bluuebunny/crossref_metadata_2025_split huggingface dataset:
1687. High-Rates of Candida auris Carriage and Co-Colonization with Multidrug-Resistant Organisms (MDROs)
Authors: Barza Ruby , Patel Parul , Patel Jignesh , Droske Lauren E , Schora Donna , Mangold Kathy , Lepinski Jeanette , Hines David , Lee Boeun , Singh Kamaljit 
Published: October 2019

Abstract

Background
Candida auris is an emerging multidrug-resistant pathogen that can persist in the environment and lead to healthcare-associated outbreaks. Residents of long-term acute care hospitals (LTACHs) are at particular risk for carriage of both MDROs and C. auris. However, there are few data on co-colonization rates of C. auris with other MDROs in LTACHs.

Methods
We conducted a point prevalence survey for MDROs, C. auris and C. difficile in a Chicago LTACH in March 2019. A combined axilla/groin E-swab (Copan) was collected and plated for C. auris isolation using CHROMagar Candida (Hardy). A rectal E-swab (Copan) was collected for C difficile PCR and MDRO detection including Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum B-lactamases (ESBLs) and Vancomycin-resistant Enterococci (VRE). Each swab was plated directly on VACC agar (Vancomycin, Amphotericin B, Ceftazidime, Clindamycin) and CHROMagar ESBL (Hardy). Bruker MALDI-TOF was used for bacterial and yeast identification and disc diffusion method for antimicrobial susceptibility testing. ESBL phenotypic confirmation was done using double-disc synergy method per CLSI guidelines. Carbapenemase production was confirmed using Xpert Carba-R assay (Cepheid). C. difficile PCR was performed using Xpert C. difficile/Epi assay (Cepheid).

Results
Of 38 patients 36 were eligible for the study (2 patients declined). Overall, 26/36 (72%) patients had an MDRO. Eight (22%) patients were positive for C. auris. Eight (22%) patients had ESBLs (2 P. mirabilis and 6 E. coli), six (17%) had CREs that were all blaKPC positive (4 K. pneumonia, 1 E. coli, and K. pneumoniae). Eight (22%) patients were positive for other gram-negative (GN)-MDROs including 1 A. baumanii, 3 P. aeruginosa, 2 E. cloacae, 1 E. asburiae and 1 P. aeruginosa, and A. baumanii. 20 patients (56%) had VRE colonization. Five (14%) were C. difficile PCR positive. 7/ 8 (87.5%) patients with C. auris were also colonized with another MDRO (2 VRE, 1 ESBL, 1 VRE, ESBL and KPC, 1 VRE and GN-MDRO, 1 VRE, ESBL and GN-MDRO, 1 VRE, KPC, and GN-MDRO).

Conclusion
We found a high rate of MDRO co-colonization among patients with C. auris carriage. Continuous active surveillance may be appropriate in LTACHs to limit the spread of C. auris and other MDROs.

Disclosures
All authors: No reported disclosures.
1700. A Rare Case of Candida glabrata Hemorrhagic Cystitis with Empagliflozin Use
Authors: Tran Ly , Thomas Mathew , Harvey Jeremy , Sampath Rahul , Rose Richard 
Published: October 2019

Abstract

Background
Hemorrhagic cystitis is an inflammatory condition of the bladder, infrequently seen after cancer chemotherapy, pelvic radiation, and viral infections in immunocompromised hosts.

Methods
We report a case of biopsy-proven Candida glabrata hemorrhagic cystitis in an immunocompetent host associated with empagliflozin use. Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, that increases urinary glucose excretion, and is associated with an increased risk of urogenital mycotic infections

Results
A 71-year-old man with a history type 2 diabetes, neurogenic bladder status post transurethral resection of the prostate, developed symptoms of pelvic pain and gross hematuria 3 months after the initiation of empagliflozin. The patient received multiple courses of empirical antibiotic therapy without any relief. Six months into the illness, the patient had significant weight loss, fatigue, progressive renal failure, and continued hematuria. Empagliflozin was self-discontinued by the patient secondary to a perceived relation between symptom onset and medication use. Urine cultures were negative. A CT scan showed mucosal thickening of the bladder wall with hydronephrosis. Cystoscopy was consistent with hemorrhagic cystitis. A bladder biopsy was negative for malignancy, stain and PCR negative for fungi, but culture positive for C. glabrata susceptible to Fluconazole. Mycobacterial stains, cultures, and PCR were negative. The patient was treated with Fluconazole for 4 weeks and experienced symptomatic improvement and resolution of hematuria one week into the therapy.

