bluuebunny/crossref_metadata_2025_split huggingface dataset:
1383. Universal Strongyloides Screening in a Heart Transplant Program in South Carolina: Just How Endemic Is It?
Authors: Adekunle Ruth , Jandhyala Deeksha , Lewis Jessica 
Published: December 2021

Abstract

Background
Strongyloides stercoralis is endemic in sub-Saharan Africa, Southeast Asia, Latin America, and the southeastern United States, particularly Appalachia, where Strongyloides seroprevalence approaches 2%. SC is considered a state in which Strongyloides is endemic, however the degree of endemnicity is not known. Here we define the epidemiology of chronic strongyloidiasis in our state, through data obtained via universal screening of heart transplant candidates at our center.

Methods
This single center retrospective study was performed at a 700 bed academic medical center that is the only comprehensive transplant center in SC. All adult patients who underwent heart transplant evaluation 1/1/2019 - 12/31/2020 were included. Routine pre-transplant evaluation by Transplant Infectious Diseases (TxID) was implemented in the heart transplant program in 2015 and universal screening with Strongyloides IgG began in late 2018. We assessed demographics, risk factors for exposure to Strongyloides, treatment, and outcomes for seropositive subjects.

Results
During the study period, 218 patients underwent heart transplant evaluation. Adherence to universal screening was 96.8% (211/218). 187 subjects (88.6%) had negative screening results (≤ 0.9 IV) and 24 subjects (11.4%) had equivocal or positive screening results (≥ 1.0 IV). Demographics and risk factors for the 24 equivocal/positive subjects are presented in Table 1.
15 equivocal/positive subjects (66.7%) received ivermectin and 9 (33.3%) did not. The majority of untreated patients were declined for transplant (8/9) and did not have a TxID evaluation (6/9). One untreated patient was waitlisted for transplant and has received ivermectin since being identified in this study. There were no episodes of hyperinfection or disseminated infection in the cohort.
Table 1. Demographics and risk factors for subjects with equivocal or positive Strongyloides IgG

Conclusion
Universal screening of adult heart transplant candidates at SC’s only transplant center detected a Strongyloides seroprevalence rate of 11.4%. The majority of subjects with equivocal/positive Strongyloides IgG were born in the US and did not have other known risk factors (residence in the Appalachian region of SC, military service, overseas travel). These data suggest a high level of endemnicity of strongyloidiasis in SC.

Disclosures
All Authors: No reported disclosures
1387. Impact of Cytomegalovirus Prophylaxis on Healthcare Resource Use and Costs among Kidney Transplant Recipients: A United States Renal Data System-Medicare Linked Database Study
Authors: Raval Amit D , Ganz Michael , Saravanan Priya , Tang Yuexin , Santos Carlos 
Published: December 2021

Abstract

Background
Cytomegalovirus (CMV) management requires a balance between reducing the risk of CMV infection and avoiding anti-viral toxicities. Limited information is available on the impact of CMV prophylaxis on the healthcare resource use (HCRU) and costs among adult kidney transplant recipients (KTRs) in the United States. Therefore, we examined HCRU and cost associated with CMV prophylaxis stratified by the CMV risk categories among KTRs at 1-year post-KT.

Methods
We identified a cohort of 22,918 adults first-time KTRs during 2011–2017 using the US Renal Data System registry-linked Medicare data. Additional inclusion criteria were to have continuous coverage in Medicare Part A & B for ≥ 6-month pre- and ≥ 12-month post KT and Medicare Part D for ≥12-month post-KT. CMV prophylaxis was confirmed as ≥ 1 prescription fill for valacyclovir/(val)ganciclovir prophylaxis doses within 28 days post-KT.

