bluuebunny/crossref_metadata_2025 huggingface dataset:
1135. The PEST Approach to Choosing Antimicrobial Therapy
Authors: Davar Kusha , Vijayan Tara
Published: January 2021

Background

Selecting an empiric antimicrobial regimen can be difficult for early learners and misuse of antibiotics can lead to adverse events and antimicrobial resistance. We describe here an approach to aid internal medicine interns in their clinical decision making, particularly when it comes to diagnosing and empirically treating infections.

Methods

The PEST model was created as a four-step approach to therapeutic reasoning and choosing an appropriate antimicrobial regimen for a given infectious disease syndrome (Figure 1).

In February 2020, we conducted two independent teaching sessions for interns on the PEST approach during noon conference. We assessed pre-and post-teaching responses to five clinical vignette-based questions to assess optimal selection of antibiotics and improvement in the use therapeutic reasoning (Figure 2). Results were presented as a percentage of interns, both pre- and post-intervention, who chose an appropriate antibiotic and a percentage of interns who provided sufficient therapeutic reasoning as defined by using at least three out of the four PEST criteria.

Figure 1 – The PEST Approach Model

Figure 2 – Clinical Vignette Examples

Results

Twenty-seven interns participated in the activity. At baseline, several interns had incorporated aspects of the PEST approach in their pre-teaching responses. While the teaching session improved therapeutic reasoning as defined by the PEST strategy (Figure 3), there was no appreciable difference in antibiotic selection (Figure 4). Ten interns commented on the usefulness of the approach, specifically highlighting the systematic approach to antibiotic selection.

Figure 3 – Differences in Therapeutic Reasoning After PEST Teaching

Figure 4 – Choosing The Correct Antibiotic After PEST Teaching

Conclusion

Our results showed fidelity in using the PEST approach to improve therapeutic reasoning after a teaching session, but the method did little to improve antibiotic selection. Perhaps antibiotic selection requires greater clinical experience in order to provide a narrower or more optimal spectrum of coverage. Interestingly, some interns used select “PEST” concepts prior to the intervention suggesting that the PEST approach may solidify prior knowledge or clinical reasoning skills. Continued incorporation of the PEST approach using a case-based framework may solidify conceptual and practical knowledge of antimicrobial selection.

Disclosures

All Authors: No reported disclosures
1140. Awareness of Cytomegalovirus (CMV) Among Postpartum Mothers: Education Needed!
Authors: Hanlon Cory T , Medoro Alexandra K , Sanchez Pablo J , Beckford Demi R , Schoenbeck Sydney , Purkey Grace
Published: January 2021

Background

Congenital cytomegalovirus (cCMV) infection is the leading cause of non-genetic sensorineural hearing loss and affects approximately 0.5%-1% of all live births in the United States. Despite its substantial burden, maternal awareness of congenital CMV disease is limited. In addition, there is no information on CMV awareness among postpartum women who ultimately would consent for CMV newborn screening. Thus our objective of this study was to determine the proportion and characteristics of postpartum women who had knowledge of CMV in an academic medical center in Columbus, OH.

Methods

From May - December 2019, 276 postpartum women who delivered a newborn at the Ohio State University Wexner Medical Center, Columbus, OH were asked if they had prior knowledge of CMV. Eligible mothers had delivered an infant who was admitted to the Newborn Nursery, were ≥ 35 weeks’ gestational age, and had no signs of congenital CMV infection. These mothers had consented for enrollment of their newborn into the University of Alabama’s Collaborative Antiviral Study Group multicenter study on CMV screening (saliva) of asymptomatic infants. Pertinent demographic and clinical data were collected and subsequently managed using REDCap electronic data capture tools hosted at Nationwide Children’s Hospital, Columbus, OH. Statistical analyses were performed using GraphPad Prism.

Results

505 eligible infants were born during the study period and 276 (55%) of the mothers were asked about their awareness of CMV infection. Of the 276 mothers (62%, white; 24%, Black; 3%, Asian; 0.4%, Native Hawaiian or Pacific Islander; 3%, biracial; 8%, not known), 30 (10%) had prior knowledge of CMV. Mothers who were aware of CMV did not differ from mothers who did not know about CMV in primigravida status (12/30 [40%] vs. 84/246 [34%], P=.55) or age (median, IQR; 33 years [29-35] vs. 31 years [26-34], P=.11). All infants had a normal physical examination, and none had congenital CMV infection.

Conclusion

Among postpartum mothers who consented to saliva screening of their newborns for congenital CMV infection, only 10% were previously aware of CMV. Such a knowledge gap should be addressed to better inform both universal and targeted newborn CMV screening among postpartum mothers.

Disclosures

All Authors: No reported disclosures
1141. Composition of Placental Cultures and Correlation with Maternal and Infant Blood Cultures in Mothers with Suspected Chorioamnionitis
Authors: Gordon Laurel , Adam Kaavya , Kelly Kristen , Amin Sachin , Harrington Amanda
Published: January 2021

Background

Placental culture is often used in combination with placental pathology in pregnant women with suspected chorioamnionitis. While multiple studies have looked at the correlation of placental cultures with neonatal outcomes, few have looked at the composition of placental cultures in terms of the number of organisms and their identification. Our study aims to describe such characteristics of placental cultures and to compare organisms found in placental cultures with those in maternal and infant blood cultures.

