bluuebunny/crossref_metadata_2025_split huggingface dataset:
2224. Aminopenicillins versus Non-aminopenicillins for Treatment of Enterococcal Cystitis
Authors: de Oca Jamison Montes , Veve Michael , Kenney Rachel M 
Published: December 2022

Abstract

Background
Aminopenicillins achieve urinary concentrations that overcome aminopenicillin resistance in Enterococcus spp. lower urinary tract infections (UTI). With this rationale, our clinical microbiology laboratory discontinued routine identification on Enterococcus urine isolates in 2012 and report “aminopenicillins are predictably reliable for uncomplicated enterococcal UTI”. The study objective was to compare outcomes of patients treated with aminopenicillins (AP) versus non-aminopenicillins (NAP) for enterococcal cystitis.

Methods
IRB approved, retrospective cohort of adults hospitalized with symptomatic enterococcal cystitis from 2013-2021. Exclusion: definitive E. faecalis, enterococcal UTI in past year, review of systems unavailable/altered mental status, urinary instrumentation except for stent/catheter, systemic infection, fever, genitourinary trauma, renal transplant. Primary endpoint: clinical and microbiologic success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of index organism. Logistic regression evaluated characteristics associated with 14-day failure. Sample size of 178 calculated for non-inferiority using α=0.025, β=0.8, 15% non-inferiority margin.

Results
178 subjects included, 89 AP, 89 NAP . VRE identified: 73 (82%) AP and 76 (85%) NAP (P=0.50). Amoxicillin (36/89, 40%) and ampicillin (36/89, 40%) used most in AP. Linezolid (41, 46%) and fosfomycin (30, 34%) most common agents in NAP. 14-day clinical composite endpoint was no different between AP and NAP groups, respectively (74 [83%] vs. 73 [82%], P=0.84). No variables independently predicted failure (Table 1). Non-inferiority analysis for AP vs. NAP for 14-day composite: mean difference 1.1% (-0.14 to 0.127, 97.5% CI; P=0.42). Definite E. faecium subgroup: 14-day clinical composite success for was no different between AP and NAP groups, respectively (27/34 [79%] vs. 53/66 [80%], P=0.916).

Conclusion
AP were non-inferior to NAP, supporting their use as first-line therapy for cystitis due to enterococci, including E. faecium. This stewardship strategy has implications to preserve VRE active therapies (e.g. linezolid) for serious infections.

Disclosures
All Authors: No reported disclosures.
2228. Antibiotic Appropriateness for UTI Treatment on Monday vs Friday in a NYC Hospital ED
Authors: LeBron Kira , Bielawski Adrienne , Popiel Patrick , Shams Setareh , Grimes Cara 
Published: December 2022

Abstract

Background
Urinary tract infections (UTI) are common and often lead to an antibiotic prescription. Prior studies have shown that antibiotic prescriptions can vary between weekdays and weekends.

Methods
This is a retrospective case series of female patients ≥18 years with simple cystitis presenting to the ED between 2019 to 2021 in a NYC community hospital. Our primary objective was to determine how often the appropriate antibiotic was prescribed and compare this between Monday and Friday. Antibiotic appropriateness was defined using the 2011 Infectious Disease Society of America clinical practice guidelines for acute uncomplicated cystitis. Criteria included antibiotic selection, dose, frequency, and duration. Per the NYC outpatient UTI antibiogram, Amoxicillin, Ampicillin, Ciprofloxacin, and TMP/SMX were not appropriate empiric therapies. Categorical data is reported as counts (%) and compared with Chi-square; age (nonparametric) is reported as median (range) and compared with Mann-Whitney. Sample size calculation estimated that 71 subjects were needed on each day to detect an effect size of 20% difference in our primary outcome (90% antibiotic appropriateness on Monday and 70% on Friday) with 80% power and an alpha error of 0.05.

Results
160 subjects were included, 80 seen on Mondays and 80 seen on Fridays. Demographics were similar between groups, except for antibiotic allergies (Table 1). There was no difference between appropriate antibiotics prescribed on Mondays compared to Fridays, 54/80 (67.5%) vs 60/80 (75%) (p-value = 0.29). Failure to meet criteria for appropriateness was due to inappropriate prescription duration (44/160) or selection (14/160). All prescriptions met criteria for dose and frequency. There was no difference in antibiotic selection, dose, frequency, or duration of prescription on Monday vs Friday (Table 2). More urine cultures were collected on Mondays (62/80) vs Fridays (49/80) (p =.03).