Results
CMV prophylaxis was utilized in 86%, 82%, and 32% of high, intermediate, and low-risk KTRs with an average cost of prophylaxis per KTRs of &16,241, &9481, and &8,648, respectively. In no prophylaxis groups, valganciclovir was utilized in 52%, 34%, and 36% of KTRs (as either pre-emptive or deferred therapy) with an average cost of &6,719, &2,722, and &431 among high, intermediate, and low-risk KTRs, respectively. Among high-risk KTRs, CMV prophylaxis group had a significantly higher prescription drug cost (&26,060 vs. &13,433) but a lower average direct healthcare medical cost (&84,914 vs. &101,268), mainly due to lower all-cause hospitalization cost (&56,758 vs. &69,852) (Table 1). CMV prophylaxis group had lower rates of all-cause rehospitalization, and CMV-and opportunistic infection (OIs)-related hospitalization compared to no prophylaxis (Table 2). In high-risk KTRs, nearly 32% had myelosuppressive events-related hospitalization, and 15% filled granulocyte colony-stimulating factors with an average cost of &4,695 per treated KTR.

Conclusion
CMV prophylaxis had a higher cost of medications but had a lower medical cost with including all-cause and CMV-related hospitalizations. Myelosuppressive events were frequent and resource-intensive especially in high and intermediate-risk KTRs.

Disclosures
Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)
158. Impact of Fluoroquinolone Cascade Reporting of Urine Samples on Antibiotic Prescribing Rates in a Network of Urgent Care Clinics
Authors: Weichman Brittani , Bushman Amanda , Rosa Rossana M 
Published: December 2021

Abstract

Background
Cascade reporting is a type of selective reporting in which susceptibility results of certain antibiotics (either with broader spectrum or cost) are only reported if an organism is resistant to other prespecified agents. This strategy has been successfully deployed in inpatient settings but its impact in outpatient settings is less well characterized. Therefore, we aimed to evaluate the impact of cascade reporting of the antimicrobial susceptibility of fluoroquinolones on prescribing rates of select antibiotics in a network of urban Urgent Care clinics.

Methods
On July 2019, the susceptibility reporting policies for urine cultures growing Enterobacterales were changed to routinely reporting a limited antibiotic panel including first and second generation cephalosporins, nitrofurantoin and trimethoprim-sulfamethoxazole (TMP-SMX), and fluroquinolone (FQ) reporting was changed to a release only in case of resistance to all agents in the limited panel. Third and fourth generation cephalosporins and carbapenems were reported only in case of resistance to all narrower spectrum agents and FQs. We then compared monthly antibiotic use in prescriptions per 1000 patient-encounters for the pre-intervention (June 2018-June 2019) and post-intervention (August 2019-December 2020) periods using an interrupted times series analysis.

Results
Immediately following the change to cascade reporting, FQ prescribing decreased by 38% (incidence rate ratio [IRR] 1.38; 95% confidence interval [CI] 0.50-0.77 p&lt; 0.0001) and no change in trend was subsequently seen (IRR 1.01, 95% CI 0.98-1.04; p=0.59) (Figure 1).Cephalexin prescribing did not immediately change following the intervention (IRR 1.20, 95% CI 1.00-1.33; p=0.05) but subsequently showed a trend towards increase use (IRR 1.04, 95% CI 1.02-1.06; p&lt; 0.0001) (Figure 1). No immediate or trend changes in the prescribing rates of TMP-SMX or nitrofurantoin were identified (Figure 1).

Conclusion
In a network of Urgent Care clinics, cascade reporting of FQ susceptibility in urine cultures growing Enterobacterales resulted in a sustained decrease in FQ prescribing without major shifts towards prescribing of other agents. Cascade reporting should be considered as a feasible antimicrobial stewardship strategy in this outpatient setting.

Disclosures
All Authors: No reported disclosures
1388. Epidemiology and Treatment Outcomes of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States
Authors: Vivian Tsai Y , Derrick Caroline , Yunusa Ismaeel , Weissman Sharon , Al-hasan Majdi N , Justo Julie Ann , Brandon Bookstaver P 
Published: December 2021

Abstract

Background
Gaps in evidence concerning the epidemiology of nontuberculous mycobacterial (NTM) organisms and their associated treatment outcomes are evident in the literature. The aim of this study was to describe NTM species distribution and susceptibility profile and associated treatment outcomes among adult patients at a tertiary referral hospital in the Southeastern United States.