Methods

We performed retrospective chart reviews on mothers and infants for whom a placental pathology and culture was sent at Loyola University Medical Center between January 2017 and December 2019. We separated the mothers based the results of their placental cultures and pathologies and on the number of organisms found in each culture. We then analyzed the identification of organisms of the positive cultures and compared these organisms with positive infant and maternal blood cultures.

Results

A total of 208 placental cultures out of 279 sent (73.84%) were positive. 63 (30.29%) positive cultures were monomicrobial, while 145 (69.71%) cultures were polymicrobial. The most prevalent organisms found in all placental cultures were coagulase negative staphylococcus (26.44%), Streptococcus anginosus (16.83%), Corynebacterium species (14.90%), Lactobacillus species (14.90%), and Gardnerella vaginalis (13.94%). A small fraction of positive placental cultures was associated with positive infant and maternal blood cultures (4.33% and 3.85%, respectively). When comparing the organisms in placental cultures with those in maternal and infant blood cultures, 100% and 71% (respectively) of cases with both positive blood and placental cultures had shared organisms.

Distribution of most common organisms found in monomicrobial and polymicrobial placental cultures.

Distribution of placental cultures based on number of organisms.

Correlation of placental cultures with infant and maternal blood cultures.

Conclusion

The data collected from this study helps provide a biological profile of organisms found in placental culture for patients with suspected chorioamnionitis. Additionally, the data suggests that the organisms found in these cultures are often consistent with those found in maternal and infant blood cultures. The overall incidence of positive infant and maternal blood cultures is low as compared to positive placental cultures.

Disclosures

Amanda Harrington, PhD, Beckman Coulter (Scientific Research Study Investigator)
1143. Late-Onset Hearing Loss and Antiviral Therapy for Congenital Cytomegalovirus Infection
Authors: Medoro Alexandra K , Hanlon Cory T , Pifer Traci , Escamilla Maria Reyes , Shimamura Masako , Findlen Ursula M , Gerth Holly , Adunka Oliver , Malhotra Prashant , Sanchez Pablo J
Published: January 2021

Background

Congenital cytomegalovirus (CMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children. While SNHL is often present at birth, as many as 25% of congenital CMV-infected infants may develop late-onset hearing loss. Antiviral therapy improves hearing outcomes, but its effect on the occurrence of late-onset SNHL is not fully known. Thus, our objective was to describe the prevalence of late-onset SNHL among congenital CMV-infected children treated with antiviral therapy in the first month of age.

Methods

From 2013 to present, infants with congenital CMV infection referred to Nationwide Children’s Hospital’s (NCH) NEO-ID Clinic, Columbus, OH underwent complete evaluation including hearing testing. Pertinent demographic, clinical, laboratory, and radiographic data were obtained and managed using REDCap electronic data capture tools. Infants who passed the newborn hearing screen and subsequently developed late-onset SNHL were identified and compared with respect to receipt of antiviral therapy in the neonatal period. Statistical analyses were performed using GraphPad Prism for macOS version 8.3.0.

Results

During the 6-year study period, 99 infants had congenital CMV infection and 69 (70%) of them passed the newborn hearing screen. 46 (46%) neonates received antiviral therapy (1, ganciclovir; 38, valganciclovir; 7, both) for clinically apparent congenital CMV infection. One (2%) child developed late-onset SNHL.This infant was born at 37 weeks’ gestation (birth weight, 2525 g) with microcephaly (head circumference, 31 cm) and cerebral calcifications and was diagnosed with congenital CMV infection at 8 days of age. Treatment with valganciclovir was initiated at 9 days of age, and he developed mild unilateral SNHL at 1 month of age while on treatment and subsequently right severe-profound SNHL and left mild-moderate SNHL. In comparison, among 23 infants with clinically inapparent disease who passed the newborn hearing screen and did not receive antiviral therapy, 5 (22%) subsequently developed SNHL (p=0.014).

Conclusion

Infants who received antiviral therapy for clinically apparent congenital CMV infection had significantly less late-onset SNHL than untreated infants, thus supporting a hearing protective effect of antiviral treatment.

Disclosures

All Authors: No reported disclosures
1144. Prevention of Mother-to-Child Transmission of Hepatitis B at UNC Hospitals
Authors: Sayre Wesley M
Published: January 2021

Background

Hepatitis B virus (HBV) contributes to liver-related morbidity and mortality on a global scale. In mothers with active hepatitis B, up to 100% of mother-to-child-transmission (MTCT) is preventable. Guidelines from the American Association for the Study of Liver Diseases (AASLD) recommend that HBV vaccination and hepatitis B immunoglobulin (HBIG) be given to HBV-exposed infants in a timely manner to prevent up to 90% of MTCT. Additionally, AASLD guidelines recommend that women with high-risk HBV (those with viral load >200,000 IU/mL and/or HBV e antigen [HBeAg] positivity) receive tenofovir prophylaxis to further prevent MTCT. In this chart review, we compared UNC Hospital’s prevention of MTCT measures to standing AASLD guidelines.

Methods

This retrospective chart review included data from all HBV-positive mothers giving birth at UNC Hospitals from April 1, 2014 through December 31, 2019. We investigated the HBV status of mothers, time to neonatal HBV vaccination, time to HBIG administration, maternal HBV viral load, maternal HBeAg status, and whether tenofovir was provided for high-risk mothers. Data was then compared to AASLD guidelines distributed in January 2017.

