Infectious Complications Among Kidney Transplant Recipients Receiving Valganciclovir Prophylaxis in the United States: An Administrative Claims Database Study
Authors: Turzhitsky Vladimir , Raval Amit D , Moise Pamela , Merchant Sanjay 
Published: December 2022

Abstract

Background
Valganciclovir (VGCV) prophylaxis is commonly utilized to prevent cytomegalovirus (CMV) infection among high (D+/R-) and intermediate (R+) risk kidney transplant recipients (KTRs). Due to the myelosuppressive effects of VGCV, KTRs may be at an increased risk of opportunistic infections (OIs) resulting in interruptions to VGCV therapy. Therefore, we aimed to quantify the clinical burden of neutropenia among adult KTRs receiving VGCV prophylaxis.

Methods
A retrospective cohort design was utilized to identify adult KTRs who received VGCV prophylaxis using the IBM MarketScan Commercial and Medicare Supplemental claims databases. First-time KTRs between 1/1/2012 - 12/31/2018 with 1 year of continuous pharmacy and medical coverage before (baseline period) and after (follow-up period) were included. KTRs with a History of other solid organ transplantation were excluded. Fills of ≥ 1 prescription of VGCV (either 450 mg or 900 mg/day) within 30 days of the kidney transplant (KT). Neutropenia events were identified as either ≥ 1 inpatient, or ≥ 2 outpatient ICD-9/ICD-10 diagnoses codes within 14 days.

Results
Of the 4,965 adults KTRs with baseline and follow-up enrollment, 3,258 (66%) used VGCV prophylaxis. 311/3256 (9.5%) developed neutropenia within 1-year post KT. Baseline characteristics were similar between those with and without neutropenia (table 1). The majority received the following pre-transplant immunosuppression: tacrolimus (78.9%), mycophenolate mofetil (62.8%) and steroids (prednisone, 79.3%, methylprednisolone 10.6%). KTRs with neutropenia had a nearly two-fold increase in the development of CMV infection compared to those without neutropenia. In addition, KTRs with neutropenia had significantly higher rate of bacterial or fungal infections compared to those without neutropenia (Table 2). Interruptions in VGCV prophylaxis (gap &gt;15 days) were more common in KTRs with neutropenia (P&lt; 0.001).

Conclusion
Our findings showed that neutropenia was associated viral, bacterial, and fungal OIs among adults KT receiving VGCV prophylaxis. The findings highlight the needs for interventions to reduce neutropenia and its associated OIs. These results suggest that clinical management steps to reduce rates of neutropenia among KT recipients may warrant further study.

Disclosures
Vladimir Turzhitsky, PhD, Merck & Co., Inc.,: Employee|Merck & Co., Inc.,: Stocks/Bonds Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Pamela Moise, PharmD, Merck & Co., Inc: Employee & Shareholder Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds.
217. A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of the Lipopeptide QPX9003 in Healthy Adult Subjects
Authors: Griffith David , Carmeli Yehuda , Gehrke Shawnee , Morgan Elizabeth , Dudley Michael , Loutit Jeff 
Published: December 2022

Abstract

Background
QPX9003 is a fully synthetic lipopeptide with potent activity against MDR Pseudomonas and Acinetobacter spp. This report describes the safety and pharmacokinetics of QPX9003 following single and multiple doses.

Methods
Twelve healthy subjects were enrolled in 2 cohorts of up to 8 subjects (each cohort randomized to have up to 6 active and 2 placebo) each in the multiple ascending dose phase (100 or 200 mg every 6 hrs). Subjects received a single dose of QPX9003 followed by 48 hours of washout, then were administered QPX9003 q6h for 7 days. All infusions were administered over 1 hour. Intensive plasma sampling was obtained after dosing and assayed for QPX9003 content using validated HPLC/MS methods.

Results
Single and multiple dose QPX9003 pharmacokinetic parameters (mean +/- SD) are shown below:
No subjects discontinued due to AEs and no SAEs were observed. There was no evidence of increasing numbers or severity of AEs with increasing dose, and all AEs were mild or moderate in severity.

Conclusion
QPX9003 was safe and well tolerated at all doses tested. QPX9003 plasma AUC and Cmax increased with increasing dose. QPX9003 plasma exposure accumulated ∼ 1.5 fold over 7 days of q6h dosing consistent with its plasma half-life. Based on the PK and safety profile, QPX9003 produces plasma exposures that exceed the PK-PD target safely and warrants further clinical development.