Conclusion
1 in 3 patients were prescribed inappropriate antibiotics for simple cystitis, though there was no difference between Mondays and Fridays. Inappropriate antibiotic duration and differences in urine culture collection indicate an inconsistent approach to treatment and missed opportunity to course correct in cases of pathogen resistance.

Disclosures
Cara Grimes, MD, MAS, Johnson and Johnson: Expert Testimony|Provepharm, Inc: Advisor/Consultant.
2234. Clinical Significance of Staphylococcus aureus Bacteriuria without Bacteremia
Authors: Ochoa Brennan , Jones Makoto M , Pupaibool Jakrapun 
Published: December 2022

Abstract

Background
Staphylococcus aureus urinary tract infection (UTI) is uncommon. Staphylococcus aureus bacteriuria (SABU) can occur in patients with urinary tract instrumentation, urinary calculi, or S. aureus bacteremia (SAB) and is associated with development of invasive diseases and death. Thus, SABU is often treated with a prolonged course of antimicrobial therapy similar to SAB. However, little is known about the significance of SABU in patients without SAB and recent urinary tract instrumentation.

Methods
We conducted a retrospective study of patients with SABU in the Veterans Affairs (VA) system nation-wide from 2017 to 2019. Patients with concomitant SAB, recent history of urinary tract instrumentation, or overt urologic abnormalities were excluded. The primary outcome was development of invasive S. aureus infections or death within 12 months. The secondary outcome was recurrent SABU within 12 months.

Results
133 patients met the inclusion criteria. 102 patients (76%) received antimicrobial treatment for SABU. The duration of treatment ranged from 3-30 (mean = 8.5) days. Compared with the non-treated group, patients treated with antimicrobials had significantly more urinary tract symptoms (p = 0.0001), microscopic pyuria (p = 0.002), and hematuria (p = 0.035). Of those treated, 11 (7.3%) died within 12 months of SABU compared to 4 patients (13%) who did not receive treatment (p = 0.749). Three percent of patients from both groups (n = 3 vs 1) developed invasive S. aureus infections within 12 months (p = 1.00). 16% of patients in the treatment group (n = 17) and non-treatment group (n = 5) were found to have recurrent SABU within 12 months (p = 1.00).

Conclusion
Patients without recent urinary tract instrumentation, overt urologic abnormalities, and SAB who were treated for SABU did not have significant differences in death, invasive diseases, or recurrent SABU at 12 months compared to those who did not receive treatment. Untreated patients did not appear to have frequent complications; however, our numbers were small and our analysis did not take confounding into account. Further analysis into SABU treatment may be warranted.

Disclosures
All Authors: No reported disclosures.
2239. Evaluating the Use of Cefuroxime for the Treatment of Outpatient Pyelonephritis at an Indian Health Service Hospital
Authors: Gopalakrishnan Vaishnavi 
Published: December 2022

Abstract

Background
In 2015, a rural Indian Health Service Hospital found itself unable to use SMX/TMP due to high E. coli resistance rates. The stewardship team decided to include cefuroxime as a first line agent for outpatient pyelonephritis to have a fluoroquinolone sparing agent. Oral B-lactams are not typically recommended over SMX/TMP or fluoroquinolones for pyelonephritis, however there is sparse literature on the use of cefuroxime. This retrospective review aims to evaluate the efficacy of cefuroxime therapy for acute uncomplicated pyelonephritis over a five-year period.

Methods
528 patients with a diagnosis of pyelonephritis from January 1st, 2015 to December 31st, 2019 were screened. Data collection included 30-day reinfection rates, emergence of ESBL isolates, duration of therapy, one time IV antibiotic administration, urine culture and susceptibility, increased risk (genitourinary abnormalities and diabetes), white blood cell count, and symptoms. Pediatric patients and patients requiring hospital admission were excluded.

Results
264 patients were included and 188 patients received cefuroxime therapy. Baseline characteristics included 94.5% female patients, median age of 44 years, and average duration of therapy of 11.6 days. 95% of the isolates were E. coli. 31 patients had treatment failure defined as a return to the ED with 30 days for UTI. 25 of those patients received cefuroxime and of those, 20 had a one-time IV antibiotic dose. 10 patients with treatment failure had a history of ESBL after the encounter and of those 3 patients had cefuroxime therapy. 5 patients who had treatment failure with cefuroxime had diabetes and genitourinary abnormality.