Results

We identified 99 HBV-positive pregnant women over a five-year period. The rate of timely administration of HBIG was 99%. The rate of timely hepatitis B vaccination was 97%. The single neonate who did not receive the HBV vaccination within 12 hours was born to a mother whose HBV testing was initially positive but confirmatory testing was negative. Most (65%) women had documented HBV viral load and 75% of women had HBeAg studies. Nine women were identified as high-risk, with only one not receiving tenofovir.

Conclusion

UNC Hospitals were compliant with AASLD guidelines regarding timely neonatal vaccination, providing nearly 99% of neonates with timely HBIG and all but three neonates with timely HBV vaccine. The majority of high-risk women identified received tenofovir prophylaxis. However, there is room for improvement in laboratory evaluation to identify other high-risk women. While initial data is reassuring, quality improvement measures include improving testing rate to determine risk status for HBV-positive mothers and further investigation of appropriate follow-up testing for both mothers and children.

Disclosures

All Authors: No reported disclosures
1145. The Role of Maternal Vaccination on Healthcare Visits for Acute Respiratory Infections in HIV-Exposed but Uninfected (HEU) Infants
Authors: Kao Carol M , Thomas Amanda S , Camacho-Gonzalez Andres , Sheth Anandi N
Published: January 2021

Background

HEU infants remain at higher risk for hospitalization and severe infection from common childhood illnesses. Maternal immunization during pregnancy with influenza and tetanus, diphtheria, pertussis (Tdap) vaccine is recommended and effective at protecting infants from vaccine-preventable infections.

Methods

We conducted a retrospective cohort study of pregnant women living with HIV (WLWH) who delivered and received prenatal care at Grady Memorial Hospital (GMH) between November 1, 2012 and June 30, 2018. Vaccination history was ascertained through the Georgia Registry of Immunization Transactions and Services or by review of electronic medical record. Mother and infant charts were reviewed. We defined acute respiratory infection (ARI) as infants who presented with symptoms or an admitting diagnosis suggestive of an ARI. Relative risks (RR) of identified care visits (clinic, ED/urgent care, hospitalization) in the 6 months post-partum between WLWH with varying vaccinations were compared with 95% confidence intervals.

Results

236 WLWH who delivered at GMH were identified (Table 1). Of those, 66 (28%) received only influenza, 32 (14%) received only Tdap vaccine, 64 (27%) received both and 74 (31%) did not receive any vaccines during pregnancy. There was a trend towards decreased risk of a clinic visit, emergency department/urgent care visit, or any healthcare-associated visit in the first 6 months of life for an ARI in infants born to mothers who received any vaccine during pregnancy versus none although not reaching statistical significance (Table 2). There was a trend towards decreased risk of hospitalization for an ARI in the first six months of life in infants born to mothers who received both influenza and Tdap vaccines during pregnancy versus unvaccinated (RR 0.55, 95%CI: 0.14-2.22). Infants born to mothers vaccinated tended to have higher gestational age than those that did not (Table 3).

Table 1. Demographic and Characteristics of Mothers

Table 2. Relative Risk of a Healthcare Visit in the first 6 months of life for URI in Vaccinated vs Unvaccinated Mothers

Table 3. Birth outcomes in HEU infants of Vaccinated vs Unvaccinated Mothers

Conclusion

There was a lower risk of healthcare visits for ARI in the first 6-months of life in HEU infants born to mothers who received antepartum vaccinations. Although not statistically significant, larger studies are needed to fully characterize the immune responses in this unique population.

Disclosures

All Authors: No reported disclosures
1147. Short Course of Voriconazole Therapy as a Risk Factor for Relapse of Invasive Pulmonary Aspergillosis
Authors: Shin Dong Hoon , Yoo Seung-Jin , Jung Jongtak , Jun Kang Il , Kim Hyungjin , Kang Chang Kyung , Song Kyung Ho , Choe Pyoeng Gyun , Park Wan Beom , Bang Ji-Hwan , Kim Eu Suk , Park Sang Won , Kim Hong Bin , Kim Nam-Joong , Oh Myoung-don
Published: January 2021

Background

Invasive pulmonary aspergillosis (IPA) is a life-threatening opportunistic infection which usually occurs in immunocompromised patients. Recommended duration of voriconazole therapy is a minimum of 6-12 weeks for IPA, despite the lack of any firm evidence. In addition, risk factors for relapse of IPA are still unclear. Here, we explored risk factors for IPA relapse after initial treatment.

Methods

All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography (CT).

Results

Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1–12.3; P=0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2–17.5; P=0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors.

Conclusion

Less improvement in CT, and short duration of voriconazole therapy were the independent risk factors for relapse after treatment of IPA. Longer duration of therapy should be considered for those at higher risk of relapse.

Disclosures

All Authors: No reported disclosures
1150. Breakthrough Invasive Fungal Disease (IFD) in Patients with Acute Myeloid Leukemia (AML)
Authors: Wasylyshyn Anastasia , Linder Kathleen A , Maurer Stephen , Sheffield Virginia , Colon Lydia Benitez , Kauffman Carol A , Miceli Marisa
Published: January 2021

Background

Despite the use of antifungal prophylaxis, IFD remains a serious complication of AML causing extensive morbidity and mortality. This study seeks to clarify our experience with breakthrough infections in patients with AML.

