bluuebunny/crossref_metadata_2025 huggingface dataset:
2568. Mechanisms of a Specific Probiotic Comprised of Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2 that Interferes with Clostridioides difficile 20291 Toxin Production
Authors: Gunaratnam Sathursha , Diarra Carine , Paquette Patrick D , Ship Noam , Millette Mathieu , Lacroix Monique
Published: October 2019

Background

Clostridioides difficile infections (CDI) result from antibiotic use and cause severe diarrhea (C. difficile-associated diarrhea, CDAD) which is life-threatening and costly. A specific probiotic containing Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2 (Bio-K+) has demonstrated benefits in preventing CDI and has a strong inhibitory effect on the growth of several nosocomial C. difficile strains in vitro. Many Lactobacilli can inhibit CD growth though lactic acidification. Here, we have investigated novel acid-independent mechanisms by which these strains impair C. difficile virulence.

Methods

The hypervirulent strain C. difficile R20291 was co-cultured anaerobically with Bio-K+ probiotic strains in various media and glucose concentrations (5 g/L, 3 g/L, 0 g/L), for 24 hours at 37°C. Parameters such as Log CFU, pH, Toxin A and B, cell cytotoxicity were measured. Statistical comparisons using ANOVA one-way was performed in order to determine whether the groups were significantly different.

Results

At 5 g/L glucose, no C. difficile toxin was produced and co-culture with these lactobacilli resulted in potent acidification and growth inhibition. At 3 g/L glucose, C. difficile toxin production occurred and acidification by the lactobacilli resulted in growth inhibition as well as >99% reduced Toxin A and B production. In the absence of glucose and a starting pH of 7.0, TY broth, the lactobacilli did not acidify the medium and C. difficile growth was normal yet Toxin A and B production was partially reduced at, 20% and 41% lower. Toxin B from the supernatant of C. difficile grown in TY was cytotoxic to human fibroblast cells, but this was less cytotoxic when co-cultured with the Lactobacilli.

Conclusion

These results suggest that the combination of L. acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2 interferes with C. difficile pathogenesis through: 1) inhibition of C. difficile growth (via lactic acid secretion), 2) reduced toxin A/B synthesis and (3) toxin neutralization. These results might explain the strain specificity of Bio-K+ probiotic bacteria in potentially preventing C. difficile-associated diarrhea in antibiotic treated patients.

Disclosures

All authors: No reported disclosures.
2572. The Impact of Antibiotics on the Composition of the Vaginal Microbiota
Authors: Sharara Sima L , Ghanem Khalil , Brotman Rebecca , Robinson Courtney , Ravel Jacques , Tuddenham Susan
Published: October 2019

Background

The impact of antibiotics on the composition of the vaginal microbiota (VMB) is poorly defined. We analyzed the VMB of women before and after the use of antibiotics.

Methods

We used samples from a cohort of reproductive-aged women who submitted vaginal swabs and clinical data over a 2-year period. 16S rRNA gene sequencing was conducted, and VMB was categorized into 7 community state types (CSTs): four dominated by Lactobacillus spp. and three low in Lactobacillus, dominated by Streptococcus spp. (CST VI), Bifidobacterium spp. (CST VII), or comprising a variety of anaerobes (CST IV). CSTs were further categorized as Lactobacillus-dominated (LD) or non-Lactobacillus-dominated (NLD). We compared paired vaginal samples collected within 48 hours prior to and 48 hours after completion of antibiotics in 40 women (N = 10 systemic metronidazole, N = 6 vaginal metronidazole, N = 5 trimethoprim-sulfamethoxazole, N = 9 amoxicillin, N = 5 azithromycin, N = 5 other), to time-matched samples in 56 controls. Exact logistic regression was used to evaluate the impact of antibiotics on LD status controlling for baseline CST, race, menses, and hormonal contraceptive use.

Results

Women who received antibiotics were 25 times more likely to be in an LD state after antibiotics compared with those who did not receive antibiotics (p = 0.0017). NLD to LD transitions occurred almost exclusively in patients receiving metronidazole. Of 13 women who began in NLD (N = 12 in CST IV) and then received metronidazole, 84.6% (N = 11) transitioned to LD (CST III, L. iners-dominated). Of 7 women who started in an NLD state and received non-nitroimidazole antibiotics, only two (receiving clindamycin or amoxicillin) transitioned to an LD state. None of the 20 women who began in a LD state transitioned to a non-LD state after antibiotics. 12 controls were in an NLD state at baseline, of these 11 remained NLD at the second time point. 44 controls started in an LD state and all remained in LD at the second time point.

Conclusion

In the short term, metronidazole results in a transition of the VMB from a NLD to a L. iners-dominated state. There was little impact of non-nitroimidazole antibiotics on the VMB. Studies assessing longer-term impact of antibiotics on the composition of the VMB are needed.

