bluuebunny/crossref_metadata_2025_split huggingface dataset:
1651. The Impact of the 2017–2018 Influenza Season on Acute Care Hospitals in the United States: A Qualitative Evaluation of Immediate Responses and Future Preparedness
Authors: Harris Gavin H , Rak Kimberly J , Kahn Jeremy M , Angus Derek C , Caplan Erin A , Mancing Olivia , Driessen Julia , Wallace David J 
Published: October 2019

Abstract

Background
The 2017–2018 influenza season was characterized by high illness severity, wide geographic spread, and prolonged duration compared with recent years in the United States – resulting in an increased number of emergency department evaluations and hospital admissions. The current study explored how US hospitals perceived the impact of influenza during this time period, including effects on patient volumes, ways in which hospitals responded, and how lessons learned were incorporated into future influenza preparedness.

Methods
We conducted semi-structured phone interviews with capacity management personnel in short-term acute care hospitals across the United States. A random hospital sample was created using Centers for Medicare and Medicaid Services annual reports. Hospitals self-identified key informants who were involved with throughput and capacity. The interview guide was developed and pilot tested by a team of clinicians and qualitative researchers, with interviews conducted between April 2018 and January 2019. We performed thematic content analysis to identify how hospitals experienced the 2017–2018 influenza season.

Results
We achieved thematic saturation after 53 interviews. Responses conformed to three thematic domains: impacts on staff and patient care, immediate staffing and capacity responses, and future preparedness (Table 1). Hospitals almost universally reported increased emergency department and inpatient volumes that frequently resulted in strain across the hospital. Strain was created by both increased patient volume and staff shortages due to influenza illness. As strategies to address strain, respondents reported the use of new protocols, new vaccination policies, additional staffing, suspected-influenza treatment areas, and more frequent hospital administration meetings. Many hospitals reported increased diversion time. Despite experiencing high levels of strain, some hospitals reported no changes to their future influenza preparation plans.

Conclusion
Acute care hospitals experienced significant strain as a result of the 2017–2018 influenza season. Hospitals implemented a range of immediate responses to seasonal influenza, but generally did not report future planning specific to influenza.

Disclosures
All authors: No reported disclosures.
1684. Clinical Profile and Outcome of Scrub Typhus-Related Acute Respiratory Distress Syndrome in Adults Presenting to a Tertiary Care Hospital in North India
Authors: Kumari Savita , Suri Vikas , Rao H R , Bhalla Ashish , Singh Inderpaul , Singh Mini P , Biswal Manisha , Goyal Kapil , Zaman K , Ratho R K 
Published: October 2019

Abstract

Background
To study the clinical profile and outcome of adult patients presenting with Scrub typhus ARDS in emergency at our institute.

Methods
Prospective observational study which included 126 adult patients presenting to emergency department at, PGIMER Chandigarh, a tertiary care referral institute in northwestern India with acute febrile illness with ARDS (acute onset respiratory distress within one week of fever or new/worsening respiratory symptoms with PaO2/FiO2 ratio less than 300 with PEEP or CPAP more than 5 cm H2O from January 2016 to December 2017.All the patients consenting for the study underwent detailed clinical evaluation and investigated for the etiology as per standard protocol followed at our institute with special emphasis to rule out tropical illnesses like scrub typhus, malaria, leptospirosis, dengue and H1N1 influenza. Patients were followed till discharge.

Results
Out of 126 patients eligible for the study, 45.2% were males and 54.8% were females. 47.6% were admitted in the monsoon/post-monsoon period. In addition to fever and dyspnea, cough (75.8%), hepatomegaly (56%), myalgia (63%), splenomegaly (31.3%), pedal edema (34.2%), pallor (40.4%), and vomiting (48.4%) were the common symptoms observed. Scrub typhus in 33.3%, followed by H1N1 influenza in 15.8%, co-infections in 12.6%, leptospirosis in (4.76%), dengue in (3.96%) and malaria in 3.17% of the patients, were the most common etiologies encountered. In 26.9% patients, no definite infective etiology could be found. Among the scrub typhus patients, 16 required ventilation. SOFA score of more than 6 was noted in 24 (57.14%) patients with scrub typhus as compared 9 (47.3%) patients with H1N1 infection. 12.1% of patients with scrub typhus succumbed to their illness when compared with 36.8% of patients with H1N1 infection. At admission in emergency female sex (P = 0.048), age less than 45 years, (P = 0.020), abdominal pain (P = 0.011), presence of hepatosplenomegaly (P = 0.001/0.010), thrombocytopenia <150,000 (P = 0.001), transaminitis (P = 0.00) were significant predictors of a diagnosis of scrub typhus when compared with a non-scrub typhus etiology of patients with fever and ARDS.

