bluuebunny/crossref_metadata_2025 huggingface dataset:
1138. Works Well Enough? Program Directors’ Perceptions of the Effectiveness and Transparency of Competency-Based Evaluations in Assessing Infectious Diseases Fellow Performance
Authors: Dora Amy V , Vijayan Tara , Graber Christopher J
Published: January 2021

Background

In July 2015, the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Internal Medicine (ABIM) jointly outlined an approach to assessing fellow performance using milestone-based core competencies for incorporation into standardized evaluation templates of trainee performance. Limited data exist regarding the clarity, effectiveness, and reproducibility of competency-based evaluations of infectious diseases fellows.

Methods

From March to May 2019, program directors of ACGME-accredited infectious diseases fellowship programs were invited to complete a Qualtrics-based survey of program characteristics and evaluation methods, including a trainee vignette to gauge evaluation reproducibility. Completed surveys were analyzed with descriptive statistics.

Results

Forty-three program directors initiated the survey, but 29 completed it. Seventeen (59%) were men, 19 (66%) were on a teaching service for over 8 weeks a year, and 19 (66%) had fewer than four first year fellows in their program. Most respondents agreed the competencies lacking the most clarity were systems-based practice (17/29, 58%), and practice based improvement (16/29, 55%). Eighteen (62%) were at least “somewhat satisfied” with their institution’s assessment tool, and 19 (66%) reported it was at least “moderately effective” in identifying academic deficiencies. Responses rating fellow performance from the vignette ranged from 1.5 to 4 on the standard milestone-based competency scale of 1-5 with 0.5 increments (median 3). For the same scenario using a qualitative ordinal scale, 66% (19/29) categorized the fellow as “early first year” and 34% (9/29) as “advanced first year.” Respondents offered a wide range of comments on milestone-based competencies, including “it works well enough” and “the process seems bloated and educratic.”

Conclusion

Clarity is needed on how to evaluate specific core competencies in infectious diseases, particularly systems-based practice and practice-based improvement. Describing anchoring milestones and evaluating fellows in accordance to stage in fellowship (i.e. early first year fellow) can help standardize responses. Further exploration on improving the evaluation process is warranted.

Disclosures

All Authors: No reported disclosures
1139. Adherence to Zika virus-related Pediatric Follow-up Care in Puerto Rico
Authors: Levison Julie H , García-Fragoso Lourdes , García García Ines E , Del Cueto Paola , Gely Leticia , Levis Maria F , Valencia-Prado Miguel , Cortés Dharma E
Published: January 2021

Background

Over three thousand children in Puerto Rico were potentially exposed to Zika virus infection during pregnancy during the 2016 Zika virus epidemic. This congenital exposure is an established risk factor for birth defects and neurodevelopmental abnormalities, which may appear after birth. Puerto Rico guidelines require consistent pediatric monitoring for early identification and intervention of children up to age five.

Methods

Our objective was to assess factors that influence caregiver adherence to Zika-related follow-up pediatric services in Puerto Rico. We conducted qualitative semi-structured focus groups and individual interviews with 57 individuals, including 35 caregivers (aged ≥18 years and a primary caregiver for a child with laboratory evidence of confirmed or possible Zika virus infection during pregnancy) and 22 healthcare providers or service coordinators. We explored participants’ views on barriers to Zika-related pediatric services and suggestions for improving appointment attendance. Interviews were recorded, transcribed, and translated. We developed and applied a coding scheme based on barriers and facilitators from the Andersen Model of Health Care Utilization and Katz Model for Adolescent Vaccine Adherence (a multi-step process influenced by adolescent and caregiver factors). Data were analyzed using thematic analysis.

Results

Three themes influencing adherence to Zika-related pediatric follow-up care were consistently reported throughout the interviews and focus groups discussions: (1) logistics of getting child to appointments based on clinic location, availability and costs associated with transportation, and physical requirements to transport child or multiple children; (2) complexity of requirements for follow-up appointments; and (3) caregiver burden including emotional, social, and time.

Conclusion

Barriers to Zika-related pediatric follow-up care in Puerto Rico are complex and multi-level. Core intervention targets should include caregiver burden, health system navigation, and coaching caregivers in communication with pediatric providers. Use of a caregiver-delivered manualized intervention led by community health workers seems appropriate to achieve these goals.

Disclosures

All Authors: No reported disclosures
1142. Increased Odds of Psychiatric Illness Among Mothers of Infants with Congenital Syphilis
Authors: Thornton Corinne R , Bleasdale Susan C
Published: January 2021

Background

Syphilis can be transmitted mother to child during pregnancy leading to multisystem birth defects if untreated. In Illinois, screening is mandated for pregnant women at first and third trimesters. The University of Illinois Hospital (UIH) serves a vulnerable patient population with a high syphilis prevalence. An understanding of risk factors associated with maternal syphilis infection can guide prevention of congenital syphilis (CS) with early prenatal diagnosis and treatment. The aim of this retrospective case control study is to describe maternal risk factors associated with CS in a clinical setting.

Methods

Using a database used for health department reporting from 2014-2018 at UIH, 106 maternal syphilis diagnoses were identified. Medical records were reviewed for CS infant diagnosis, sociodemographic information, medical history, and potential risk factors, including multiple sex partners, HIV status, drug use, history of incarceration or sex work, and having sex with men who have sex with men (MSM). Cases were matched with controls of pregnant women with syphilis testing that was not indicative of infection.