Disclosures

All authors: No reported disclosures.
2573. Impact of Anaerobic Antibacterial Spectrum on Cystic Fibrosis Lung Microbiome Diversity and Pulmonary Function
Authors: Jason. Bozzella Michael , Chaney Hollis , Sami Iman , Perez Geovanny , Koumbourlis Anastassios , Bost James , Freishtat Robert , Crandall Keith , Hahn Andrea
Published: October 2019

Background

Next-generation sequencing has shown the cystic fibrosis (CF) lung microbiome to be a complex polymicrobial community. Anaerobic bacteria decrease in relative abundance with older age and disease progression, and may impact host inflammatory state. Persons with CF suffer from recurrent pulmonary exacerbations (PEs) that are treated with broad-spectrum antibiotics. Our objectives were to examine the effect of broad-spectrum (BS) vs narrow-spectrum (NS) anaerobic antibacterial treatment on bacterial diversity, and on pulmonary function recovery.

Methods

Pulmonary function tests (PFTs) and respiratory samples were collected as part of a prospective 18 month longitudinal study in CF patients at 4 time points, baseline (B), pulmonary exacerbation (E), end of exacerbation treatment (T), and follow-up (F). Treatment antibiotics were classified as broad or narrow based on anaerobic activity. 16S rRNA sequencing generated operational taxonomic units for analysis. Alpha diversity (relative abundance) was calculated via Shannon Index and Inverse Simpson formulas and β diversity (similarity in community composition) by Morisita-Horn (MH). Differences in diversity indices and PFTs were compared with regard to BS vs NS anaerobic activity, and statistical significance determined by GLS regression.

Results

Changes in alpha diversity for BS vs NS were not significantly different (P > 0.05) (Figures 1 and 2). Community composition measured by MH was consistently more similar for NS than BS (T-B: 0.66 vs. 0.45, P = 0.04; F-B: 0.75 vs. 0.47, P < 0.01) (Figure 3). Recovery of forced expiratory volume in 1 second (FEV1) from E to F was significantly higher in the NS group (25.4 vs. 21.0, P < 0.01) (Figure 4).

Conclusion

While antibiotic spectrum did not influence bacterial abundance, BS therapy led to higher changes in community composition from B and E onset following antibiotic administration compared with NS therapy. The differences in β diversity suggest BS therapy can have a lasting impact on community composition. As those receiving NS therapy had similar or better recovery of pulmonary function than those with BS, there is no indication that NS therapy leads to worse clinical outcomes. A limitation may be that children receiving BS therapy tended to have more severe disease.

Disclosures

All authors: No reported disclosures.
151. Comparing the Clinical Utility of Rapid Diagnostic Tests for Gram-Negative Bloodstream Infection Using a Desirability of Outcomes Ranking
Authors: Claeys Kimberly C , Schlaffer Kathryn , Kpadeh-Rogers Zegbeh , Jiang Yunyun , Evans Scott R , Kristie Johnson J , Leekha Surbhi
Published: October 2019

Background

Rapid diagnostic testing (RDT) technology in bloodstream infections (BSI) has outpaced provider understanding of how to effectively use it. To optimize the use of RDT platforms and antibiotic therapy, decision makers must determine which RDTs to implement at their institutions. A thorough understanding of which platform to choose extends beyond simple analytic measures of sensitivities and specificities and should include a robust analysis of how these RDTs could impact clinical decisions.

Methods

Retrospective study of adult patients with Gram-negative (GN) BSI from at University of Maryland Medical Center. The clinical microbiology laboratory used Verigene® BC-GN in clinical practice. Discarded blood samples were run on BioFire® FilmArray BCID. Final organism identification/susceptibility, antibiotic exposures, and clinical outcomes were reviewed. DOOR was applied to theoretical therapy decisions based on both actual prescribing adherence to institutional algorithm recommendations; 1 being most and 6 being least desirable (Table 1). A partial credit scoring system was applied to DOOR from most (100) to least desirable (0) outcome. Comparisons were made in a paired manner.

Results

77 patients met inclusion. The median age was 58 (IQR 47, 68), 44.2% were in the ICU, and 75.3% had ID consult within 24 hours of BSI. Organism identification included: E. coli (35.1%), K. pneumoniae (23.4%), P. mirabilis (10.4%), S. marcescens (10.4%), Enterobacter spp. (9.4%), P. aeruginosa (3.9%). The only resistance determinant was CTX-M (11.6%). An antibiotic change occurred in 26.2% of cases, divided between antibiotic escalation and de-escalation. Based on the actual utilization of RDT results, median DOOR was not different between BC-GN and BCID (3 [IQR 3.4] vs. 4 [IQR 3.4], P = 0.44). Using a partial credit scoring system, the mean score was not different between platforms (49.8 [SD 26.8] vs. 47.7 [SD 20.3], P = 0.44). Through pairwise comparisons, BC-GN would have resulted in an optimal outcome of 15.3% (95% CI 4.7% to 19.3%) more often than BCID.

Conclusion

Based on the actual use of RDTs for GN BSI there was no difference in potential clinical outcomes between platforms in this relatively small sample. DOOR is a novel mechanism to quantitate clinical utility and compare RDTs.

Disclosures

All authors: No reported disclosures.
2606. A Divergent Ferrichrome Receptor Associated with an Insertional Element (IS3) Identified on Novel Locus in Clinical Strain of Pseudomonas aeruginosa
Authors: Adenikinju Adenike , Garner Dorothy C , Kerkering Thomas , Jensen Roderick , Rao Jayasimha
Published: October 2019

Background

Pseudomonas aeruginosa is an aerobic Gram-negative bacterium that causes life-threatening acute and chronic infections in humans. Genotypic mutations and phenotypic variations are key features of its antimicrobial resistance and adaptation to the host environment. Pyoverdine associated genes and divergent receptors play a key role in acute Pseudomonas infections. This study seeks to address the heterogeneity of ferrichrome-iron receptor (fpvA) expression, its effect on pathogenicity and its propensity to cause acute infections clinically. Genetic and phenotypic variation of a clinical isolates of P. aeruginosa (PA097 and PA115) were identified by complete genome sequencing method.