Disclosures
David Griffith, n/a, Qpex Biopharma: Employee Yehuda Carmeli, MD, Allecra Therapeutics: Advisor/Consultant|MSD: Advisor/Consultant|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex Pharmaceuticals: Advisor/Consultant|Roche: Advisor/Consultant|Shinogi: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant Shawnee Gehrke, n/a, Qpex Biopharma: Employee Elizabeth Morgan, n/a, Qpex Biopharma: Employee Michael Dudley, n/a, ArrePath: Board Member|Qpex Biopharma: Board Member|Qpex Biopharma: Employee Jeff Loutit, MBChB, Qpex Biopharma: Employee.
219. A Randomized, Double-Masked, Placebo-Controlled Phase IIB Trial of Azithromycin and Trimethoprim-Sulfamethoxazole as Bacterial STI Prophylaxis in Pregnant Women with HIV
Authors: Dionne Jodie , Pol Barbara Van Der , Long Dustin , Tih Pius , Mbah Rahel , Ngah Edward , Pekwarake Seraphine , Kifem Mirabelle , Fondzeyuf Anthony , Bruxvoort Katia J , Tita Alan , Marrazzo Jeanne 
Published: December 2022

Abstract

Background
This phase IIB randomized clinical trial was designed to test the efficacy of a novel regimen to prevent bacterial sexually transmitted infections and malaria in pregnant women with HIV in Cameroon, where HIV prevalence in pregnancy is 5.7%. Here we present the analysis of STI rates.

Methods
Pregnant women in prenatal care with confirmed HIV, gestational age &lt; 28 weeks and singleton pregnancies were randomized to monthly azithromycin (AZ) 1 gram daily for 3 days and daily trimethoprim-sulfamethoxazole (TMPS) or the standard regimen of daily TMPS with monthly placebo AZ.
The main outcome of interest was the proportion of women with a composite STI measure: chlamydia, gonorrhea and/or incident syphilis at delivery. Nucleic acid amplification testing (NAAT) for CT/NG was performed on provider-collected vaginal swabs. Incident syphilis was defined serologically as a newly positive treponemal test or 4 fold increase in RPR/VDRL titer since baseline. The proportion was compared by relative risk with 95% confidence intervals and a significant p value set at &lt; 0.05.

Results
A total of 308 women were enrolled at three hospital facilities between March 2018 and August 2020. In all, 155 women were randomized to the AZ/TMPS arm and 153 women to the TMPS arm. A total of 260 women (84%) had delivery samples collected. Both groups were similar with median age 32 years, maternal education (71% secondary school or university), HIV diagnosis 3 years prior, and 94% reported excellent adherence to antiretroviral therapy (ART). Median CD4 count was 473 cells/mm3 (IQR 326-663). At baseline, prevalence of chlamydia was 1.4%, gonorrhea 1.0% and syphilis 1.9%. There was no difference in the proportion of women with the composite STI measure (3.2% in the AZ/TMPS arm and 3.3% in the TMPS arm; RR 0.78 (95% CI 0.21 – 2.84); p=0.70). Adverse birth outcomes were lower in the AZ/TMPS arm, but not significantly (preterm delivery 5% vs 10.3% [p=0.1], low birthweight 2.8% vs 5.1% [p=0.34], composite adverse birth outcome 8.4% vs 13.1% [p=0.19]. Table 1:Baseline Characteristics of Study Participants (n=308)Table 2:Efficacy Outcomes at Delivery by Arm - Intention to Treat Analysis (n= 278)

Conclusion
The addition of monthly azithromycin to standard daily TMPS prophylaxis in pregnant women living with HIV in Cameroon did not reduce the rate of bacterial STI at delivery. Women reported excellent ART adherence and rates of STI, malaria, and adverse birth outcome were low.

Disclosures
Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|Gilead: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support.
241. Antibiotic Prescription in COVID Intensive Care Unit (ICU): Empiric Treatment vs. FilmArray Pneumonia (FAP) Panel Guided Treatment
Authors: Jimenez Maria F , Garcia Bayron , Ordonez Karen M , Moreno German A 
Published: December 2022

Abstract

Background
The empiric prescription of antibiotics in COVID 19 ICU patients is frequent due to the severity of disease and presentation of patients with septic shock. In this study we compared two approaches of antimicrobial prescription: empiric use vs. FilmArray pneumonia (FAP) panel guided treatment. We evaluated costs of intervention, clinical outcomes as development of hospital acquired infections (HAI), length of stay and mortality.

Methods
Retrospective study. Patients with severe COVID-19 infection hospitalized in ICU of two institutions in Pereira were included. The prescription of antibiotic without FAP panel was defined as empiric. The prescription according to FAP panel results was defined as guided. Data analysis was performed in Epiinfo version 7.5.2.0. The study protocol was approved by the ethics committee of Universidad Tecnologica de Pereira.