Conclusion
Scrub typhus is an important, treatable tropical infection causing ARDS especially in monsoon/post-monsoon seasons in Northwestern India.

Disclosures
All authors: No reported disclosures.
1692. Epidemiology, Clinical Characteristics, and Outcomes of Candidemia in a Tertiary Hospital in the Dominican Republic
Authors: Rojas Fermin Rita , Germosen Edwin , Mena Lora Alfredo J , Guzman Anel E , Tolari Gilda , Bleasdale Susan C 
Published: October 2019

Abstract

Background
Candidemia is a major cause of morbidity and mortality in hospitalized patients. The global epidemiology of invasive Candidiasis is changing, with distribution of species and resistance varying in different geographic and healthcare settings. There is a paucity of data on candidemia in the Dominican Republic (DR). Understanding epidemiologic risk factors and resistance rates may improve early diagnosis and empiric antifungal selection.

Methods
We performed a retrospective review of patients with positive Candida blood cultures from January 2017 to December 2018. Data were extracted from medical records. Clinical and demographic information, including co-morbidities, antifungal sensitivities, and outcomes were collected.

Results
A total of 52 cases were identified, 34 in 2017 and 18 in 2018. Ages ranged from <1 to 89 years and was distributed in various groups (Figure 1). The most common comorbidities included DM (38%), nephropathy (37%), cerebrovascular accident (25%), and malignancy (19%). Device use and prior antimicrobial exposure were the most common risk factors (Table 1). There was no antifungal resistance to amphotericin, voriconazole, or echinocandins. No fluconazole resistance was found in 2017, compared with 11% resistance in 2018 in C. albicans, C. glabrata, and C. tropicalis species. Mortality was 64% in 2017 and 61% in 2018.

Conclusion
Candidemia with non-albicans Candida species was common (87%). Susceptibilities and species varied by year but did not affect mortality. Resistance to fluconazole is rising but remains low and other antifungals retain susceptibility. Indwelling catheters, mechanical ventilation and antibiotic exposure were common risk factors in our cohort. Mortality for candidemia was high. Rapid diagnostic testing and early empiric therapy with echinocandins for patients at risk may curb mortality.

Disclosures
All authors: No reported disclosures.
1695. Clinical and Microbiological Characterization of Candida parapsilosis Complex Infection in a Tertiare Care Hospital from Cali, Colombia
Authors: Martinez Luisa F , Sanz Ana M , Martinez Diana M , Rosso Fernando , Parra Claudia M 
Published: October 2019

Abstract

Background
Candidemia and invasive candidiasis are major causes of morbidity and mortality among critically ill patients and neonates. Every year more than 250,000 people develop invasive candidiasis, causing more than 50,000 deaths worldwide. Candida albicans is the most frequently isolated species worldwide. However, species distribution, epidemiology, and resistance have changed. C. parapsilosis complex (CPC), which has a global rate of fluconazole (FCZ) resistance range between 2 and 5% and has been related to echinocandins resistance, is the second most isolated species at Fundación Valle del Lili (FVL). We aim to describe the clinical and microbiological characteristics of fungal infections by C. parapsilosis, and determine FCZ resistance rates.

Methods
An observational prospective study was conducted. The study included patients with CPC isolations attended at FVL from 2016 to 2017. The strains were identified by mass spectrometry (MALDI TOF® Bruker, Biotyper 3.1). Minimal inhibitory concentrations (MIC) were determined by broth microdilution (M27 A3 CLSI). Statistical univariate analysis was performed; Differences between resistant cases and nonresistant cases were assessed through U Mann–Whitney test, Pearson chi-squared test or Fisher exact test.

Results
55 patients had CPC isolations during the study period: 18 newborns, 13 children, and 24 adults. Most isolations were from blood cultures (n = 31) (14 of them newborns), bronchoalveolar lavage (n = 9), peritoneal fluid (n = 8), and catheter tips (n = 3). The resistance was 36%. 52 strains were C. parapsilosis ss, of them, 20 were FCZ resistant; 3 strains were C. orthopsilosis, all of them FCZ sensitive. The MIC50 = 1 µg/mL and MIC90 = 16 µ/mL. Patients with previous antifungal treatment had a higher risk of FCZ resistance (RR: 2.14, 95% IC 1.07–4.26). The mortality brute rate was 30%, patients with diabetes and renal failure death risk (RR: 3.1, 95% CI: 1.4 – 6.9) and (RR: 2.96, 95% CI: 1.4 – 6.4), respectively. Candidemia was present in 50% of deaths among children with parenteral nutrition.