Methods

An IRB-approved prospective study collected 38 P. aeruginosa clinical isolates and stored at Carilion Medical Center. Two genetically unrelated clinical strains were selected from tracheal aspirates: PA097 and PA115. These isolates were characterized by pyoverdine (pvd) quantification in planktonic culture filtrate at OD405 nm. Multiplex PCR was carried out using primers for fpvA receptors. Quantification of iron acquisition was done on chrome azurol S (CAS) agar. Genomes for PA115 and PA097 were sequenced by Illumina Next-generation DNA sequencing.

Results

Genome assembly shows a 6.3 Mb genome size in PA115 with G+C content of 66.4%. Seven insertion sequence elements were located. We found a 101 kb locus for pvD and a highly diversified fpvA associated with an insertional element (IS3). PA115, exhibits rich green pigment of pvd followed by PAO1 and PA097 in LB media (Figure 1A) and also in Planktonic culture filtrate (Fig 1B) for quantitative estimation of pvd (Figure 1C). On CAS agar, PA115 showed high uptake of iron by orange pigment compared with lower pigmentation in PAO1 and PA097 (Fig 1D). We confirmed the ferrichrome-iron receptor as fpvAIIb in PA115 by Multiplex PCR seen in sequencing of PA115 (Figure 2).

Conclusion

We found high genetic and phenotypic variation in clinical isolate of P. aeruginosa (PA115) from an acute pneumonia patient. The novel IS element found in its receptor gene locus suggests an increased role in pvd expression and iron uptake from the host. Increased pvd expression and diversified fpvAIIb association with an IS3 element may indicate higher virulence in the PA115 strain.

Disclosures

All authors: No reported disclosures.
2608. Restriction of Rhinovirus Infection Depends on Virus Sensing and Early IFN Induction
Authors: Rathe Jennifer A , Gale Jr. Michael , Knoll Megan
Published: October 2019

Background

Human rhinovirus (RV) infections are ubiquitous, underestimated, and costly. RV causes 3–12 infections per year per individual with a wide range of clinical presentations from mild upper respiratory infections to severe viral pneumonias (1). The virus-host interactions that control RV infection are poorly understood. Thus, there are no vaccines or antiviral medications available. RV infection begins at the airway epithelial surface where the virus first encounters the host cell immune defenses, including type I and III interferon (IFN). IFN actions are critical for defense against RV infection wherein interferon-stimulated genes (ISG)s direct antiviral actions to limit RV infection.

Methods

We hypothesized that the timing of IFN induction is a critical determinant of RV restriction by host innate immune defenses in the human respiratory tract. Thus, an immortalized bronchial epithelial cell line was infected with RV-14 with multiplicity of infection (MOI) ranging from 0.1 – 10 and under conditions of pre/post infection treatment with IFN-β or IFN-λ. Host and viral RNA, protein, and RV infectious particle levels were analyzed.

Results

We found that RV infection induces IFN-β and IFN-λ production and subsequent ISG induction, including expression of IFIT-1, OAS1, and MX1. RV-14 infection induced IFN-β and IFN-λ in a dose-dependent manner, with a maximum fold increase of IFN expression at 48hours post infection. ISGs were induced in a similar pattern to IFNs. Viral titers increased significantly over the first 24hours post infection and then plateaued through 96hours. IFN-β and IFN-λ pre- and posttreatment conditions significantly decreased maximum viral titers achieved but with continued viral plateaus 24–96 hours post infection.

Conclusion

Our observations demonstrate that RV induces innate immune activation and the production of type I and III IFN during acute infection of airway cells. Sustained viral titer plateaus, despite antiviral ISG induction, suggests viral blocking of IFN pathway mechanisms that can be overcome by early IFN induction to significantly restrict RV viral replication.

1. Royston L, Tapparel C. 2016. Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC. Viruses 8.

Disclosures

All authors: No reported disclosures.
154. Do I Really Need a Transesophageal Echo? Comparing Echocardiographic Modalities in Native Valve Infective Endocarditis due to Methicillin-Resistant Staphylococcus aureus
Authors: Livesay James , Lorson William , Eric Heidel R , Shorman Mahmoud
Published: October 2019

Background

Methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is associated with high morbidity and mortality. Management commonly includes six-weeks of antibiotics and surgical intervention, if the patient has complications. Current guidelines recommend obtaining an echocardiogram. Transesophageal echocardiogram (TEE) is preferred over transthoracic echocardiogram (TTE). We wanted to evaluate the role of a TEE in changing management of MRSA IE.

Methods

A retrospective cohort of patients with MRSA IE was analyzed between January 2013 and July 2017 at a tertiary care facility in East Tennessee. Patients with prosthetic valves or cardiac devices were excluded. Demographic, echocardiographic, antibiotic, blood culture, mortality, and intravenous drug use data were collected (Figure 1).

