bluuebunny/crossref_metadata_2025 huggingface dataset:
2543. Implementation of a Fellow-Driven Β-Lactam Allergy De-Labeling Initiative on an Inpatient ID Consult Service
Authors: Mulliken Jennifer S , Bystritsky Rachel , Anstey Karen , Otani Iris M , Doernberg Sarah B
Published: October 2019

Background

Approximately 10% of patients in the US report a penicillin (PCN) allergy, but more than 90% can safely receive β-lactam (BL) antibiotics. Having a reported BL allergy (BLA) is associated with increased length of stay, cost of care, adverse events, and mortality. As part of our institutional quality improvement incentive program for graduate medical trainees, the Infectious Diseases (ID) and Allergy/Immunology (AI) fellows implemented a protocol-driven approach to BLA evaluation. We sought to evaluate the success of this implementation.

Methods

This is a pre–post investigation of our BLA protocol. As an initial pilot phase prior to house-wide deployment, the ID and AI services implemented a BLA guideline incorporating thorough history-taking, graded challenge, and focused penicillin skin testing for patients on the ID consult service. All patients seen by the ID consult service from July 1, 2018 through June 30, 2019 with a documented BLA were included (baseline period April 1, 2018 through June 30, 2018). The primary endpoint was the proportion of patients meeting any one of the following: receipt of a BL, inpatient or outpatient referral to AI, or removal of BLA from the medical record by the time of discharge. Data were tracked quarterly and fed back to ID and AI fellows electronically. The Chi-square test was used to compare pre-post outcomes.

Results

Over the first three quarters, 258 patients with BLA were evaluated by the ID consult service. Our baseline compliance was 65%, which increased to an average of 81% over the subsequent three quarters (P = 0.003). Among patients with BLA seen by the ID consult service during the intervention, 177 (69%) received a BL, 37 (14%) underwent inpatient AI evaluation, 11 (4%) received discharge referrals to AI, and 126 (49%) had their BLA removed. Several patients met more than one primary endpoint.

Conclusion

Implementation of a protocol-driven BLA guideline by ID and AI fellows was feasible and led to an increase in the number of patients either receiving BLs in the hospital or undergoing timely evaluation or removal of BLA. In conclusion, the implementation of a β-lactam allergy de-labeling initiative is an effective way to empower trainees to incorporate BLA de-labeling into their practice.

Disclosures

All authors: No reported disclosures.
2555. Relationship-Based Communication to Enhance ACGME Infectious Disease Fellowship Competencies
Authors: Howell Alan C , Howell Martha , Cooper Stacy
Published: October 2019

Background

Relationship Centered Communication (RCC) acknowledges the physician’s expertise as well as the patient’s perspective.1 Clinician empathy also serves to improve patients’ ability to cope with chronic diseases.2 Furthermore, effective communication aids with diagnosis and improves treatment adherence.3 Hence, the need to teach and assess competence in Interpersonal Communication - Communicates effectively with patients, caregivers and interprofessional teams milestones. Created in conjunction with the Academy of Communication in Healthcare, RCC training for faculty is encouraged by our organization. Having attended the inter-professional workshop, ID faculty collaborated with the training program to afford the fellows the same opportunity to learn RCC skills.

Methods

Faculty have reported limited opportunities to observe/assess their learners. Trainees report infrequent and nonspecific feedback regarding areas for improvement.4 Given these challenges, the ID fellows began a multi-step plan to hone new communication skills after attending the RCC workshop. Activities included both real and simulated encounters as well as didactic presentations. Each scenario built upon the previous one providing continuity of care. Upon completing both outpatient and inpatient encounters, the fellow joined the debriefing team (standardized patient, Program Director and RCC coach) to discuss areas of competence as well as opportunities for improvement. The fellows were also evaluated by faculty in actual patient encounters in addition to choosing a RCC skill to highlight during didactic conference.

Results

Activities provided fellows RCC teaching opportunities, interaction with a standardized patient and learn how the interaction was perceived from the patient’s perspective. Ability to practice in a safe simulation environment, access to coaching and real-time assessment was reported as valuable for all parties. The RCC training afforded both parties the ability to give and receive specific/objective feedback for a competency usually perceived as subjective.

Conclusion

Varied activities urged the fellows to establish consistent communications habits. The program generated a framework for sustainability of skills and objective assessment.

Disclosures

All authors: No reported disclosures.
2564. What Predicts Journal Publication Tier and Audience Engagement in the Infectious Diseases Literature? A Review of 146 Publications
Authors: Cortes-Penfield Nicolas W , Salemi Jason
Published: October 2019

Background

As part of an online medical education project (www.idjournal.club), we surveilled the infectious diseases (ID) literature, selecting subsets of what we deemed the most clinically impactful articles on a monthly basis using a prespecified search algorithm. We used this resource to perform a broad overview of articles published in the field and examine factors associated with publication in higher tier journals and higher rates of public and ID community engagement.

Methods

We examined articles reviewed on www.idjournal.club between June and September 2018. For each article, we recorded the publishing journal, subfield of ID, study type, nation and degree of the lead author, and sample size, and we assigned the paper up to three topic keywords. Our outcomes of interest were the publishing journal’s Scimago Journal Rank (SJR), a surrogate for journal tier, and the article’s Altmetric score, a surrogate for audience engagement.