Methods
A retrospective cohort study of adult patients with NTM infections from January 1, 2010 to June 30, 2020 was performed. Included patients had a positive culture for NTM species and clinical suspicion of infection. Patients were excluded if they had concurrent positive culture for M. tuberculosis (MTB) or monomicrobial culture for M. gordonae. Study endpoints included predictors for favorable treatment outcome, species distribution, and susceptibility at baseline. Favorable treatment outcome was defined as physician-guided cessation of therapy due to clinical improvement. Univariate followed by multivariate regression analysis was used to analyze favorable predictors.

Results
A total of 250 and 78 patients were included in microbiologic and outcomes cohorts, respectively. Among treated patients, 47 (60%) had a favorable treatment outcome. The outcomes cohort consisted primarily of non-Hispanic Caucasians (71%) with pulmonary infection (67%). The most common isolates observed were Mycobacterium avium complex (MAC) (67%) and M. abscessus (18%). Being self-pay, underweight, history of MTB treatment, and concurrent asthma were more common in those with unfavorable treatment outcomes. The significant favorable predictors included antibiotic change not due to escalation or de-escalation of therapy and private insurance. Among MAC isolates, clarithromycin and amikacin were highly susceptible; however, M. abscessus has reduced susceptibility to first-line agents such as amikacin, clarithromycin, and cefoxitin (Table 1).
Table 1. Baseline Susceptibility

Conclusion
Considering the long incubation time, knowledge of prevalence, antimicrobial susceptibility patterns, and outcomes could guide empirical antimicrobial selection for NTM infections. This is particularly useful for M. abscessus infections where most isolates carry significant resistance to one or more first-line agents.

Disclosures
Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)
1389. Nontuberculous Mycobacterial Infections of the Upper Extremity
Authors: Polveroni Thomas M , Scott Kelly , Renfree Kevin J , Vikram Holenarasipur R , Mead-Harvey Carolyn 
Published: December 2021

Abstract

Background
Although uncommon, nontuberculous mycobacterial infections (NTMI) of the upper extremity cause significant morbidity based on their natural history, delay in diagnosis, prolonged duration of antimicrobial therapy often combined with surgical debridement, and functional loss. Herein we describe our experience with such infections.

Methods
Records for adult patients from two academic, tertiary facilities with culture-proven NTMI involving the upper extremity were retrospectively reviewed. Demographic information, co-morbidities, laboratory and microbiological evaluation, management, and outcomes were extracted. Patients were analyzed based on pathogen identified and immune suppression.

Results
77 patients were identified. The mean age was 59 years and 65% of patients were male. 48% reported a preceding injury, with the hand being most frequently involved (58%). 41% were considered immune compromised; 19% of them were organ transplant recipients. Mean symptom duration prior to presentation was 203 days. Mean time to culture identification was 33 days, and 25 different species of NTM were identified (subcategorized as rapid or slow growers). 77% had solitary lesions, with cutaneous/subcutaneous location as the most common site. All patients underwent surgical debridement with four undergoing amputation to control infection. 69% received combination antimicrobial therapy for a mean duration of 184 days. Immunosuppressed patients were treated with antimicrobial therapy for a longer duration (mean 243 vs 155 days). One-third of patients experienced complications and/or recurrence regardless of organism type.

Conclusion
NTMI of the upper extremity is often misdiagnosed leading to significant delays in appropriate management. Knowledge of its protean manifestations and early consideration in the differential diagnosis of chronic, painful swelling of the hand or wrist, nodular or inflammatory lesions, or septic arthritis is crucial. A low threshold for surgical or biopsy with specimens sent for histopathology as well as microbiologic analysis is warranted. A combined approach with surgical debridement and prolonged combination antimicrobial therapy is necessary for optimal outcomes; however, adverse reactions from such therapy are commonly encountered.