Results

Seventy-eight patients met the inclusion criteria. TTE was performed on 73 patients while five patients proceeded directly to TEE. Of the 73 patients that had a TTE, 33 (45.2%) detected the presence of vegetation and 40 (54.8%) did not. Of the 33 patients with a positive TTE, 15 subsequently underwent TEE, confirming IE. Out of the 40 patients with a negative TTE, 34 underwent TEE, of which 22 (64.7%) showed a vegetation. (Figure 2). A total of ten patients (12.8%) from the study underwent surgery. Of these ten, three (30%) had a positive TTE only, with no subsequent TEE. Five (50%) had both a positive TTE and TEE, and two (20%) had a negative TTE but positive TEE.

Conclusion

Transthoracic echocardiogram was adequate to visualize vegetations in 45.2% of patients. Completing a TEE increased the sensitivity of visualizing a vegetation, but management was most often not altered. Only two patients (5%) with a negative TTE, but positive TEE proceeded to surgery because of the findings. This causes us to question whether a subsequent TEE needs to be pursued when a TTE is negative in the setting of definite or possible IE by the modified Duke criteria. Even if a vegetation is seen on TEE the patient would most likely receive the same treatment, 6 weeks of intravenous antibiotics, as if no vegetation was seen. Forgoing a TEE reduces risk to the patient of undergoing a procedure, and reduces costs to the healthcare system.

Disclosures

All authors: No reported disclosures.
2620. Respiratory Syncytial Virus Rapid Antigen Detection Test, Can It Be Trusted?
Authors: Titze Nicole , Singh Jasjit , Gornick Wendi
Published: October 2019

Background

Many emergency departments and urgent care settings use the commonly available Respiratory Syncytial Virus Rapid Antigen Detection Test (RSV RADT) to diagnose children with RSV. We noted discordant results between RADT and definitive testing. Our study looked at the positive predictive value (PPV) and the false discovery rate (FDR) of the RSV RADT at our facility.

Methods

We pro- and retrospectively reviewed all patients with positive RSV RAPD tests from July 1, 2017 through March 31, 2019. The test utilized was the QuickVue® RSV Test Kit (QUIDEL Corp, CA, USA), which detects the viral fusion protein present in RSV. Of the tests performed, we chose patients who had definitive testing with either a direct fluorescent antibody (DFA) or a polymerase chain reaction (PCR). We then calculated the PPV as well as the FDR of the RSV RADT during the total interval period, as well as off-season periods (April 1 through October 31) and in-season periods (November 1 through March 31).

Results

During the study period there were 1128 RSV RADT tests performed, of which 232 had definitive testing with either DFA or PCR (Figures 1 and 2). We found the overall PPV during the study period was 63.3%. During the off-season 30 positive RSV RADT received definitive testing, of which 6 were positive, which yields a PPV of only 20%. In season, 202 RSV RADT received additional testing with 141 positive for RSV. The PPV was 69.8%. The FDR correlated with 36.7% throughout the entire studied period, 80% during the off-season and 30.2% during in-season. As expected, the PPV was higher during times of higher prevalence (Figure 3).

Conclusion

Based on our results, utilization of the RSV RADT during time of low prevalence yields a high false detection rate and should therefore be discouraged. The use during times of high prevalence yields only modest results and is unlikely to aid in clinical decision-making. Our results differ from those published by the manufacturer (PPV 84%), and may reflect differences in sample collection in the acute care setting.

Disclosures

All authors: No reported disclosures.
2621. Influence of HIV Exposure Status on Carriage Rates and Density of Streptococcus Pneumoniae and Pneumocystis Jirovecii in Zambian Children
Authors: Camelo ingrid Y , Gill Christopher , Thea Donald M , Weinstein John
Published: October 2019

Background

Low rates of mother to child HIV transmission in Zambia, translates into a high number of children who are HIV exposed but uninfected (HEU) who have increased mortality and morbidity when compared with children HIV unexposed and uninfected (HUU). We performed a secondary analysis on The Pneumonia Etiology Research in Child Health (PERCH), a case–control study focused on identifying the etiologies of pediatric pneumonia including two pathogens, Streptococcus pneumoniae and Pneumocystis jirovecii in Zambian children to evaluate if HIV exposure status influences carriage rates and density for these pathogens.

Methods

Children ages 1–59 months were enrolled as cases if they met the World Health Organization (WHO) definition of severe or very severe pneumonia. Controls did not have a diagnosis of pneumonia and were matched by age and HIV status to cases. Each case and control had a nasopharyngeal (NP) swab and an oropharyngeal (OP) swab specimen. A multiplex real-time polymerase chain reaction (PCR) assay was used to test the NP/OP specimens for S. pneumoniae and P. jirovecii. A density of log10 copies/mL in microbiology confirmed cases compared with controls was used to define positive infection with S. pneumoniae and P. jirovecii.