Methods

This retrospective study included all adult patients undergoing induction chemotherapy for a new diagnosis of AML from June 2014 – Dec 2019 at the University of Michigan Hospital. Chart review determined co-morbidities, chemotherapy regimens, allogeneic hematopoietic cell transplant (HCT), antifungal prophylaxis, development of IFD, and outcomes. Patients were followed for 1 year from first induction chemotherapy. EORTC-MSGERC definitions for proven, probable, and possible IFD were used, as were MSGERC-ECMM definitions for breakthrough IFD.

Results

Of 251 patients, mean age was 61.8±14 years, 55% were men, and 73 (29%) underwent allogeneic HCT, 52 of whom developed GVHD. Thirty-one patients developed 33 IFD (12.3%): 4 proven, 12 probable, and 17 possible IFD. Four IFD occurred in patients with GVHD post-HCT; all were treated with high dose steroids and one received an anti-TNF agent. Of the 16 proven and probable IFD, 8 were breakthrough IFD. Mucormycosis occurred in 2 patients on voriconazole; fusariosis occurred in 3 patients taking fluconazole (2), or posaconazole (1). Aspergillosis occurred in 2 patients taking isavuconazole (1) or fluconazole (1), and pneumocystosis occurred in a patient receiving inhaled pentamidine. There were 8 non-breakthrough IFD, including 2 pneumocystosis, 4 aspergillosis, and 2 candidiasis. Risk for IFD increased with subsequent episodes of induction chemotherapy, p=.04.

Six of 8 patients with breakthrough IFD and 5 of 8 without breakthrough IFD died within 12 weeks of IFD diagnosis. Excluding the 15 patients who had only possible IFD, 69% (11/16) patients with proven/probable IFD died compared with 35% (77/220) patients without IFD, p=.01.

Conclusion

Patients with AML remain at risk for fatal IFD despite the use of antifungal prophylaxis. Failure of prophylaxis in our patients who developed breakthrough IFD was associated with a shift towards less common fungi.

Disclosures

All Authors: No reported disclosures
1153. Characterization of Invasive Mold Infections in Acute Leukemia and Hematopoietic Stem Cell Transplant Recipient Patients and Risk Factors for Mortality - a Single Center Experience
Authors: Kubat Ryan , Subramanian Praveen , Li Yanming , Hammoud Kassem , Eid Albert , Dias Ajoy , El Atrouni Wissam
Published: January 2021

Background

Invasive mold infections (IMIs) remain a significant cause of morbidity and mortality in patients with acute leukemia (AL) and those undergoing hematopoietic stem cell transplantation (HSCT). We describe the epidemiology of IMIs, the incidence of IMI in patients with acute myelogenous Leukemia (AML) post HSCT, and risk factors for mortality.

Methods

Patients were identified using ICD9 and ICD10 codes using a University of Kansas internal database from 2009-2019, microbiology records, and an AML HSCT database and were followed through May 1st, 2020. Patients’ electronic medical records were reviewed for inclusion. IMI was defined as proven or probable using the 2009 National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) guidelines. Incidence was calculated as IMI cases/100-person-years. Risk factors for overall mortality were evaluated using a Cox regression model.

Results

We included 138 patients: 79 developed IMI after HSCT (8 autologous, 71 allogeneic) and 59 developed IMI after AL diagnosis. Seventeen of the AL patients underwent HSCT after IMI diagnosis (12 within 100 days of IMI). Proven IMI occurred in 45 (32.6%) and probable IMI occurred in 93 (67.4%) patients. The most common prophylactic agent prior to IMI diagnosis was fluconazole (31.2%), with 21.0% receiving none. Aspergillus was the most commonly identified mold with 91 (65.9%) cases. The average treatment duration was 101 (range 0 - 799) days. The incidence of IMI in patients with AML who underwent HSCT was 2.35 cases/100 person-years. All-cause mortality among patients with AL or HSCT who developed IMI was 23.1% at 6 weeks, 34.1% at 12 weeks, and 61.2% at 1 year. On univariate Cox model, Karnofsky performance status > 70 was associated with lower mortality (hazard ratio (HR) 0.317, 95% confidence interval (CI) [0.110, 0.914]) among HSCT recipients. ICU admission within 7 days prior to IMI diagnosis (HR 6.469, 95% CI [1.779, 23.530]) and each one point increase in BMI (HR 1.051, CI [1.001, 1.103]) were associated with increased mortality in the AL group.

Figure 1 - Invasive mold infections by pathogen in HSCT-recipients and acute leukemia patients from 2009-2019.

Figure 2 - Antifungal prophylactic agents prescribed for at least one week at time of IMI diagnosis

Table 1 - Univariate survival analysis calculated using a Cox proportional-hazards regression model among patients who developed IMI after HSCT and patients who developed IMI after acute leukemia diagnosis

Conclusion

IMIs are associated with significant mortality in HSCT recipients and AL patients; patients at higher risk for mortality include those with lower baseline Karnofsky scores, recent ICU admissions, and higher BMI at time of IMI diagnosis.

