bluuebunny/crossref_metadata_2025 huggingface dataset:
2798. Respiratory Viral Infections in Patients with Lymphoma and Multiple Myeloma: Risk Factors Associated with Progression to Lower Respiratory Tract Infection and Mortality
Authors: Martinez Daniel De La Rosa , Vilar-Compte Diana , Batista Marjorie V , Khawaja Fareed , Haddad Lynn El , Ariza- eredia Ella J , Chemaly Roy F , Chemaly Roy F
Published: October 2019

Background

Respiratory viral infections (RVIs) commonly infect immunocompromised patients, and may cause increased morbidity and mortality. However, data on lymphoma and multiple myeloma (MM) patients with RVIs is scarce. The objectives of our study were to identify risk factors for progression to lower respiratory tract infection (LRTI) and fatal outcome in this patient population with RVIs.

Methods

All lymphoma or MM patients at our center who were diagnosed with either influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV) or human metapneumovirus (hMPV) from January 2016 and July 2018 were included in our study. All demographics and clinical data were collected from electronic medical records retrospectively. Patients were classified as having an upper respiratory tract infection (URTI) if nasal wash was positive for the respiratory virus with no radiological evidence of lower respiratory tract involvement. Patients were deemed with lower respiratory tract infection (LRTI) if nasal wash was positive for the respiratory virus and with new or progressive infiltrates on chest imaging with (proven LRTI) or without (probable LRTI) microbiological evidence of the respiratory virus in the lower airways.

Results

A total of 353 patients were included in our study; of those 207 (59%) were MM patients. Most patients were on active chemotherapy (317, 90%) and steroids (242, 69%) at the time of diagnosis. Majority of the patients were infected with PIV and influenza (figure). A total of 150 (43%) patients had an LRTI, of those 36 (24%) were proven. Mortality was 12% (n = 18) within 30 days of onset of infection. Diagnosis of MM, active disease, the use of steroids (regardless of dose), prior stem cell transplantation, nosocomial infection and lymphopenia ≤ 200 cells/mL were significantly associated with LRTI (table).

Conclusion

Although mortality from these different viruses was uncommon, the proportion of patient with LRTI was high. Several risk factors for LRTI were identified. These findings may help us identify patients at high-risk for worse outcomes and who may benefit from antiviral therapies.

Disclosures

Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.
2805. Kinetics of Anti-Zika Virus (ZIKV) Antibodies after Acute Infection in Pregnant Women
Authors: Carpentier Mathieu , Gaete Stanie , de Lamballerie Xavier , Tressières Benoit , Herrmann-Storck Cécile , Vingadassalom Ingrid , Deloumeaux Jacqueline , Funk Anna Louise , Fontanet Arnaud , Hoen Bruno
Published: October 2019

Background

The kinetics and specificity of anti-ZIKV antibodies after acute ZIKV infection is not well known, especially in areas where different flaviviruses circulate. The objective of this study was to describe the kinetics of anti-ZIKV antibodies in pregnant women in whom an acute ZIKV infection was identified during pregnancy.

Methods

Within a cohort of pregnant women living in Guadeloupe and exposed to ZIKV during the 2016 zika outbreak, we identified 65 women who presented with an acute, symptomatic PCR-confirmed ZIKV infection at various times of their pregnancy, with a known date of first Zika symptom. Anti-ZIKV neutralizing antibodies (using a Virus Neutralisation Test (VNT)) and anti-ZIKV NS1 antibodies (using IgM and IgG ELISA Euroimmun® kits) were searched for on frozen serum samples obtained from blood drawn at the time of delivery in all women and at various times between acute infection and delivery in 23 women.

Results

Patients’ mean age was 30 years and ZIKV infection had occurred during the first, second, and third trimester of pregnancy in 14 (21%), 35 (54%), and 16 (25%) women, respectively. ZIKV serology on delivery samples was positive in 65/65 (100%; one-sided 97.5% CI: 94.4%–100%) women by both VNT and IgG ELISA assays and in 5/65 (8%) women by IgM ELISA assay. In these 5 cases, median time between first symptom and sampling date was 36 days. Results of ELISA assays on the intermediate samples were as follows: IgG antibodies were negative in all 5 samples that had been drawn within 7 days of first symptom and positive in the 18 samples that had been drawn afterwards; IgM antibodies were positive in 10 of the 19 samples that had been drawn within 3 months of first symptom and negative in 2 of the 4 samples that had been drawn afterwards.

Conclusion

After acute ZIKV infection, IgG antibodies developed and remained detectable until delivery by a commercially available ELISA assay in all women tested. These antibodies were specific of ZIKV, with concomitantly positive VNT results. From these findings, the absence of ZIKV antibodies at delivery would strongly indicate the absence of infection during pregnancy.

Disclosures

All authors: No reported disclosures.
177. Clinical Outcomes of Daptomycin vs. Anti-Staphylococcal β-Lactams in Definitive Treatment of Methicillin-Susceptible Staphylococcus aureus (MSSA) Bloodstream Infections
Authors: Agnello Sydney , Day Shandra R , Wardlow Lynn , Reed Erica E , Smith Jessica M , Stevenson Kurt , Coe Kelci E
Published: October 2019

Background

The preferred management of patients with MSSA bacteremia includes definitive therapy with intravenous anti-staphylococcal β-lactam antibiotics. In β-lactam allergic or intolerant patients, daptomycin has been targeted as a viable alternative. The objective of this study was to assess clinical outcomes of daptomycin compared with nafcillin or cefazolin for the treatment of MSSA bacteremia.