Results

Of 146 articles included in the analysis, the most common study types were retrospective observational (n = 47), randomized controlled trial (n = 23), in vitro (n = 20), and prospective observational (n = 19). The median sample size was 238; median sample sizes were higher for randomized controlled trials (n = 400) and lower for in vitro and pharmacokinetic/pharmacokinetic studies (n = 53 and n = 44). Lead authors were based in the United States in 38% of cases and in North America or Europe in 86% of cases. Physicians accounted for 65% of lead authors, PhDs 23%, and PharmDs 10%. The most commonly referenced pathogens were HIV, MDR Gram-negative bacteria, S. aureus, and C. difficile; the most commonly referenced disease states were bacteremia, sexually transmitted infection, respiratory tract infection, and UTI. The mean SJR was 3.5 (SD 3.1) and the mean Altmetric score was 54.5 (SD 143). SJR and Altmetric score were associated with study type, sample size, and key topics; Altmetric score was also associated with publishing journal. In multivariate analysis, SJR was associated with study type and sample size, and Altmetric score was associated with ID subfield, journal, and sample size.

Conclusion

We present a descriptive overview of the ID literature and identify article factors associated with journal tier and audience engagement after publication.

Disclosures

All authors: No reported disclosures.
2571. Norovirus Infection and Gut Microbiota in Transplant Recipients
Authors: Chong Pearlie P , Chong Pearlie P , Hussain Sarah K , Poulides Nicole , Coughlin Laura , Koh Andrew Y
Published: October 2019

Background

In vitro studies have shown that enteric viruses require the gut microbiota (specific members of the Enterobacteriaceae family) for efficient infection of the gastrointestinal tract. Human norovirus (NV) infection in transplant recipients may be chronic and severe. The role of gut microbiota has not been defined in this setting. We hypothesized that gut microbiota diversity and composition are different in norovirus-infected transplant patients.

Methods

We performed a single-center, pilot, prospective cohort study of adult solid-organ transplant and hematopoietic stem cell transplant recipients with diarrhea. Serial fecal samples were collected and processed for gDNA. Norovirus levels were quantified by PCR and gut microbiota profiling determined by 16S rRNA gene sequencing.

Results

Twenty-five transplant recipients were included: 9 with NV infection and 16 without. Age (61 ± SEM 2.3 years vs. 54 ± 3.5 years; P = 0.172), duration of diarrhea prior to diagnosis (105 ± 43 days vs. 20 ± 7 days; P = 0.146), prior cumulative antibiotic use (42 ± 12 days vs. 46 ± 17 days; P = 0.646), anti-anaerobic antibiotic use (7 ± 3 days vs. 11 ± 6 days; P = 0.643) and length of hospitalization (12 ± 6 days vs. 12 ± 3 days; P = 0.624) were not different between transplant recipients with and without NV infection. Interestingly, the relative abundance of Enterobactericeae was significantly higher in NV-infected transplant recipients compared with those without NV infection (26 ± 5.8% vs. 6.2 ± 2.8%; P = 0.017, Mann–Whitney) (Figure 1). In contrast, the abundance of the Phyla Bacteroidetes (11.2 ± 5.2% vs. 26.3 ± 6.5%; P = 0.191), and Firmicutes (26.8 ± 7.6% vs. 24.9 ± 4.7%; P = 0.803), were not significantly different between those who were NV and not NV-infected. Of note, the diversity metrics of Shannon (3.5 ± 0.4 vs. 3.8 ± 0.3; P = 0.637) and inverse Simpson indices (1.3 ± 0.1 vs. 1.1±0.1; P = 0.419) were not significantly different between the two groups.

Conclusion

Norovirus-infected transplant recipients had a significantly higher relative abundance of Enterobactericeae in their gut microbiota compared with transplant recipients without norovirus infection. Future studies are needed to explore if this association is mechanistically important for norovirus infection.

Disclosures

All authors: No reported disclosures.
2596. Invasive Fungal Disease in Patients with GATA2 Variant Hematologic Malignancy
Authors: Bold Tyler D , Vedula Rahul S , Cheng Matthew P , Marty Francisco M , Lindsley R Coleman
Published: October 2019

Background

Patients with hematologic malignancies (HM) are at risk of invasive fungal disease (IFD). Identification of those patients at the highest risk for IFD would help optimize prophylactic or preemptive treatment decisions in this population. We previously found that among patients with myeloid malignancies who develop invasive aspergillosis, 15% had a mutation in the gene GATA2. Here, we report the incidence of IFD in a cohort of patients with HM related to a pathogenic sequence variant of GATA2.

Methods

We identified 6343 patients cared for at Dana-Farber/Brigham and Women’s Cancer Center between January 2014 and August 2018 who underwent a next-generation sequencing assay of 95 genes recurrently mutated in hematologic malignancy. Those found to have a pathogenic GATA2 sequence variant were selected for retrospective chart review with respect to serious infectious complications including IFD.

Results

We identified 54 patients with a pathogenic GATA2 variant. 5 had a germline mutation related to familial GATA2 deficiency. The other 49 had a HM, mostly (41/49) acute myeloid leukemia or myelodysplastic syndrome. The frequency of the variant GATA2 allele in this group ranged from 2.5 to 92.0% of sequencing reads. 14 patients were excluded due to lack of sufficient follow-up, often related to treatment at another institution. Of the remaining 35 patients, 13 (37%) had proven/probable invasive fungal infection (IFI). Fourteen others had syndromes consistent with possible IFD. In total, 16 of these 35 patients (46%) received antifungal therapy for proven, probable or possible IFD. Four of the patients not treated with antifungals were diagnosed with a serious infection including 2 cases of Staphylococcus aureus bacteremia, and one case of disseminated Mycobacterium avium complex.