Disclosures

Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)
89. A Collaborative & Novel Antimicrobial Stewardship Initiative– Mandatory Approval of Peripherally Inserted Central Venous Catheters
Authors: Patel Sonal , Vazquez Jose A , Chase Aaron , Ebong Eti
Published: January 2021

Background

Central line-associated bloodstream infections result in thousands of deaths and billions of dollars annually. At the Augusta University Medical Center (AUMC), it was identified that ~50% of peripherally inserted central venous catheters (PICCs) that were placed for intravenous (IV) antibiotic administration were unnecessary. A novel initiative was implemented, which required antimicrobial stewardship/infectious diseases approval for PICC insertions if the indication was for IV antibiotic administration only. The objective of this study was to determine the impact of this initiative.

Methods

A retrospective observational study was conducted at the AUMC. All adult patients with a PICC line insertion order for IV antibiotic administration, between December 2017 and May 2019 were included. The vascular access team would forward requests for PICC insertions to the antimicrobial stewardship pharmacist. The pharmacist would approve/disapprove the PICC or recommend an infectious diseases consult. The variables collected were: infection types, infectious diseases consultation, reason for PICC denial and 30-day PICC-related complications.

Results

A total of 215 requests for PICC insertion (for IV antibiotics) were placed. Of these, 54% of the requests were denied, while 46% were approved. The reasons for PICC denial included: midline catheter preferred (47%), switched to oral antibiotics (33%), further work-up required (10%), or no antibiotics needed (7%). The types of infections treated were: bone and joint infections (28%), urinary tract infections (13%), intra-abdominal infections (12%), endocarditis/endovascular infections (11%), skin soft tissue infections (9%), pneumonia (7%), catheter-related bloodstream infections (6%), central nervous system infections (6%), bacteremia (4%) and others (4%).The infectious diseases consult team was involved in the care of 79% of the patients. Of those that received a PICC line, only 5% experienced any PICC-related complications. The overall cost savings for PICCs that were denied was ~ $294,000.

Conclusion

Mandatory antimicrobial stewardship/infectious diseases approval for PICC insertion can decrease healthcare cost and reduce the number of unnecessary PICC lines placed.

Disclosures

All Authors: No reported disclosures
1155. Clinical and Epidemiological Characteristics of Patients with Paracoccidioidomycosis in Asuncion Paraguay
Authors: Núñez Fátima M , Woc-Colburn Laila , Arredondo Norma , Samaniego Maria S , Benitez Gustavo G
Published: January 2021

Background

Paracoccidioidomycosis (PCM) is an endemic systemic fungal disease caused by Paracoccidioides brasiliensis. It is obtained exclusively in Latin American countries, and presents with a greater prevalence in South America. It is acquired through inhalation and spreads by lympho-hematogenous dissemination. Once the fungus has established itself in the body, it can affect any organ or tissue, but most commonly the skin, mucous membranes and lungs. It is a neglected disease, without mandatory notification, its impact is unknown.

Methods

Descriptive, observational, retro-prospective study with analytical components, The patients were adults (>18 years), diagnosed with paracoccidioidomycosis who were hospitalized at the Instituto De Medicina Tropical Asunción-Paraguay during 2010-2019.

Results

There were 33 patients included in this study. Most patients were male (90%) and 10% were female, the mean age of 48. The main reason for consult was: oral lesion(s) (21%), difficulty swallowing (15%), and skin lesions (15%). The geographic regions with the highest prevalence rates (Fig1) were: Central, Cordillera and Caaguazú. The major risk factors for acquiring Paracoccidioidomycosis were farming (51%), smokers (66%) and alcoholism (42%). Only one patient was co-infected with HIV. The diagnosis was made either by culture or by biopsy results (Fig 2). All the patients were started on treatment with amphotericin B deoxycholate, with an average dose of 1,020 mg for induction and continued maintenance treatment with imidazoles. The mortality rate was 9.09%. The outpatient clinic follow up was low at 15% and 12 patients (80%) were treated successfully.

Figure 1: Paraguay Coutnry Map showing the most affected areas with Paracoccidioidomycosis.

Figure 2: Culture result.

Conclusion

This study suggests that paracoccidioidomycosis mainly affects men, farmers, associated with high tobacco consumption in Paraguay. Common clinical manifestations were oral lesion, skin lesions, and difficulty swallowing. There are no current IDSA guidelines for treatment thus we use the national Paraguayan treatment guidelines. This study highlights the need to further study PCM and establish global guidelines.

Disclosures

All Authors: No reported disclosures
1158. D-index as a Novel Index to Predict Invasive Fungal Disease in High-Risk Neutropenic Pediatric Cancer Patients and Hematopoietic Stem Cell Transplantation
Authors: Alali Muayad , Pisano Jennifer
Published: January 2021

Background

Prolonged and profound neutropenia are risk factors for invasive fungal disease (IFD) during febrile neutropenia (FN) episodes. The D-index combines both depth and duration of neutropenia in a single assessment and has been proposed as a useful tool to exclude or predict IFD in high-risk adult patients. We assessed the D-index as a predictor of IFD in pediatric cancer patients.

Methods

We conducted a retrospective study of pediatric oncology patients with FN at UCM Comer Children’s Hospitals. IFD was stratified as possible, probable, and proven according EORTC/MSG criteria. Patients considered high risk of IFD were receiving intensive chemotherapy with expected prolonged neutropenia >7 days, including, but not limited to, AML, high-risk acute ALL, and hematopoietic stem cell transplantation (HSCT). The D1-index was equal to 2t1 + 3t2, where t1, and t2 are the number of days from the first day of neutropenia < 500mm3 and < 100/ mm3 respectively, until the development of IFD. The D2-index approximates the area over the neutrophil curve during neutropenia. A cumulative D-index (c-D-index) was also calculated using the first day of neutropenia until the date of the first clinical manifestation of IFD. We compared duration of neutropenia vs D-index vs c-D-index as a predictor of IFD using receiver operating characteristic curve (ROC)/AUC analysis.