Methods

This was a retrospective cohort study of patients hospitalized from November 1, 2011 to October 31, 2018 at The Ohio State University Wexner Medical Center with MSSA bacteremia. Patients treated with nafcillin, cefazolin or daptomycin were included with 1:1:1 random selection. The primary outcome was a composite of clinical failure, defined as a change in therapy due to persistent/worsening signs and symptoms, bacteremia recurrence or persistence, or inpatient infection-related mortality. Secondary endpoints included 30-day infection-related mortality, duration of bacteremia, 30-day all-cause mortality and adverse events (AEs) necessitating a change in therapy.

Results

Among patients with MSSA bacteremia, 162 received at least one dose of daptomycin. Of those, 29 received at least 14 days of daptomycin and/or received daptomycin as definitive therapy and thus were included in the analysis. There was no difference in the primary outcome of composite clinical failure comparing daptomycin vs. nafcillin/cefazolin (P = 0.71). In addition, no difference was observed in 30-day infection-related mortality (P = 0.51), duration of MSSA bacteremia (P = 0.9), or 30-day all-cause mortality (P = 0.64). A higher number of AEs necessitating change in therapy were seen in the daptomycin group (P = 0.0002), reflecting initial β-lactam intolerance.

Conclusion

No difference in clinical failure was identified in patients treated with daptomycin vs. nafcillin/cefazolin suggesting that daptomycin may serve as a non-inferior alternative for treatment of MSSA bacteremia. A higher number of AEs occurred in the daptomycin group indicating β-lactam intolerance as a primary indication for daptomycin therapy. Given the small sample size, subsequent studies are needed to further evaluate the use of daptomycin in the treatment of MSSA bacteremia.

Disclosures

All authors: No reported disclosures.
191. Appropriateness of Empiric Antibiotics for Enterobacteriaceae Bacteremia
Authors: Smith Brandon J , Kois Abigail , Gartland Nathan , Tholany Joseph , Arbulu Ricardo
Published: October 2019

Background

Appropriate empiric antibiotic therapy is associated with decreased mortality and recurrence in patients with Enterobacteriaceae bacteremia (EB). Increasing bacterial resistance adds an additional layer to this complex clinical scenario. Swift utilization of appropriate antibiotics is crucial for improved patient outcomes. However, prolonged and excessively broad antibiotic coverage is not without its own complications. Our study aimed to review the appropriateness of empiric antibiotics for EB.

Methods

A retrospective chart review of all patients >18 years of age who were admitted to a single academic community hospital during 2018 EB anytime throughout their hospitalization. The primary endpoint was the appropriateness of empiric antibiotic therapy, defined as receiving active therapy prior to the return of antimicrobial sensitivities that were susceptible to the empiric agents used. Appropriateness was further adjusted for standard of care (SOC) practices. Specifically, despite in vitro susceptibility of piperacillin/tazobactam and cefepime, carbapenem therapy is preferred for ESBL infections.

Results

Our study identified 178 patients with EB. Most common organisms included E.coli (64.6%), K. pneumoniae (11.8%) and P. mirabilis (7.3%). Resistance patterns included 1 CRE (0.57%) and 17 ESBL (9.7%) isolates. Most common sources of infection included urinary (63.5%) and intraabdominal (13.5%). Based on the sensitivity reports of tested isolates, 83.7% of patients received appropriate empiric antibiotics. After adjustment for SOC, 11.8% of ESBL patients (2/17) and 0% of CRE (0/1) patients received appropriate therapy. Comparatively 89.0% of patients without ESBL or CRE (137/154) received appropriate care (P < 0.0001).

Conclusion

The results of this study demonstrate that across our patient population, over 80% of patients received appropriate empiric antibiotics for EB; however, this percentage was dramatically lower for patients with ESBL or CRE infections. This highlights room for improved rapid diagnosis and identification of risk factors predisposing to resistant organisms thereby decreasing the time to appropriate antibiotic therapy.

Disclosures

All authors: No reported disclosures.
194. Description of Positive Blood Culture Results not Identified by Verigene Informs Empiric Antibiotic Selection
Authors: Deri Connor , Nesbitt Whitney , Nelson George , Keefe Jessica
Published: October 2019

Background

Bloodstream infections are a leading cause of mortality amongst hospitalized patients. Optimizing time to pathogen identification and receipt of appropriate antibiotic therapy significantly decreases mortality, morbidity, and length of hospitalization. Rapid diagnostic tests, such as Verigene, assist in the early identification of bacteria and resistance determinants from positive blood cultures; however, Verigene assays are limited to the detection of 13 gram-positive and 9 gram-negative bacteria.

Methods

The purpose of this study was to describe gram-negative and gram-positive aerobic bacteria identified from positive blood cultures with no Verigene target detected and to use the susceptibilities to create an antibiogram to assist in empiric antibiotic selection. A total of 2325 positive blood cultures resulted between January 2017 and October 2018 underwent Verigene testing.

Results

Of the 2325 isolates, 383 (16.5%), had no Verigene organism or resistance mechanism detected. Of these, there were 239 (62.4%) gram-positive isolates, 141 (36.8%) gram-negative isolates, and 3 yeast isolates with 96 unique organisms. Seventy-six (19.8%) of the organisms identified by standard culture, but not Verigene testing, are included on Verigene panel. We analyzed nine common antibiotics active against gram-negative organisms to determine percent susceptibilities against the isolated aerobic pathogens: amikacin (92.1%), cefepime (93.5%), ceftazidime (94.0%), ceftriaxone (79.7%), ciprofloxacin (88.5%), gentamicin (91.9%), levofloxacin (86.9%), piperacillin–tazobactam (83.8%), and tobramycin (85.5%). Additionally, four antibiotics active against gram-positive organisms were analyzed for gram-positive susceptibilities: cefotaxime (91.8%), ceftriaxone (98.1%), levofloxacin (82.5%), and vancomycin (91.8%).