Results

The highest S. pneumoniae carrier rates were seen in HIV unexposed controls and the lowest carrier rates seen in HIV-infected controls. HIV-infected children who were S. pneumoniae carriers and were classified as controls had the highest S. pneumoniae density of all groups. Overall, the HIV-infected group had the highest S. pneumoniae density rates. There was minimal variation in the S. pneumoniae density of those in the HIV exposed and HIV unexposed. P. jirovecii was present only in 31% of HIV-infected cases and 7% of the same group controls. HIV exposed cases had half the carrier rates of their counterparts in the HIV-infected group, but the P. jirovecii carriage rates were the same as the carriage rates in HIV-infected controls. The P. jirovecii carriage density in HIV-infected and HIV-exposed cases was similar.

Conclusion

HIV exposure status in children can be a predictor factor in S. pneumoniae and P. jirovecii carriage and density. The results of our analysis could potentially explain the high rates of pneumonia in children exposed to HIV but uninfected. Our findings open the door to more in-depth studies about the immunological status in children exposed to HIV but uninfected.

Disclosures

All authors: No reported disclosures.
2623. Bacterial Co-detection and Outcomes for Infants with Bronchiolitis Requiring Emergency Department Intubation for Respiratory Failure
Authors: Akande Manzilat , Moore-Clingenpeel Melissa , Jamieson Nathan , Spencer Sandra , Karsies Todd
Published: October 2019

Background

Viral bronchiolitis is a common cause of respiratory failure requiring intubation and ICU admission for infants. Bacterial codetection from respiratory cultures is common but its association with outcomes is unclear.

Methods

We conducted a retrospective cohort study over 5 years of infants <1 year with suspected bronchiolitis who were intubated in our ED with subsequent ICU admission. We evaluated the association between bacterial codetection (bacteria + many PMNs) and outcomes (mechanical ventilation (MV) duration, ICU LOS). Analysis was performed using gamma regression. Results are reported as risk ratios (RR) or adjusted risk ratios (aRR).

Results

149 patients were analyzed (median age 1.3 months, 59% male, 54% prematurity). 91% had confirmed viral infection (56% RSV, 35% non-RSV, 13% polyviral); 52% had codetection. Median MV duration was 5.1 days; median ICU LOS was 6.8 days. Prematurity, PRISM3 score, RSV, black race, and positive non-respiratory culture were associated with longer MV duration. Prematurity, RSV positivity and positive non-respiratory culture were associated with longer ICU LOS. Bacterial codetection (RR 0.82; 0.68–1.0) was associated with shorter MV duration and shorter ICU LOS (RR 0.80; 0.67–0.94); this remained true after adjusting for confounders (aRR for shorter MV duration: 0.82; 0.69–0.98; aRR for shorter ICU LOS: 0.81; 0.69–0.94). 95% of patients with positive cultures (109/115) had appropriate ED antibiotics; median time to correct antibiotics was 1.4 hours. Further investigation showed that bacterial codetection was associated with decreased MV duration in those with time to correct antibiotics of ≤1.4 hours (aRR 0.70; 0.54–0.89) but not in those whose time to antibiotics was >1.4 hours (aRR 0.98; 0.78–1.24).

Conclusion

In infants intubated in the ED for bronchiolitis, bacterial codetection was associated with shorter ICU LOS overall and with shorter MV duration among patients with rapid time to correct antibiotics; however, there was no significant association between bacterial codetection and MV duration among patients with longer time to correct antibiotics. Further research is needed to elucidate the true impact of bacterial codetection as well as empiric antibiotic administration on outcomes in infants intubated for bronchiolitis.

Disclosures

All authors: No reported disclosures.
2629. Respiratory Syncytial Virus Epidemiology and Factors Associated with Severity among Hospitalized Infants in Four Middle-Income Countries, 2015–2017
Authors: Biggs Holly , Simoes Eric A , Abu-Khader Ilham Bulos , Thompson Mark G , Gordon Aubree , Hunt Danielle R , DeGroote Nicholas , Whitaker Brett L , Wang Lijuan , Marar Basima , Gresh Lionel , de Jesus Joanne , Bino Silva , Porter Rachael M , McMorrow Meredith , Campbell William , Zhang Yange , Lindstrom Stephen , Thornburg Natalie J , Langley Gayle , Langley Gayle , Peret Teresa C T , Simaku Artan , Gerber Susan I
Published: October 2019

Background

Respiratory syncytial virus (RSV) is the most commonly identified viral pathogen among young children with acute lower respiratory tract infection. Understanding global RSV epidemiology and risk factors for severe illness in low- and middle-income settings is critical as new vaccine candidates become available.

Methods

We prospectively enrolled infants aged < 1 year hospitalized with any acute illness from sites in Albania, Jordan, Nicaragua and Philippines during 2015–2017. Standardized parental interviews and medical record review were conducted. Respiratory specimens collected during enrollment were tested for RSV using rRT–PCR. RSV A or B subgroup was determined using a CDC-developed rRT–PCR assay. Very severe RSV illness was defined as requiring ICU admission or supplemental oxygen. Factors potentially associated with severity were assessed using individual logistic regression models to adjust for age and study site.