Conclusion
Fluconazole resistance in CPC has increased in the last decade. Newborns receiving parenteral nutrition had a higher proportion of CPC fungemia; we also found higher mortality rates among this population.

Disclosures
All authors: No reported disclosures.
1697. Comparison of Candidemia in Patients in Neonatal Intensive Care Unit and Pediatric Patients and Big Data Analysis on Candidiasis and Candidemia in Korean Children
Authors: Choi Joon-sik , Yoon Yoonsun , Jun Kwak Soon , Kim Yae-Jean 
Published: October 2019

Abstract

Background
Fungal infection is a serious health threat in high-risk pediatric population. Data on pediatric epidemiology of candidemia in Korea are limited.

Methods
A retrospective chart review was performed in patients aged 0–18 years who were diagnosed with candidemia from 2009 to 2018 in a tertiary teaching hospital. Patients were divided into two groups; the neonatal group was comprised of babies with postnatal age 28 days or younger and any patients hospitalized in neonatal intensive care unit and rest of the patients were grouped into pediatric group. Only the first candidemia episode for each patient was included. In addition, the number of patients with candidemia and candidiasis and health cost was estimated among patients 19 years or younger who requested reimbursement to Health Insurance Review and Assessment Service (HIRA) Korea during the 9 year period from 2010 to 2018.

Results
Total 81 patients with candidemia were identified; 42 in the neonatal group and 39 in pediatric group. In neonatal group, prematurity was 95.2%, while hematology-oncology diseases were the most common underlying conditions in pediatric group. Among cultivated candida spp., C. parapsilosis was the most common pathogen (34.6%) followed by C. albicans (32.1%) and C. glabrata and C. tropicalis (11.1%, respectively). In neonatal group, C. parapsilosis (n = 17, 40.5%), C. albicans (n = 16, 38.1%), C. glabrata (n = 5, 11.9%) and unidentified species non-albicans candida (n = 4) were isolated. In pediatric group, C. parapsilosis (n = 11, 28.2%), C. albicans (n = 10, 25.6%), C. tropicalis (n = 9, 23.1%), C. glabrata (n = 4, 10.3%), C. krusei (n = 2), C. orthopsilosis (n = 1), C. lusitaniae (n = 1), C. kefyr (n = 1) were isolated. From HIRA data analysis, 47 patients were found to have candidemia and health cost was estimated as 1.27 million dollars and 66,286 patients were found to have candidiasis and health cost was 2.14 million dollars.

Conclusion
Discrepancies in numbers for candidemia between national reimbursement data and our retrospective data implies a significant underestimation of candidemia. Increased awareness for fungal infection documentation is needed to better estimate the true burden of invasive candida infection in the pediatric population.

Disclosures
All authors: No reported disclosures.
1703. Bacterial or Fungal Co-Infection in Patients with Mucormycosis
Authors: Choi Sungim , Son Hyo-Ju , Jung Jiwon , Jae Kim Min , Pil Chong Yong , Lee Sang-Oh , Choi Sang-Ho , Hee Woo Jun , Soo Kim Yang , Kim Sung-Han 
Published: October 2019

Abstract

Background
There is a growing concern on infections with multiple organisms including fungi in patients with mucormycosis. However, limited data are available on co-infection in patients with mucormycosis.

Methods
Patients with proven mucormycosis were retrospectively enrolled at a tertiary hospital from July 2009 to January 2019. Proven mucormycosis was defined as positive fungal culture result for mucormycosis from a sterile biopsy specimen and/or histologic evidence of tissue invasion of hyphae with positive mucormycosis immunohistochemistry test result. We reviewed other pathogens isolated from sterile or non-sterile sites before and after 7 days from the biopsy for infected tissue that suggested invasive fungal infection.