Conclusion

The results of this study provide clinicians with antibiotic susceptibilities against organisms that were not identified through Verigene to better guide timely and appropriate antibiotic therapy against gram-negative and gram-positive aerobic bacteria.

Disclosures

All authors: No reported disclosures.
234. Reversal of Carbapenem and Amikacin Susceptibilities in Isogenic Klebsiella pneumoniae From a Patient with Persistent Bacteriuria
Authors: Rojas Laura J , Marshall Steven , Yasmin Mohamad , Rudin Susan D , Perez Federico , Donskey Curtis , Hecker Michelle , Bonomo Robert A
Published: October 2019

Background

Genomic tools permit a detailed analysis of antibiotic resistance determinants in bacteria, or resistome. Here we discuss variations in antibiotic resistance in K. pneumoniae (Kp) not explained by changes in the resistome

Methods

We compared Kp strains with divergent carbapenem and aminoglycoside susceptibilities. After identification of bacteria, antibiotic susceptibility testing was performed according to CLSI guidelines. Draft genome sequences were generated using Illumina MiSeq (Nextera paired-end library) and assembled using CLC Genomics Workbench (CLC bio, Cambridge, MA). Resistome, plasmid types and MLST were investigated using the CGE platform (http://cge.cbs.dtu.dk), while capsular type and virulence genes were investigated using the Pasteur BIGsDB database (https://bigsdb.pasteur.fr).

Results

While receiving amoxicillin-clavulanate, a 44-year old man with diabetes mellitus and paraplegia with neurogenic bladder grewKp resistant to carbapenems and amikacin from urine. He was treated with fosfomycin and amikacin, followed by imipenem and plazomicin, prior to lithotripsy. Three months later, while off antibiotics, urine cultures grew Kp susceptible to carbapenems and amikacin (figure). Genetic comparison between resistant (November 20, 2018) and susceptible (January 30, 2019) strains revealed they were isogenic, only differing by 559 SNPs (table). Both were ST14, presented capsular type 16, and shared cehalosporinase (blaSHV-28, blaCTX-M-15, blaTEM-1B, blaOXA-1) and aminoglycoside modifying enzyme (AME) (aph(3’’)-Ib, aph(6)-Id, aac(6’)-Ib-cr) genes. Although both had mutations in the outer membrane porin OmpK36, these differed (stop AA125 and frameshift AA183, respectively)

Conclusion

Carbapenem resistance in the initial Kp is likely explained by overexpression of cephalosporinases in combination with changes in membrane permeability, while amikacin resistance is likely due to AMEs. Since no significant gene variation was observed in the susceptible Kp, reversal of resistance was likely due to decreased expression of cephalosporinases and AMEs after antibiotics were stopped. Incorporation of antibiotic history and host factors can explain clinically important changes in antibiotic resistance

Disclosures

All authors: No reported disclosures.
236. The Comparative Utility Of Metagenomic Next-Generation Sequencing and Universal PCR for Pathogen Detection on Cerebrospinal Fluid: A Retrospective Analysis From a Tertiary Care Center
Authors: Kerkhoff Andrew D , Matzko Michelle , Chiu Charles , Miller Steve , Babik Jennifer M
Published: October 2019

Background

Many neurologic syndromes are underpinned by infectious etiologies that are difficult to diagnose. Broad-range, universal PCR (uPCR), and metagenomic next-generation sequencing (mNGS) are emerging molecular techniques that may allow for enhanced pathogen detection in challenging cases. To date, their comparative clinical utility for pathogen detection in cerebrospinal fluid (CSF) has not been described.

Methods

We searched the electronic medical record at University of California, San Francisco for all patients who had mNGS and uPCR results available from the same CSF specimen. Using all available clinical information, patients’ clinical episodes were categorized into one of four categories: (1) confirmed central nervous system (CNS) infection, (2) likely CNS infection, (3) confirmed/likely noninfectious etiology, (4) unknown etiology. We also determined whether mNGS and/or uPCR results changed clinical management.

Results

We identified 75 patients with 78 paired mNGS and uPCR results on CSF. 14/78 (17.9%) had a confirmed CNS infection underpinning their clinical presentation, 11 (14.1%) had a likely CNS infection, 33 (42.3%) had a likely noninfectious cause, and 20 (25.6%) had etiologies that could not be determined. Of the 14 patients with confirmed CNS infection, n = 4 (28.6%) were diagnosed by mNGS and n = 1 (7.1%) by uPCR (Table 1). Most diagnoses missed by mNGS and uPCR were made by CSF serology or from sites other than CSF. Overall, mNGS detected a pathogen in n = 10/78 (12.8%) cases, compared with n = 4/78 (5.1%) using uPCR (Table 2). Among those with a positive mNGS result, n = 6/10 represented a true or likely true positive result, while the remaining were likely contaminants. Of those with a positive uPCR result, n = 1/4 represented a true positive result, while n = 3/4 were likely contaminants. Clinical management was changed by the mNGS or uPCR result in two cases (Table 2).

Conclusion

mNGS appears to have superior clinical utility to that of universal PCR for pathogen detection in CSF samples, in large part because of additional ability to detect DNA and RNA viruses. Further studies are required to determine the clinical contexts in which mNGS is likely to have maximal diagnostic yield and to better define the utility of uPCR for CNS infections.