Results

Overall, 1,129 (31%) of 3634 enrolled infants had RSV infection. The median age of RSV-positive infants was 2.7 (range: < 1 to 11.9) months, 665 (59%) were male, and 63 (6%) had ≥1 underlying medical condition. RSV subgroup was determined for 1,028 (91%); RSV A and B co-circulated at all sites with alternating predominance by study year (figure). 583 (52%) infants had very severe RSV illness, which was significantly associated with younger age (median: 2.0 vs. 4.3 months; P < 0.01), study site (aOR: Jordan 5.0, Albania 2.9, Philippines 1.2, Nicaragua reference; P < 0.01), birth by cesarean section (aOR: 1.4; 95% CI [CI] 1.0–1.8; P = 0.03), having received ICU care after birth (aOR: 1.6; CI 1.0–2.4; P = 0.03), chronic heart or respiratory tract disease (aOR: 1.9; CI 1.0–3.4; P = 0.04), and a low weight-for-age Z score (aOR: 1.8; CI 1.3–2.7; P < 0.01). RSV subgroup was not associated with severity (aOR: 1.0; CI: 0.7–1.3; P = 0.72).

Conclusion

RSV was associated with a substantial proportion of acute illness among hospitalized infants in middle-income countries. Subgroups co-circulated across sites and study years with varying predominance and resulted in similar illness severity. Significant comorbidities were uncommon, but factors including younger age, low weight-for-age and chronic heart or respiratory tract disease were associated with more severe illness.

Disclosures

All authors: No reported disclosures.
2631. Influenza-Associated Intensive Care Unit Hospitalizations and Deaths in Children, During 2010–2019 in Greece
Authors: Magaziotou Ioanna , Tsiodras Sotirios , Andreopoulou Anastasia , Mouratidou Elisavet , Vernardaki Alexandra , Gkolfinopoulou Kassiani , Panagiotopoulos Takis , Kossyvakis Athanasios , Exindari Maria , Mentis Andreas , Papa Anna , Theodoridou Maria , Georgakopoulou Theano
Published: October 2019

Background

The clinico-epidemiological characteristics of children with severe influenza-related intensive care unit (ICU) admissions in Greece during 2010–2019 are described.

Methods

All laboratory-confirmed influenza cases (real-time PCR), in children 0–16 years old, admitted to Pediatric ICUs throughout the country, are reported using a mandatory notification system to the National Public Health Organization of Greece. Case fatality rates (CFR) were analyzed according to age and presence of comorbidities.

Results

From October 2010 to April 2019, 131 influenza cases [7.2/100,000 children, 65 (49.6%) girls] with PICUs admissions were recorded. The majority of cases (n = 78; 60%) occurred in the age group 0–4 years-old [31 (24%) children were < 12 months-old]. Sixty-five (49.6%) children had underlying comorbidities (22 neurological disease, 12 congenital syndromes, 7 cancer, 5 chronic respiratory, 19 other). The most common diagnosis was febrile ARDS and 67 (51.14%) had severe pneumonia (40% viral, 7% bacterial). Seventy-five (57.2%) children required invasive ventilation. Influenza A accounted for 102 (77.86%) of cases; out of 86 (84.31%) subtyped, 68 (79%) were AH1N1pdm09, and 18 (21%) were AH3N2. Influenza B accounted for 29 (22.13%) of cases. All children received oseltamivir. Median length of stay was 10 days (range 1–90). A total of 32 deaths was recorded (CFR 24.4%, total rate: 1.76/100,000 children); 13 (40.1%) deaths occurred in children with no known co-morbidity. Mortality rates were higher in children aged > 4 years (18/53, 33.9% vs. 14/78, 17.9%, P = 0.04) while there was a trend for children with comorbidities (19/65, 29.2% vs. 13/66, 19.69%, P = 0.1). Only 4% of children were previously immunized against influenza.

Conclusion

AH1N1pdm09 accounted for the vast majority of severe cases and influenza associated deaths in children in Greece over the last 10 years. Severe disease occurred also in children with no comorbitidies. Longitudinal clinico-epidemiological data should be considered in shaping the national immunization program.

Disclosures

All authors: No reported disclosures.
2641. The Characteristics of Influenza-Like Illness (ILI) Management in Japan
Authors: Tsuzuki Shinya , Yoshihara Keisuke
Published: October 2019

Background

Influenza-like illness (ILI) is a common disease that imposes a severe disease burden at the population level. ILI management is important in view of population health, and Japan’s management is distinct from that in other countries, especially regarding diagnosis and treatment of seasonal influenza. This study’s main objective was to quantitatively assess ILI management in Japanese healthcare settings.

Methods

In February 2019, we conducted an online survey of 600 participants in 200 households concerning ILI and its management in Japan. Respondents reported ILI episodes they and/or their family members experienced during January 2019. The 12-Item Short-Form Health Survey, Version 2 (SF-12v2) was included in the questionnaire to estimate quality of life (QOL) lost through ILI, and quality-adjusted life years (QALYs) lost in that way. We analyzed participants’ healthcare-seeking behavior to clarify the characteristics of Japanese ambulatory care for ILI.

Results

Of the participants, 261 of 600 (43.5%) reported at least one episode of ILI during January 2019. Of these, 194 (75.5%) visited healthcare facilities and 167 (86.1%) visited facilities within 2 days of symptom onset. A rapid influenza diagnostic test (RIDT) was given to 169 of 191 (88.5%) and 101 patients received a diagnosis of influenza, rather than ILI. Antivirals were used to treat 92.2% of the influenza cases. The median values of QOL and QALYs lost during a symptomatic period of ILI were 0.67 (interquartile range: 0.60–0.79) and 0.0055 (interquartile range: 0.0040–0.0072), respectively.