Results

Of the maternal syphilis diagnoses identified, there were 8 cases in which CS was possible or highly probable, 68 in which CS was less likely or unlikely, and 30 that were lost to follow up. Of the possible and probable infants’ mothers, 38% had a psychiatric illness (6.80 OR, 95% CI 1.06-43.48) and 25% were homeless (12.00 OR, 95% CI 0.94-153.89). Late or scant prenatal care was seen in 75% (4.15 OR, 95% CI 0.72-23.95) and 75% had inadequate syphilis treatment. None were HIV positive or reported incarceration, intravenous drug use, sex work, or having sex with MSM.

Conclusion

Among infants with probable or possible CS, there was a 6.80 increased odds of maternal psychiatric illness compared to those born to mothers not diagnosed with syphilis, which may have complicated prenatal care and delayed diagnosis or treatment. Psychiatric illness outnumbered several other known risk factors; however, these may be less often discussed during clinical encounters. Psychiatric illness history may be a risk factor and means to identify women in the clinical setting who need close follow up and outreach after a prenatal syphilis diagnosis to prevent or mitigate congenital transmission.

Disclosures

All Authors: No reported disclosures
1146. Thrombocytosis in Infants with Congenital Cytomegalovirus Infection Being Treated with Valganciclovir
Authors: Murtagh Kathleen , Toia Jacquie , Scardina Tonya , Rowley Anne H , Mithal Leena B
Published: January 2021

Background

Congenital CMV (cCMV) is associated with sensorineural hearing loss and neurodevelopmental disabilities. Infants with symptomatic cCMV infection benefit from 6 months of oral valganciclovir (vGCV) therapy. Neutropenia, thrombocytopenia, and hepatotoxicity are adverse effects vGCV, for which we monitor. We observed a pattern that cCMV infants treated with vGCV developed an uptrend in platelets and/or thrombocytosis (platelet count >450,000/uL) while on therapy. This observation has not previously been reported.

Methods

Medical records and laboratory results from our multi-disciplinary cCMV clinic led by Infectious Diseases at Lurie Children’s Hospital were reviewed (2017-2020). Data included cCMV signs/symptoms, cCMV treatment prescribed, indication for ganciclovir/vGCV treatment, and complete blood count prior to, during, and post- vGCV therapy.

Results

Of 21 cCMV infants referred to clinic, 14 received >1 month of vGCV for symptomatic disease, 1 discontinued vGCV < 1 month due to perceived fussiness, and 1 was part of a clinical trial. Four infants were initially treated with ganciclovir for ≤1 month and transitioned to vGCV. Of the 14 patients treated with vGCV, 10 (71%) had sensorineural hearing loss (50% unilateral), 12 (86%) had central nervous system abnormalities (including cystic lesions on head ultrasound), 5 (36%) had thrombocytopenia, and 7 (50%) were intrauterine growth restricted [Table 1]. Eleven infants (79%) developed thrombocytosis. Thirteen infants (93%) had an uptrend in platelet count [not including normalization of initial thrombocytopenia (platelets < 150,000/uL)]. Figure 1 shows platelet counts by time with respect to vGCV treatment. Neutropenia (absolute neutrophil count < 500/uL) occurred in 1 patient that required temporary discontinuation of vGCV.

Table 1

Figure 1

Conclusion

We observed an interesting trend of rising platelet count and the development of thrombocytosis in the majority of our cCMV patients on vGCV. Platelet elevation associated with vGCV has not previously been described. This observation is limited by small number of patients and thrombocytosis is not a definitive association/adverse effect. With increasing use of vGCV and interest in its effect on bone marrow function, this observation is notable and warrants further study.

Disclosures

All Authors: No reported disclosures
1165. Epidemiology, management and outcomes of fungal keratitis: A single center study from tertiary hospital in Thailand
Authors: Puttiteerachot Thitiwat , Vanichanan Jakapat , Jutivorakool Kamonwan , Puangsricharern Vilavun , Kasetsuwan Ngamjit , reinprayoon Usanee , Kittipibul Thanachaporn , Satitpitakul Vannarut
Published: January 2021

Background

Fungal keratitis is known as an important cause of sight threatening infection worldwide. Variation of clinical characteristics and treatment have been observed among different geographic regions. Currently, clinical data of fungal keratitis in South East Asia remain scarce.

Methods

A retrospective single study was conducted at King Chulalongkorn Memorial Hospital in Thailand. Medical records of patient with diagnosis of fungal keratitis between January 2016 and December 2018 were reviewed. Cases were identified using ICD-10 code. Data on demographics, clinical presentations, investigations and outcomes were collected. Mycological diagnosis was made in patients who had clinical presentation compatible with fungal keratitis and positive fungal detection in clinical specimen.

Results

During study period, fungal keratitis was diagnosed in 59 pts including 31 by mycological and 28 by clinical diagnosis. KOH preparation of corneal scraping was positive in 19 of 53 pts (35.8%). Culture from cornea, aqueous and vitreous yielded positive result in 18 of 53 (33.9%), 2 of 14 (14.3%), respectively. ITS sequence analysis was positive in 7 of 15 (46.7%) from cornea, 1 of 6 (16.7%) from aqueous and 2 of 2 (100%) from vitreous. Culture and molecular detection from clinical specimens provided additional mycological diagnosis in 8 and 5 cases with negative KOH preparation. Fusarium was the most common pathogen (33%) followed by Paecilomyces (9.7%), Aspergillus (6.4%), Candida (6.4%). Ten patients (32.2%) had only positive KOH preparation. All patients received treatment with topical antifungal agent, while 38 pts (64%) required systemic, 24 pts (40.7%) received intrastromal, 22 pts (37.2%) received intracameral and 3 pts (5.1%) received intravitreal antifungal therapy. Operation was performed in 21 pts (35.6%) which 6 (28.5%) required evisceration. Twenty-three patients (39%) had visual improvement after complete treatment.