Conclusion

We identified a high incidence of IFD among patients with HM related to a pathogenic sequence variant of GATA2. The wide range of variant allele frequency observed raises the possibility that either inherited or acquired GATA2 dysfunction could incur predisposition to infection. These data suggest that personalized genetic diagnostics of patients with HM may be useful for assessment of infectious risk.

Disclosures

All authors: No reported disclosures.
2610. A Deadly Intrusion: Competitive Strain Displacement among Dengue Virus Strains in Sri lanka
Authors: Gallegos Dylan C , Rodriguez Stacy , Hansen Immo , Hanley Kathryn
Published: October 2019

Background

Mosquito-borne dengue virus (DENV), the agent of dengue hemorrhagic fever (DHF), is genetically diverse, and new strains regularly invade distant locations and displace existing strains. Invasive strains often cause higher rates of DHF than displaced strains, so it is critical to identify the mechanisms that enable invasion. We tested the hypothesis that invasive strains are less susceptible to RNA interference (RNAi), the major antiviral defense in mosquitoes, than displaced strains.

Methods

We knocked-down (KD) RNAi in vivo in Aedes aegypti, the DENV vector, by injecting mosquitoes with double-stranded RNA against Argonaute 2 (Ago2), a key enzyme in the RNAi pathway, or a control dsRNA. Ago2 KD and control mosquitoes were fed bloodmeals containing 1 of 3 isolates each of 3 different strains of DENV that had undergone sequential competitive displacement in Sri Lanka, termed, in order of displacement, Pre-DHF, Post-DHF and Ultra-DHF. We predicted that the Pre-DHF strain, which we have previously shown to be less infectious for mosquitoes than the other two strains, would show a greater increase in infectivity than those strains. Engorged mosquitoes were incubated for 10 days, homogenized, and assayed for virus.

Results

Ago2 KD efficiency ranged from 79% to 98%, as determined by semi-quantitative PCR and band densitometry. The percentage of mosquitoes infected following Ago2 vs. control KD was not significantly different (33% vs. 47%; paired t-test, DF = 8, P = 0.08). However, among infected mosquitoes, virus titer was significantly higher in Ago2 KD mosquitoes (3.98 vs. 3.38 log10 plaque forming units/body; t-test, DF = 14, P = 0.02). Contra our prediction, a two-factor ANOVA did not reveal a significant interaction between the effect of virus strain and treatment (DF = 5, P = 0.58), indicating that Pre-DHF viruses did not show a larger response to Ago2 KD than Post and Ultra-DHF viruses.

Conclusion

These data support the role of RNAi as a key mosquito defense against virus replication in mosquitoes but indicate that the differences in competitive success among the 3 DENV strains studied are not due to differences in interactions with Ago2 during initial stages of mosquito infection.

Disclosures

All authors: No reported disclosures.
2619. Clinical Characteristics and Etiology of Community-Acquired Pneumonia in Children: A Contemporary, Prospective, Multicenter Study in Ohio, 2015–2018
Authors: Yun Ki Wook , Wallihan Rebecca , Desai Ankita P , Alter Sherman J , Ambroggio Lilliam , Cohen Daniel M , El-Assal Osama , Marzec Sarah , Florin Todd A , Florin Todd A , Keaton Meghan , Shah Samir S , Mejias Asuncion , Ramilo Octavio , Ramilo Octavio
Published: October 2019

Background

Worldwide, pneumonia is the leading cause of death in children <5 years of age and the second most common reason for hospitalization in children in the United States and Europe. This study was designed to describe the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children.

Methods

We conducted a prospective, multicenter, observational study of CAP among previously healthy children aged 2 months through 18 years in six children’s hospitals in Ohio. Blood, pleural fluid, and nasopharyngeal swabs were collected for pathogen detection by culture and/or molecular diagnostics. Patient clinical management including antibiotic therapy and respiratory support, followed the standard of care at each study site. Follow-up information regarding clinical outcomes was collected via a survey 6–8 weeks after enrollment.

Results

We enrolled 441 children (n = 380, 86% hospitalized) with CAP from 2015 to 2018. Median age was 5 years (IQR: 2.1–8.9y). Intensive care and respiratory support were required for 15% and 49% of children, respectively. Consolidation and pleural effusion were identified in 26% and 21%, respectively. Among hospitalized children, 99% received antibiotics during hospitalization, and 91% continued antibiotic treatment at discharge. There were no children with any kind of sequelae or deaths from CAP, but 4.4% were readmitted within 30 days after discharge. Pathogens were identified in 64% patients; including pyogenic bacteria in 4%, atypical bacteria in 9%, and viruses in 56%. A total of 18 (4%) children had both bacterial (9 pyogenic and 9 mycoplasma) and viral pathogens. Among children with a virus detected (n = 245), 17% had more than one virus. The most commonly detected bacteria were M. pneumoniae (n = 39) and S. pneumoniae (n = 10). Rhinovirus was the most common virus detected (RV; n = 81, 28%), followed by respiratory syncytial virus (RSV; n = 75, 26%).

Conclusion

In this multicenter cohort, the most commonly detected viruses in children with CAP were RV and RSV, and M. pneumoniae and S. pneumoniae among bacteria. Clinical outcomes in children with CAP were overall good, but there was a high burden of hospitalization and antibiotic use.