Disclosures

All authors: No reported disclosures.
243. Transflection Fourier Transform Infrared Spectroscopy as a Real-Time Strain Typing Technique: A Vancomycin-Resistant Enterococcus faecium (VRE) Typing Prospective Study
Authors: Tsutsumi Tamao , Frenette Charles , Doherty Nancy , Sedman Jacqueline , Ismail Ashraf
Published: October 2019

Background

Rapid bacterial strain typing for nosocomial outbreak surveillance is critical for timely outbreak detection and implementation of appropriate infection control protocols in hospitals. Pulsed-field gel electrophoresis (PFGE) remains the gold standard for strain typing, but it has the disadvantages of being time-consuming and costly. Transflection Fourier transform infrared (FTIR) spectroscopy is a nondestructive and reagent-free technique for rapid microbial identification and subspecies-level discrimination. The potential of employing transflection FTIR spectroscopy as a rapid, real-time typing technique was evaluated in the present study.

Methods

Transflection FTIR spectra were acquired from vancomycin-resistant Enterococcus faecium (VRE) isolates obtained from rectal swabs (n = 36) of patients in 6 units at a Montreal hospital over a 3-month period and from environmental screening samples (n = 2). Upon confirmation as VRE using a transflection FTIR spectral database previously developed in our laboratory, isolates were further typed by unsupervised hierarchical cluster analysis and principal component analysis of the FTIR spectral data with the use of a feature selection algorithm.

Results

Analysis of the FTIR data identified independent cases of VRE outbreak in 2 of 6 units; these outbreaks were confirmed retrospectively by PFGE. Based on the PFGE typing results for all 38 isolates included in this study, FTIR spectral analyses successfully identified 95% (n = 18) of isolates related to the outbreaks and 95% (n = 18) of non-outbreak-related isolates, resulting in a false-positive (n = 1), and a false-negative (n = 1), rate of 5%. Additionally, the two environmental isolates were identified as part of the outbreak from one of the outbreak-positive units.

Conclusion

The results in this study indicate that transflection FTIR spectroscopy-based typing can be considered as an alternative typing technique to PFGE, providing real-time results to track the spread of antibiotic-resistant pathogens within hospitals. Furthermore, when combined with the use of a transflection FTIR spectral database, both identification and typing of an isolate can be achieved from a single spectral measurement, thereby reducing the time and cost required for outbreak investigation.

Disclosures

All authors: No reported disclosures.
254. National Trends in the Japanese Distribution of Major Candida Species Causing Candidemia During 2003–2017: A Report by the Epidemiological Investigation Committee for Human Mycoses in Japan
Authors: Kakeya Hiroshi , Shibata Wataru , Yamada Koichi , Kaneko Yukihiro
Published: October 2019

Background

Candida species are a common cause of nosocomial bloodstream infections, and candidemia is associated with high mortality rates among adults and neonates. There is limited epidemiological data regarding candidemia in Japan. Therefore, the Epidemiological Investigation Committee for Human Mycoses in Japan performed a retrospective epidemiological survey of candidemia and causative Candida species.

Methods

Blood culture results from 2003 to 2017 were retrospectively evaluated. The data included the center-specific numbers of annual blood cultures, bacterial isolates that included fungi, numbers of fungi, and Candida species. Data were collected from 10 Japanese university hospitals located on all over Japan.

Results

A total of 433,961 blood cultures were included. The prevalence of fungi in all cultures and in positive cultures were 0.53 ± 0.07% and 3.78 ± 0.47%, respectively. Among the results that were positive for Candida species (N = 2,270), C. albicans was the most common species (39.2%) and was followed by C. parapsilosis (22.8%), C. glabrata (15.6%), C. tropicalis (9.7%), C. krusei (2.2%), and others. And the temporal changes in the five major Candida species’ distributions were analyzed. The frequency of C. albicans was 48% in 2003 and 2004, approximately 40% during 2005–2011, approximately 30% in 2012 and 2014, and 40% in 2015–2017. The next most common species were C. parapsilosis and C. glabrata. The frequency of C. parapsilosis was approximately 16% in 2003, approximately 28% during 2005–2009 and 21.7% during 2010–2017. There was a significant difference in the C. parapsilosis rates for the first and second halves of the study period (24.8% vs. 21.7%, P = 0.03). The frequency of C. glabrata was <10% during 2004–2006, and approximately 17% after 2010. C. glabrata was significantly more common in the second half of the study period, compared with in the first half (12.0% vs. 17.3%, P = 0.004). The frequency of C. tropicalis remains stable, and C. krusei was significantly less common in the second half of the study period, compared with in the first half (4.3% vs. 1.6%, P <0.001).

Conclusion

The frequency of C. albicans has varied in each year in Japan, while that of C. glabrata has increased. Additional surveys are needed to continuously monitor the trends in the distribution of candidemia in Japan.

Disclosures

All authors: No reported disclosures.
260. Detection of Aspergillus fumigatus Infection in Mice with 2-Deoxy-2-[18F]fluorosorbitol
Authors: Yu Yohan , ji Kang Seung , Kim Dong-Yeon , Pyo Ayoung , Ji Sehyeon , Chuluunkhuu Baigali , Kim Soosung , un Shin Sung , Hoon Oh Tae , Jin Kim Uh , Eun Kim Seong , Jang Hee-Chang , Park Kyung-Hwa , In Jung Sook , Min Jung-Joon
Published: October 2019

Background

Invasive aspergillosis is a major cause of infectious morbidity and mortality in immunocompromised patients.However, definitive diagnosis of invasive Aspergillus infection is still difficult due to the lack of a rapid, sensitive and specific diagnostic methods. In this studies, we investigated 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS) which has been reported to be accumulated in Gram-negative bacteria but not in Gram-positive bacteria or healthy mammalian or cancer cells, for the imaging detection of Aspergullus fumigatus infections with PET in vivo.

