bluuebunny/crossref_metadata_2025_split 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.