bluuebunny/crossref_metadata_2025_split huggingface dataset:
1984. Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy
Authors: McComsey Grace A , Sattar Abdus , Albar Zainab , Ansari Gilani Kianoush , Labbato Danielle , Foster Theresa , Ross Eckard Allison 
Published: November 2023

Abstract

Background
Lipohypertrophy (central adipose tissue (AT) accumulation) is a common and significant problem in people with HIV (PWH). Pathogenesis remains elusive; yet, AT abnormalities are key drivers of cardiometabolic co-morbidities in HIV. We aimed to assess effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on AT in PWH with lipohypertrophy.

Methods
We conducted a randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥ 18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥ 25 kg/m2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Computed tomography and whole-body dual-energy X-ray absorptiometry were used to measure area/density in abdominal AT [total (TAT), visceral (TAT), and subcutaneous (SAT)] and body composition [lean body mass (LBM), limb/trunk/total body fat (TBF)], resp. Semaglutide effects were estimated using generalized estimating equations or simultaneous quantile regressions on outcome variables.

Results
108 participants were enrolled (N = 54 semaglutide: median age = 52 years, 70% male, 61% Black, 83% integrase inhibitor). Groups were well-matched at baseline. In unadjusted models, semaglutide group had greater reductions (P &lt; 0.05) in BMI, homeostatic model of insulin resistance (HOMA-IR), trunk fat, TBF (at quantile ≥ 75th), TAT, and SAT with trends (P &lt; 0.1) for limb fat and VAT (Fig 1/Table 1). Semaglutide effects remained significant for BMI, HOMA-IR, trunk fat, TAT, and VAT after adjusting for age, sex, CD4, and ART duration (Table 2); caloric intake was also significant at ≤ 50th quantile. No differences were seen in LBM, AT density, or VAT/TAT ratio. Semaglutide was well-tolerated; serious adverse events were rare.

Conclusion
Semaglutide significantly decreased central fat in PWH with lipohypertrophy, primarily driven by reductions in VAT. Semaglutide may offer an effective treatment to decrease visceral adiposity and reduce co-morbidity risk. Further investigation is needed to determine mechanisms by which reductions in visceral adiposity occur.

Disclosures
Grace A. McComsey, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support
1331. High direct costs caused by Cryptococcal meningitis treated with Amphotericin B deoxycholate in a public hospital in Lima, Peru. 2021-2022
Authors: Vilcarromero Stalin , Luque Arturo , Luarte Norka , Mateo-Pacora Jimmy , Mendo Fernando 
Published: November 2023

Abstract

Background
Cryptococcal meningitis (CM) is a severe disease caused by a ubiquitous fungus that affects both immunocompetent and immunosuppressed people. The treatment of choice includes liposomal amphotericin plus flucytosine; however, in Peru, both medications are not available. Hence, in Peru, CM is usually treated with Amphotericin B deoxycholate, despite adverse events that include longer hospital stays and a higher frequency of complications resulting in higher direct costs. The objective of this study is to evaluate the direct cost of CM in adults in the infectious disease service of the Edgardo Rebagliati Martins National Hospital in Lima, Peru. To do this, the clinical histories of adult patients hospitalized during the 2021 and 2022, and diagnosed by positive culture in the cerebrospinal fluid, were reviewed (Fig 1)

Methods
Nine positive CM cases were identified; only six met the inclusion criteria. Daily hospitalization costs were estimated using published rates of IETSI-ESSALUD, a public employer-based health insurance. Costs for images and laboratory were based on private sector costs.
Positive culture in the cerebrospinal fluid for Cryptococcus sp

Results
Three of the six cases were female and the mean age was 52.6 [39-61]. All six presented headache, nausea and vomiting. Three had HIV infection. All presented renal injury and hematological toxicity (Table 1). Three presented nosocomial infections. The average hospital stay was 66 days [30-90 days] with a total cost for all six patients of USD 35,168. The average direct cost per patient was USD 5,024 with the following distribution: average cost per hospital bed per person: USD 3,584.28; average cost of complete treatment with amphotericin b deoxycholate: USD 119; average cost for laboratory tests was USD 935; average cost for imaging was USD 385 USD (Table 2).