Results
252 patients were included, 180 received empiric therapy and 72 were FAP panel guided. The median age was 65 years (IQR 53-73), the PaO2/FiO2 ratio mean was 108 (IQR 64-130). In the group of empiric treatment, 21 (11.67%) patients presented confirmed bacterial infection. Patients on guided antimicrobial therapy presented less HAI (RR 0,54 (IC 95% 0.30-0.95) p 0.02). The median length of stay in ICU was 16 days for both groups. Klebsiella pneumoniae was the most frequent bacteria identified during the first episode of infection followed of Pseudomonas aeruginosa. Mortality on guided group was 54% Vs. 42% on empiric group (p&lt; 0,3). Meropenem was the main antibiotic prescribed (DDD empiric 3.17 Vs. 1.8 DDD guided) followed of cefepime (DDD empiric 0.9 Vs. DDD guided 0.12). The median cost of antimicrobial treatment in the empiric group was US$530 (US$30-US$1579) per patient compared to the median cost of guided prescription that was US$292 (US$16-US$8767). When including the cost of FAP panel, the median cost per patient treatment course was US$429 (US$153-US$8904) p&lt; 0.7.

Conclusion
Implementation of a guided antimicrobial therapy using FAP panel could be useful and cost effective in COVID-19 ICU patients to reduce antimicrobial consumption and adverse outcomes related to the inappropriate use of antibiotics without significant impact on mortality or length of stay.

Disclosures
Karen M. Ordonez, MD, AstraZeneca: Expert Testimony|Biomerieux: Expert Testimony|Farma de Colombia: Expert Testimony|MSD: Expert Testimony|Pfizer: Expert Testimony.
254. Clinical significance of antineutrophil cytoplasmic antibody positivity in patients infected with SARS-CoV-2
Authors: Lee Lucy Eunju , Jeong Wooyong , Park Yong-Beom , Jeong Su Jin , Lee Sang-Won 
Published: December 2022

Abstract

Background
The Coronavirus Disease 2019 (COVID-19) is well-known for its broad spectrum of immune-related phenotypes similar to those seen in autoimmune or inflammatory diseases. Furthermore, evidence has gradually accumulated that COVID-19 may induce systemic inflammatory manifestations such as multisystem inflammatory syndrome, haemophagocytic syndromes, and systemic vasculitis. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis characterised by necrotising vasculitis. So far, there have been several case reports regarding AAV occurrence after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which have indicated a triggering potential of SARS-CoV-2 infection for AAV occurrence. This study investigated the rate of ANCA positivity and its clinical significance in COVID-19 patients.

Methods
This study included 178 patients infected with SARS-CoV-2 who were enrolled in a cohort of a single center. Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA from the stored blood sera were measured using the immunoassay kits. Mortality, mechanical ventilator care, and severe infection were assessed as poor outcomes. Severe infection was defined as a medical condition that required a high-flow nasal cannula and/or mechanical ventilator care. The 2022 American College of Rheumatology and the European Alliance of Associations for Rheumatology classification criteria for the three subtypes of AAV were applied only to patients who had MPO-ANCA or PR3-ANCA among the study subjects

Results
The detection rate of ANCA positivity was 18.5%: MPO-ANCA and PR3-ANCA were found in 22 (12.4%) and 14 (7.9%) patients. Patients with ANCA positivity exhibited a lower cumulative survival rate than those without, but the difference was not statistically significant (P = 0.057). However, neither MPO-ANCA nor PR3-ANCA affected the three poor outcomes. According to the new criteria, 12 (6.7%) and 21 (11.8%) patients were classified as having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) FIGURE 1.Comparison of the cumulative survival rate
Neither ANCA positivity nor ANCA subtype (MPO-ANCA and PR3-ANCA) positivity had a significant influence on poor outcomes of SARS-CoV-2.
ANCA: antineutrophil cytoplasmic antibody; MPO: myeloperoxidase; PR3: proteinase 3; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Conclusion
SARS-CoV-2 infection may increase the rate of ANCA positivity, which may not affect poor outcomes but contribute to the classification of GPA and MPA despite uncertain clinical significance

Disclosures
All Authors: No reported disclosures.
266. Cumulative Steroid Dose in Hospitalized Patients and COVID-19 Associated Pulmonary Aspergillosis
Authors: Ramonfaur Diego , Salto-Quintana Jack , Hernández-Mata Nadia , Aguirre-García Gloria Mayela , Villanueva-Lozano Hiram , Martínez-Reséndez Michel 
Published: December 2022

Abstract

Background
Severe COVID-19 elicits a hyperimmune response frequently amenable by high-dose steroids, although treatment may increase the risk for opportunistic infections. Invasive pulmonary aspergillosis (IPA) is a known complication of COVID-19, termed COVID-19 associated pulmonary aspergillosis (CAPA). While steroid use is a known risk factor for CAPA, the role of cumulative steroid dose in the development of CAPA is unclear. This study evaluates the relationship between cumulative steroid dose in hospitalized individuals and the risk for CAPA.