Results
A total of 61 patients with proven mucormycosis were analyzed. The primary site of infection was as follows; lung (n = 38, 62.3%), rhino-sinus (n = 21, 34.4%), and orbito-cerebral (n = 15, 24.6%). Based on sterile culture results, 4 patients (6.6%) had the evidence of co-infection with other fungi including Candida species (from 3 cases; C. albicans from 1, C. glabrata from 1 and C. krusei from 1), A. flavus (1), and F. solani (1), and 23 patients (37.7%) had the evidence of co-infection with bacteria including E. faecium (VRE) (8), P. aeruginosa (5),coagulase-negative staphylococci (5), methicillin-susceptible S. aureus (4) and others. Based on non-sterile culture results, 10 patients (16.4%) had the evidence of co-infection with fungi other than mucormycosis including Aspergillus species (5, A. fumigatus from 1, Aspergillus not fumigatus from 1 and A. oryzae from 1), Candida species (5, C. albicans from 2, C. tropicalis from 2 and C. glabrata from 1), Penicillium species (1), S. cerevisiae (1) and P. jirovecii (1), and 24 patients (39.3%) had evidence of bacterial co-infection including S. maltophilia (5), methicillin-resistant S. aureus (5), E. faecium (VSE) (3), K. pneumonia (3), P. aeruginosa (3), and others.

Conclusion
Bacterial or fungal co-infections appear to frequently occur as appreciated before in patients with mucormycosis. These data provide us important information to select empirical antifungal and antibacterial agents.

Disclosures
All authors: No reported disclosures.
1725. Shear Forces Induce a Transient, Calcineurin-Dependent Hyper-Virulent Phenotype in Mucorales via Soluble Factors
Authors: Wurster Sebastian , Tatara Alexander M , Albert Nathaniel D , Mikos Antonios G , Ibrahim Ashraf S , Bruno Vincent M , Kontoyiannis Dimitrios P 
Published: October 2019

Abstract

Background
Myocutaneous mucormycosis is encountered in settings of extreme mechanical forces such as combat-related blast injuries or natural catastrophes. It is unclear whether the virulence of Mucorales is affected by mechano-biological factors such as shear forces (SF).

Methods
Spores of clinical strains of Rhizopus arrhizus, Rhizomucor pusillus, and Mucor circinelloides (107/mL in PBS) were either kept in static culture (control) or exposed to shear forces (SF) by magnetic stirring for 30 minutes. Mycelial expansion was monitored in the IncuCyte time-lapse microscopy system. For in vivo studies, the dorsal thorax of wild-type Drosophila melanogaster flies (n = 66–76 per condition) was pricked with a needle dipped in control or SF-exposed spore solutions. Flies were also infected with non-exposed spores suspended in cell-free supernatant taken from SF-exposed spores. Survival was monitored for 7 days post-infection.

Results
Growth rates and morphogenesis of all isolates were not altered by SF. However, SF-exposed spores of all tested Mucorales isolates exhibited increased pathogenicity in the fly model (7-day survival: SF 8–14%, control 36–44%, P < 0.001). Introducing different resting periods after SF resulted in gradual attenuation of the hyper-virulent phenotype, with survival rates of infected flies returning to the level seen with non-SF-exposed spores after 120 min post-SF resting (Panel A). To gain a mechanistic insight, we added cyclosporine A (CsA, 100 µg/mL) during shear challenge. Compared with SF-exposed spores, CsA addition improved 7-day survival of R. arrhizus-infected flies from 1% to 29% (P < 0.001), whereas the pathogenicity of non-SF-exposed spores was not influenced by CsA. Interestingly, supernatants from SF-exposed R. arrhizus rendered non-exposed spores hyper-virulent (Panel B, P = 0.003).

Conclusion
SF induces a transient hypervirulent phenotype of Mucorales. Our findings suggest that soluble mediators contribute to increased pathogenicity. Largely attenuated hyper-virulence in the presence of CsA corroborated the previously described relevance of the calcineurin pathway in fungal mechano-biology. RNA sequencing studies are in progress to identify epigenetic alterations in Mucorales following SF.

Disclosures
All authors: No reported disclosures.
1726. Candida albicans Virulence Genes Induced During Intra-abdominal Candidiasis (IAC) in the Absence of Antifungal Exposure Mediate Echinocandin Resistance
Authors: Clancy Cornelius J , Samanta Palash , Cheng Shaoji , Squires Kevin , Nguyen Minh-Hong 
Published: October 2019

Abstract

Background
We developed and validated a mouse model of C. albicans IAC that mimics peritonitis and abscesses (IAA) in humans, and that is amenable to temporal–spatial transcriptional profiling and virulence studies.

Methods
We measured C. albicans SC5314 gene expression by RNA-Seq (RiboPure extraction; Illumina MiSeq) in triplicate during early peritonitis (within 30 minutes of infection), late peritonitis (24 hours) and IAA (48 hours). Differential expression was defined by ≥2-fold differences at false discovery rate ≤0.01.