Conclusion

Fungal keratitis is not an uncommon disease. Fusarium was the most common etiologic agent similar to study from other region. Unfavorable outcomes were observed in majority of cases. Appropriate fungal culture and molecular detection from clinical specimens can be considered as they may increase diagnostic yield in some patients.

Disclosures

All Authors: No reported disclosures
1166. Evaluating the Impact of the 2016 Candidemia Guidelines on the Incidence of Ocular Complications of Candidemia
Authors: Hillenbrand Molly , Apewokin Senu
Published: January 2021

Background

The incidence of Candida bloodstream infections has risen over the last several decades. Complications of candidemia include endogenous fungal endophthalmitis which can result in devastating outcomes including vision loss. In 2015, the IDSA guidelines were updated to recommend echinocandins as initial therapy for candidemia. Given the poor ocular penetration of echinocandins there has been some concern this change may portend an increased incidence of ocular complications in candidemic patients. We sought to examine whether patients who received empiric echinocandin therapy developed higher rates of ophthalmic complications of candidemia.

Methods

We identified patients in our healthcare system who had blood cultures positive for Candida species and a completed ophthalmology consult between January 1, 2014 and April 30, 2019. Chi-squared analysis was used to compare antifungal prescribing patterns before and after release of the updated IDSA guidelines. We assessed whether the switch to empiric echinocandin therapy as directed by the guidelines was associated with higher rates of abnormal eye exams.

Results

47 patients treated before the guideline change were compared to 57 patients treated after the guideline change. There was no significant difference in age, gender, or comorbid diabetes and hypertension between the groups. Before the guideline change, 24/47 (51%) of patients received eye-penetrating antifungals. This decreased to 21/57 after the updated guideline (37%, p=0.21). The percentage of patients with positive eye exams was nearly equal before and after the updated guidelines, 10/47 (21%) before vs 13/57 (22%) after (p=1). After the guideline change, 7/21 (33%) of the patients treated with penetrating antifungals had positive eye exams vs 6/36 (16%) who received echinocandins (p=0.19).

Conclusion

Echinocandins are known to have poor ocular penetration yet our data demonstrate no change in the incidence of ophthalmic complications of candidemia after the 2016 guideline endorsed echinocandins as empiric therapy. The prevalence of positive eye exams throughout our study period was 22%, suggesting ongoing utility for these exams. Ongoing investigation is necessary to confirm and further study these findings.

Disclosures

All Authors: No reported disclosures
1182. The Real-World Use of Isavuconazole as Primary or salvage Therapy of Invasive Fungal infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant
Authors: dagher Hiba , Hachem Ray Y , Chaftari Anne-Marie , Jiang Ying , Ali Shahnoor , Deeba Rita , Shah Shivan , Raad Issam I , Raad Issam I
Published: January 2021

Background

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with hematologic malignancies (HM) and stem cell transplants (SCT). Isavuconazole was approved by FDA as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. The aim of this study is to look at the real-world use of Isavuconazole in patients with HM and evaluate their clinical outcomes and safety.

Methods

We conducted a retrospective study of 200 HM patients at MD Anderson Cancer Center who had definite, probable or possible mold infections between April 2016 and January 2020 and were treated with Isavuconazole for a period of at least 7 days. Clinical and radiological findings were assessed at baseline and at 6 and 12 weeks of follow up.

Results

HM patients with IFIs were classified as definite (11), probable (66) and possible (123). IA was the most commonly isolated pathogen followed by mucor and candida. The majority of patients (65%) received prophylaxis with anti-mold therapy, 73% consisted of azoles and 22% of echinocandins. Isavuconazole was used as a primary therapy in 57.5% of patients, and as salvage therapy in 42.5%. The switch to Isavuconazole was driven by failure of the primary therapy in 50% of the cases and by adverse effects in 28%. These included elevated liver function tests (LFTs), subtherapeutic voriconazole levels and prolonged QT. Isavuconazole was used as monotherapy in 30% of the cases and combination in 70% mostly with a polyene (54%) and/or an echinocandin (27%). A favorable response with Isavuconazole was observed in 57% at 6 weeks of therapy. Adverse events possibly related to Isavuconazole were reported in 6 patients (3%) leading to drug discontinuation. These included 5 elevated transaminases and 1 nausea. All-cause mortality was reported in 46% of patients and IFI-attributable mortality in 25%.

Conclusion

Selecting Isavuconazole therapy was mainly driven by failure of other antifungal agents or adverse events to other antifungals such as increased LFTs, subtherapeutic voriconazole levels or prolonged QT. Isavuconazole seems to have a promising clinical response and a good safety profile as an antifungal therapy in high risk cancer patients with HM.

Disclosures

Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)
1185. Association Between Blood Product Transfusion and Development of Hospital Acquired Infections or Mortality in Patients Admitted to the Hospital Wards. A Retrospective Case-Control Study
Authors: Aravagiri Arunmozhi S , Napatkamon Ayutyanont , Sharma Sabhyata , Collins Timothy , Ubbaonu Chimezie , Mufti Hoveda
Published: January 2021

Background

Transfusion of blood products has been shown to be associated with increased mortality and risk of infections in critically ill patients and following cardiac surgery [1-2]. However, there is scarce data evaluating this association in patients admitted to hospital wards. Here we seek to see if transfusion of blood products carries the same risk of infection and mortality in more stable patients.