Conclusion
This is the first reported case of C. glabrata hemorrhagic cystitis in an immunocompetent host associated with empagliflozin. Invasive candida infections in the genitourinary system are rare in immunocompetent patients. We believe that empagliflozin-induced glycosuria may have been a predisposing factor.

Disclosures
All authors: No reported disclosures.
1701. Differences in Diagnostic Performance of β-d-Glucan Testing in Patients with Varying Degrees of Susceptibility to Invasive Fungal Infections
Authors: Nham Eliel , Kim Si-Ho , Lee Hyunjoo , Ko Jae-Hoon , Huh Kyungmin , Young Cho Sun , Kang Cheol-In , Ryeon Chung Doo , Ran Peck Kyong 
Published: October 2019

Abstract

Background
Usefulness of β-d-glucan (BDG) testing in high-risk patients for invasive fungal infection (IFI) diagnosis has been well demonstrated. However, data on its usefulness in patients without risk factors are limited. We evaluated differences in the diagnostic performance of BDG testing in patients with varying degrees of susceptibility to IFI.

Methods
From April 2017 to May 2018, all consecutive patients (≥18year-old) who were performed BDG testing (Beijing Gold Mountainriver Tech) were enrolled. Patients were classified into three groups: Group A for patients with host factors defined by 2008 European Organization for Research and Treatment of Cancer-Mycoses Study Group diagnostic (EORTC-MSG) criteria, Group B for patients with malignancy receiving recent chemotherapy within 1 month without host factors, and Group C for others. Cases of proven and probable IFI defined by EORTC-MSG criteria, Pneumocystis pneumonia and all fungemia were considered as true IFIs. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were calculated with a cut-off value for positivity ≥80 pg/mL.

Results
Among 473 eligible patients, 190, 142, and 141 patients were classified into group A, B, and C, respectively. Rates of true IFI were significantly different in each group (57/190, 19/142, and 10/141 in each group, P < 0.001). Sensitivities were 0.83, 0.68, and 0.70 and specificities were 0.62, 0.59, and 0.63 in group A, B, and C, respectively. PPVs were considerably different among three groups (PPV for 0.48, 0.20, and 0.12; NPV for 0.89, 0.92 and 0.97 in each group, respectively).

Conclusion
The BDG test is a useful assay for IFI diagnosis; however, the clinical interpretation should be different by patient risks. Whereas BDG testing could be considered as a tool for predicting IFI in high-risk patients, it only could be a tool for excluding IFI in patient without risk factors.

Disclosures
All authors: No reported disclosures.
1704. Geotrichum spp. Invasive Infection: Experience From a Third-Level Referral Center in Mexico
Authors: Rajme-López Sandra , Gonzalez-Lara María F , Rangel-Cordero Andrea , Ponce de Leon Alfredo 
Published: October 2019

Abstract

Background
Geotrichum spp has been recognized as an emergent pathogen that causes invasive infection in immunosuppressed hosts. There is no data in Latin America about invasive Geotrichum spp. infections. Our objective was to describe the epidemiology, clinical characteristics, and outcomes of patients with this infection.

Methods
We conducted a retrospective survey from 2001 to 2018, of all the Geotrichum spp. isolated from clinical samples at our institution. Data on demographic, clinical, laboratory findings, and imaging studies were obtained from medical records. All cases classified as proven or probable invasive fungal infections (IFI) according to the EORTC/MSG criteria were included. Isolates with unavailable clinical information were excluded. Descriptive analysis was made.

Results
We found 18 patients with a proven/probable Geotrichum spp. IFI. The mean age was 48.5 years and 55.5% were male. The most common predisposing condition was hematological malignancy (55.5%), autoimmune diseases (22.2%) and HIV, chronic granulomatous disease, and solid-organ malignancy in 1 case, respectively. Fifteen (83.3%) received immunosuppressors (cancer chemotherapy or steroids); 27.7% had neutropenia at the time of diagnosis. The most common clinical syndromes were lower respiratory tract infection and persistent fever (83.3%). Chest abnormalities were present in 15/16 CT scans, pulmonary nodules were the most common finding (62.5%). Geotrichum spp. was isolated from bronchoalveolar lavage, 77.7%; blood culture, 22.2%; and peritoneal dyalisis fluid, 5.6%. Seven patients were coinfected with other pathogens: 4 Aspergillus spp., 1 H. parainfluenzae, 1 P. aeruginosa, and 1 E. coli. Fifteen patients received antifungal treatment: 7 amphotericin B, 8 voriconazole, and 1 itraconazole. Among survivors (11), 72.7% received antifungal therapy at discharge: 4 voriconazole and 4 itraconazole. Three patients did not receive any antifungal: 1 was diagnosed postmortem and 2 were considered colonization (both were alive at 30 days). Overall mortality was 38.8%.