Methods

[18F]FDS was synthesized by reduction of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) using NaBH4. When the reaction was complete, the mixture was adjusted to a pH value to 6.5–7.5. Subsequently, the solution was filtered directly into a sterile product vial through a Sep-Pak Alumina N cartridge with a sterile filter. The probe uptake assay was performed by incubating bacterial cell and fungi with [18F]FDS (20 µCi) at 37°C for 2 h. Female BALB/c were immunosuppressed with cyclophosphamide and cortisone acetate prior to A. fumigatus intranasal, intramuscular, brain infection. The mircoPET images were obtained at 2 h after i.v. injection of [18F]FDS in infected mice.

Results

In vitro uptake test revealed significantly higher accumulation of [18F]FDS at 2 hin A. fumigatus, C. albicans and R. oryzae rather than with bacterial strains (Figure 1). PET imaging of BALB/c mice with pulmonary A. fumigatus infections showed obvious accumulation of [18F]FDS in the infected lungs compared with control (Figure 2). [18F]FDS PET imaging also detected A. fumigatus muscle and brain infection in mice. In infected shoulder muscle of mice, [18F]FDS PET imaging showed high legion-to-background ratio at 2 h. (4.05 ± 1.59, Figure 3).

Conclusion

[18F]FDS PET study demonstrated stable uptake in infected tissue with A. fumigatus and rapid clearance from the blood and other organs. [18F]FDS could be a useful imaging probe visualizing the invasive aspergillosis in vivo.

Disclosures

All authors: No reported disclosures.
263. Advances in Diagnosis of Progressive Coccidioidomycos: Experience in 164 Cases and 508 Controls
Authors: Myers Robert , Eric Holbrook , Wheat Lawrence J , Kassis Christelle , Durkin Michelle
Published: October 2019

Background

Antibody detection is the main method for diagnosis of coccidioidomycosis but has limitations including sensitivity and turnaround time. The MVISTA Coccidioides antigen enzyme immunoassay (EIA) is recommended for testing CSF in suspected Coccidioides meningitis. The early reports on urine and serum antigen testing evaluated small numbers of patients who were mostly immunocompromised with advanced disease.

Methods

A retrospective study, including all patients in whom Coccidioides antigen testing was performed between January 2013 and May 2017, was conducted at Maricopa Integrated Health System (MIHS). Sensitivity and specificity of antigen testing at MiraVista Diagnostics and antibody testing at MIHS or commercial laboratories were evaluated in 164 cases and 508 controls.

Results

The sensitivity of antigen testing was 51% and specificity was 99%. The sensitivity of antigen detection was highest if both urine and serum were tested (57%) than if only urine was tested (38%). The sensitivity of antibody testing was 84% and the specificity was 94% by immunodiffusion (ID). The sensitivity and specificity of antigen or ID antibody testing both were 94%. Sensitivity of antigen testing was 57% in proven and 58% in probable cases, ID antibody in 85% of proven and 75% of probable and antigen or ID antibody in 93% of proven and 95% of probable cases. Antigen was detected more often in disseminated (79%) than pulmonary cases (42%) as was ID antibody, 91% and 79%, respectively. Antigen testing was more sensitive in immunocompromised (76%) than non-immunocompromised patients (41%) while ID antibody was less sensitive in immunocompromised (74%) than in non-immunocompromised patients (93%). Combined antigen and ID antibody testing provided the highest sensitivity, 94% in all cases, 94% in immunocompromised and 95% in non-immunocompromised patients.

Conclusion

These findings support testing urine and serum for Coccidioides antigen and serum for ID antibodies for diagnosis of progressive pulmonary or disseminated coccidioidomycosis.

Disclosures

All authors: No reported disclosures.
264. Biofilm cells of Trichosporon asahii Show Higher Resistance Than Planktonic Cells to Various Abiotic Stresses
Authors: Metok Yang , Hosuru Subramanya Supram , Nayak Niranjan
Published: October 2019

Background

Biofilms of Trichosporon asahii are known to resist the effects of antifungal drugs, but the study of their susceptibility to various abiotic stresses remains sparse. This study was thus undertaken to compare the level of in vitro resistance of T. asahii biofilm and planktonic cells to various stress factors.

Methods

In this study, one T. asahii clinical isolate identified by amplifying IGS1 sequencing and one reference strain (NCCPF940033) were used. Biofilm and planktonic cells of T. asahii were exposed to increasing concentrations of NaCl (0.5–6 M) and d-sorbitol (3–13 M) for inducing osmotic stress; H2O2 (5–50 mM), menadione sodium bisulfate (0.048–100 mM) and ox bile (1–12%) for oxidative stress; PH 1 to 13 for PH stress; congo red (600–10,000 µg/mL) for cell wall stress; CuSO4·5H2O/ZnSO4/FeSO4 (1.25–2,560 mM) and MgSO4 (250–3,000 mM) for metal stress. The biomass and metabolic activity of biofilms were quantitatively determined by crystal violet method and XTT reduction assay, respectively. Further, spot assay of serially diluted (10–1 to 10–6) planktonic cells was performed on agar plates containing stress and non-stress control to determine relative percentage growth of strains.

