bluuebunny/crossref_metadata_2025_split huggingface dataset:
1705. Clinical Characteristics and Outcomes of Cryptococcosis in a Tertiary Care Center in Kentucky, 2005 to 2017
Authors: Bhatt Mahesh , Ribes Julie A , Arora Vaneet , Myint Thein 
Published: October 2019

Abstract

Background
Cryptococcosis is an invasive fungal infection that causes pneumonia and extrapulmonary infection. This study explores its presentations, diagnostic tests, and outcome in different groups over a 12-year period at an academic medical center.

Methods
This was a retrospective study of the patients treated at University of Kentucky HealthCare from October 16, 2005 to October 15, 2017. Inclusion criteria were positive cryptococcal antigen (Ag), positive culture, or presence of yeast morphologically consistent with Cryptococcus on cyto- or histopathology. Patients were divided into HIV-infected, solid-organ transplant (SOT) recipients, and non-HIV/non-transplant groups. Cryptococcal meningitis comprised of either positive CSF Ag, culture, cytology or histopathology.

Results
A total of 114 patients were identified; 23 HIV-infected, 11 SOT recipients and 80 non-HIV/non-transplant patients (Table 1). Cryptococcus neoformans was the most common yeast isolated (91.8%). Cryptococcal meningitis was seen in 56% of total patients whereas 27% had isolated cryptococcal pneumonia (P < 0.01). Blood cultures and serum Ag were positive in 34% and 70%, respectively. Only 8.7% of HIV-infected patients had isolated pulmonary cryptococcosis compared with 36.4% in SOT recipients (P < 0.01). In patients with cryptococcal meningitis, abnormal CSF cell count, protein, or glucose was noted in 85.3%; India ink was positive in 61.3% and CSF culture was positive in 73.4% (Table 2, Figure 1). CSF cryptococcal Ag was detected in 95.6% cases if CSF cultures were positive, whereas serum Ag was positive in only 85.1% of meningitis cases. Mortality was seen in 48.6% (17/35) of patients with cirrhosis/liver disease, compared with 21.5% (17/79) of non-cirrhosis/liver disease (P = 0.003). Transplant group had 54.5% mortality compared with 26.1% in HIV group (P = 0.016).

Conclusion
Cryptococcal meningitis was the most common presentation for cryptococcal disease in all three groups. Isolated pulmonary disease was least common in the HIV-infected group. Inpatient mortality rate was higher in patients with cirrhosis/liver disease and transplant group compared with those without cirrhosis/liver disease and HIV group, respectively. It is imperative to rule out meningitis in immunosuppressed patients with cryptococcal pneumonia.

Disclosures
All authors: No reported disclosures.
1714. Testing a Novel Clinical Surveillance Case Definition for Invasive Mold Infections
Authors: Beer Karlyn , Kelly Hilary , Blakney Rebekah , Chambers Taylor , Perry Lewis , Singleton Sabrina , Matkovic Eduard , Hale Gillian , Thomas Stepy , Oliver Nora , Dretler Alexandra , Tsay Sharon , Farley Monica M , Jackson Brendan R 
Published: October 2019

Abstract

Background
Invasive mold infections (IMI) such as aspergillosis and mucormycosis are often fatal among immunosuppressed patients and have caused high-profile outbreaks. Surveillance for IMI is challenging because distinguishing a case from colonization or contamination is complex. The established case definition, Mycoses Study Group (MSG) criteria, lacks sensitivity. Because the need for surveillance remains, we designed a pilot IMI surveillance system within the Georgia Emerging Infections Program. Here, we describe cases identified through this system, using both the MSG criteria and a novel, more sensitive clinical case definition.

Methods
To identify potential IMI cases, we captured fungal cultures positive for mold, histopathology specimens with evidence of fungal tissue invasion, and positive galactomannan results within a 60-day window at three large hospitals in Atlanta during March 2017–2018. We excluded dimorphic fungi and hair and nail specimens. Of 194 potential cases, we selected 24 for complete medical chart review. Two physicians classified cases as proven, probable, or non-case according to MSG criteria. Cases that partially met MSG probable criteria and included antifungal treatment were classified as clinical cases; definitions were mutually exclusive (Figure 1).

Results
Of 24 potential IMI cases, 16 (66%) met an IMI case definition, including 5 proven, 2 probable and 9 clinical cases. Inter-rater agreement was 92%., Most (5/7) MSG cases involved Aspergillus and were more likely to have cancer, a transplant, or other immunosuppression compared with clinical cases (Figure 2 and 3). Clinical cases included conditions not specified in MSG criteria, including burns (1), wounds (1) or eye (4) infections. MSG and clinical cases more often had antifungal treatment (16/16 vs. 1/8) or died (4/16 vs. 0/8) compared with non-cases.