Conclusion
Eighteen cases of Geotrichum spp. were found. The majority had lower respiratory tract infection. Despite antifungal therapy 38.8% died. Geotrichum spp. should be recognized as an emerging pathogen in immunosuppressed hosts.

Disclosures
All authors: No reported disclosures.
1716. Baseline Serum C-Reactive Protein Level Predicts Mortality in Cryptococcal Meningitis
Authors: Chesdachai Supavit , Engen Nicole , Rhein Joshua , Tugume Lillian , kiiza. Kandole Tadeo , Abassi Mahsa , Williams Darlisha A , Skipper Caleb , Hullsiek Kathy H , kisekka. Musubire Abdu , Meya David , Boulware David 
Published: October 2019

Abstract

Background
C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker widely used in various infections, particularly for following the progression and resolution of infection. We aimed to determine the association between baseline CRP level and cryptococcal meningitis outcome.

Methods
We reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline serum samples collected within 5 days from diagnosis had CRP levels measured and categorized into quartiles. We compared baseline serum CRP with 18-week survival using unadjusted time-to-event analysis.

Results
Of 168 participants, the first quartile of baseline serum CRP was 83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by quartile. Participants with CRP > 49.5 mg/L more likely presented with Glasgow Coma Scale <15 (P = 0.03). The 18-week mortality rate was 54.8% (46/84) in the highest two quartile CRP groups (49.5 mg/L), 40.5% (17/42) in the mid-range CRP group (29–49.5 mg/L), and 14.3% (6/42) in the low CRP group (<29 mg/L) (P < 0.001) (Figure 1).

Conclusion
Higher baseline serum CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. The serum CRP could be a surrogate marker for undiagnosed co-infections or may reflect immune dysregulation leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis. Additional studies investigating more specific inflammatory biomarkers and the longitudinal trend in CRP with effective therapy would be informative.

Disclosures
All authors: No reported disclosures.
1717. Cryptococcal Meningitis: A Comparison of Clinical Features and Outcomes by HIV Status
Authors: Pate Amy , Franco-Paredes Carlos , Henao-Martinez Andres 
Published: October 2019

Abstract

Background
Cryptococcal meningitis is an opportunistic fungal infection associated with HIV and other forms of immunosuppression. We lack a clear understanding of cryptococcal meningitis (CM) among HIV-negative patients in the United States. Our aim was to compare clinical features and outcomes across HIV status in patients with laboratory-confirmed cryptococcal meningitis.

Methods
We conducted a retrospective cohort study of patients with laboratory-confirmed (positive culture or antigen test) cryptococcal disease treated at a tertiary care center from January 2000 to September 2018. Patients were identified via local laboratory and TrinetX datasets. Data were gathered on demographics, HIV status, site of infection, clinical presentation, cerebrospinal fluid (CSF) profiles, hospital course, and mortality. Organ transplant recipients and/or non-meningeal infections were excluded.

Results
Seventy patients with cryptococcal disease were identified. Our final sample included 36 CM patients with a mean age of 48.8 ± 13.2 years; 66.7% (n = 24) had HIV. Median (IQR) absolute CD4 count for the HIV group was 35/μL (10–80/μL). Non-HIV patients were significantly older (P < 0.001) and had higher rates of altered mental status (AMS) on presentation (58.3% vs. 25%, P = 0.05). There was no significant variation in temperature, blood pressure, white blood cell count, serum sodium, or CSF opening pressure. Non-HIV patients had significantly higher CSF cell count (P = 0.02) and protein (P < 0.001), and lower glucose (P = 0.005) compared with HIV patients. There was no significant variation in length of stay or rates of intensive care unit admission. Overall, 90-day all-cause mortality was 19.4%: mortality rates were significantly higher in non-HIV patients at both 90 days (P = 0.017) and one year (P = 0.047).

Conclusion
Compared with individuals with HIV, non-HIV cryptococcal meningitis patients have a more inflammatory CSF profile at the time of diagnosis, higher rates of AMS on presentation, and higher rates of 90-day and 1-year all-cause mortality. We postulate that reversible immunosuppression among HIV patients may partially explain these findings. Further research is needed to identify hallmarks of cryptococcal meningitis in non-HIV patients to facilitate early intervention.