Methods

This was a retrospective case-control study of patients admitted to the internal medicine wards who received packed red blood cells (PRBC), fresh frozen plasma (FFP) or platelet transfusions, using data from the HCA Healthcare administrative database from 2016 to 2019. Patients admitted with an infection, on steroids or other immunosuppressant medications were excluded. ICD-10 codes at discharge were used to determine hospital acquired infections (HAI). The presence of HAI was the dependent variable. A multivariable logistic regression was used to determine the effects of the independent variables on development of HAI after adjusting for age and Carlson’s Comorbidity Index. Odds ratios and 95% confidence intervals were calculated. Primary outcome of study was presence of HAI, while secondary outcome was mortality in transfused vs. non-transfused patients.

Results

A total of 1952 subjects were included in the study analysis. Of these, 653 or 33.4% had a HAI during their admission. Adjusted multivariable model showed transfusion of PRBC (OR 1.14, 95%CI 0.85-1.52), platelets (OR 1.41, 95% CI 0.93-2.10) or FFP (OR 1.27 95%CI 0.90-1.75) was not associated with increased odds of having a HAI. The multivariable model however, did show an increase in odds of mortality in patients who were transfused with PRBC (OR 2.51, 95%CI 1.78-3.54), platelets (OR 3.17, 95%CI 2.01-5.0) or FFP (OR 2.78, 95% CI 1.89-4.08) compared to non-transfused.

Conclusion

Our data failed to show association between transfusion of blood products and HAI. However, it showed there was significant increase in mortality in patients that had received blood products during their admission.

Disclosures

All Authors: No reported disclosures
1187. CFTR Function Impacts Proinflammatory Cytokine Expression of Bronchial Epithelial Cells During Pseudomonas aeruginosa and Staphylococcus aureus Infections
Authors: Phuong Melissa S , Sad Subash
Published: January 2021

Background

Cystic fibrosis (CF) is a genetic disease in which opportunistic respiratory infections are common, particularly with P. aeruginosa and S. aureus. It has been suggested that dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR) could impact host immune response to these infections. The aim of this study was to determine if dysfunction in the CFTR gene could impact host cell death and the expression of proinflammatory cytokines.

Methods

We used two human bronchial epithelial (HBE) cell lines NuLi-1 and CuFi-1, which were recovered from individuals without and with CF, respectively. THP-1 cells were also differentiated into a macrophage phenotype with 50ng/mL PMA, and 10 µM CFTRinh-172 was used to impair CFTR function in these cells. Laboratory reference strains PAO1 and S. aureus 6538 were used to conduct in vitro infections. Host cell death at various MOIs was evaluated using a neutral red uptake assay, and cytokine expression was measured using ELISAs.

Results

No differences in THP-1 cell death or cytokine expression were observed for infections with S. aureus 6538 or PAO1 with and without CFTRinh-172. No differences in cell death for infections with the HBE cells and either bacteria were noted. S. aureus 6538 induced higher levels of IL-1β when infecting CuFi-1 cells in comparison to NuLi-1 cells across all MOIs (P < 0.001) and induced higher levels of IL-6 at an MOI of 100 (P < 0.01). S. aureus 6538 also induced higher levels of IL-8 when infecting CuFi-1 cells in comparison to NuLi-1 at MOIs of 1 and 10 (P < 0.05 and P < 0.01, respectively). Meanwhile, PAO1 induced less IL-6 expression when infecting CuFI-1 cells at an MOI of 1 and 10 (P < 0.01 and P < 0.01, respectively). CuFi-1 cells infected with PAO1 had less IL-8 expression in comparison to infected NuLi-1 cells for all MOIs (P < 0.01), but no differences in IL-1β expression were observed when infecting either cell line with PAO1.

Conclusion

Bronchial epithelial cells with and without functional CFTR appear to respond differently to infections with either P. aeruginosa or S. aureus. Further elucidating how various immune response pathways are impacted by CFTR dysfunction may lead to alternative approaches to therapy to reduce morbidity observed among CF patients.

Disclosures

All Authors: No reported disclosures
1195. Influence of Histoplasma capsulatum Infection on Endothelin-1 mRNA Gene Expression in Bone Marrow Derived Macrophages
Authors: Ajayi Eloho , Deepe George S , Buesing William R
Published: January 2021

Background

Endothelin-1 (ET-1) is increasingly recognized as an immune modulator; it exerts a pro-inflammatory effect by increasing the release of cytokines like interferon gamma. ET-1 is secreted by a variety of cells such as macrophages, neurons and endothelial cells. Activation of the endothelin system has been implicated in the pathogenesis of sepsis caused by bacteria, viruses and even parasites. However, there are no published studies that have explored the role of ET-1 in Histoplasma capsulatum infection. Studying the role of ET-1 in histoplasmosis is important because understanding its role in the host defense mechanism may serve as the foundation for future discovery of novel therapeutic options.

Methods

Bone marrow cells were isolated from mice and set up for tissue culture. Bone marrow derived macrophages (BMDM) were harvested after 5-7 days of incubation, and infected with varying ratios (0.5,1 and 5) of yeasts to macrophages. RNA was extracted from the BMDM after 3, 6, 24 and 48 hours of infection. For comparison, RNA was also extracted from uninfected BMDM at the same time points. Real-time PCR (polymerase chain reaction) was performed on complementary DNA. ET-1 (Edn1) messenger RNA (mRNA) gene expression was quantified relative to the expression of the house keeping /endogenous control gene that encodes for beta-2 microglobulin (B2m).