Conclusion
In this preliminary analysis of potential IMI cases, most represented true invasive infections, indicating effective exclusion of most colonization. Most of the 16 cases were classified as clinical, however, and would have been missed in a system relying on the MSG criteria alone. Results suggest that a less-specific clinical case definition incorporating antifungal treatment may improve the sensitivity and utility of IMI surveillance.

Disclosures
All authors: No reported disclosures.
1715. Coccidioidomycosis Outcomes Among Hospitalized Pregnant and Postpartum Women—California, 2000–2016
Authors: Chu Victoria , Sondermeyer Cooksey Gail L , Readhead Adam , Vugia Duc , Jain Seema 
Published: October 2019

Abstract

Background
Coccidioidomycosis (CM) in pregnancy has been associated with severe, disseminated disease. Publications are largely limited to case reports. Using California administrative hospital and birth registry data, we describe maternal and neonatal outcomes among pregnant and post-partum women hospitalized with CM.

Methods
We extracted California records from 2000 to 2016 for women 14–45 years, hospitalized with CM discharge codes; and used the birth registry to identify women who were pregnant or post-partum (≤30 days of childbirth) during their hospitalization. We used chi-squared tests to compare pregnant/post-partum women hospitalized with CM to nonpregnant women hospitalized with CM, and birth outcomes for infants of mothers hospitalized with CM to other California infants. We used multivariable logistic regression, controlling for demographics and comorbidities, to determine the risk of pregnancy on CM dissemination.

Results
We identified 2,372 women with ≥1 CM hospitalization; 187 (8%) were pregnant/post-partum and there were 188 infants (one set of twins). Pregnant/post-partum women were more likely to be Hispanic (59% vs. 44%, P < 0.01), younger (median age 27 vs. 35 years, P < 0.01), without comorbidities (60% vs. 36%, P < 0.01), and have disseminated CM (32% vs. 21%, P < 0.01) than nonpregnant women. Hospitalized pregnant/post-partum women with CM were more likely to have CM dissemination compared with hospitalized non-pregnant women with CM (odds ratio 2.0, 95% confidence interval 1.4–2.8). Among infants of pregnant women hospitalized with CM, 18 (10%) were born < 34 weeks gestational age and 11 (8%) of 134 term (>37 weeks) infants had a birth weight <2,500 g; compared with 3% and 3% (P < 0.01) of other California liveborns, respectively.

Conclusion
This study is the largest cohort of pregnant women hospitalized with CM to date and corroborates that pregnant/post-partum women are more likely to develop disseminated CM than non-pregnant women. Their infants may be more likely to be born <34 weeks gestational age and have a low birth weight. This highlights the need for clinicians caring for pregnant/post-partum women who may live or travel to an area where CM occurs to be aware of the risks for these women and their infants.

Disclosures
All authors: No reported disclosures.
1728. A Retrospective Analysis of 49 Cases of Histoplasmosis in Inflammatory Bowel Disease Patients on Tumor Necrosis Factor-α Antagonists
Authors: Harris Courtney , Jansson-Knodell Claire , Loftus Edward , Walker Randall , Enzler Mark , Virk Abinash 
Published: October 2019

Abstract

Background
Tumor necrosis factor (TNF)-α antagonist therapy has revolutionized the practice of management of inflammatory bowel disease (IBD); however, these medications carry a boxed warning from the Food and Drug Administration for risk of serious infection. We aimed to study the invasive fungal infection, histoplasmosis, in the setting of TNF-α antagonist therapy.

Methods
We performed a retrospective review of patients with IBD receiving TNF-α antagonist therapy who developed histoplasmosis during the time period January 2001–May 2018 at the Mayo Clinic, Rochester, MN. The medical records of patients were reviewed for demographics, medications, symptoms, diagnosis, treatment, and outcomes including mortality. IBD was diagnosed by biopsy, radiographic, or endoscopic evidence of disease.

Results
We identified 49 patients (age range 19–74; median 44 years) with a confirmed diagnosis of histoplasmosis while receiving a TNF-α antagonist. 73.5% of cases were classified as disseminated. Median time from starting TNF-α antagonist to histoplasmosis diagnosis was 2.1 years. Liposomal amphotericin B was given in 17 cases as the initial treatment. Itraconazole was given to all 49 patients. Initial treatment was split evenly between inpatient (49%) and outpatient (51%) locations with 6 patients (12%) requiring ICU-level care. Median length of stay was 9.5 days. The total length of treatment for all antifungals was 38.4 weeks, with 20.4% of patients developing documented antifungal side effects. TNF-α antagonist was continued in 9 patients (18.4%) and another 10 patients resumed TNF-α antagonist. Half of those who resumed TNF-α antagonists were on antifungal therapy. There was one histoplasmosis recurrence while off TNF-α antagonist, and three deaths (6%).