Disclosures

Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.
2632. Cord Blood Vitamin D and Maternal Vaccination Status Associated with Decreased Laboratory Confirmed Influenza Infections in Infants
Authors: Betz Kristina , Fenchel Matthew , Steinhoff Mark C , Schlaudecker Elizabeth P
Published: October 2019

Background

Maternal influenza vaccination has been demonstrated to reduce influenza infections in infants. Influenza infections generally peak during the winter season, and several studies support the association between low levels of vitamin D during winter months and an increase in respiratory infections, including influenza. We examined the effects of vitamin D and maternal influenza vaccination status on laboratory confirmed influenza infections in infants less than 6 months of age.

Methods

Pregnant Bangladeshi mothers were randomized to receive influenza vaccine or pneumococcal vaccine as part of the Mother’s Gift study. Mothers reported breastfeeding frequency, along with episodes of infant respiratory illness with fever, every week for the first 6 months of life. If a respiratory illness with fever was reported, nasal swabs were obtained from the infant and tested with a commercial rapid influenza test. Infants with confirmed influenza disease were matched with four controls by birth month and sex, for a total of 84 controls. We measured 25-hydroxyvitamin D levels from cord blood in all cases and controls. A conditional logistic regression was performed to test the effect of vitamin D on the odds of laboratory confirmed influenza while controlling for birth weight, gestational age, crowding, number of siblings, and socioeconomic status score.

Results

A total of 21 infants had laboratory confirmed influenza disease. There were no significant differences in birth weight, crowding, family size, gestational age, socioeconomic status score, infant gender, and smokers in the home between cases and controls (Table 1). Frequency of maternal influenza vaccine was lower in cases when compared with controls (23.81% vs. 58.33%). Serum vitamin D was lower in cases than in controls (8.73 ± 3.34 vs. 10.67 ± 4.08, Table 2).

Conclusion

Both vitamin D levels and maternal vaccination status have medically relevant, and statistically significant, independent effects on the odds of infants contracting influenza. Although the vitamin D levels in the infants at birth were low, there was a significant association of lower levels at birth with an increased risk of influenza virus infection. Further study with a larger sample-size is needed to explore these effects.

Disclosures

All authors: No reported disclosures.
2637. Third Trimester Immunization with an Respiratory Syncytial Virus F Protein Vaccine for the Prevention of RSV Lower Respiratory Tract Infection in Infants
Authors: Fries Louis F , Cho Iksung , Thomas D Nigel , Wen Judy L , Spindler Michelle S , Fix Amy B , Plested Joyce S , Chen Chang-Min , Glenn Gregory M
Published: October 2019

Background

Respiratory syncytial virus (RSV) is the leading viral cause of severe lower respiratory tract infection (LRTI) in infants worldwide, with severe disease occurring in the first months of life. We assessed the efficacy of maternal immunization with an RSV F protein vaccine against RSV LRTI over the first 180 days of life.

Methods

We enrolled 4,636 women with low-risk third trimester singleton pregnancies in 11 countries to receive RSV F vaccine or placebo in a randomized, observer-blind trial. Women were followed for 6 months post-delivery, and infants for ~1 year. Surveillance for RSV LRTI in infants, identified by RT–PCR detection of RSV, physical examination, and pulse oximetry, was carried out for 180 days from delivery.

Results

The RSV F vaccine induced modest reactogenicity and no excess fever. Live births resulted from 98.7% of pregnancies, with no difference between treatment groups in prematurity (< 37 weeks) or mean interval from treatment to delivery. There were no apparent negative impacts on pregnancy, delivery, or infant well-being. Vaccine immunogenicity resembled that in non-pregnant women. Transplacental transfer of vaccine-induced antibodies was markedly more efficient when the interval from immunization to delivery was ≥30 days. 85 to 95% of primary and secondary endpoint RSV LRTI events in the placebo group occurred in the first 90 days of life (see Figure 1). Overall, through 180 days of infant life, RSV was associated with 11.3% of all acute respiratory illnesses and 16.7% of all LRTI, but 49.1% of LRTI with SpO2 < 95% or tachypnea, and 60.3% of all LRTI with SpO2 < 92% in the placebo group. Vaccine efficacy was greatest in the first 75 days of life but clearly persisted to the primary, per-protocol analysis at 90 days, and was supported by the ITT analysis, per Table 1. Efficacy against all-cause LRTI with severe hypoxemia (46.0%) or hospitalization (27.8%) was observed in the per-protocol population, as well as an apparent impact on the clinical diagnosis of pneumonia through both 180 and 364 days.

Conclusion

RSV F vaccine in the third trimester was safe and had clinically-meaningful impacts on RSV and all-cause LRTI over the first 6 months of life.

Disclosures

All authors: No reported disclosures.
2663. Impact of Pre-Transplant Microbiology on Acute Outcomes in Cystic Fibrosis Patients Receiving Bilateral Lung Transplants
Authors: (Michael) Ji Xincheng , Jain Raksha , Greenberg David E
Published: October 2019

Background

Lung transplantation is a life-prolonging intervention for cystic fibrosis (CF) patients; however, their tendency to be colonized with multiple respiratory pathogens poses a unique risk for post-transplant complications. While infections with certain CF-related pathogens have been identified as contraindications for transplant, much remains uncertain about the influence of pre-transplant microbiological factors on post-transplant outcomes.