Results

Biofilm cells of both the strains exhibited significantly higher (ANOVA) stress resistance than planktonic cells and on an average showed at least 100 times more resistant to stresses than planktonic cells [Minimum Biofilm Eradication Concentration (MBEC) vs. Minimum Inhibitory Concentration (MIC)]; H202 >50 mM vs. 10 mM, Ox bile >12% vs. 2%, Menadione >100 mM vs. 0.39 mM, Zn/Fe/Cu >2,560 mM vs. 10 mM, Mg >3,000 mM vs. 1,000 mM, NaCl >6 M vs. 1.5 M, d-sorbitol >13 M vs. 5 M and Congo red >10,000 µg/mL vs. 800 µg/mL. Besides optimal PH 5–10, extreme acidic and alkaline PH led to complete inhibition of viable planktonic cells. Highest biomass reduction (77.2%) and highest viability inhibition (69%) of biofilm were observed at PH 3 and 13, respectively. Menadione reduced 86.9% biomass and 89.3% viability which accounted the highest biofilm inhibition.

Conclusion

This is the first report on comparing the susceptibility of planktonic and biofilm T. asahii cells to various stress factors. The increased resistance of T. asahii biofilm may serve as a survival advantage against the host adversity.

Disclosures

All authors: No reported disclosures.
266. Clinical Profile and Treatment Outcomes of Candida auris Isolates from a Tertiary Care Hospital in South India
Authors: Warrier Anup R , Wilson Arun , Babu Rachana , Prakash Shilpa , Bhargava Madhav
Published: October 2019

Background

Candida auris is an emerging multidrug-resistant fungus that is rapidly spreading worldwide. In publications from India, it has already accounted for >5% of candidemia in a national survey of ICUs and as much as 30% of candidemia at individual hospitals,but data on treatment outcomes is scarce. This study reviews the various clinical syndromes in our case series, the treatment regimens we opted and their clinical outcomes.

Methods

The present study was a retrospective observational analysis of candida auris isolates obtained from patients admitted in a Aster Medcity, Kochi. Duration of study was 4 months (September 2018 to December 2018). Laboratory confirmation of the candida auris isolates was done as per CDC recommendations for Vitek2. Vitek2 was also used for obtaining the antifungal sensitivity pattern for these isolates.

Results

We had 18 cases of Candida auris identified. The most common syndrome was surgical site infections, 9 out of 18 (50%), followed by Catheter-Associated Urinary Tract Infection (CAUTI 5/18; 28%). We had 3 patients with Central Line-Associated Blood Stream Infections (CLABSI) and one patient who had secondary peritonitis. The overall mortality was 28% (5/18)—mostly contributed by the CLABSI. Considering breakpoints from CLSI as well as CDC, all isolates had their minimum inhibitory concentration (MIC) in the sensitive range for Caspofungin. Both Amphotericin b and Voriconazole had MICs in susceptible range for less than 50% of the isolates and almost all isolates were having very high MICs for Fluconazole, highlighting the increased levels of antifungal resistance which has made this Candida species notorious.

Conclusion

Candida auris is an emerging nosocomial pathogen in India with serious outbreak potential. The anti-fungal susceptibility is indicative of a multidrug-resistant pattern—with favorable MIC to Echinocandin and Voriconazole. Complicated bloodstream infections had high mortality inspite of early Echinocandin use. Of note, 6 patients out of 18, were managed successfully without any anti-fungal use; as they had either mild UTI (fever spikes resolved with catheter removal) or superfical SSI which could be treated with topical wound management.

Disclosures

All authors: No reported disclosures.
269. Epidemiology and Outcomes of Invasive Aspergillosis (IA) Among Pediatric Immunocompromised Patients: A 12-Year, Single-Center Experience
Authors: Al Dhaheri Fatima , Lee Rose , Nakamura Mari M , Marty Francisco M
Published: October 2019

Background

IA remains a leading cause of morbidity and mortality in immunocompromised children, and our understanding regarding epidemiology and outcomes of IA are limited and based on adult studies.

Methods

We conducted a retrospective evaluation of cases of proven or probable IA according to the 2008 EORTC/MSG criteria cared for at Boston Children’s Hospital from 2007 to 2019. We collected data including demographics, clinical characteristics, diagnosis modality, antifungal treatment, and survival. Survival curves over one year were estimated using the Kaplan–Meier method and univariate and multivariate Cox modeling was used to evaluate for risk factors for mortality.

Results

67 patient cases were identified, 20 (30%) with proven IA and 47 (70%) with probable IA. The mean age at diagnosis was 11.9 years (6 months–28 years). Underlying conditions included hematopoietic-cell transplantation (HCT) in 45%, cancer in 21%, and solid-organ transplantation in 18%. Pulmonary IA was the most common (70.1%) presentation. Diagnostic modalities included positive microbiology alone (18%), fungal PCR alone (1.5%), galactomannan alone (28%), and multiple modalities for the remaining cases (52.5%). 44.8% of patients were neutropenic at diagnosis and 78.5% of patients with malignancies were receiving chemotherapy. Immunosuppressive drugs included glucocorticoids in 34.3%, calcineurin inhibitors in 31.3%, and IMDH inhibitors in 25.3%. Voriconazole was the most common treatment used (72%). Twenty-two (33%) deaths occurred in the cohort attributable to IA (6 of which underwent autopsies and 4 had histopathological confirmation) Most deaths occurred in the BMT patients (15 patients, 45% of deaths). The 6 week mortality was 18% while the 12 week mortality was 25.4%. No antifungal or immunosuppressive regimen had a statistically significant impact on mortality.

Conclusion

We demonstrate in our >10-year retrospective cohort analysis of immunocompromised hosts that IA is associated with 49% all-cause mortality with particular impact on the BMT population. No protective nor harmful association was also noted with a particular antifungal or immunosuppressive regimen.