Figure 1

Figure 2

Results

We identified 455 FN episodes in 203 high-risk patients. 53/455 (11.6%) had IFD, 12 (2.6%) proven, 23 (5%) probable, and 18 (4%) possible. The median of D1, D2 indexes and c-D-index were significantly higher in patients developing IFD (38, 5225, 7352) compared to the non-IFD group (26, 3857, 5169) (P=.001, P=.001, and P=.01) respectively. The ROC curve of D-index and c-D-index (figure 1,2,3) showed better performance (AUC of 0.85,0.89, 0.81) respectively compared to the duration of neutropenia alone. The ROC was highest when D-index was combined with prolonged fever >5 days (AUC 0.94)

Figure 3

Figure 4

Conclusion

The D-index may be a useful tool to stratify high-risk pediatric patients according to risk of IFD. The c-D-index, particularly, may be a useful tool to guide for empiric antifungal therapy and diagnostic testing. Prospective multi-center studies using these tools are required to refine the clinical approach to IFD.

Disclosures

All Authors: No reported disclosures
1160. Ecological Study for Pulmonary Blastomycosis
Authors: Wang James L , Shorman Mahmoud
Published: January 2021

Background

There has been a global increase in people who are intravenous drug user, diabetic, and elderly (aged greater than 65 years). These characteristics may alter the incidence of new diseases and potentially affect how diseases are diagnosed. As such this study’s purpose was to investigate baseline characteristics of patients with pulmonary blastomycosis. Case studies for Blastomyces have demonstrated positive cultures in 72% to 87% of patients. Therefore data will be analyzed to determine if there is any significant difference in culture results.

Methods

This study was a retrospective single-center ecological study. Patient charts were identified via ICD code search for blastomycosis. All protected health information was de-identified following data collection.

Results

32 patients were identified with either pathology or culture proven blastomycosis. 8 patients (25%) had positive fungal cultures for blastomycosis. The average age of patients with pulmonary blastomycosis was 59.5 years old with 11 elderly patients (34%). There were 11 females (34%); 2 with hepatitis C (6%); 12 with diabetes (38%); 10 with immunosuppression (pancytopenia, chronic steroid usage, organ transplant, cystic fibrosis) (32%); 9 with COPD (32%); 21 with Tobacco abuse (67%); 7 with cancer (22%); 7 with work exposure (working around turned dirt or indoor mold) (22%) and 1 with opiate use (3%). No significant difference was found for culture results.

Baseline Characteristics

Culture Characteristics

Conclusion

Our culture results were exceedingly low in part due to some samples not being collected for fungal culturing and having to send-out the samples. The average age was consistent with the endemic region of Tennessee around 59 the previous 10 years.. 2/3 of the patients were tobacco abusers which may have contributed to some impaired ability to clear the fungal spores. Less than half of the patients were elderly, diabetic, immunosuppressed, or intravenous drug users therefore endemic inoculation may still be the main cause.

Disclosures

All Authors: No reported disclosures
1161. Effectiveness of Posaconazole in the Treatment of Rare Invasive Fungal Infections: A Systematic Literature Review
Authors: Bernauer Mark , Waskin Hetty , Cossrow Nicole , Kaminski Allysen , Campbell Havilland , Patel Dipen
Published: January 2021

Background

Rare invasive fungal infections (IFIs) such as chromoblastomycosis (CBM), fungal mycetoma (mycetoma), hyalohyphomycosis/phaeohyphomycosis (hyalo/phaeo), and mucormycosis (mucor) cause significant morbidity and mortality in immunocompromised patients. Few effective treatment options are available for these IFIs, therefore we assessed the clinical efficacy of posaconazole, a broad-spectrum triazole antifungal compound with demonstrated activity against IFIs.

Methods

We performed a systemic literature review of Medline and EMBASE to identify studies published from 2005 (year of posaconazole approval) to October 30, 2019, reporting the efficacy/effectiveness of posaconazole monotherapy or combination therapy for treating CBM, mycetoma, hyalo/phaeo, and mucor. Two reviewers screened and extracted data based on predefined PICOS criteria. Effectiveness outcomes included cure, response, relapse, radiologic improvement; mortality and any other effectiveness measures reported. Study quality was assessed using National Institute for Health and Care Excellence-recommended checklists. A narrative descriptive summary was used to summarize study findings.

Results

Of 2612 articles identified, 351 articles (mostly case reports) were included. Positive clinical outcomes with posaconazole therapy were observed in most patients with CBM (73.9%, 17/23), mycetoma (100%, 2/2), hyalo/phaeo (53.3%, 49/92), and mucor (66.7%, 564/845). The population for mycetoma was small; only 2 positive cases (Figure). Overall survival was ~70% or greater across the IFIs examined. Posaconazole efficacy and mortality differed by line of therapy as well as for monotherapy versus combination therapy. Positive response was higher in second line monotherapy than first line monotherapy in CBM and mucor. Higher mortality was observed with combination therapy than monotherapy in hyalo/phaeo and mucor infections (except for first line use in mucor).