Results

In BMDM infected with H. capsulatum there was upregulation of Edn1 after 3, 6 and 24 hours of infection. During this same time points, the expression of ET-1 mRNA in the uninfected BMDM remained constant. Expression of Edn1 was highest in the BMDM infected with 5x H. capsulatum after 3 and 6 hours of infection. After 24 hours, the expression of ET-1 mRNA decreased markedly in all concentrations of H. capsulatum. At 48 hours post-infection the Edn1 was downregulated in the 0.5,1 and 5-fold quantities of H. capsulatum across all time the time intervals.

Figure 1

Conclusion

Results from this study indicate that H. capsulatum infection induced an upregulation of the Edn-1 in BMDM. This may correlate with an increase in levels of ET-1 production by the BMDM in the face of H. capsulatum infection. These results provide a platform in which to examine the influence of ET-1 on the host response to this fungus.

Disclosures

All Authors: No reported disclosures
1217. Clinical and Microbiological Characteristics of Patients with Bacteremia and Normal Procalcitonin at Single Tertiary Care Medical Center
Authors: Boussi Leora , Popli Tarun , Feola Nicholas , Nog Rajat
Published: January 2021

Background

Procalcitonin (PCT) is a serum biomarker used to diagnose bacterial infections and guide antibiotic therapy. Many studies highlight its high sensitivity, specificity, and negative predictive value for bacteremia. PCT > 2ng/mL has been reported to be strongly indicative of systemic bacterial infection, with values of .5-2ng/mL suggesting localized infection and < .5ng/mL strongly suggesting absence of infection. However, emerging reports have raised concerns about PCT in bacteremia, demonstrating low sensitivity. Few studies have characterized patients with bacteremia and low PCT. We aimed to analyze the clinical and microbiological characteristics of patients with bacteremia and PCT < 2ng/mL.

Methods

Adult patients admitted at Westchester Medical Center with bacteremia and associated PCT level within 24 hours (hrs) prior to 48 hrs post blood culture collection from 1/1/2014-9/30/2019 were included. Demographic, clinical, laboratory, and microbiological data were retrospectively collected and analyzed.

Results

There were 414 total cases of bacteremia with an associated PCT level within 24 hrs prior to 48 hrs post blood culture collection. 209 of 414 (50.5%) patients had PCT < 2ng/mL. Of these, 86 were excluded (73 contaminants, defined as bacteremia not causing systemic inflammation and not treated, 10 fungal cultures, and 3 lacking data). Of the remaining 123 (37.5%) patients with PCT < 2ng/mL, 66 (53.7%) had PCT<. 5ng/mL. The leading infection source was endovascular/line-related at 31.7%, followed by intraabdominal/gastrointestinal and urinary. 30.9% of bloodstream organisms were gram negative. Among these 123 patients with PCT < 2ng/mL, in-hospital mortality with bacteremia clinically contributing to death was 13%.

Characteristics of patients with bacteremia and procalcitonin < 2ng/mL

Conclusion

Despite literature supporting the use of PCT algorithms in initiation and de-escalation of antibiotics in patients with suspected bacterial infections, a substantial percentage of bacteremic patients can have low PCT but significant infection-related mortality. Therefore, PCT should not be the only factor utilized by clinicians in the management of such patients, including initiating or deescalating antibiotics. Further studies are needed to characterize patient characteristics as contributing factors for bacteremia with low PCT.

Disclosures

All Authors: No reported disclosures
1222. Fosfomycin Susceptibility Testing using the new ETEST®FO
Authors: Halimi Diane , Pompilio Marion , Fontaine Sandrine , Martelin Roland , Franceschi Christine , Zambardi Gilles
Published: January 2021

Background

Fosfomycin (FO) is a bactericidal antibiotic with a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. Oral FO is mainly used in the treatment of urinary tract infections, particularly those caused by E. coli and E. faecalis. In order to determine MICs to FO, the ETEST® FM is already available but the reading can be difficult especially with E. coli. To resolve this issue, a new ETEST® with FO, called ETEST® FO, has been developed (not FDA cleared, yet). The purpose of this study is to compare this new strip to the agar dilution reference method (AD) on a panel of E. coli and E. faecalis.

Methods

A total of 39 isolates comprising 20 E. coli (ESBL or CPE) and 19 E. faecalis (VRE or VSE) were tested by ETEST® FO and Agar dilution. The isolates were sub-cultured on Columbia agar plates supplemented with 5% sheep blood before testing. After incubation, suspensions of the isolates were prepared in 0.85% saline. These suspensions were used to inoculate both AD and ETEST® plates. Results were read after 16-20 hours incubation at 35°C +2°C in ambient air. Following CLSI QC guideline, 4 QC organisms were tested. Results were analyzed using the FDA/CLSI breakpoints for FO (S < 64µg/mL, I=128 µg/mL, R> 256 µg/mL). Performance was evaluated using FDA performance criteria, essential agreement (EA, ≥ 90%), category agreement (CA, ≥ 90%), major error rate (ME, ≤3.0%) and very major error rate (VME, ≤2.0%).

Results

All the QC strains MICs were within the CLSI ranges. For the panel results, see the table below:

Performance for ETEST® FO on E. coli and E. faecalis

Conclusion

This first and preliminary study shows that ETEST® FO can potentially meet the FDA acceptance criteria and could be a valuable tool for determining FO MIC for E. coli harboring various resistance mechanisms and E. faecalis including VRE. Moreover, in comparison with the current ETEST FM strip, this new strip brings a real reading improvement and resolve the issue for E. coli. The clinical study phase will determine the product’s performance.