Disclosures
All authors: No reported disclosures.
1722. Histoplasmosis Acquired in Alberta, Canada, 2011–2018
Authors: Dingle Tanis , Fathima Sumana , Sonpar Ashlesha , Saxinger Lynora M , Schwartz Ilan S 
Published: October 2019

Abstract

Background
Histoplasmosis is a serious fungal infection caused by the geographically restricted, dimorphic fungus Histoplasma capsulatum. In Canada, the geographic range of H. capsulatum is classically thought to be restricted to southern parts of Ontario and Quebec. Over the past decade, histoplasmosis has occasionally been diagnosed in patients in Alberta without travel to areas of known geographic risk (Figure 1). We studied the epidemiology and geographic distribution of histoplasmosis in Alberta to assess evidence for locally-acquired infections.

Methods
We retrospectively reviewed all laboratory-confirmed (culture, antigen and/or immunodiffusion positive) cases of histoplasmosis diagnosed from January 1, 2011 to June 30, 2018. Data collected by public health and clinical charts were reviewed for clinical presentation, exposure and travel histories, and geographic distribution of cases. Cases of histoplasmosis in patients who had not left Alberta or associated with a local point source were classified as definite local acquisition; cases in patients with remote travel but with local exposures and appropriate timing of disease onset were deemed “probable” cases of local infection. University of Alberta’s Research Ethics Board approved this study.

Results
We identified 45 laboratory-confirmed cases of histoplasmosis, including 17 cases that were locally acquired. Among these, there were 12 cases of definite local acquisition, including 8 patients from 3 point-source outbreaks—all involving exposure to bats and/or their droppings in chimneys or attics of private dwellings or churches—and 4 sporadic cases in patients who had never traveled. Of the other 5 cases probably acquired in Alberta, patients had previously traveled (n = 4) or travel history was incomplete (n = 1) but local exposures preceding infection were considered compelling. The mean incidence rate of locally acquired infection was 0.062/100,000 population with incidence increasing since 2014. Table 1 shows features of locally acquired cases.

Conclusion
This study, for the first time, establishes Alberta as a region of geographic risk for histoplasmosis. The diagnosis should be considered in patients with compatible symptoms and exposure history, even in the absence of travel.

Disclosures
All authors: No reported disclosures.
1723. Human Serum Albumin Regulates the Growth of Candida auris in vitro
Authors: Sakai Jun 
Published: October 2019

Abstract

Background
Candida auris is commonly detected in human ear secretions. However, C. auris occasionally causes bloodstream infections even in immunocompetent patients resulting in poor prognosis. It was speculated that C. auris growth within the blood might be regulated by proteins in the bloodstream. Thus, in this study, the potential role of blood proteins in the regulation of C. auris growth was investigated.

Methods
Five Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis) were incubated overnight. Colony suspensions for each species were prepared and adjusted to OD 1.0 at absorbance 0.1. Then, human serum albumin (HSA) and bovine serum albumin (BSA) were diluted (2.5 g/dL–0.002 g/dL) and mixed with the suspensions. Mixed samples were adjusted to 100 μL and incubated on MHA plates at 35°C for 2 days. Then, 50 μL of the combined sample was extracted and streaked onto Yeast extract-Peptone-Dextrose (YPD) agar. The remaining 50 μL sample was analyzed using an XTT assay. Further testing was then conducted on the effects of a specific blood protein albumin on Candida. Thereby, C. albicans and C. auris were cultured following the procedure above and stained with Annexin V and PI.

Results
The growth of C. auris mixed with a high albumin concentration (2.5~0.15 g/dL) was regulated compared with that of other Candida species (P < 0.01) (Figures 1 and 2); however, the growth of C. auris mixed with a lower albumin concentration was similar to that of other species. The wash-out study showed that C. auris growth and survival in the high albumin concentration was not different than that of other species.

Conclusion
HSA and BSA regulated C. auris growth which led to increased necrosis of C. auris. Conversely, growth of the other Candida species was not regulated. Therefore, albumin might be involved in the growth and necrosis of C. auris. As the highest concentration at which albumin regulated C. auris growth was similar to that found in human serum, it is possible that serum albumin might help prevent C. auris from entering the bloodstream via the ear or skin.