Figure. Overall Results of Posaconazole Treatment

Conclusion

Despite the rarity of these IFIs, substantial data have been published since posaconazole’s initial approval in the year 2005, and the evidence demonstrates that posaconazole is an effective therapeutic option alone or in combination for the treatment of these rare IFIs.

Disclosures

Mark Bernauer, BPharm, RPh, Merck & Co, Inc. (Consultant) Hetty Waskin, MD/MPH, Merck & Co, Inc. (Employee) Nicole Cossrow, PhD, Merck & Co, Inc. (Employee) Allysen Kaminski, BA, Merck & Co, Inc. (Consultant) Havilland Campbell, BS, Merck & Co, Inc. (Employee) Dipen Patel, BPharm, PhD, Merck & Co, Inc. (Consultant)
1162. Engraftment fever (EF) in Pediatric stem cell transplantation (SCT): Risk Factors, Etiology and Outcomes
Authors: Alali Muayad , Elmuti lena , Bartlett Allison
Published: January 2021

Background

Engraftment fever (EF) during stem cell transplantation (SCT) is likely due to non infectious causes like immune reconstitution syndrome (IRS) or engraftment syndrome (ES). Few studies have looked at the rate of infection causing fever during engraftment. There is no good evidence to guide the approach to evaluation and empiric treatment of infections during EF.

Methods

Retrospective record review of pediatric SCT (autologous and allogenic) patients with a diagnosis of febrile neutropenia (FN) during engraftment period (days +7 to +30 post transplant). FN episodes classified as either EF or non-engraftment fever (NEF). EF = new onset fever in temporal relationship to neutrophil recovery (4 days before through 1 day after neutrophil engraftment (ANC >500/mm3). NEF = fever without signs of neutrophil recovery (ANC < 100/mm3 without significant rise ±4 days of fever onset). Only first FN during engraftment was included. Episodes meeting neither criteria were excluded.

Results

112 patients had 115 FN episodes (FNEs) identified: NEF 81 (71.5%); EF 34 (29.5%). In multivariable analysis: Neuroblastoma as underlying diagnosis (odds ratio [OR]=3.2, 95% CI 2.31-6.54, P< 0.01), G-CSF administration before day +7 (OR=2.8, 95% CI 1.92-4.65, P=0.03), absolute monocyte count (AMC) >100/mm3 at FN presentation (OR=2.9, 95% CI, 1.11 to 7.55, P=0.02), were associated with an increased risk of EF compared with NEF. Most EF episodes (26/34, 76%) had no specific infectious etiology identified; 8 had IFIs (24%) [3 proven, 2 probable, 3 possible). IFI rate was higher in EF than NEF group (24% vs 5%) (OR=4.5, 95% CI, 2.11 to 9.55, P< 0.01. EF episodes were more likely to be admitted to the intensive care unit (OR=2.3, 95% CI, 1.88 to 6.35) and had higher 30-day mortality (OR =4.52, 95% CI, 0.37 to 6.55) than NEF.

Table 3

table 2

Conclusion

Engraftment fever may have an infectious component. Work-up to exclude IFI and empirical antifungal therapy should be considered especially with prolonged fever and supportive clinical or radiological data. Large multi-center prospective studies are needed to further define infectious complications and determine the approach to engraftment fever. Early detection of IFI in this high-risk group may lead to improved morbidity and mortality.

Disclosures

All Authors: No reported disclosures
1163. Epidemiology of Candidemia: Can Candida Spread from Patient to Patient in the Hospital?
Authors: Erayil Serin Edwin , Selmecki Anna , Kline Susan E
Published: January 2021

Background

Candidemia has become an increasingly important infection in recent years. Antifungal drug resistance in non-albicans species of Candida is increasingly common. Recent global emergence of Candida auris is a concern, owing to person-to-person transmission and survival on fomites. Our study aimed to determine if hospital transmission of diverse Candida species is occurring similar to what is seen in Candida auris. We analyzed all candidemia infections for signatures of transmission, including species, geographical, and temporal clusters. Here we present our preliminary data from December 2019 - May 2020.

Methods

This is a prospective and retrospective analytical observational study. Patients with candidemia were identified with the help of the Clinical Microbiology Lab at a University Medical Center. Data was collected on all identified patients by retrospective chart review. Data was described in terms of frequency distributions and percentages, and analyzed using SPSS. Isolates have been stored prospectively as glycerol stocks at -80 C for ongoing analyses.

Results

37 patients were identified (Tables 1 and 2). Clusters of candidemia were seen in the months of January (C. parapsilosis, 3 patients), February (C.glabrata, 3 patients), March (C.albicans, 5 patients) and April (C.glabrata, 3 patients). 33/37 (89%) had a central line prior. Lines were removed in 73% (24/33) of these patients, the remaining patients were deceased before lines could be removed. Pancreatic pathology was seen in 15/37 (40.5%) patients (Table 3). 25/37 (67.5%) had an Ophthalmology consult.

Table 1. Patient demographics

Table 2. Epidemiology of candidemia

Table 3. Pancreatic pathology in candidemia

Conclusion

It is possible that the clusters identified shared equipment or other environmental factors that caused nosocomial transmission. We plan to use Whole Genome Sequencing to determine clonality among these isolates. The association of candidemia with pancreatic pathology was curious. It is to be evaluated whether this was simply a confounder or an actual risk factor that perhaps warrants consideration of prophylaxis. Rates of Ophthalmology consults to evaluate for endophthalmitis need to be improved in our setting. We hope that this study would prove valuable for infection control efforts and help us be better prepared to tackle emerging pathogens of this genus.