Disclosures

Marion Pompilio, BioMérieux (Employee) Gilles Zambardi, biomerieux (Employee)
1225. Next-Generation Sequencing in Clinical Practice: A Survey of Infectious Disease Providers
Authors: Vasishta Shilpa , Graber Christopher J , Vijayan Tara
Published: January 2021

Background

Next-generation sequencing (NGS) has emerged as a promising diagnostic tool in Infectious Diseases (ID). The platform offers high sensitivity, detecting difficult-to-isolate organisms. However, limitations remain in employing NGS broadly, including high cost, unstandardized methods, and unclear significance of many results. To date, there is no consensus on appropriate use of NGS. Here, we describe perceived utility of NGS among ID physicians at one academic medical center.

Methods

A survey exploring four clinical scenarios was disseminated electronically to ID attendings and fellows. Scenarios #1 (immunocompetent patient without localizing signs) and #2 (immunosuppressed patient with localizing signs) were followed by questions exploring likelihood of sending NGS. Scenarios #3 (immunocompetent patient with prosthetic joint infection) and #4 (immunosuppressed patient with cavitary lung lesion) were followed by questions exploring interpretation of NGS data.

Results

Twenty-six physicians responded. Respondents were more likely to send NGS for an immunosuppressed than an immunocompetent patient (8/26 vs. 2/26 respondents, p=0.024), with more respondents noting in the latter casethat NGS might “yield unhelpful/misleading results” (26 /26 vs. 17/23, p=0.0054) or might “not be cost-effective” (21/26 vs. 13/23, p=0.066). Those with over five years of experience tended to be more likely to send NGS (8/27 vs. 2/23 responses across two scenarios, p=0.065), noting more frequently that NGS might “yield a diagnosis not otherwise considered” (16/25 vs. 6/23 responses, p=0.0084) and“avoid painful/high-risk testing” (16/26 vs. 8/23 responses, p=0.062). In scenarios with available NGS data, nearlyhalf (21/49 responses across two scenarios) favored obtaining further diagnostics.

Conclusion

Our results suggest that patient immunosuppression is a salient factor in determining clinical utility of NGS and that physician experience may affect utilization. While NGS is perceived as a useful adjunct to existing data to guide initial management, results are still interpreted with caution and rarely supersede more established methods for definitive diagnosis. Further study is needed to guide evidence-based NGS use.

Disclosures

All Authors: No reported disclosures
1243. Semi-Quantitative Benefit-Risk Assessment for a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals 2 Years of Age and Older
Authors: Neveu David , Kürzinger Marie-Laure , Chen Aiying , Dhingra Mandeep S
Published: January 2021

Background

MenACYW-TT is a new quadrivalent meningococcal conjugate vaccine approved by the US FDA for use in individuals 2 years and older. We present the structured benefit-risk assessment conducted by Sanofi Pasteur in support of the initial biological license application for MenACYW-TT.

Methods

The safety and immunogenicity of MenACYW-TT in subjects ≥ 2 years was evaluated in 5 pivotal randomized, active-controlled clinical trials. Collectively, 4,919 subjects received either a single primary dose (n=4517) or a booster dose (n=402) of MenACYW-TT. A semi-quantitative framework was used to establish favorable and unfavorable effects of MenACYW-TT relative to comparators: MenACWY-CRM in children 2-9 years and adolescents 10-17 years, MenACWY-D in adolescents 10-17 years and adults 18-55 years, and MPSV4 in older adults ≥ 56 years. Benefit outcome measures included vaccine seroresponse and seroprotection (titers ≥ 1:8) at D30 evaluated by serum bactericidal assay using human complement, for each serogroup. Risk outcome measures included rates of solicited injection site and systemic reactions (including grade 3 reactions) within 7 days after vaccination, and rates of serious adverse events within 6 months after vaccination. The differences in rates for MenACWY-TT vs comparator vaccines were calculated along with 95% confidence intervals.

Results

For all benefit criteria, and in all age groups, rate differences favored MenACYW-TT in meningococcal vaccine-naïve individuals. Immune response differences were more pronounced for serogroup C. Differences showed favorable (seroresponse criteria) or comparable (seroprotection criteria) effects for MenACYW-TT in adolescents and adults previously primed with MenACWY-D or MenACWY-CRM. For the risk criteria, rate differences generally showed comparable effects between MenACYW-TT and MenACWY-D or MenACWY-CRM in children, adolescents and adults, while the rate differences for both solicited injection site and systemic reactions favored MPSV4 in older adults. The latter was possibly due to the use of a protein carrier in MenACYW-TT.

Conclusion

The benefit risk-profile of MenACYW-TT in individuals ≥ 2 years is considered favorable relative to comparator licensed vaccines.

Disclosures

David Neveu, MPharm, Sanofi Pasteur (Employee) Marie-Laure Kürzinger, MSc, Sanofi (Employee) Aiying Chen, PhD, Sanofi Pasteur (Employee) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee)
1244. Assessment of the In Vivo Activity of Human-Simulated Exposure of WCK 4282 (High Dose Cefepime [FEP]-Tazobactam [TZB]) against Enterobacterales (EB) and Pseudomonas aeruginosa (PA) in the Neutropenic Murine Thigh Infection Model
Authors: Gill Christian M , Abdelraouf Kamilia , Nicolau David P
Published: January 2021

Background

Carbapenems are often used for infections due to extended-spectrum-β-lactamase (ESBL) and cephalosporinase (CSase)-producers. As increased carbapenem utilization is associated with the development of carbapenem resistance, antimicrobial stewardship has targeted non-carbapenem options. WCK 4282 (FEP 2 g-TZB 2 g) offers pharmacodynamically optimized TZB exposure and demonstrated potent activity in vitro against ESBL-phenotype isolates. We describe the pharmacodynamics of a WCK 4282 human-simulated regimen (HSR) in the neutropenic murine thigh model.