Results
≥7 million C. albicans reads were detected in each experiment. 67% of C. albicans reads mapped to coding sequences, covering 93% of open reading frames. The 50 C. albicans genes most highly expressed during early peritonitis were associated with pH (including RIM101 and PHR1) and oxidative stress responses, and adhesion/hyphal growth (e.g., ALS3, HWP1, ECM331, SAP6). The corresponding 50 C. albicans late peritonitis genes were associated with neutrophil/macrophage responses and nutrient acquisition (glyoxylate cycle, fatty acid β-oxidation, iron homeostasis). Responses within IAA included DNA damage and iron metabolism, reflecting stress response and nutrient/metal limitation. The top 50 core gene responses for all stages were associated with adhesion, stress response, and glucose transport. Among the most up-regulated genes in late peritonitis and IAA compared with early peritonitis were those involved antifungal drug resistance (CDR family, MDR1, FLU1, and ERG family), although mice were not exposed to antifungals. Null and reconstitution mutants for genes involved in adhesion (ALS3), copper transport (CCC2), DNA (DDI1) and cell wall damage responses (DAP1 homologs), and glycerol biosynthesis (RHR2) were attenuated for virulence in temporal-spatial fashion during peritonitis and IAA, and/or hyper-susceptible to phagocytosis and echinocandins (table).

Conclusion
C. albicans relies upon diverse biologic processes to cause peritonitis and IAA. Multiple genes induced in response to stress during IAC mediate virulence, phagocyte, and echinocandin resistance. Therefore, pathogenic strategies used by C. albicans during IAC may lessen responses to echinocandin treatment, even in the absence of drug exposure or FKS mutations.

Disclosures
All authors: No reported disclosures.
1727. Candida albicans Phosphatidylinositol-(4,5)-Bisphosphate (PIP2) Directs Aberrant Cytokinesis and Septation in Response to Echinocandins, Which Correlates with Fungicidal Activity and Attenuated Virulence
Authors: Badrane Hassan , Nguyen Minh-Hong , Clancy Cornelius J 
Published: October 2019

Abstract

Background
We previously showed that highly dynamic PIP2, septin, and PKC-Mkc1 cell wall integrity pathway responses correlate with echinocandin activity against C. albicans and attenuated virulence during invasive candidiasis. Our objectives were to determine whether PIP2 dysregulation in response to an echinocandin results in aberrant localization of the septation and cytokinesis apparatus, and to quantitate aberrant localization.

Methods
Live cell imaging (LCI) was performed for 3 hours (Nikon A1 confocal microscope, NIS Elements software; Tokyo) on C. albicans irs4 mutant and wild-type SC5314 expressing fluorescently labeled PIP2 and Cdc10 (septin), Act1 (actin), or Myo1 (myosin).

Results
C. albicans irs4, in which PIP2 5’-phosphatase is disrupted, mislocalizes PIP2 and septins, and over-activates the PKC-Mkc1 pathway in a manner similar to echinocandin-exposed C. albicans SC5314. LCI revealed that PIP2 co-localized with Act1 and Myo1 at aberrant sites in C. albicans irs4, similar to PIP2-Cdc10 co-localization. 83% of co-localizing patches were in cells undergoing active cytokinesis. 78% of patches were at sites of cytokinesis, which reflected both normal budding and abnormal, wide-necked budding; 5% of patches localized to aberrant plasma membrane sites during cytokinesis. 17% of co-localizing patches were in cells that were not undergoing active cytokinesis. 6% of patches were at old cytokinesis sites; 11% of patches were at aberrant plasma membrane sites. Similar PIP2-septin-actin-myosin dysregulation was observed in C. albicans SC5314 immediately upon 4x MIC caspofungin exposure (Figure; videos).

Conclusion
Dysregulated C. albicans PIP2 recruits the septation and cytokinesis apparatus, including septins, actin, and myosin, to sites of incomplete cytokinesis at bud necks and to sites of aberrant, ectopic septation in plasma membranes of both dividing and non-dividing cells. Our data support a model in which a dysregulated PIP2 response is triggered immediately upon echinocandin exposure, over-activates the PKC-Mkc-1 pathway, and correlates with the extent of fungicidal activity and attenuated virulence. PIP2-septation-cytokinesis dysregulation is likely to lead to C. albicans death by promoting cell lysis, or selecting cells to undergo apoptosis.

Disclosures
All authors: No reported disclosures.