Conclusion
This review suggests a lower rate of bacteriological cure of acute uncomplicated pyelonephritis with cefuroxime therapy with or without a one-time IV antibiotic dose with a cephalosporin or aminoglycoside.

Disclosures
All Authors: No reported disclosures.
14. Monkeypox viral detection from different body sites. Northern California, June–July 2022
Authors: Srinivasan Krithika , Yuk-Wai Ho Dora Y , Contag Caitlin A , Grant Philip , Karan Abraar , Kappagoda Shanthi , Dieringer Thomas , Styczynski Ashley , Pinsky Benjamin A , Salinas Jorge 
Published: December 2022

Abstract

Background
Unlike prior outbreaks of monkeypox, the 2022 outbreak is unique because lesions have been predominantly noted in the anogenital area, especially among persons identifying as gay, bisexual, or other men who have sex with men. The role of various body sites in monkeypox transmission is currently unclear. We assessed monkeypox PCR positivity from various body sites.

Methods
We collected demographic, clinical, and laboratory data from patients with confirmed monkeypox at Stanford during June–July 2022. We obtained samples from skin lesions, oropharynx, saliva, conjunctiva, urine, semen, and rectum. Monkeypox DNA analysis was performed on site using a quantitative PCR modified from published CDC assays.

Results
During June–July 2022, 10 patients were confirmed to have monkeypox. All were men; median age was 40 (range 24–46). Four patients identified as Hispanic, three as Caucasian, two as African American, and one as Asian. Additionally, three had HIV infection and the remaining seven were on HIV pre-exposure prophylaxis. At the time of diagnosis, eight patients (80%) described a prodrome of fever and malaise. Seven (70%) had genital lesions; the remaining three (30%) presented with only extra-genital lesions. Complications included two patients with proctitis (20%), one with phimosis (10%) and one with tonsillar involvement and impending airway compromise (10%). A total of seven (70%) received tecovirimat, and one was hospitalized. Median time from symptom onset to sample collection was seven days (range 3–14). All patients had at least one skin lesion sample positive for monkeypox virus DNA (Table 1). Six rectal samples (100%), Eight oropharyngeal samples (89%) and two (66%) urine samples were also positive.

Conclusion
We found monkeypox PCR positivity from different body sites. Public health messaging should consider targeting behaviors that involve body sites beyond skin, with particular consideration to mucosal surfaces.

Disclosures
All Authors: No reported disclosures.
LB1531. Administration of Abatacept or Infliximab Reduces Mortality in Hospitalized Patients with COVID-19 Pneumonia: Results from the ACTIV-1 IM Master Protocol
Authors: Ko Emily R 
Published: December 2022

Abstract

Background
Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care.

Methods
We conducted a double-blind, randomized, placebo-controlled trial evaluating abatacept (given as a single infusion of 10mg/kg, to a maximum of 1000 mg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was median time to recovery by day 29. Key secondary endpoints included 28-day mortality.

Results
A total of 1019 patients received an infusion (509 assigned to abatacept and 510 to placebo), constituting the analyzed modified intention-to-treat cohort. The mean age 54.9 years (SD 14.65), 60.5% were male, 44.2% Hispanic or Latino and 13.7% black. Patients were evenly matched in terms of severity of illness, and comorbidities. Participants randomized to abatacept did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.135 (95% CI 0.996-1.294, p=0.057) compared to placebo. The median (IQR) time to recovery was 9 days (8, 10) for both groups. The 28-day mortality in the abatacept arm was 11.0% and in control arm 15.0% (OR 0.62 (95% CI 0.41, 0.94)), with a 37.8% lower odds of dying in patients receiving abatacept. The improvement in mortality was demonstrated for patients requiring low or high flow O2 at baseline but was not seen in patients who required mechanical ventilation or ECMO at time of randomization. Subgroup analysis identified the strongest effect in those with baseline CRP &gt;75mg/L, age &gt;65 and diabetics. Safety data demonstrated slightly lower risk of adverse events. Rates of secondary infections were similar (abatacept 16.1% and placebo 14.3%).

Conclusion
Although single-dose IV abatacept did not demonstrate statistically significant improvement in time to recovery, it did show a substantial reduction in 28-day mortality compared to standard of care.