Methods

19 clinical strains harboring ESBLs or CSase (EB; n=8 and PA; n=4) or serine-carbapenemases (EB; KPC n=4 or OXA-48-like n=3) were tested in vivo. Per CLSI, 19, 18, and 17 isolates were cefepime, ceftolozane/tazobactam, and piperacillin/tazobactam (TZP) non-susceptible, respectively. Thighs of neutropenic, female, CD-1 mice (3 per group) were inoculated with ~107 CFU/mL of bacterial suspension 2 h prior to dosing. Mice received WCK 4282 HSR, FEP HSR, or saline (controls) for 24 h. WCK 4282 HSR and FEP HSR provided plasma exposures in mice that were similar in f%T > MIC and fAUC to FEP-TZB 2 g-2 g and FEP 2 g, respectively, as IV infusions over 1.5 h q8h in humans. Bacterial densities and their changes at 24 h relative to 0 h controls were determined to assess efficacy and reported as mean±SD log10 CFU/thigh.

Results

Bacterial burdens were 5.81±0.36 at 0 h and 9.29±0.88 at 24 h in untreated controls. WCK 4282 produced potent activity against ESBL/CSase producing EB and PA with WCK 4282 MIC ≤ 16 mg/L; mean change in log10 CFU from 0 h was -1.70±0.77, while growth was observed with FEP alone. WCK 4282 produced variable activity against OXA-48-like harboring EB. Against KPC-harboring EB, WCK 4282 produced stasis to growth. Mean Log10 CFU changes are reported in Table 1 and Figure 1.

Table 1. Comparative efficacy of FEP HSR and WCK 4282 HSR by genotypic β-lactamase

Figure 1. Mean Change in log10CFU/thigh for 24 h controls, FEP HSR, and WCK 4282 HSR across the tested MIC distribution.

Conclusion

WCK 4282, a novel TZB containing regimen, resulted in enhance in vitro potency against ESBL/CSase and OXA-48-like producers. Humanized exposures of WCK 4282 produced substantial kill in vivo against ESBL/CSase producers with MICs ≤ 16 mg/L including FEP resistant/TZP non-susceptible PA. These data support further evaluations of WCK 4282 as a carbapenem-sparing regimen for ESBL/cephalosporinase harboring strains.

Disclosures

David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)
1247. Dalbavancin in Osteomyelitis and Joint Infections: An Analysis From an Observational, Multicenter, Retrospective Cohort Study of the Real-World Use in Adult Patients
Authors: Diaz Julia Garcia , McGregor Jennifer , Ramani Anathakrishnan , Lock John , Golan Yoav , Gonzalez Pedro
Published: January 2021

Background

Dalbavancin (DAL) is approved in the United States (US) and Europe for acute bacterial skin and skin structure infections and exhibits broad spectrum activity against clinically important Gram-positive pathogens including methicillin-sensitive and methicillin-resistant Staphylococcus aureus, and Streptococcus spp. We describe the use of DAL in patients with osteomyelitis or joint infection from a phase 4 observational, multicenter, retrospective cohort study of the real-world use of DAL in adult patients across the US: Dalvance Utilization Registry Investigating Value and Efficacy (DRIVE).

Methods

Data were collected between 03/25/2017 and 11/27/2018 and included demographics, disease and pathogen characteristics, antibiotic use, clinical outcome, and safety. Patients with a determinate clinical outcome (success/failure) were included in the evaluable population.

Results

Data for 96 patients with osteomyelitis and 33 patients with joint infection (safety population) were entered into this subanalysis. Patient demographics and medical history were broadly similar for patients with osteomyelitis or joint infection. The majority (80.4–100%) of patients received DAL as concurrent therapy and clinical success, defined qualitatively, was achieved in 64.7-87.5% of patients (Fig. 1). Most patients received 1 or 2 IV DAL doses (osteomyelitis, 33.3% and 34.6%, respectively; joint infection, 37.5% and 31.3%, respectively); 11.5% and 6.3% of patients with osteomyelitis or joint infection, respectively received >4 doses (Fig. 2). Staphylococcus spp. was the most frequently isolated organism at baseline (Fig. 3); 61.1% and 35.7% of osteomyelitis and joint infection isolates tested, respectively were resistant to oxacillin. At 60 days post-DAL treatment, numbers of Staphylococcus spp. isolated from both groups decreased (Fig. 3), confirming microbiological cure. The rate of serious adverse events was low (16 events in 7 [7.3%] patients with osteomyelitis, 2 events in 2 [6.1%] patients with joint infection) and consistent with the safety profile of DAL.

Fig. 1

Fig. 2

Fig. 3

Conclusion

In this real-world study in patients with Staphylococcal osteomyelitis and joint infection, DAL resulted in high rates of clinical and microbiological success.