Disclosures

All authors: No reported disclosures.
290. Hepatitis E Virus Serostatus: A Retrospective Assessment of Demographics and Comorbidities to Assess High-risk Populations
Authors: Stone Eric C , Esquer Garrigos Zerelda , Sohail Muhammad R , Razonable Raymund R , O’Horo John C
Published: October 2019

Background

Demographic and epidemiologic characteristics of Hepatitis E virus (HEV) infected patients in the United States are not well-described. HEV infection may result in severe complications and lead to chronic infection and cirrhosis, especially in immunocompromised patients. There are no widely accepted guidelines for HEV screening and testing in the United States. Identifying traits of known seropositive patients and comorbidities may inform better screening and prevention strategies. In this study, we describe rates of liver disease, transplant status, chronic kidney diseases, and diabetes mellitus among patients serologically tested for HEV at our institution.

Methods

We retrospectively reviewed all patients for whom HEV IgM or IgG serologic testing was performed across the Mayo Clinic enterprise using the Advanced Cohort Explorer tool. For patients with any documented HEV serologic test, we abstracted baseline patient characteristics and underlying comorbidities at the time of testing. We then grouped subjects according to serologic testing results by antibody type. Survival at one year from date of testing was also assessed.

Results

A total of 979 unique subjects were identified. The preponderance of subjects was Caucasian (781, 79.8%). Of subjects tested for HEV with serology, 123 (12.6%) had any positive serology. Breakdown of baseline characteristics and selected comorbidities are summarized in Table 1. The largest proportion of subjects, 458 (46.8%), were both IgG and IgM negative and 432 subjects received only IgM or IgG testing. Liver disease was more prevalent in patients with positive vs. negative testing (5.8% vs. 2.1%) as was higher age (average 55.1 years vs. 52.2). One-year survival was similar in all groups.

Conclusion

HEV serology is not commonly tested. Among those tested, seropositivity is uncommon. Our data show higher HEV seropositivity in older adults, which may represent increase risk of exposure over time. Higher percentage of positive testing was also observed in subjects with liver disease, which may indicate a possible etiologic association. Further population-based studies are needed to estimate prevalence of HEV infection and associated liver disease, outcomes in infected patients, and indications for testing in at-risk populations.

Disclosures

All authors: No reported disclosures.
292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
Authors: Rohde Maximilian , Carter Wendy
Published: October 2019

Background

Direct-acting antivirals (DAAs) have substantially increased the rate of sustained virologic response in patients with hepatitis C compared with interferon therapy (IFN), while causing fewer adverse events. However, five recent case series and retrospective studies (Table 1) have reported a possible link between DAA treatment for hepatitis C and reactivation of varicella-zoster virus (VZV). Reported VZV reactivation rates in these studies were 0.23%, 0.72%, 1.50%, 1.74%, and 8.00%.

Methods

To further investigate these reported observations, we analyzed 37 prospective registrational DAA clinical trials, including 13,816 subjects in our analysis. Treatment arms were classified as DAA (N = 7,901), DAA + ribavirin (RBV) (N = 4,348), placebo (N = 997), DAA + IFN (N = 327), or IFN (N = 243). 1,068 (8%) subjects were HIV-coinfected, and 9,024 (65%) subjects were over age 50, both known risk factors for VZV reactivation. Herpes zoster (HZ) events occurring while on-treatment or during follow-up were identified using MedDRA preferred terms.

Results

We identified 36 (0.26%) subjects with HZ events. Thirty-two cases occurred during treatment, and 4 during follow-up. One event was considered severe, and the remaining were mild or moderate in severity. Of the 36 total cases reported, 11 (0.14%) were in DAA arms, 21 (0.48%) were in DAA+RBV arms, 4 (0.40%) were in placebo arms, and none were in DAA+IFN or IFN arms (Table 2). For a more direct comparison, we examined a subset of eight trials (N = 3835) containing both a DAA or DAA+RBV arm and a placebo arm. Of the 8 (0.21%) cases reported, 4 (0.14%) were in the DAA/DAA +RBV arms (N = 2838), and 4 (0.40%) were in the placebo arms (N = 997). While rates of VZV reactivation were increased for HIV-coinfected subjects (0.47% vs. 0.24%) and those over age 50 (0.31% vs. 0.17%) (Table 3), they remained similar to or lower than rates reported in previous studies (Table 1).

Conclusion

Data from prospective DAA clinical trials including 13,816 subjects do not provide evidence for an association between DAAs and VZV reactivation as reported in recent case series and retrospective studies. Low rates of VZV reactivation were observed, particularly in low-risk groups such as those below the age of 50, as would be expected in naturally occurring reactivation.

Disclosures

All authors: No reported disclosures.
328. Kaposi Sarcoma in High Population ART Utilization Setting: An Observational Study in Botswana
Authors: Hysell Kristen , Musimar Zola , Elmore Shekinah N C , Kayembe Mukendi K A , Suneja Gita , Efstathiou Jason , Kovarik Carrie , Wanat Karolyn , Slaught Christa , Triant Virginia A , Lockman Shahin , Dryden-Peterson Scott
Published: October 2019

Background

Despite population antiretroviral treatment (ART) utilization exceeding UNAIDS 90-90-90 targets, Kaposi sarcoma (KS) remains one of the most prevalent malignancies in Botswana. We sought to examine the characteristics and outcomes of KS in the context of high ART utilization.

Methods

Consenting patients at one of four oncology centers for KS treatment were enrolled prospectively (October 2010 to March 2019) and followed quarterly for 5 years. Survival was estimated using Kaplan–Meier estimator and predictors assessed with Cox proportional hazards modeling.