Disclosures

All Authors: No reported disclosures
90. Impact of Discrepant Rapid Diagnostic Test (RDT) Results on Antimicrobial Stewardship Program (ASP) Interventions in Patients with Bloodstream Infections (BSI) due to Gram-Negative Bacilli (GNB)
Authors: Robinson Evan D , Cox Heather L , Attai April E , Donohue Lindsay , Shah Megan , Hill Brandon , Elliott Zach , Mathers Amy J , Mathers Amy J
Published: January 2021

Background

Implementation of the Accelerate PhenoTM Gram-negative platform (AXDX) paired with ASP intervention projects to improve time to definitive institutional-preferred antimicrobial therapy (IPT). However, few data describe the impact of discrepant RDT results from standard of care (SOC) methods on antimicrobial prescribing. Here we evaluate the prescribing outcomes for discrepant results following the first year of AXDX + ASP implementation.

Methods

Consecutive, non-duplicate blood cultures for adult inpatients with GNB BSI following combined RDT + ASP intervention were included (July 2018 – July 2019). AXDX results were emailed to the ASP in real time then released into the EMR upon ASP review and communication with the treating team. SOC identification (ID; Vitek® MS/Vitek® 2) and antimicrobial susceptibility testing (AST; Trek SensititreTM) followed RDT as the reference standard. IPT was defined as the narrowest susceptible beta-lactam, and a discrepancy was characterized when there was categorical disagreement between RDT and SOC methods. When IPT by AXDX was found to be non-susceptible on SOC, this was characterized as “false susceptible“. Conversely, “false resistance” was assessed when a narrower-spectrum agent was susceptible by SOC. Results were also deemed discrepant when the AXDX provided no/incorrect ID for on-panel organisms, no AST, or a polymicrobial specimen was missed.

Results

Sixty-nine of 250 patients (28%) had a discrepancy in organism ID or AST: false resistance (9%), false susceptible (5%), no AST (5%), no ID (4%), incorrect ID (2%), and missed polymicrobial (2%). A prescribing impact occurred in 55% of cases (Table 1), where unnecessarily broad therapy was continued most often. Erroneous escalation (7%) and de-escalation to inactive therapy (7%) occurred less frequently. In-hospital mortality occurred in 4 cases, none of which followed an inappropriate transition to inactive therapy.

Conclusion

Though the AXDX platform provides rapid ID and AST results, close coordination with Clinical Microbiology and continued ASP follow up are needed to optimize therapy. Although uncommon, the potential for erroneous ASP recommendations to de-escalate to inactive therapy following AXDX results warrants further investigation.

Disclosures

Amy J. Mathers, MD, D(ABMM), Accelerate Diagnostics (Consultant)
1164. Epidemiology of Cryptococcal Infections in Non-HIV Patients: A 20-year Single Center Experience
Authors: Kumar Rebecca Nirmal , Nam Hannah , Roberts Scott C , Penugonda Sudhir , Angarone Michael , Stosor Valentina
Published: January 2021

Background

Cryptococcus has a worldwide distribution, with C. neoformans and C. gattii being two of the most common species causing disease. Despite advances in therapy, disseminated infection often results in significant morbidity and mortality.

Methods

We conducted a single center retrospective cohort study over a twenty-year period spanning from January 2000 through May 2020 to determine epidemiology and outcomes of non-HIV-associated cryptococcosis at Northwestern Memorial Hospital. Cases were identified by positive culture data or positive cryptococcal antigen in the serum or cerebrospinal fluid (CSF). Epidemiology of risk factors, morbidity, and mortality was evaluated.

Results

81 cases were identified of which, 67 had Cryptococcus spp isolated from culture and the remaining patients diagnosed by cryptococcal antigen and/or histopathology. The cohort was primarily Caucasian (56.8%, n=46) and male gender (67.9%, n=55), with a median age of 59.5 (IQR: 52.75-66.25) years old. Common predisposing conditions were diabetes (37%, n=30), chronic kidney disease (34.6%, n=28), and liver disease (28.4%, n=23). Solid organ transplant recipients and use of immunosuppression accounted for, respectively, 32.1% (n=26) and 29.6% (n=24) of the cohort. Sites of infection include lung (65.4%. n=53), central nervous system (33.3%, n=27), blood (30.9%, n=25), peritoneum (6.2%, n=5), musculoskeletal (2.5%, n=2), and prostate (1.2%, n=1). Mean opening pressure on lumbar puncture was 25.3 mmHg (range: 9 -52 mmHg). In hospital mortality at time of diagnosis was 27.2% (n=22), and mortality at 12 months post diagnosis was 51.9% (n=42).

Conclusion

At our center, those with cryptococcosis commonly had risk factors such as immunosuppression either secondary to solid organ transplant or otherwise. Morbidity and mortality remain high.

Disclosures

Sudhir Penugonda, MD, MPH, AbbVie, Inc. (Employee, Other Financial or Material Support, ownership and/or investment interests) Michael Angarone, DO, Abbvie (Other Financial or Material Support, Data Safety Monitoring Board)Allergan (Speaker’s Bureau)