Disclosures

Jennifer McGregor, RPh, AbbVie (Employee) Anathakrishnan Ramani, MD, FACP, AAHIVS, CIC, Allergan (prior to its acquisition by AbbVie) (Speaker’s Bureau) John Lock, PharmD, BCPS, AQ-ID, AbbVie (Employee) Pedro Gonzalez, MD, MT, AbbVie (Employee)
99. Comparison of Procalcitonin Testing to a Targeted Audit-and Feedback Strategy on Prescribed Durations of Therapy for Community-Acquired Pneumonia
Authors: Clark Lauren , Dumkow Lisa E , Buss Paige , Beuschel Thomas , Jameson Andrew
Published: January 2021

Background

The procalcitonin (PCT) assay is FDA-approved to help guide antimicrobial treatment of respiratory tract infections, however, conflicting data exist regarding its impact on shortening durations of therapy. The purpose of this study was to compare the impact of PCT to a targeted audit-and-feedback (TAF) strategy on prescribed antibiotic durations of therapy for community-acquired pneumonia (CAP).

Methods

A retrospective cohort study was conducted at two community teaching hospitals, one implementing PCT with routine audit-and-feedback and one implementing a TAF strategy recommending 5 days of therapy for uncomplicated CAP. The primary objective of this study was to compare the impact of PCT implementation to TAF implementation on durations of therapy prescribed for suspected CAP. Secondary objectives included comparing length of stay, 30-day readmission, mortality, and rates of Clostridioides difficile. Adult inpatients with an antibiotic ordered with an indication of pneumonia were eligible for inclusion. Those who were critically ill, immunocompromised, had concurrent infections, were made comfort care, discharged or expired within 48 hours were excluded.

Results

311 patients were included (Pre-TAF n=80, Pre-PCT n=80, Post-TAF n=80, Post-PCT n=71). Average duration of therapy prescribed for CAP at baseline was similar between groups, Pre-TAF 7.0 days vs. Pre-PCT 7.8 days (p=0.1). After implementation of the respective interventions, there remained no difference in the average duration of therapy between groups, Post-TAF 5.5 days vs. Post-PCT 5.4 days (p=0.8). Both PCT and TAF strategies demonstrated significant improvement in prescribed durations for CAP between their respective Pre- and Post-intervention groups (p< 0.001 and p=0.002, respectively). The PCT protocol was followed 41% of the time in the Post-PCT group. There were no differences in readmission, mortality, or C. difficile between groups.

Conclusion

PCT and TAF were equally effective antimicrobial stewardship strategies in reducing total days of antibiotic therapy prescribed for CAP with no differences observed in patient outcomes.

Disclosures

All Authors: No reported disclosures
1272. Efficacy of a Non-Peptide, Small Molecule Mimic of Host Defense Proteins in Mouse Models of Disseminated Candidiasis and Aspergillosis
Authors: Scott Richard W , Baugh Simon D P , Freeman Katie B , Weaver Damian G , Chaly Anna L , Whitman David B , Thanna Sandeep , Diamond Gill , Nguyen Phung , Deviney Ashley , Weiss William J , Pulse Mark E , Reitz Allen B
Published: January 2021

Background

We are developing a series of small nonpeptide mimics of host defense proteins (smHDPs) for antifungal applications. MICs < 0.1 µg/ ml have been demonstrated against multiple yeast and mold species. Their potential therapeutic utility has been evaluated in animal models of disseminated fungal infections.

Methods

Susceptibility testing against clinical isolates of Candida albicans (CA) and Aspergillus fumigatus (AF) was done according to CLSI guidelines. Cytotoxicity (CC50) in mouse 3T3 and human HepG2 cells was determined in an MTS assay (Promega Cell Titer 96). For candidiasis, neutropenic CD-1 mice were infected IV with 3.5 x 104 CFU CA and test agents were administered subcutaneously (SC) once (QD) or twice (BID) daily beginning 2 hrs post-infection (PI). The positive control was fluconazole (20 mg/kg PO QD). Kidney burdens were measured at 24 hrs PI (n = 5/grp) and survival was measured at 2 weeks after 5 days of treatment (n = 8/grp). For aspergillosis, neutropenic CD-1 mice were infected IV with 4.5 log10 spores AF and test agents were administered SC BID for 5 days beginning 24 hrs PI. The positive control was posaconazole (20 mg/kg PO QD). Liver and kidney fungal burdens were measured 24 hrs after the last dose (n = 10/grp).

Results

The lead smHDP, FC-5096, has MICs of 0.08 and 0.024 ug/ml, respectively, against the CA and AF clinical isolate strains used in the mouse efficacy studies. Selectivity for antifungal vs. mammalian cell cytotoxicity (MIC/CC50) was >1,000 fold. In the disseminated candidiasis model, FC-5096 significantly reduced fungal kidney burdens relative to untreated mice to levels found at treatment onset (P < 0.0001). Full survival over 2 weeks was observed after 5 days of BID treatment with FC-5096. All untreated mice succumbed between days 3 – 6 PI. Efficacy was comparable to fluconazole. In the disseminated aspergillosis model, FC-5096 produced up to 2.5 log10 reductions in fungal liver burdens and efficacy was significantly better than posaconazole (P = 0.0251). In kidney, both FC-5096 and posaconazole caused > 1.6 log10 reductions in fungal burdens that exceeded the limit of detection.

Conclusion

The high antifungal potency, low cytotoxicity and robust in vivo efficacy support further study of FC-5096 for clinical development.

Disclosures

Richard W. Scott, PhD, Fox Chase Chemical Diversity Center (Employee) Simon DP Baugh, PhD, Fox Chase Chemical Diversity Center (Employee) Mark E Pulse, MS, Fox Chase Chemical Diversity Center (Independent Contractor)