Disclosures
All Authors: No reported disclosures.
LB1532. The Impact of COVID-19 on nursing home residents’ clinical, functional, and psychosocial outcomes
Authors: Popejoy Lori , Vogelsmeier Amy , Petroski Gregory , Mehr Daivd , Rantz Marilyn , Miller Steven , Ilboudo Christelle , Johnson Justina Yevu , Dardis Michelle 
Published: December 2022

Abstract

Background
Data on COVID-19 related nursing home infections and mortality accumulated at a rapid pace; yet little is known about the impact of nursing homes’ response to COVID-19 on resident clinical, functional, and psychosocial outcomes.

Methods
We examined aggregated Minimum Data Set (MDS) assessments to describe resident outcomes using an interrupted times series methodology for three timeframes: pre-COVID (1/2019 to 2/2020), pandemic (3/2020–12/2021), and vaccination (1/2021-6/2021). Data included 307,558 federally mandated resident MDS assessments from 60,846 resident in 489 nursing homes in a Mid-Western state. We calculated MDS based quality measures (QM) using definitions available from Centers for Medicare and Medicaid Services. Each QM-based outcome was fit to a logistic regression model using the method of generalized estimating equations.

Results
None of the QMs displayed a statistically significant trend pre-COVID. The prevalence of excessive weight loss and ADL decline increased sharply during the pandemic and reversed that trend with vaccination. Pressure ulcers among high-risk residents followed a similar trend, although pandemic and vaccination-related regression parameters for that QM were only marginally significant (p = .08). Pain worsened during the pandemic and vaccination period approaching significance (p=.07). Antipsychotic medication use worsened in the pandemic (p&lt; .001) and did not improve in the vaccination period. Other QMs including any fall, fall with major injury, and incontinence did not exhibit statistically significant change in trend.
Prevalence Profiles
Circles: Observed proportions, Dashed Line: Model expected value, Solid Lines: 95% confidence limits for expected values

Conclusion
We noted significant changes in QMs for antipsychotic use, ADL loss, and weight loss, with the latter two improving in the vaccination period. Isolation, disease outbreaks, and staffing issues in facilities could have affected these QMs. Data variability may have limited our ability to detect other changes. Antipsychotics may have increased with the need to reduce wandering and other behaviors common in the nursing home population; behaviors high risk for spreading COVID-19. Why antipsychotic use did not improve during the vaccination period is less clear. Data beyond June of 2021 may help clarify the pattern of antipsychotic use.

Disclosures
Lori Popejoy, PhD, RN, FAAN, New Path: Board Member|New Path: Ownership Interest Amy Vogelsmeier, PhD, RN, FAAN, New Path: Board Member|New Path: Ownership Interest Marilyn Rantz, PhD, RN, FAAN, New Path: Board Member|New Path: Ownership Interest.
LB1531B. Administration of the TNF-alpha inhibitor, infliximab, reduces mortality in hospitalized patients with COVID pneumonia. Results of a randomized controlled trial
Authors: O'Halloran Jane A , Anstrom Kevin J , Kedar Eyal , McCarthy Matthew W , Ko Emily R , Melsheimer Richard , Boucher Cynthia , Chang Soju , Bozzette Samuel , Powderly William G 
Published: December 2022

Abstract

Background
Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if the TNF-alpha inhibitor, infliximab (IFX), provides additional benefit over standard of care.

Methods
We conducted a double-blind, randomized, placebo-controlled trial of IFX (single infusion of 5 mg/kg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was time to recovery by day 29. Key secondary endpoints included 14-day clinical status and 28-day mortality.

Results
A total of 1033 patients received study agent (517 assigned to IFX, 516 to common placebo), constituting the analyzed modified intention-to-treat cohort. Mean age 54.8 years, 60.3% were male, 48.6% Hispanic/Latino and 14% Black. Randomization was balanced for severity of illness and comorbidities. Participants randomized to IFX did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.13 (95% CI 0.99-1.27, p=0.0631) compared to placebo. The median (IQR) time to recovery was 8 days (7, 9) for IFX and 9 days (8, 10) for placebo. Patients assigned to IFX were more likely to have an improved clinical status at day 14 (OR 1.32; 95% CI 1.05, 1.66). The 28-day mortality was 10.1% in the IFX arm and 14.5% in the placebo (OR 0.59 (95% CI 0.39, 0.90)), with a 40.7% lower odds of dying in patients receiving IFX. The improvement in mortality was demonstrated in patients requiring low- or high-flow O2 at baseline but not in those requiring mechanical ventilation or ECMO. Subgroup analysis identified the strongest effect in those with baseline CRP &gt;75mg/ml. There was no imbalances in serious adverse events. Secondary infections were similar between groups (IFX 18.0%, placebo 16.5%).