Conclusion
Histoplasmosis outcomes in IBD patients on TNF-α antagonists were mostly favorable; however, approximately half required hospitalization. Many patients were young with few co-morbidities, and over one-third were able to continue or resume TNF-α antagonists without documented recurrence of histoplasmosis. Practitioners should be vigilant for histoplasmosis infections in this patient population who reside in histoplasma-endemic regions.

Disclosures
All authors: No reported disclosures.
1733. Voriconazole Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplant: How Much Is Enough, Are Low Voriconazole Levels Associated With Opportunistic Infections, and What Are the Reasons for Discontinuation?
Authors: Hadjivassiliou Giorgos , Rummage Claire , Hoesley Craig , Brown Matthew L 
Published: October 2019

Abstract

Background
Patients who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) are at increased risk for invasive fungal infections with associated high morbidity and mortality that necessitates the use of prophylactic antifungals. Voriconazole is commonly used for prophylaxis, but there are no recommendations for therapeutic drug monitoring. The purpose of this study was to characterize voriconazole therapeutic drug monitoring and associated outcomes in this patient population.

Methods
AlloHSCT patients receiving voriconazole prophylaxis at the University of Alabama at Birmingham Hospital between March 2015 and March 2018 were included in the analysis. Serum voriconazole levels (SVL) were evaluated to determine what percentage of patients achieved prophylactic or therapeutic concentrations. Incidence of invasive fungal infections (IFI) and voriconazole discontinuation was also assessed.

Results
Voriconazole prophylaxis was used in 151 of 162 alloHSCT patients, and 120 patients (79%) had SVL drawn correctly (≥4 days after initiation of course). We found that 35 (29%) patients achieved a subtherapeutic level (<0.5 μg/mL), 17 (14%) prophylactic level (0.5 to 1 μg/mL), 68 (57%) therapeutic level (1 to 5.5 μg/mL), and no patients achieved a supratherapeutic level (level ≥5.5 μg/mL). Voriconazole prophylaxis was discontinued early in 60 of 151 patients. Most common etiologies for discontinuation included liver function test abnormalities (44%) and encephalopathy (21%). The average SVL was 1.2 μg/mL in those requiring discontinuation. Four patients (3%) developed an IFI while receiving prophylactic voriconazole, of which only 1 had subtherapeutic level.

Conclusion
Even though approximately one-third of patients achieved a subtherapeutic SVL, there was no correlation with breakthrough IFI. There was also no linear correlation between SVL and risk of adverse effects requiring discontinuation. Our observational data do not support a need for therapeutic drug monitoring in alloHSCT patients receiving prophylactic voriconazole.

Disclosures
All authors: No reported disclosures.
1735. Epidemiology of Invasive Fungal Infections During Induction Chemotherapy in Adults With Newly Diagnosed Acute Myeloid Leukemia Without Antifungal Prophylaxis: A Retrospective Cohort Study
Authors: Miranti Eugenia , Enriquez Kyle , Medeiros Bruno , Subramanian Aruna , Ho Dora , Epstein David J 
Published: October 2019

Abstract

Background
While invasive fungal infections (IFIs) are common in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy, little current data exist on the epidemiology of IFIs in this patient population given widespread use of antifungal prophylaxis. Because our institution does not administer antifungal prophylaxis, we are in a unique position to study the natural history of IFIs in these patients.

Methods
We evaluated the incidence of IFIs using established definitions in adults with AML undergoing induction chemotherapy at Stanford Health Care from 2012 to 2017. We also analyzed incidence of antifungal treatment, impact of IFI diagnosis on survival, and risk factors for IFI development. Patients were followed for up to 12 weeks after beginning induction chemotherapy.

Results
Of 488 patients analyzed, 243 were eligible for inclusion. The median age was 57 (interquartile range 45–65). Men composed 134 (55%) of the patients and 157 (65%) where white. Fifty-four (22%) had antecedent myelodysplastic syndrome; most received a “7 + 3” regimen involving cytarabine and an anthracycline. Thirty-one (13%) developed a proven or probable IFI; 104 (43%) developed a proven, probable, or possible IFI. Most IFIs were due to lower respiratory tract disease. Eighteen identified organisms were Candida, including six C. albicans. Eight organisms were mold, including four Aspergillus isolates (all but one A. fumigatus) and one isolate each of Fusarium solani, Rhizomucor, Rhizopus, and Scedosporium apiospermum/Pseudallescheria boydii. One hundred ninety patients (78%) received antifungals during their initial admission and 99 (46%) of patients surviving their initial admission were discharged on antifungals. Only 66.7% of patients with a proven or probable IFI survived through 12 weeks, compared with 92.2% of those without (P = 0.007). Baseline absolute neutrophil count ≤500 cells/μL and longer duration of neutropenia were significantly associated with development of proven or probable IFIs.