Methods

A retrospective cohort study was performed for all CF patients receiving bilateral lung transplants at a single center during the 2016–2018 period. Patient and microbiological data were collected and analyzed from 1 year pre-transplant to 3 months post-transplant. Patients were categorized according to pre-transplant microbiology, with consideration to multidrug-resistant organisms (MDROs) and chronic organisms (positive culture in ≥ 50% of encounters).

Results

Twenty-seven CF patients received a transplant during this time period. Twenty-five patients (92.6%) had re-isolation with ≥ 1 pre-transplant organism in the 3 month period post-transplant, with 16 (59.3%) developing infectious complications, and 11 (40.7%) developing rejection. Isolates associated with chronic infections were the principal factor in determining re-isolation post-transplant (OR = 4.353, 95% CI = 1.455–13.027, P = 0.009). Multidrug-resistance (P = 0.095) and species (P > 0.3) were not significant predictors of re-isolation. There was no difference in early post-transplant outcomes (infectious complications, rejection, FEV1% predicted, ICU and hospital LOS) for patients chronically infected with MDROs vs. those who were not (P > 0.3). Chronic infections with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus were not predictors of poor outcomes (P > 0.3). However, chronic fungal infections (n = 7) produced more infectious complications (median 2 vs. 0, P = 0.0453) and longer ICU stays (median 22 days vs. 5 days, P = 0.0191).

Conclusion

Chronic infections are associated with a greater risk of post-transplant re-isolation of pathogens in CF patients, more so than drug resistance or species. Chronic infections with fungi were associated with worse transplant outcomes.

Disclosures

All authors: No reported disclosures.
2665. Intestinal Microbiome of Patients Submitted to Hematopoietic Stem Cell Transplantation Using Lactobacillus plantarum to Decolonized Multidrug-Resistant Bacteria
Authors: Moraes Bruna G C , Martins Roberta C R , Franco Lucas A M , Lima Victor A C C , Pereira Gaspar C O , Santos Juliana T , Fernandes Tamiris H , Guimaraes Thais , Rocha Vanderson G , Sabino Ester C , Costa Silvia F
Published: October 2019

Background

Patients colonized by multidrug-resistant bacteria (MDR) have high risk for infection after hematopoietic stem cell transplantation (HSCT). Probiotic is a strategy that can be used to decolonize patients. Our aim was to describe the impact of use of Lactobacillus plantarum (LP) on decolonization, MDR infections and intestinal microbiome (IM) of autologous HSCT patients colonized by vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Gram-negative (CRGN).

Methods

A prospective study was conducted at Hospital das Clinicas of University of Sao Paulo Brazil from 2017 to 2018. Candidates for auto-HSCT colonized by MDR received LP in capsules, 5 × 109 CFU twice daily until neutropenia (NP). Rectal swabs were performed and cultured using selective media as well as PCR for carbapenemases, vanA and vanB. Stool samples for IM analysis were collected weekly as baseline (before LB use) until the NP. The V4 region of 16S rDNA gene were sequenced by Ion Torrent PGM and analyzed using alpha and β diversities by Qiime. Demographic and clinical data including previous antibiotics use were evaluated; CDC criteria was applied for colonization and infection.

Results

All of seven patients were colonized by VRE and CRGN (Table 1). Only one patient remained colonized by CRGN after 61 days of LP. Four patients developed seven bloodstream infections (BSI) during the NP, two of them by CRGN. There was no infection caused by VRE neither by LP. One patient, with low adherence to LP use (66%), died due to MDR K. pneumoniae BSI. We observed a decrease of Clostridia, Verrucomicrobiae, Blautia and an increase of Enterobacteriaceae. Baseline samples from patients who used TMP/SMX had higher concentrations of Bacteroidetes when compared with those who had not use it. The Shannon index in controls ranged 1.98–5.55 and during NP 1.15–5.99. The β diversity analysis showed no clear patterns between patients.

Conclusion

We observed a heterogeneity among IM of auto-HSCT patients prior and after LP. It was not possible to establish an IM pattern, probably, because of small number of patients. Although, clinical infections by CRGN occurred despite of LP use, no cases of colonization and infection by VRE were identified. Thus, it seems that LP is a good and safe strategy to decolonized HSCT.

Disclosures

All authors: No reported disclosures.
2670. Clostridioides difficile Infection (CDI) in Solid-Organ (SOT) and Hematopoietic Stem Cell Transplant (HCT) Recipients: A Prospective Multinational Study
Authors: Blumberg Emily , Gary Collins , Young Jo-Anne H , Nguyen Minh-Hong , Michonneau David , Temesgem Zelalem , Origuen Julia , Barcan Laura , Obeid Karam , Belloso Waldo , Gras Julien , Corbelli Giulio Maria , Neaton James , Lundgren Jens , Snydman David R , Molina Jean-michel
Published: October 2019

Background

CDI is an important cause of morbidity and mortality in SOT and HCT patients (pts). In retrospective single-center analyses, severe disease and relapse were common. We undertook a multicenter prospective observational study to evaluate outcomes of CDI among both SOT and HCT patients.

Methods

Adults with a first episode of CDI, defined as 3 liquid stools/24 h with the detection of C. difficile toxin in stool, within the first 2 years of SOT or HCT were recruited from 12 centers internationally in the INSIGHT network. At enrollment, demographics, comorbidities, medication histories and outcomes were collected prospectively over 90 days to assess clinical cure, recurrences and complications and to define baseline risk factors for clinical cure and recurrent CDI.

Results

132 patients (81 SOT, 51 HCT (32 allogeneic)) were enrolled: median age 56 years, 62.1% were males, 97% were hospitalized. 80.3% were diagnosed by DNA assay. CDI occurred a median of 20 days post transplant (IQR: 6–133). 108 patients were on PPIs. 98.5% were on antibiotics before CDI. 1st line treatment regimen was oral vancomycin in 66 patients (40 SOT, 26 HCT), metronidazole in 48 patients (27 SOT, 21 HCT), both drugs in 14 (10 SOT, 4 HCT), fidaxomicin (3) and linezolid (1). Rejection within 60 days before CDI was uncommon (6.2% SOT) as was GVHD (27.5%). 110 patients (83%, 95% CI: 46–89)) (65 SOT, 45 HCT) had clinical cure; 18% (95% CI: 11–27) had recurrent CDI, 2 were admitted to the ICU due to CDI, 11 (8.3%) died (2 HCT related to CDI). Among baselines variables, only first-line regimen was associated with a higher rate of clinical cure (P = 0.003), most notably for SOT. Factors that did not have a statistically significant negative impact on clinical cure included sex, age > 60, race, country, transplant type, steroids, diabetes, CMV viremia/disease, WBC > 15,000, creatinine > 1.5 mg/dL, or specific antibiotic given prior to CDI. Higher recurrence rates were associated with metronidazole-only regimen (OR: 4.6, 95% CI: 1.6–12.8; P = 0.004) and a history of CMV after transplant (OR: 5.2, 95% CI: 1.7–15.7; P = 0.003).

Conclusion

Despite their immunosuppressed state, recurrence, ICU admission and mortality occurred in a minority of SOT and HCT with CDI. Initial use of metronidazole and CMV viremia/disease were associated with higher recurrence rates.

Disclosures

All authors: No reported disclosures.
2674. Microbiome and Cumulative Antibiotic Use as Predictors of Stenotrophomonas maltophilia Infection in Patients with Acute Myeloid Leukemia Receiving Remission-Induction Chemotherapy
Authors: Aitken Samuel L , Aitken Samuel L , Shelburne Samuel A , Shelburne Samuel A , Galloway-Peña Jessica
Published: October 2019

Background

S. maltophilia infections are increasingly common in patients with acute myeloid leukemia (AML) and associated with high mortality. S. maltophilia is a frequent colonizer in AML patients but relatively little is known about factors that drive S. maltophilia infection. We sought to evaluate the utility of cumulative antibiotic use and the microbiome as predictors of S. maltophilia infection in AML patients receiving remission induction chemotherapy (RIC).

Methods

We performed a subanalysis of a prospective, observational cohort study between September 2013 and August 2015 of adult patients with AML receiving RIC. In this study, fecal and oral microbiome samples collected every 96 hours from the start of RIC until neutrophil recovery were assessed for the relative abundance of S. maltophilia via 16s rRNA quantitation. The primary outcome, microbiologically proven S. maltophilia infection, was analyzed using a time-varying Cox proportional hazards model accounting for S. maltophilia relative abundance and cumulative antibiotic exposure. Patients were censored at neutrophil recovery or death.

Results

90 patient were included; of whom, 8 (9%) developed S. maltophilia infection (pneumonia, n = 6; skin/soft-tissue infection, n = 2). 4/8 (50%) patients were bacteremic. 7/8 (88%) patients with S. maltophilia infection had detectable oral 16s oral reads mapping to S. maltophilia vs 22/82 (27%) without infection (P < 0.01). An oral S. maltophilia relative abundance of 36% predicted infection (sensitivity: 96%, specificity 93%, likelihood ratio +: 17.08). No association of S. maltophilia infection with the fecal relative abundance was seen. Cumulative meropenem exposure was associated with increased infection risk (hazard ratio [HR] 1.17, 95% CI 1.01 – 1.35, P = 0.03), while levofloxacin was associated with decreased infection risk (HR 0.83, 95% CI 0.66 – 1.04, P = 0.10).

Conclusion

The oral microbiome may play an important role in S. maltophilia pathogenesis in AML patients. Cumulative antibiotic exposure likely modifies S. maltophilia infection risk. These data suggest that real-time molecular monitoring of the oral cavity for S. maltophilia in AML patients could identify patients at high risk for S. maltophilia infection and improve targeted therapy.

Disclosures

Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
2684. The Prospective Pilot Study of Infectious Complication Surveillance in Active Systemic Lupus Erythematosus Patients with Intense Immunosuppressive Therapy: Cellular Response and Clinical Outcomes
Authors: Rotjanapan Porpon , Kirdlarp Supachok , Suangtamai Tanitta , Bruminhent Jackrapong , Ngamjanyaporn Pintip , Pisitkun Prapaporn
Published: October 2019

Background

Despite a common complication, the real interplays between the infectious sequelae and systemic lupus erythematosus (SLE) with intense immunosuppressive therapy (IT) are not fully understood.

Objective

To identify the cellular biomarkers that justify the risk for overall infection in active SLE patients with intense IT.