Conclusion
The direct cost for CM treatment with amphotericin B deoxycholate is approximately USD 5,024; as a reference, the minimum monthly salary in Peru is USD 277. This high cost is not due to the drug, which is cheaper for the health system, but due to the long hospital stay and complications that occur. The small sample size is a great limitation; however, it partially reveals financial considerations that should be further and more thoroughly evaluated in the public health system in Peru.

Disclosures
All Authors: No reported disclosures
2150. In Vitro Activity of Cefepime-Taniborbactam and Comparators Against Genotypically Characterized Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) from the United States, 2018-2021
Authors: Wise Mark G , Hackel Meredith , Sahm Daniel F 
Published: November 2023

Abstract

Background
Taniborbactam, a cyclic boronate-based β-lactamase inhibitor with activity against serine-, and NDM & VIM metallo-β-lactamases (MBLs), in combination with the fourth-generation cephalosporin, cefepime, is in development for treatment of complicated urinary tract infections. This study examined the in vitro activity of cefepime-taniborbactam against clinical isolates from the US, with a focus on carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA).

Methods
From 2018-2021, as part of the GEARS Antimicrobial Surveillance Program, 4,220 Enterobacterales and 1,222 P. aeruginosa were collected from 38 clinical sites in the US. MICs of cefepime with taniborbactam fixed at 4 µg/mL and comparators were determined by broth microdilution according to CLSI guidelines and interpreted using 2023 CLSI breakpoints. CRE was defined by resistance to meropenem; CRPA was defined by resistance to meropenem and/or imipenem. Isolates with cefepime-taniborbactam MIC ≥16 µg/mL were characterized by whole genome sequencing. Isolates resistant to meropenem were screened for acquired β-lactamases by multiplex PCR/Sanger sequencing.

Results
In total, 97.1% of the 68 CRE isolates were inhibited by ≤16 µg/mL of cefepime-taniborbactam. The majority of CRE (51/68; 75.0%) produced a carbapenemase (40 KPC, 9 MBLs, 2 OXA-48) and 98.0% were inhibited by ≤16 µg/mL cefepime-taniborbactam, a substantially greater percentage than the most active comparator, meropenem-vaborbactam (82.4% susceptible). Cefepime-taniborbactam at ≤16 µg/mL inhibited 92.9% of all CRPA (n=308), 88.7% of meropenem-resistant P. aeruginosa (n=177), and 90.6% of carbapenemase-negative, meropenem-resistant P. aeruginosa (n=170) whereas the most active comparator, ceftazidime-avibactam, covered 84.7%, 75.7%, and 77.6% of these resistant subsets, respectively.

Conclusion
Cefepime-taniborbactam inhibited ≥94.1% of CRE isolates from the US, regardless of carbapenemase carriage. Similarly potent activity was observed for cefepime-taniborbactam against CRPA, including meropenem-resistant strains without a detected carbapenemase. The continued development of cefepime-taniborbactam appears warranted.

Disclosures
Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
137. Penicillin (PCN) Gradient Diffusion Overcalls Resistance and Promotes Unnecessary Vancomycin (VAN) Use in Enterococcus faecalis Bloodstream Infections (BSI)
Authors: Donohue Lindsay E , Cox Heather L , Thomas Jenni , Kidd Tiffany S , Mohammed Hiba N , Mathers Amy 
Published: November 2023

Abstract

Background
Reports of a PCN-resistant (R), ampicillin-susceptible (S) Enterococcus faecalis (PRASEF) phenotype associated with elevated piperacillin and imipenem minimum inhibitory concentrations (MICs) may drive hesitation to use these agents when a PCN MIC is unknown and/or result in the addition of a glycopeptide. However, PCN MICs by broth microdilution are not readily available in many clinical laboratories and some commercial methods may overcall PRASEF. We sought to assess the rate of overcalling PCN MICs by gradient diffusion compared to broth microdilution and the impact of PCN test requests and results on vancomycin (VAN) prescribing attributed to possible PRASEF BSI at a single academic medical center.