Conclusion
Among patients receiving induction chemotherapy for AML, IFIs due to Candida and mold remain frequent absent antifungal prophylaxis and are associated with worse survival. Our findings support the use of antifungal prophylaxis in this patient population.

Disclosures
All authors: No reported disclosures.
1736. Evaluation of Targeted vs. Universal Antifungal Prophylaxis (AP) for Invasive Fungal Infections (IFI) After Lung Transplant (LTx)
Authors: Linder Kathleen A , Patel Twisha S , Kauffman Carol A , Fitzgerald Linda J , Miceli Marisa H , Miceli Marisa H 
Published: October 2019

Abstract

Background
LTx patients (pt) are at increased risk for IFI. Systemic AP is widely used, but the optimal strategy remains unclear. Our LTx program changed from universal to targeted AP in July 2016; we compared outcomes between the 2 strategies.

Methods
All adult pt who underwent LTx at U. Michigan from July 1, 2014 to December 31, 2017 were studied for 18 mo post-LTx. Universal AP consisted of itraconazole (itra) ± inhaled liposomal amphotericin-B (iAmB) for 6 months. Pt received targeted AP with voriconazole for 3 months if they had a history of pre-LTx Aspergillus colonization or invasive pulmonary aspergillosis (IPA); 14 days of a yeast-active azole was given if donor or recipient had Candida colonization at the time of LTx. All other pt received no AP. Demographics, LTx characteristics, occurrence of proven/probable IFI defined by EORTC/MSG criteria, and mortality data were recorded.

Results
Of 105 LTx patients, 73 (70%) were men and 84 (80%) received a double LTx. The most common indication for LTx was idiopathic pulmonary fibrosis (38, 36%). Of 59 pt receiving universal AP, 36 (61%) received itra, and 23 (39%) received itra+iAmB; outcomes did not differ between these 2 regimens. Of 46 patients in the targeted AP cohort, 10 (22%) received antifungals based on predefined criteria. Overall, 19 proven/probable IFI occurred: 14 IPA, 3 invasive Candida infections, 1 Cryptococcus pneumonia, and 1 mold wound infection. IFI occurred in 5 patients (8%) in universal AP group vs. 13 patients (28%) in targeted AP group, P = .008. All but 1 IFI in the targeted AP group occurred among pt for whom antifungals were not recommended or given. IPA occurred in 4 patients (7%) in universal AP group and 9 patients (20%) in targeted AP group, P = 0.05; Candida infections occurred only among patients in the targeted AP cohort. Time to IFI was similar between the 2 AP strategies with the majority occurring <180 days post-LTx (median 109 days). Death occurred in 11 patients (8 in the universal AP cohort and 3 in the targeted AP cohort, P = .34); no deaths were related to IFI.

Conclusion
When compared with universal AP, targeted AP strategy was associated with a significant increase in IFI post-LTx. Universal AP for 6 months appears to be more effective than our targeted AP strategy for prevention of IFI post-LTx.

Disclosures
Marisa H. Miceli, MD, FIDSA, Astellas: Advisory Board, Research Grant; Scynexis: Research Grant.
1740. Title: Outcomes of a Clinical Algorithm for the Early Diagnosis and Treatment of Invasive Fungal Sinusitis among Children with Hematologic Malignancy or Prior Hematopoietic Stem Cell Transplantation
Authors: Warraich Gohar , Winick Naomi , Slone Tamra , Aquino Victor M , Donner Kimberly , Shah Gopi , Sue Paul K 
Published: October 2019

Abstract

Background
Invasive fungal sinusitis (IFS) is a cause of significant morbidity and mortality among children with hematologic malignancy and hematopoietic stem cell transplant (HSCT) recipients, with an estimated mortality of 18–80%. Since 2007, our center has employed a clinical algorithm for the early detection and treatment of IFS among children with prolonged febrile neutropenia.

Methods
We reviewed all EORTC defined cases of proven IFS among children with underlying hematologic malignancy or prior HSCT admitted to our institution between July 1, 2004 and December 31, 2018, and compared clinical characteristics and outcomes (including underlying malignancy, chemotherapy regimen at the time of viremia, absolute neutrophil count, absolute lymphocyte count, treatment regimens, and 6 month mortality) between the pre (July 1, 2004–December 31, 2006) and post-protocol (January 1, /2007–December 31, 2018) periods.