Methods
This retrospective cohort study includes 130 hospitalized patients with RT-PCR-confirmed COVID-19 pneumonia at a specialized center in north Mexico. Patients who developed CAPA were matched by age and gender to two patients who did not develop CAPA. CAPA was defined according to 2020 ECMM/ISHAM criteria. Patients with either possible, probable, or proven CAPA were considered positive cases. Steroid dose was converted to dexamethasone equivalents according to potency and duration. Cumulative dose was obtained in every patient from admission until discharge or diagnosis of CAPA. We assessed the risk of CAPA by the continuous cumulative steroid dose using a logistic regression model.

Results
A total of 42 patients were diagnosed with possible, probable, or confirmed CAPA and were matched to 88 controls. Mean age was 61 ± 14 years, 94 (72%) were male, 11 (12%) were smokers, and 55 (50%) were obese. Mean cumulative steroid dose was 66 ± 75 in patients without CAPA vs 195 ± 226 in patients with CAPA (P&lt; 0.001) (Figure Panel A). The risk for CAPA was higher as the cumulative dose of steroids increased, in a near-linear relationship (OR 1.008; 95% CI 1.003, 1.013, P&lt; 0.001) (Figure Panel B).

Conclusion
Patients who develop CAPA have a history of higher cumulative steroid dose during hospitalization. The risk for CAPA increases in a near-linear fashion as the cumulative steroid dose during hospitalization increases. While causality cannot be drawn by this study, caution while prescribing high-dose steroids is warranted among individuals hospitalized with COVID-19 pneumonia. Clinical suspicion of CAPA should increase in individuals with a high cumulative dose of steroids and clinical decline.

Disclosures
All Authors: No reported disclosures.
267. Delayed Pulmonary Tuberculosis (PTB) Diagnosis During the COVID-19 Pandemic: A Case Series
Authors: Khaitov Mikhail , Salomon Nadim , Perlman David , Humphreys Sarah 
Published: December 2022

Abstract

Background
The COVID-19 pandemic has been associated with underreporting of pulmonary tuberculosis (PTB). Overlapping risk factors, clinical features, and chronicity of post COVID-19 sequelae can lead to attribution of respiratory disease solely to COVID-19 and result in delayed recognition of PTB.

Methods
Identification of inpatients with both sputum (spu) culture (clt) positive TB and SARS-CoV-2 + PCR was achieved using data extraction tool Slicer Dicer Epic system during 3/2020-1/2022 followed by a retrospective review of electronic medical records. We defined COVID-PTB as a patient (pt) who had positive spu clt for TB ≤ 12 months (mos) following a COVID-19 diagnosis.

Results
8 pts had both PTB and COVID-19. Two had PTB &gt; 5 mos prior to, and one had PTB &gt; 12 mos after COVID-19. 3/8 were promptly suspected to have PTB [1 with right upper lobe (RUL) infiltrate; 1 RUL cavitary infiltrate; 1 with miliary nodules and cavities]; in these 3, spu was tested for MTB ≤ 48 hours (h) (hrs) of presentation. 5/8 had COVID-PTB. All 5 had fever and/or respiratory symptoms and ≥ 1 risk factors for TB identified at the time of presentation with COVID-19. Spu was tested for MTB in 48 hs in 1 with RUL cavitary infiltrate, and 5 days after chest CT findings of apical densities and scattered nodules in another. In the remaining 3, spu testing was delayed a median of 36 days (range, 8-133) after initial TB consistent CT findings (LUL opacity and nodular densities in 1; RLL cavitary infiltrate in 1; and clustered RML nodules in 1) and despite immigration from high burden TB countries in all 3; known LTBI in 2; diabetes in 1, and immunosuppressive therapies in 2.

Conclusion
We observed a delay in sputum collection after COVID-19 diagnosis in the presence of epidemiological risk factors for TB disease and clinical features consistent with PTB. Lack of familiarity with the range radiological TB features, a diagnostic bias towards more typical radiographic (e.g., cavities, miliary patterns) and COVID-19 anchoring bias may have contributed to delayed PTB diagnosis. PTB should be considered, when clinically appropriate, in the setting of COVID-19 or apparent post COVID-19 sequelae.

Disclosures
All Authors: No reported disclosures.