Disclosures
All Authors: No reported disclosures
1390. Durlobactam, a Diazabicyclooctane (DBO) β-lactamase Inhibitor (BLI), Inhibits BlaC and Peptidoglycan (PG) Transpeptidases of Mycobacterium tuberculosis (Mtb): A Novel Approach to Therapeutics for Tuberculosis (TB)?
Authors: Nguyen David , Bethel Christopher , Taracilla Magdalena A , Li Qing , Dousa Khalid M , Kurz Sebastian G , Nguyen Liem , Kreiswirth Barry N , Boom Wilem , Bonomo Robert A 
Published: December 2021

Abstract

Background
Novel therapies for multidrug-resistant TB are needed and new BLIs could answer this call. Mtb encodes for BlaC, a class A β-lactamase. BlaC is inhibited by clavulanate (CLA) while the DBO avibactam (AVI) is an inefficient inhibitor (low k2/K value). Carbapenems are hydrolyzed slowly by BlaC (low kcat/Km value) making them “dual action” compounds that inhibit both BlaC and PG transpeptidases, the intended β-lactam targets. DBOs inhibit PG transpeptidases in other bacteria. To explore the therapeutic potential of new DBOs against Mtb, we compared the inhibitor activity of AVI, relebactam (REL), and durlobactam (DUR, formerly ETX2514) against BlaC and Mtb PG transpeptidases using a biochemical approach. We also investigated the ability of DUR to lower minimum inhibitory concentrations (MICs) of β-lactams against Mtb H37Rv.

Methods
Mass spectrometry was performed to capture acyl-enzyme complexes (AECs) of purified BlaC and PG transpeptidases (PonA1, LdtMt1, LdtMt2, LdtMt3, and LdtMt5) with β-lactams and BLIs. Steady-state enzyme kinetics were determined using nitrocefin as a substrate. MICs with amoxicillin (AMX), meropenem (MER), CLA, and DUR alone and in combination against Mtb H37Rv were assessed using a microdilution method.

Results
DUR alone had a MIC of 2 µg/mL with Mtb H37Rv (Table 1). BlaC formed AECs with all carbapenems and BLIs. BlaC had lower Ki app and higher k2/K with DUR than those with AVI and REL and comparable to those with CLA; however, with a period of pre-incubation, AVI fully inhibits BlaC (Table 2). The carbapenems and DUR formed the most AECs with PG transpeptidases of the β-lactams and BLIs respectively; PG transpeptidases had lower Ki app values with DUR than those with AVI (Table 3).
Table 1. Minimum Inhibitory Concetrations for Mycobacterium tuberculosis H37Rv

Conclusion
DUR alone has some antimicrobial activity against Mtb H37Rv. The likely mechanism that underlies this activity is inhibition of BlaC and several PG transpeptidases. Inhibition of enzyme targets with DUR was more potent and efficient than AVI and REL. DUR in combination with β-lactams lowered MICs but the DUR concentration used was higher than its MIC. Our findings support the exploration of novel BLIs against BlaC and PG transpeptidases with the ultimate goal of repurposing these drugs for the treatment of TB.

Disclosures
Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
1391. Body Mass Index and Leptin Levels at Different Stages of the Tuberculosis Spectrum
Authors: Askar Wajih , Feria Manuel G , Jose Shinsmon , Madan Rajat , Huaman Moises A 
Published: December 2021

Abstract

Background
Leptin is an adipose tissue-derived cytokine that plays a role in energy regulation and immune functions. High leptin levels and obesity have been associated with decreased risk of developing active TB. We aimed to characterize the association between body mass index (BMI) and leptin levels in patients at different stages of tuberculosis (TB).

Methods
Data from a cross-sectional cardiovascular risk study of 40 to 70 years old individuals enrolled in Lima, Peru, and Cincinnati, US, were analyzed. Four categories based on TB and treatment status were defined: no TB infection (QuantiFERON-TB test negative; n= 31), latent TB infection (LTBI; QuantiFERON-TB test positive; n= 43), active TB on treatment (in the continuation TB treatment phase; n= 30), and post-TB (within one year of TB treatment completion; n=16). BMI and plasma leptin levels were compared among the four groups using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if differences were found in the Kruskal-Wallis test. Multivariate ordered logistic regression models were used to assess factors associated with leptin levels, adjusted for potential confounders.