Results
We identified 33 cases of proven IFS during the study period, with 6 in the pre-protocol and 27 in the post-protocol period. The most common underlying primary diagnosis was acute lymphoblastic leukemia (ALL) at > 50% with 8% of individuals with prior HSCT. Twenty-five cases (92%) during the protocol period were diagnosed via nasal endoscopy per protocol, with 17 (63%) reporting no clinical complaints of sinusitis. Median absolute neutrophil count (ANC) at the time of IFS diagnosis was 155/mm3 (IQR 0 – 375/ mm3; n = 12) with median duration of neutropenia 16.5 days (IQR 10.5–18.25, n = 12) at the time of diagnosis. Most individuals required one definitive debridement. Isolated fungal specimens included Bipolaris spp. (24%), Aspergillus spp. (20%), Curvularia spp. (20%), with Fusarium and Exserohilum spp. each at 12%, and Rhizopus spp. At least one patient had a co-infection with more than one fungal species. Pre-protocol cause-specific mortality at 6 months was 33.3% compared with 14.8% (P = 0.29) in the post- protocol period.

Conclusion
IFS is a cause of significant morbidity and mortality among children with hematologic malignancy or prior HSCT. An aggressive protocol with early nasal endoscopy and targeted debridement may help decrease morbidity and mortality associated with this entity. Additional well-designed studies are needed to assess the potential benefits of this approach in the diagnosis and management of IFS among high-risk children.

Disclosures
All authors: No reported disclosures.
1761. A Single-Center Experience with Cidofovir for the Treatment of Double-Stranded (ds) DNA Viruses in Hematopoietic Cell Transplant (HCT) Recipients
Authors: Stern Anat , Su Yiqi , Neofytos Dionysis , Papanicolaou Genovefa 
Published: October 2019

Abstract

Background
Cidofovir (CDV), a nucleotide analog antiviral, is active against multiple dsDNA viruses relevant in HCT recipients. Despite a broad spectrum of activity, CDV utility is limited due to nephrotoxicity. We describe our experience with CDV in a large contemporary cohort from a single Institution.

Methods
Retrospective review of adult HCT recipients who received CDV for any indication from 2011 to 2017. Initiation and duration of CDV treatment were at physicians’ discretion. CDV exposure and indications, Serum Creatinine (SCr) and outcomes were extracted from medical records and hospital databases.

Results
Of 1,235 HCT recipients, 54 (4.4%) received ≥1 dose of CDV. Stem cell source was peripheral blood in 39 (72%) patients, cord blood in 13 (24%) and marrow in 2(4%); 42 (78%) patients received CD34+ selected HCT. At CDV initiation, 23 (43%) patients had active GvHD and 16 (30%) received systemic steroids. CDV was started a median of 85.5 days (range 14–335) post HCT, given for a median of 3 doses (range 1–13) for a median of 2 weeks (range 1–17). Indications were adenovirus (ADV) infection in 35 patients, CMV in 19, BK virus in 21 and HHV6 in 3 patients. Nineteen (35%) patients had >1 dsDNA virus. Forty-one (76%) patients received CDV (3–5 mg/kg) once weekly, mainly for ADV or CMV, and 13 received CDV (≤1 mg/kg) once to thrice weekly, mostly for BK hemorrhagic cystitis (N = 12).
Baseline sCr was mean 0.88 mg/dL (standard deviation [SD] = 0.37) at CDV initiation, mean 1.07 mg/dL at end of treatment (EOT) (SD = 0.57, N = 48, P = 0.004) and mean 1.23 mg/dL at EOT + 2 weeks (SD = 0.72, n = 28, P = 0.027). At EOT, 13 patients (24%) had acute kidney injury (AKI, ≥1.5-fold increase from baseline sCr). Of those, 12 (92%) received concomitant nephrotoxic drugs. AKI was attributed to other etiologies by treating physician in six patients. Of 51 patients with follow-up at EOT, 29 (57%) had clinical response to CDV treatment. Nineteen (35%) patients died ≤ 4 weeks from last CDV dose.

Conclusion
24% of highly immunocompromised HCT patients experienced AKI following CDV treatment for dsDNA viruses. The co-administration of nephrotoxic medications and the direct effect of infection limit our ability to assess the relative impact of CDV on renal function. Our data underscores the need for safer treatment options for HCT patients with life-threatening infections with dsDNA viruses.

Disclosures
All authors: No reported disclosures.