Conclusion

In Japan, most ILI patients visit healthcare facilities in the early phase of symptoms, and most physicians examine them using the RIDT. Most laboratory-diagnosed influenza cases are treated using antivirals. Future work should examine the relation between this early diagnosis and treatment practice, and the duration and severity of ILI symptoms.

Disclosures

All authors: No reported disclosures.
2648. Terminating the Troll of Transplantation: Letermovir for Cytomegalovirus Prophylaxis
Authors: Hedvat Jason , Lake Patrick , Swamy Siddharth , Zecchini Julia , Pereiras Maribel , Sebti Rani
Published: October 2019

Background

Letermovir is a novel antiviral that was approved for cytomegalovirus (CMV) prophylaxis after allogeneic hematopoietic stem cell transplant (allo-HSCT). The objective was to assess the real-world outcomes of CMV prophylaxis with letermovir compared with preemptive therapy (PT) alone.

Methods

This retrospective pre- and post-study evaluated the clinical impact of using letermovir prophylaxis in CMV-seropositive allo-HSCT recipients at our institution. The electronic medical record was used to identify patients that received PT alone from July 2016 to November 2017 and letermovir prophylaxis from November 2017 to March 2019. The primary endpoint was the proportion of patients with CMV infection requiring PT through week 24 after transplant. Secondary endpoints included the proportion of patients with CMV infection requiring PT through week 14 after transplant, time to CMV infection requiring PT, incidence of CMV disease, CMV-related hospitalization and all-cause mortality through week 14 and 24 after transplant. Safety data included incidence and time to engraftment and adverse effects due to letermovir. Chi-squared and t-test were utilized for categorical and continuous data respectively.

Results

The baseline characteristics were similar (Table 1) and 78.7% of patients were high risk for CMV. Fewer patients in the letermovir group (n = 50) than in the historic control group (n = 100) had CMV infection requiring PT through week 24 after transplant (9 [18%] vs. 63 [63%], P < 0.001). The mean time to CMV infection requiring PT through week 24 after transplant was 93.4 days (28–161) in the letermovir group vs. 37.4 days (11–126) in the historic control group (P < 0.001). The all-cause mortality and incidence of CMV-related hospitalization were not statistically different between the two groups through week 24 after transplant (Table 2). The incidence and time to engraftment were not statistically different between the two groups (Table 3).

Conclusion

Letermovir prophylaxis in the real-world setting resulted in less CMV infection requiring PT when compared with a historic control of patients receiving PT alone. The majority of patients in the letermovir group experienced delayed-onset CMV reactivation. Letermovir was well-tolerated with no apparent myelosuppressive toxicities.

Disclosures

All authors: No reported disclosures.
2650. Evaluating Antiviral Agents for Human Noroviruses Using a Human Intestinal Enteroid Model
Authors: Cortes-Penfield Nicolas W , Ramani Sasirekha , Neill Frederick , Ettayebi Khalil , Atmar Robert , Estes Mary
Published: October 2019

Background

Norovirus can cause chronic infections with serious morbidity and mortality in immunocompromised patients. While there are no FDA-approved medications for these infections, nitazoxanide, ribavirin, and enterally administered pooled immunoglobulin (IVIG) are used off-label on the basis of expert opinion. Nitazoxanide and ribavirin show antiviral activity in a murine norovirus infection model and an in vitro replicon model of genotype GI.I human norovirus RNA expression, respectively. However, these drugs have not been evaluated in in vitro infections with GII.4 human noroviruses, responsible for most human norovirus disease. We used the stem cell-derived nontransformed human intestinal enteroid (HIE) system, which supports GII.4 human norovirus replication, to evaluate the antiviral activities of nitazoxanide, ribavirin, and IVIG.

Methods

We inoculated HIEs with GII.4 human norovirus in the presence of half-log dilutions of nitazoxanide (3 µM to 100 µM), ribavirin (10 µM to 10 mM), or IVIG (1:100 to 1:3,000) and a media control. One and 48 hours after inoculation, we extracted and quantified GII.4 norovirus RNA from the HIEs. To demonstrate that replication inhibition was not due to cytotoxicity, we performed quantitative lactate dehydrogenase release assays on the HIEs across the therapeutic range of each compound.

Results

Nitazoxanide reduced GII.4 replication at 48 hours in a dose-dependent manner, achieving a >90% reduction in viral replication at 10 µM without cytotoxicity. These findings were confirmed in multiple HIE lines representing different intestinal segments and established from different donors. IVIG completely inhibited GII.4 replication at up to a 1:1,000 dilution and was not cytotoxic at therapeutic concentrations. Ribavirin did not reduce GII.4 replication at concentrations up to 10 mMµM, well in excess of levels achieved in human sera with standard doses.

Conclusion

Nitazoxanide and IVIG, but not ribavirin, potently inhibit GII.4 human norovirus replication in a biologically relevant in vitro model of human norovirus infection. These data highlight the use of HIEs as a new pre-clinical model for developing therapeutics for human norovirus disease.