Results
The median age was 53 years, and 51% were female. BMI was different between study groups (p&lt; 0.01), with LTBI individuals having the highest BMI compared to other groups; see Figure 1A. Leptin levels were marginally low in the group with active TB on treatment, but no significant differences were found between groups (p=0.44; see Figure 1B). In multivariate analysis, leptin was associated with female sex (OR 23, 95%CI, 9-58), BMI (OR, 1.5, 95%CI, 1.2-1.7), and coronary plaque ≥25% stenosis (OR, 0.29, 95%CI, 0.08-0.99). Body mass index (BMI) and plasma leptin levels in participants with negative QuantiFERON-TB test (QFN-), latent tuberculosis infection (LTBI), active tuberculosis on treatment (ATBT), and post-TB treatment (TB-treated).

Significance was determined using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if the Kruskal- Wallis test p-value was &lt;0.05.

Conclusion
LTBI individuals had a higher BMI compared to persons with active TB on treatment and post-TB. Higher leptin levels were associated with higher BMI, but we found no association between leptin and TB status in our cohort.

Disclosures
All Authors: No reported disclosures
1392. Nontuberculous Mycobacteria Isolated from Wisconsin Residents, 2010-2018
Authors: Vonasek Bryan J , Gusland Daniele Y , Hash Kevin P , Tans-Kersten Julie L , Gibbons-Burgener Suzanne N , Misch Elizabeth A 
Published: December 2021

Abstract

Background
Wisconsin is one of a handful of states in which laboratory identification of nontuberculous mycobacteria (NTM) from clinical samples is reportable to public health. The aims of this study were to characterize the demographic features of Wisconsin adults with NTM, assess the relative abundance of NTM species recovered, and describe trends in NTM isolation over the study period.

Methods
We conducted a retrospective cohort study of Wisconsin residents 18 years of age and older from whom NTM isolates were recovered and reported to the Wisconsin Electronic Disease Surveillance System (WEDSS) between 2010 and 2018. Isolates of M. gordonae were excluded. For the analysis of NTM frequency, multiple reports from the same individual were enumerated as separate isolates when non-identical or collected from different sites. Because NTM were usually reported into WEDSS without clinical data, this study couldn’t discern the clinical significance of the isolates.

Results
A total of 9,032 NTM isolates from 7,722 adults were analyzed. The average annual number of reported NTM cases was 950 (21.7/100,000 adults) during 2011-2018. Table 1 shows the demographic characteristics of individuals with NTM isolates, stratified by specimen collection site and NTM species. M. avium complex (MAC) accounted for 75.7% of respiratory isolates. An important pathogenic NTM, M. xenopi, accounted for 8.9% of non-MAC respiratory isolates. As shown in Table 2, M. chelonae, a rapidly growing mycobacteria (RGM), was the most common species isolated from skin and soft tissue, head, ears, nose and throat, and eye specimens. MAC was the most common isolate from other tissue sites.
Table 1. Demographic characteristics of individuals with NTM isolates.

Categorization was based upon the initially recovered sample when multiple samples were obtained from a given individual. “Respiratory” samples included sputum, bronchoalveolar lavage, and tracheal aspirate specimens. IQR, interquartile range. RGM, rapidly growing mycobacteria (M. chelonae and the M. abscessus, M. chelonae-abscessus, and M. fortuitum groups). SST, skin and soft tissue.
Table 2. Most common NTM species isolated from non-respiratory sites.

*’Respiratory specimens’ was inclusive of sputum, bronchoalveolar lavage, and tracheal aspirate specimens. CNS, central nervous system. HENT, head, ears, nose, or throat. SST, skin and soft tissue.

Conclusion
Consistent with prior studies, MAC is the predominant NTM isolated from respiratory specimens in Wisconsin. RGM are important minority respiratory pathogens, and predominate as skin and soft tissue NTMs. We highlight M. xenopi as an important pathogen in Wisconsin compared to other parts of the United States. In contrast to recent reports of increasing incidence of NTM disease, we found a stable annual incidence of NTM isolation between 2010 and 2018.

Disclosures
All Authors: No reported disclosures