bluuebunny/crossref_metadata_2025 huggingface dataset:
1838. Bare Below the Elbows vs. Sleeved Attire: A Pilot Study Comparing Microbial Flora of Healthcare Workers
Authors: Assi Mariam , Major Yvette , Hess Olivia , Styslinger Emily , Srivastava Tara , Doern Christopher , Cooper Kaila , Godbout Emily , Stevens Michael , Bearman Gonzalo , Doll Michelle
Published: October 2019

Background

Bare Below the Elbows (BBE) is an approach to healthcare worker (HCW) attire that limits patient contact with contaminated HCW clothing. While supported by biological plausibility, the practice is controversial. Critics cite limited evidence that bare skin is less contaminated in comparison to sleeved garments such as white coats. This study is a comparison of the flora and bioburden between BBE and sleeved HCW.

Methods

HCW on 2 progressive care units were asked to allow swab sampling of their dominant wrist/forearm (Figure 1). Non-clinicians were excluded. Hand hygiene was not performed prior to sampling. HCW agreeing to participate completed informed consent, and a survey regarding bathing and laundering. Swabs were inoculated into TSA broths, and incubated for 24 hours at 37°C. Bioburden was estimated using McFarland standard optical densities by 2 independent blinded evaluators. The broth was streaked on blood agar and MacConkey plates. Colonies consistent with possible Staphylococcus spp. were tested with latex agglutination, and positive isolates were plated on CHROMagar™ MSSA/MRSA. Fisher’s exact/Wilcoxon rank-sum tests were used to compare the categorical/numerical data between BBE and sleeved providers using SAS version 9.4.

Results

Sixty-three HCW participated; 30 were BBE and 33 sleeved. A comparison of the 2 groups is shown in Table 1. The majority of bacterial growth was morphologically consistent with skin flora; no Gram-negative rods grew. The bioburden estimates and presence of Staphylococcus aureus were not different between the groups (P = 0.099 and 0.325, respectively). Surveys indicated that BBE providers were more likely to be working in freshly laundered garments (P < 0.0001); this was true for all BBE providers except 2 HCW on shift >24 hours. Three sleeved individuals could not remember when they last laundered the garment in which they were providing clinical care.

Conclusion

HCW laundering practices remain suboptimal, particularly among sleeved HCW. The potential impact of hand hygiene on comparative bioburden between sleeved and BBE HCWs remains unknown and is the focus of future investigations.

Disclosures

All Authors: No reported Disclosures.
1874. Comparison of the Risk of Birth Defects in Live Births From Pregnant Women Infected and Not Infected by Zika Virus in Guadeloupe, 2016–2017
Authors: Louise Funk Anna , Hoen Bruno , Tressières Benoit , Vingadassalom Ingrid , Janky Eustase , Kadhel Philippe , Ryan Catherine , Gaete Stanie , Fontanet Arnaud
Published: October 2019

Background

In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was estimated at 7% among fetuses/infants in a cohort of 546 women who developed a symptomatic RT-PCR confirmed ZIKV infection during pregnancy (NEJM 2018;378:985–94). There was no concomitant prospective cohort of pregnant women without ZIKV infection to use as a control group.

Methods

In Guadeloupe, one of the 3 FTAs that participated in the FTA cohort study, pregnant women were recruited at the time of delivery and tested for ZIKV infection. Women who had a confirmed negative IgG serology test for ZIKV at delivery and no other positive ZIKV test during pregnancy were considered to be ZIKV noninfected. Information on the course of the pregnancy was collected retrospectively and outcomes of live born infants of ZIKV noninfected women were analyzed, using the same definition criteria as those used for the FTA cohort study. Pregnancy outcomes were compared with those of the 241 ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA cohort.

Results

Of the 490 live born infants without in-utero exposure to ZIKV, 42 infants (8.6%) had neurological abnormalities that were described as “potentially linked to ZIKV infection”; all but one of these were microcephaly without any other brain or clinical abnormalities. The proportion of such abnormalities was not statistically different from that observed in the 241 live born infants with ZIKV exposure (6.6%, P = 0.36). When re-considering the combined 8 fetuses and 241 infants of women with confirmed ZIKV infection in Guadeloupe from the FTA cohort, only two (0.8%) live born infants and three (1.2%) medically aborted fetuses had birth defects that could still be linked to ZIKV infection.

Conclusion

Isolated anthropometric and other mild neurological abnormalities had the same prevalence among live born infants with and without in utero ZIKV exposure. The high prevalence of isolated microcephaly among ZIKV noninfected women in our study population suggests that the sensitive definition for microcephaly, using a −2 SD cut-off with international growth curves, may lead to an overestimate of the rate of neurological complications of ZIKV infection during pregnancy.

Disclosures

All Authors: No reported Disclosures.
1876. A Hepacivirus-Like Protein Is Targeted by the Antibody Response to Kawasaki Disease (KD)
Authors: Rowley Anne , