bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.