Disclosures

All authors: No reported disclosures.
2653. Epidemiology and Risk Factors for Healthcare-Associated Viral Infections in Children
Authors: Hanley Samantha E , Odeniyi Folasade , Feemster Kristen , Coffin Susan E , Sammons Julia S
Published: October 2019

Background

Healthcare-associated viral infections (HA-VI) are common in hospitalized children and are increasingly recognized as a cause of preventable harm. Yet, epidemiology and modifiable risk factors related to pediatric HA-VI are currently poorly understood.

Methods

We performed a prospective case–control study to identify the risk factors and outcomes associated with pediatric HA-VI at a quaternary care children’s hospital between November 2016 and August 2018. Prospective surveillance for HA-VI was performed hospital-wide by certified infection preventionists using NHSN definitions. Cases were matched 1:1 to controls by age, duration of hospitalization, and hospital unit. We abstracted data from the electronic medical record and conducted semi-structured interviews with patient caregivers to identify potential exposures beginning 4 days prior to HA-VI identification date. We also measured length of antibacterial therapy (LOT) in the 7 days following enrollment.

Results

During the study period, we identified 143 eligible patients with HA-VI and enrolled 64 matched case–control pairs. In total, 79 viruses were identified among 64 case patients, of which 53 (67.1%) were respiratory viruses and 26 (32.9%) were GI. Case patients were more frequently exposed to a sick visitor, specifically either caregiver or sibling, compared with controls (18.8% vs. 9.4%; P = 0.20, Fisher exact test). During the exposure period, case patients also had a significantly higher number of hospital procedures performed when compared with controls (n = 320 vs. 232; X2 = 58.43, P < 0.001). Case, when compared with control, patients had a greater average LOT (2.89 vs. 1.08).

Conclusion

Results of study show that exposure to a sick visitor is a potentially modifiable risk factor for pediatric HA-VI. In addition, hospitalized children with HA-VI have increased exposure to antibacterial antibiotics when compared with matched controls. Prevention of pediatric HA-VI may have implications for antibiotic stewardship. Our findings suggest that hospital policies may need to be revised, with emphasis on visitor screening and partnership with families, to reduce the incidence of pediatric HA-VI during hospitalization.

Disclosures

All authors: No reported disclosures.
2655. A Prospective Study of Cytomegalovirus Infection in Active Systemic Lupus Erythematosus Patients with Intense Immunosuppressive Therapy: Epidemiology, Associated Risk Factors, Pathogenesis, and Clinical Outcomes
Authors: Bushyakanist Asalaysa , Rotjanapan Porpon , Ngamjanyaporn Pintip , Suangtamai Tanitta , Bruminhent Jackrapong , Pisitkun Prapaporn
Published: October 2019

Background

Systemic lupus erythematosus (SLE) patients with intense immunosuppressive therapy (IT) are at higher risk for cytomegalovirus (CMV) reactivation and may develop the end-organ disease. However, the real epidemiology, associated risk factors, pathogenesis, and clinical outcomes have not been fully elucidated.

Objectives

To investigate the associated risk factors, possible predictors in the aspect of immunology of CMV infection and to study epidemiology, and clinical outcomes prospectively in active SLE patients within 3 months after intense IT.

Methods

A prospective cohort study of active SLE patients required intense IT from November 2017 to March 2019 was conducted. We collected patients’ demographics, potential risk factors, onset and presentations of CMV infection after intense IT, data on IT, cytokine panels, and flow cytometry at weeks 0, 2, 4, 8, and 12 after enrollment. Intense IT was defined as an induction therapy of active SLE disease with either the National Institute of Health or Euro-Lupus Nephritis Trial protocol regimens.

Results

A total of 24 patients have enrolled with a median age of 32 years old and 22/24 patients were female. Renal involvement was the most common and found in 79.2% of the patients. Median SLE disease activity index at enrollment was 14 (25%-75% interquartile range (IQR) = 8–19). At week 0, no CMV infection was documented, 91.7% of the patients had positive CMV IgG, and the median absolute lymphocyte count was 938 cells/mm3. At week 12, the median cumulative corticosteroid dose was 0.74 mg/kg/day (25%-75%IQR = 0.34–1.20) and the prevalence of CMV infection was 12.5%. Elevated interleukin-23 and tumor necrotic factor-α levels were associated with protective effect (hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02–0.58, p = 0.009 and HR 0.55, 95% CI 0.31–0.99, p = 0.049, respectively). Neurologic involvement was the independent factor that increased the risk of CMV infection (HR 0.26; 95% CI 0.08–0.79, p = 0.018). No mortality was detected.

Conclusion

CMV infection is common when IT is used, but only some SLE patients with intense IT develop CMV infection. Certain characteristics of the patients may assist predict future CMV infection following IT. However, further study on a larger scale is encouraged.

Disclosures

All authors: No reported disclosures.
2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study
Authors: Tamzali Yanis , Scemla Anne , Taupin Pierre , Randhawa Sunny , Moal Valérie , Garandeau Claire , Levi Charlène , Matignon Marie , Fihman Vincent , Le Quintrec Moglie , Luque Yosu , Retbi Aurelia , Bertrand Dominique , Thervet Eric , Cherrak Ilham , Chemouny Jonathan M , Barrou Benoît , Tourret-Arnaud Jerôme
Published: October 2019

Background

The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population.

Methods

We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected.

Results

Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%).

The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively.

Conclusion

Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population.

Disclosures

All authors: No reported disclosures.