Methods

An observational, prospective cohort pilot study was conducted in active SLE patients with intense IT aged >15 years from November 2017 March 2019 at Ramathibodi Hospital, Bangkok, Thailand. Clinical data and T-cell subpopulation analyses, at weeks 0 (at enrollment), 2, 4, 8, and 16 were obtained. Every patient was monitored over a 24-week period. The infections of interest were any emerging infections other than cytomegalovirus infection (CMV). 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 23 active SLE patients were enrolled, 91.3% were female with the median age (interquartile range, IQR) of 27.7 (23.0–42.1) years old. The median SLE disease activity index (IQR) was 16 (10–20) and 73.9% had renal abnormality. At week 12, the prevalence of infection was 39.1% being bacterial infection in 77.8% and viral infection in 22.2%. There was no mortality in this study. Non-infection group had higher proportions of absolute lymphocyte count (ALC), CD3+ T cell, and CD3+CD56+ natural killer T (NKT) cell numbers compared with the infection group; [median of 1169.8 (694.4–1921.4) vs 716.1 (429.0–882.0) cells/µL; P = 0.044, 585.1 (245.1–669.2) vs. 204.9 (73.9–286.5) cells/µL; P = 0.017, and 50.5 (13.7–152.2) vs. 4.35 (2.44–52.9) cells/µL, P = 0.040, respectively]. Patients with NKT cells >9.31 cells/µL had longer median infection-free day of 25.3 days (19.7–25.3) vs. 2.0 days (1.7–4.0) in patients with lower NKT cell count (log rank P < 0.001). The Cox-proportional hazard ratio was 0.03, P = 0.003 (95% confidence interval 0.004–0.300).

Conclusion

Bacterial infections are common in active SLE patients with intense IT. Monitoring of ALC, CD3+ T-cell, and NKT-cell counts can potentially be used as the infectious risk prognosticators. However, a study in a larger scale is encouraged to verify these findings.

Disclosures

All authors: No reported disclosures.
2685. Oral Third-Generation Cephalosporins vs. Levofloxacin for Antibacterial Prophylaxis in Neutropenic Patients with Hematologic Malignancies
Authors: DeVoe Catherine , Trinh Trang D , Moises Joshua , Pham Binh C , Tran Allen V , Vuong Lisa , Doernberg Sarah B
Published: October 2019

Background

Fluoroquinolone (FQ) prophylaxis for high-risk neutropenic patients has been shown to reduce rates of febrile neutropenia and is standard at many centers. For patients who cannot receive a FQ, oral third-generation cephalosporins (OTGCs) are often used as an alternative; however, this strategy is not well studied. We sought to compare clinically-relevant outcomes in patients receiving FQ vs. OTGC prophylaxis.

Methods

This was a retrospective cohort study of adults who were admitted to the Malignant Hematology service at the University of California, San Francisco between December 2012 and June 2018 and received >48 hours of an OTGC (cefdinir or cefpodoxime) or an FQ (levofloxacin) for neutropenic prophylaxis. For each OTGC patient, an FQ patient was randomly selected from the same admission year. Exclusion criteria were fever on admission, receipt of systemic antibiotics prior to or during the prophylaxis period, diagnosis of acute promyelocytic leukemia, and crossover. A multivariable logistic regression analysis adjusting for age, QTc, Charlson Comorbidity Index, underlying diagnosis, receipt of stem cell transplant (SCT), and duration of neutropenia was used to compare the groups with respect to a primary composite outcome of 30-day in-hospital mortality, intensive care unit (ICU) admission, and bacteremia.

Results

Of 520 patients screened, 173 (33.3%) were included in the study; 76 of these received an OTGC and 97 received an FQ. Hematologic diagnoses included multiple myeloma (38.2%), acute myeloid leukemia (29.5%), acute lymphoblastic leukemia (8.7%), B-cell lymphoma (12.7%), aplastic anemia (2.9%), and others (3.5%). During admission, 9.2% underwent allogeneic SCT and 28.3% underwent autologous SCT. Outcomes are shown in Table 1.

Conclusion

Prophylaxis with an OTGC rather than a FQ was not associated with worse outcomes in this pragmatic evaluation of a heterogeneous group of patients with hematologic malignancies. In this multivariable model, neutropenia lasting more than 7 days was the only consistent predictor of failure across outcomes, suggesting that degree of immunosuppression is a much more significant driver of poor outcomes in this population than is prophylaxis choice. Further evaluation of the role of prophylaxis is needed.

Disclosures

All authors: No reported disclosures.
2690. Infectious Complications in Adult Leukemic Patients with Prolonged Neutropenia Undergoing Induction Chemotherapy
Authors: Sabapathy Vidhya , Klinkova Olga , Balbona Joseph , Greene John
Published: October 2019

Background

Induction chemotherapy in patients with the diagnosis of acute leukemia is associated with a high incidence of infectious complications. While prior studies provide information regarding infectious complications in this patient population, more research is needed to evaluate infection complications in a subgroup of leukemic patients with prolonged neutropenia who often require repeat induction chemotherapy.

Methods

This was a retrospective analysis of 61 patients ages 18–85, between January 1, 2010 and March 14, 2018 who were diagnosed and being treated for acute leukemia. All selected patients experienced severe neutropenia (defined as absolute neutrophil count <500/μL) for ≥7 days. 33 patients underwent their first induction chemotherapy while 28 patients underwent repeat induction chemotherapy. Patient characteristics and infectious complications were examined. Analysis was performed to further study blood stream infections in this patient population.