Methods
Retained clinical E. faecalis blood isolates with Etest® (BioMérieux, Inc.) PCN MICs collected from 2019 – 2022 were tested via automated broth microdilution (aBMD) plates (Sensititre™ Thermo Fisher Scientific, Inc.). MICs were interpreted according to CLSI breakpoints and compared for essential agreement (EA) and categorical agreement (CA) of Etest to aBMD. A retrospective chart review of all PCN-S or PRASEF BSI from 1/2021 – 12/2022 identified via antibiogram report generation (Theradoc® Premier, Inc.) plus all patients with a retained isolate was conducted to measure VAN days of therapy (DOT) attributed to concern for PRASEF.

Results
Of the 5 PCN-S and 19 PCN-R isolates via Etest MIC for which aBMD was performed, all tested PCN-S with an MIC50/90 of 4/8 mcg/mL. EA was 33% and CA was 21%, with a 79% major error rate (called resistant when susceptible). A total of 124 patient charts were reviewed (n=25 Etest PCN-R, n=99 Etest PCN-S). Total attributable VAN DOT was 102 across 19 patients (n=3 Etest PCN-R, n=16 Etest PCN-S), with a mean VAN DOT of 17 in PCN-R and 3 in PCN-S isolates.

Conclusion
False resistant PCN Etest MICs, as determined by aBMD comparison and consistent with published reports, fed concern regarding potential PRASEF emergence at our institution and led to unnecessary concomitant VAN in 15% of patients. Caution is advised when interpreting PCN susceptibility via this method. Inclusion of E. faecalis in the FDA indication for in vitro diagnostic use of benzylPCN Etest should be reconsidered.

Disclosures
Amy Mathers, MD, D(ABMM), Merck: Advisor/Consultant
2740. Letermovir for the Prevention and Treatment of Cytomegalovirus Infection in Solid Organ Transplant Recipients
Authors: Xhemali Xhilda , Urzen Courtney A , Blackmer Kristen A 
Published: November 2023

Abstract

Background
Cytomegalovirus (CMV) is a common infection that can lead to end-organ damage and graft rejection in solid organ transplant (SOT) recipients. Due to the increase in drug-resistant CMV and unfavorable side effect profile of available CMV-active agents, there is a need for additional prophylactic and treatment strategies in this patient population. The goal of this study is to evaluate SOT recipients prescribed letermovir for prophylaxis and/or treatment of CMV.

Methods
This study was a retrospective review of adult SOT recipients in the Cleveland Clinic Health System prescribed letermovir from 11/8/2017 to 8/1/2022. The primary objective was to describe the utilization of letermovir in SOT recipients. Secondary objectives included: proportion of SOT recipients that experienced CMV breakthrough on letermovir prophylaxis, proportion of SOT recipients that experienced refractory CMV infection on letermovir treatment, prevalence of letermovir resistance, and letermovir-induced adverse effects.

Results
A total of 45 patients were included in the study, with 52 letermovir courses. Lung was the most commonly transplanted organ (35%), followed by kidney (22%). 78% of patients were high-risk CMV and the most common immunosuppression regimen consisted of a calcineurin inhibitor in combination with a corticosteroid (82%). 11 patients received letermovir for primary CMV prophylaxis, with only one patient experiencing new/worsening viremia while on the agent. Of the 34 patients who received letermovir for secondary CMV prophylaxis, 11 experienced new/worsening viremia. 7 patients received letermovir for CMV treatment, at a median viral load of 991 IU/mL (IQR 603-2,738) on initiation and peak viral load of 3,892 IU/mL (IQR 1,407-10,209) while on therapy. No patients in the treatment group experienced refractory infection. 7/52 (13.5%) letermovir courses were discontinued due to new/worsening viremia, with no letermovir resistance identified. No letermovir-related adverse effects were documented.

Conclusion
Our study shows that letermovir appears to be effective in suppressing CMV viremia. Letermovir may be an alternative option for SOT recipients who are unable to tolerate or have resistance to traditional CMV therapeutics.