Conclusion
Although single-dose IV IFX did not demonstrate statistically significant improvement in time to recovery, it was associated with improvement in clinical status at day 14 and showed a substantial reduction in 28 day mortality compared to standard of care.

Disclosures
Jane A. O'Halloran, MD PhD, Janssen Scientific Affairs, LLC: Grant/Research Support Richard Melsheimer, n/a, Janssen Pharmaceuticals, a Johnson & Johnson Company: Employee of Janssen/J&J|Janssen Pharmaceuticals, a Johnson & Johnson Company: Stocks/Bonds William G. Powderly, MD, Merck: Advisor/Consultant.
LB2303. Single High-dose of Liposomal Amphotericin B in HIV/AIDS-related Disseminated Histoplasmosis: a Randomized Trial
Authors: Pasqualotto Alessandro C , Godoy Cassia M , Lana Daiane Dalla , Leitao Terezinha S , Bay Monica B , Damasceno Lisandra S , Soares Renata B , Falci Diego R , Kist Roger , Silva Larissa R , Melo Marineide , Guimaraes Taiguara F , Guimaraes Marilia R , Vechi Hareton T , Mesquita Jaco , Macedo Erianna Y , Adenis Antoine A , Bahr Nathan C , Spec Andrej , Boulware David R , Israelski Dennis , Chiller Tom M 
Published: December 2022

Abstract

Background
Histoplasmosis is a major AIDS-defining infection in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is limited.

Methods
Prospective randomized open-label trial of induction therapy with L-AmB for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy (started on the day after L-AmB was finished). We conducted this trial at 6 centers in Brazil (2019-2022). We randomized subjects to 3 arms of: Single dose 10 mg/kg of L-AmB;10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3;3 mg/kg of L-AmB for 2 weeks (control).
As a non-inferiority trial, 80% power could detect &gt; 20% non-inferiority margin for a one-sided alpha=0.05 with a sample size of 29 subjects per arm. Clinical response at day 14 was the primary outcome.

Results
Of 512 screened patients, 118 subjects were randomized (Arm 1, n=40; Arm 2, n=39; Arm 3, n=39). Median CD4 was 25 cells/µL. Subjects presented with weight loss (70%), pulmonary complaints (67%), fever (66%), abdominal findings (59%), skin lesions (38%), lymphadenopathy (38%), and oral lesions (36%). Clinical and lab findings did not differ among arms. Histoplasmosis diagnosis was predominantly via urine antigen (97%).
Infusion-related toxicity on D1 was similar in each arm (p=0.56). Kidney toxicity was similar on D3 (p=0.83), D7 (p=0.10), and D14 (p=0.17) as was frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity (all p &gt;0.05). No subject withdrew due to drug toxicities.
D14 clinical response was 82% for Arm 1, 68% Arm 2, and 72% Arm 3 (p=0.69). Absolute risk difference for Arm 1 was 10.3% (95%CI, -8.3% to 28.8%) vs. Arm 3 controls; Arm 2 was -4.2% (95%CI, -24.9% to 16.4%) to controls. Overall survival on D14 was 89.5% (34/38) for Arm 1, 78.4% (29/37) for Arm 2, and 92.1% (35/38) for Arm 3 (p=0.82); 2 subjects were excluded from efficacy analysis due to meningitis and tuberculosis, and 3 were lost to follow up.

Conclusion
Induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although efficacy is likely to be non-inferior to standard L-AmB therapy, a confirmatory phase III trial is needed. Such a strategy would markedly reduce drug-acquisition costs (&gt; 4-fold), therefore improving access to L-AmB across the globe.

Disclosures
Alessandro C. Pasqualotto, FECMM, Gilead: Grant/Research Support|United Medical: Advisor/Consultant|United Medical: Honoraria Diego R. Falci, MD, United Medical: Advisor/Consultant|United Medical: Honoraria Andrej Spec, MD, MSCI, Astellas: Grant/Research Support Dennis Israelski, MD, Gilead Sciences: Empoyee.