Results

Sixty-one patients, mean age of 55 ± 17, were included in this study. Acute myelogenous leukemia was the most common diagnosis (n = 47, 77%). The average duration of neutropenia in single vs multiple induction group was 40 vs. 47.2 days (P = 0.38), respectively. 198 culture-proven infections were identified. Overall, bloodstream infections were the most common site (n = 78, 39.4%), followed by respiratory tract infections (n = 39, 19.7%). Gram-positive organisms were the leading etiology of bacteremias (n = 50, 64%). Bacteremia episodes were more common in the patients undergoing multiple induction chemotherapy comparing to a single treatment (45 vs. 33 episodes). Patients undergoing multiple induction chemotherapy experienced a higher rate of Gram-negative blood stream infection episodes comparing to a single induction group (n = 18/78, 23.1% vs. n = 10/78, 12.8%).

Conclusion

Overall, bacteremia was the most common infection in this patient population, followed by respiratory tract infections. Gram-positive pathogens were the most common etiology of bacteremia when all patients were analyzed. However, in the subset of patients undergoing multiple induction chemotherapy, Gram-negative pathogens were the leading cause of the blood-stream infections.

Disclosures

All authors: No reported disclosures.
2691. Comparison of Incidence and Mortality of Kaposi’s Sarcoma Amongst Solid-Organ Transplant Recipients
Authors: Gummadi Padma Priya , Aurit Sarah , Destache Christopher J , Walters Ryan , George Elizabeth K , Vivekanandan Renuga , Velagapudi Manasa
Published: October 2019

Background

Kaposi’s sarcoma (KS) is a lymphatic endothelium-derived tumor caused by Human Herpes Virus 8 (HHV-8). Organ transplant recipients are at increased risk of this malignancy due to use of immunosuppressive therapy. In this observational trial, the incidence of KS in different organ transplant recipients as well as mortality were investigated.

Methods

Patient information was retrieved from the United Network for Organ Sharing (UNOS) database to identify all liver, kidney, heart, or lung transplant recipients, and those who were subsequently diagnosed with KS. Patients were stratified by transplant organ, clinical and demographic information was obtained to characterize each population. Unadjusted differences in incidence, mortality, and patient characteristics were examined with chi-square or Fisher exact test for categorical variables; continuous variables were examined with the Kruskal–Wallis test which was Bonferroni adjusted for multiple comparisons. Patients < 18 years of age, who had missing information concerning the development of a Kaposi’s sarcoma, or who underwent multiple organ transplant were excluded. SAS, v. 9.4, was used for statistical analysis; P < 0.05 was considered significant.

Results

Patient demographics are described in Table 1. The development of KS was significantly different among organ transplant types. Kidney transplant recipients had a higher incidence of KS in comparison to liver transplant recipients (P < 0.001). Mortality was the highest in lung transplant recipients who developed KS, which was significantly higher than kidney (P < 0.001) or liver transplant recipients (P = 0.005). Finally, it was determined that there was a significant difference in age and race (white vs. non-white) among the various organ transplants (P < 0.001, respectively)

Conclusion

Although incidence of KS is significantly higher post renal transplant, mortality is highest in lung transplant recipients. Further investigation is needed to understand differences in mortality among transplant recipients. This will help identify at risk subjects and develop interventions to reduce mortality.

Disclosures

All authors: No reported disclosures.
2697. The Impact of Universal Deceased Donor Screening on Donor-Derived Toxoplasmosis in Solid-Organ Transplant: Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC)
Authors: Strasfeld Lynne , La Hoz Ricardo M , Vece Gabe , Wolfe Cameron R , Michaels Marian G
Published: October 2019

Background

Donor-derived toxoplasmosis (DDT) is a severe and potentially life-threatening infection after solid-organ transplantation (SOT). Serologic testing for Toxoplasma gondii is required for all deceased donors per OPTN policy as of 4/6/17. To assess the impact of universal donor testing and the optimal approach to DDT prevention, we analyzed potential DDT cases reviewed by DTAC.

Methods

All potential Toxoplasma donor-derived transmission events adjudicated by DTAC from 2008 to 2018 were reviewed. A standardized classification algorithm was used to adjudicate each event as proven, probable, possible, unlikely, excluded or intervention without disease transmission.

Results

Twenty-eight potential DDT events were reported between 2008 and 2018. Proven or probable (p/p) DDT developed in 16 organ recipients from 15 donors. In the 9 years prior to the new testing requirement (January 2008–March 2017) 11 organ recipients from 10 donors had p/p DDT (0.13 transmissions per 1,000 donors); in the first 21 months of the new testing requirement 5 recipients from 5 donors had p/p DDT (0.27 transmissions per 1,000 donors), rate ratio 2.15; 95% CI 0.577, 6.90;P = 0.18. 10.2% of 18,328 donors tested between April 6, 2017 and December 31, 2018 were Toxoplasma IgG seropositive. Recipient pre-SOT serostatus was unknown in 4 of 5 and negative in 1 case of p/p DDT. Trimethoprim/sulfamethoxazole prophylaxis was either stopped at < 3 months or not used in all 5 cases. Infection was diagnosed a median of 103 days (range 42–153) post-transplant. Four of the 5 recipients died.

Conclusion

DDT remains a morbid infection in both heart and non-heart recipients. Despite an apparent increase in DDT reporting to DTAC, it is unlikely that the actual incidence of this donor-derived event is increasing. Rather, with universal serologic screening of deceased donors and wider access to molecular diagnostics, DDT is increasingly recognized and diagnosed. To decrease risk for illness and death related to DDT, broader pre-transplant recipient serologic testing and use of prophylaxis or monitoring for high-risk serostatus recipients (Toxoplasma D+/R−) is critical. The optimal duration of prophylaxis is uncertain at this time and warrants further study.

Disclosures

All authors: No reported disclosures.