Disclosures
All Authors: No reported disclosures
2751. Cefiderocol Use in Treating Patients with Confirmed Stenotrophomonas maltophilia Infections in US Hospitals During January 2020 - June 2022
Authors: Cai Bin , Nguyen Sean T , Copeland Jennifer D , Song Hyun Jin , Slover Christine M 
Published: November 2023

Abstract

Background
Stenotrophomonas maltophilia (SM) infections have been associated with high mortality rates (21% to 69%), particularly in critically ill patients because of SM inherent resistance to many antibiotics, including carbapenems. This study describes cefiderocol (CFDC) treating hospitalized patients infected with SM in the US.

Methods
This retrospective observational study used January 2020-June 22 Premier Healthcare Database. Inclusion criteria are age ≥18 years, non-COVID, a positive SM culture without other Gram-negative pathogens identified within ±3 days and received CFDC ≥3 days on or after first SM culture. This study describes the patient characteristics, cefiderocol use pattern, and overall, 14-day and 28-day in-hospital all-cause mortalities (IHACM) with 95% confidence intervals (CI). First SM culture is the Index culture.

Results
Of 19 patients meeting the inclusion criteria, median age was 62 years with an interquartile range (IQR) of 56-76 years, 57.9% were male, 63.2% came from home, and 89.5% were admitted via emergency room or urgent care. Top comorbidities at admission were renal disease (68.4%), congestive heart failure (52.6%), chronic pulmonary disease (31.6%), and peripheral vascular disease (31.6%). Over 68% of patients were in the ICU, with the same rate of receiving both mechanical ventilation and vasopressor support at the time of index culture. Also 68.4% of index cultures were from respiratory and 10.5% from blood. CFDC was initiated ≤5 days of index culture in 8 (42.1%) patients, 6-20 days in 9 (47.4%) patients, and &gt;20 days in 2 (10.5%) patients. Median days on CFDC was 8 days (IQR: 4-12), longer for patients who started CFDC later. All 19 patients received other antibiotics prior to CFDC. Twelve (63.2%) patients received other antibiotics during CFDC treatment, and the most common antibiotics were levofloxacin (50.0%), eravacycline (50.0%), cefepime (33.3%), or minocycline (33.3%). Median of hospital stays after index culture was 18 days (IRQ:8-30). Crude overall IHACM was 36.8% (95%CI: 15.8%-58.5%). Crude 28-day IHACM from index culture was 21.1% (95%CI: 2.7%-39.4%).

Conclusion
SM is a rare Gram-negative pathogen with limited treatment options. CFDC offers an additional treatment option against this pathogen. Further investigation is warranted.

Disclosures
Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Jennifer D. copeland, MS, Shionogi, Inc.: Employee (Medical/Micro) Christine M. Slover, PharmD, Shionogi,INC: Employee
2818. Investigating Urinalysis Criteria that Predict UTI: Impact of age, sex, and urine culture thresholds
Authors: Advani Sonali , North Rebecca M , Turner Nicholas A , Ahmadi Sahra , Denniss Julia , Francis Adero , Hasan Anum , Johnson Rachel M , Mirza Faryal , Pardue Sarah , Rao Meghana V , Rosshandler Yasmin , Tang Helen , Schmader Kenneth E , Anderson Deverick J 
Published: November 2023

Abstract

Background
Urinalysis (UA) results are used by clinicians and laboratories to aid in the diagnosis of UTI. However, optimal UA parameters have not been systematically investigated or validated for different populations. Our objectives were to assess the performance of UA in predicting UTI and to stratify UA performance by age, sex, and culture thresholds.

Methods
We conducted a retrospective cohort study of adult non-catheterized inpatient and ED encounters with paired UA and urine cultures (24 hours apart) from 5 community and academic hospitals in three states (NC, VA, GA) between 01/01/2017 and 12/31/2019. Trained abstractors collected clinical and demographic data for a random sample of patients. Patients were classified as having UTI, asymptomatic bacteriuria or ‘not UTI’ based on IDSA guidelines using signs/symptoms and microbiology data. We evaluated the performance of relevant UA parameters in predicting UTI by assessing sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria (Figure 1) and used area under receiver operating curves (AUROC) to identify the 5 best-performing models, and stratified results by age, sex, and lower urine culture bacterial threshold (1000 colony forming units).