Disclosures
All authors: No reported disclosures.
1724. Plasmid-free CRISPR-Cas9 System for Genetic Engineering of Rhizopus delemar
Authors: Gu Yiyou , Baldin Clara , Gebremariam Teklegiorgis , Alqarihi Abdullah , Mamouei Zeinab , Wang Ping , Nagy Gabor , Skory Christopher , Ibrahim Ashraf S 
Published: October 2019

Abstract

Background
Mucormycosis is a serious infection caused by fungi of the order Mucorales. Rhizopus delemar is the most common etiologic agent of mucormycosis. Pathogenesis studies of mucormycosis have been hampered by poor genetic trackability of the organism, owing to rare chromosomal integration events and multinucleated nature of the cells. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) system has been widely used in genetic manipulation through efficient homologous and non-homologous break points in a variety of organisms including R. delemar. However, plasmid-free CRISPR/Cas9 system has not been previously described in the fungus. Here, we introduce a rapid plasmid-free system for inducing orotidine 5’-phosphate decarboxylase (pyrF) gene mutation in R. delemar.

Methods
Protoplasts of R. delemar 99–880 strain were transformed with 20 nucleotide gRNA targeting the N-terminus of pyrF gene and the Cas9 enzyme. Screening for pyrF auxotrophy was carried out by plating transformed protoplasts on potato dextrose agar (PDA) plates containing 1 mg/mL 5-fluoroorotic acid (5-FOA) and 100 µg/mL uracil. Putative mutant strains were selected for uracil auxotrophy by plating simultaneously on media with or without uracil. pyrF disruption was verified by using PCR and qRT–PCR.

Results
Approximately100 transformants were generated through plating on 5-FOA plates. Only three transformants did not grow on minimal medium lacking uracil, indicating that they were true pyrF null mutants. PCR analysis showed that these three transformants have undergone nucleotide deletion events within the pyrF gene. The lack of pyrF gene expression was further verified by using qRT–PCR relative to wild-type R. delemar 99–880.

Conclusion
Similar to the plasmid-based genome manipulation strategy, the plasmid-free CRISPR/Cas9 system can induce gene editing in R. delemar. This rapid and simple approach adds an additional tool in our conquest to understand pathogenesis of mucormycosis.

Disclosures
All authors: No reported disclosures.
1730. Invasive Fusarium Species in Mayo Clinic Patients with Hematologic Malignancies
Authors: Harris Courtney , Tosh Pritish , Tande Aaron J 
Published: October 2019

Abstract

Background
The epidemiology of fungal infections in hematologic malignancies has changed in the past decade. Triazole prophylaxis has decreased Candida spp infections while infections due to other molds such as Aspergillus and Fusarium species have increased. Fusariosis has very poor prognosis, and after aspergillosis, is the most common invasive fungal infection in this patient population. We sought to describe fusariosis in patients with hematologic malignancy at the Mayo Clinic.

Methods
We performed a retrospective review of patients with culture-positive Fusarium infection from January 2003 to October 2016 at the Mayo Clinic, Rochester, MN. The records of patients were reviewed for demographics, diagnosis, treatment, and outcomes including mortality. Patients without a diagnosis of hematologic malignancy were excluded. Patients were classified with proven or probable Fusariosis based on the Revised Definitions of Invasive Fungal Disease from the EORTC/MSG Consensus Group.

Results
We identified 14 patients with hematologic malignancies (age range 17–76 years; median 60 years) with a confirmed culture diagnosis of Fusarium infection classified as proven (9 patients) or probable (5 patients). Two cases were isolated pulmonary infections, 3 extra-pulmonary, and 9 disseminated cases. Two patients had previously undergone stem cell transplantation. Eight patients (57%) were receiving antifungal prophylaxis at the time of diagnosis: 2 on voriconazole, 1 on posaconazole, 1 on fluconazole, 3 on echinocandins, and 1 on Amphotericin B. Nine patients (64%) were neutropenic at the time of diagnosis. Amphotericin was the initial treatment in 7 (50%) patients, with voriconazole added for 4 patients for combination therapy the first week. Voriconazole monotherapy was given initially in 5 patients. Seven patients (50%) were deceased at 6 weeks after culture positivity, with an additional 2 patients deceased by 12 weeks.

Conclusion
Fusarium infection outcomes in patients with hematologic malignancies are poor. Neutropenia was common in those diagnosed, and infections were more likely to be disseminated, with high mortality rates. Amphotericin was commonly used as initial treatment, with many physicians recommending combination therapy with two agents, commonly voriconazole.

Disclosures
All authors: No reported disclosures.