Results

A total of 408 KS patients were enrolled and of those, 396 (97%) were HIV-positive and included in analyses. Median age at diagnosis was 40 years (IQR: 34.1, 46.7) and 247 patients (62%) were male. The median CD4 cell count at the time of KS diagnosis was 253 cells/mL (IQR: 134, 364) and 279 (73%) were receiving ART at the time of KS diagnosis. Among those on ART, the median duration of ART prior to KS diagnosis was 11.9 months (IQR: 2.7, 46.7). The proportion receiving ART prior to KS increased during the surveillance period from 58% to 80% (P < 0.001). Of the 248 (62.6%) patients with recent measurement, 91% had HIV-1 RNA < 1000 copies/mL. Five-year overall survival was 73% (95% CI 68–78%). In multivariable analysis, Female sex and higher income were associated with improved survival, but not age or CD4 cell count. The duration of ART was significantly associated with survival (P = 0.02), with improved survival for individuals on ART < 6 months compared with longer ART (HR 0.54; 95% CI 0.29–0.98). The incidence of KS cases declined by nearly 50%, but has remained relatively stable since 2015.

Conclusion

Survival rates in this cohort were comparable to other KS cohorts. While KS treatment initially declined with ART expansion, KS remains a significant disease burden in Botswana with 80% of cases occurring among individuals receiving ART.

Disclosures

All authors: No reported disclosures.
338. Patients Living with HIV Infection Are Less Likely to Receive the Correct Intensity of Statin Therapy for Cardiovascular Disease Risk Reduction
Authors: Schafer Jason J , Patel Roshni , Hastain Nicholas V , Miano Todd
Published: October 2019

Background

Patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD) should receive risk reduction interventions recommended in current guidelines. This includes routine ASCVD risk assessments and when eligible, statins selected and dosed to achieve appropriate low-density lipoprotein cholesterol (LDL-C) reduction. Recent studies suggest that statins are underprescribed in PLWH, but none have assessed if eligible patients receive the correct statin intensity compared with uninfected controls.

Methods

This retrospective study evaluated statin eligibility and prescribing among consecutive patients in an HIV clinic and an internal medicine clinic at an urban, academic medical center from June-September 2018. To determine statin eligibility, the 2013 American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk was used. Patients aged 40–75 that had a lipid panel obtained within the last year were included. All patients were assessed to determine eligibility for and actual treatment with appropriate statin therapy. Characteristics of patients correctly and incorrectly treated with statins were compared with chi-square testing and predictors for receiving correct statin therapy were determined with logistic multivariable regression.

Results

A total of 221/300 study subjects were statin eligible (Table 1). While many eligible PLWH were receiving a statin (54/106), considerably fewer were on the correct statin intensity for their benefit group (33/106). In the univariate analysis (Table 2), correctly treated patients were less likely to be PLWH or female, and were more likely to have polypharmacy and hypertension. In the multivariable logistic regression analysis (Table 3), PLWH (OR 0.26, CI95 0.12–0.57)) were significantly less likely to receive correct statin therapy, while those with concomitant polypharmacy were significantly more likely to receive correct statin therapy (OR 5.52, CI95 1.94, 15.69).

Conclusion

This study reveals that PLWH may be at a substantial disadvantage in terms of receiving correct statin therapy for ASCVD risk reduction. This finding may be particularly important given the heightened risk for ASCVD in this patient population.

Disclosures

All authors: No reported disclosures.
344. HIV and Diabetes in the Era of Antiretroviral Therapy
Authors: Sabbaj. Spieler Gabriel , Overton Edgar T , Willig Amanda , Burkholder Greer A , Varshney Mohit , Westfall Andrew O
Published: October 2019

Background

With advancements in ART, non-AIDS comorbidities are becoming more common among people living with HIV (PWH). In this analysis, we identified PWH followed at a single Ryan White HIV Clinic in Alabama and determined the overall prevalence of diabetes (DM). We then evaluated the cohort for risk factors associated with DM.

Methods

The records of all PWH who attended at least one routine care HIV primary provider visit from 2009 to 2018 at the UAB 1917 HIV Clinic in Birmingham, AL were abstracted. We defined DM as individuals having ≥1 of the following: (1) diagnosis of DM and receiving any diabetic medication, (2) Hgb A1c ≥ 6.5%, (3) any glucose >200 mg/dL. We evaluated the association of traditional, demographic, and HIV-specific risk factors with PWH with and without DM using Chi-square and Wilcoxon rank-sum testing. Univariate significance and amount of missing data were considered when constructing the multivariable logistic regression model to identify independent associations.

Results

Of the 5247 PWH assessed, 1178 were female (23%), 45 transgender persons (1%); 3235 (62%) black, 1834 (35%) white. At baseline, the median age was 37.5 years, median BMI 24.5 kg/m2, median CD4+ count 333 c/mm3. Overall, 1110 PWH developed DM (21%). By univariate analysis, numerous traditional, demographic and HIV-related risk factors were associated with diagnosis of DM (see Table 1). By multivariable analysis, the following factors were independently associated with DM: traditional (antihypertensive use, aspirin use, glucocorticoid use, statin use, comorbid CKD, comorbid liver disease), demographic (black race, female gender, older age), and HIV-related (nadir CD4) (P < 0.05 for all).

Conclusion

Over 20% of PWH had a diagnosis of DM. Both traditional and HIV-related factors were independently associated with DM. Notably, lower nadir CD4 and longer time to ART initiation were key HIV-related factors. Additionally, a majority of PWH with DM had multimorbidity (85%) and polypharmacy (90%). Despite the lower complexity of modern ART, the care of PWH remains challenging, partly because of cardiometabolic comorbidities, including DM. Effective diabetes prevention and treatment strategies for PWH should be prioritized.

Disclosures

All authors: No reported disclosures.