Results
Of 219,338 encounters, 3392 charts were included and reviewed; 723 (21.3%) patients met criteria for UTI. Females and older adults had a higher incidence of UTIs and ASB (P&lt; 0.05; Table 1). Absence of pyuria (or leukocyte esterase) had a high NPV for UTI (Table 2). Combined UA parameters performed better than pyuria alone with regards to NPV and AUROC, specifically models 1 and 5 (Table 3). UA parameters used in these models performed differently based on age, sex and urine culture thresholds, with limited utility in older women and UTIs with lower bacterial threshold (Table 4).

Conclusion
Our review of laboratory and symptom data from a diverse population dataset revealed that combined UA parameters were better at predicting UTI, but performance of UA parameters differs based on age, sex, and urine culture thresholds. Our approach highlights the need to move away from a one-size fits all approach to using population specific UA cut-offs for patients with UTI symptoms.

Disclosures
Sonali Advani, MBBS, MPH, FIDSA, bioMérieux: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant Nicholas A. Turner, MD, MHSc, PDI: Research contract to assess efficacy of cleaning agent
668. The clinical effectiveness of Fidaxomicin compared to Vancomycin in the treatment of Clostridioides difficile infection in immunocompromised hosts, a single center study
Authors: Alsoubani Majd , Chow Jennifer K , Rodday Angie Mae , Kent David , Snydman David R 
Published: November 2023

Abstract

Background
Patients with immunocompromising conditions are at increased risk of C.difficile infection (CDI) and recurrence. Fidaxomicin reduces the risk of recurrence in immunocompetent hosts. However, there is limited data on fidaxomicin effectiveness in hosts with immunocompromising conditions.

Methods
We retrospectively assessed the treatment of CDI among patients with immunocompromising conditions who were diagnosed between 2011 and 2021 at Tufts Medical Center. Patients were considered to be treated by fidaxomicin or vancomycin if they received ≥72 hours of the agent. Patients less than 18 years, those who did not receive treatment for CDI, and those treated with metronidazole only were excluded. The study outcome was a composite of failure to achieve clinical cure within 72 hours of treatment initiation, relapse within 30 days following completion of initial treatment and death due to CDI. Time to event analysis used a cause specific Cox proportional hazards to compare the rate of the composite outcome in the two groups, accounting for the competing risk of death from other causes. Multiple imputation was used for missing variables but not the outcome.

Results
A total of 238 patients with immunocompromising conditions received vancomycin (n= 38) or fidaxomicin (n= 200) for treatment of CDI. Patients who received vancomycin were significantly more likely to be male (51.5% vs 26.2%, p 0.005) and to have had community acquired infection (31.1% vs 9.5%, p 0.03) compared to fidaxomicin (Table 1). The composite outcome occurred in 48 (24%) patients in the vancomycin group compared to 5 (13.2%) in the fidaxomicin group. In the multivariable model adjusted for sex, number of antecedent antibiotics, antibiotics during treatment, severity and type of immunosuppression, fidaxomicin was associated with 65% reduction in the hazard of the composite outcome compared with vancomycin (HR 0.35, 95% CI 0.12-0.99) (Table 2).

Conclusion
The use of fidaxomicin was more effective than vancomycin in preventing poor CDI outcomes among patients with immunocompromising conditions. The study may have residual confounding by indication and limited generalizability based on a single site. Future studies should confirm our findings.

Disclosures
Jennifer K. Chow, MD, MS, Kamada: Grant/Research Support|Merck: Grant/Research Support|Moderna: DSMB David Kent, MD, W.L. Gore: Grant/Research Support David R. Snydman, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres therapeutics: Advisor/Consultant|Seres Therapeutics: Grant/Research Support|Summit Therapeutics: Grant/Research Support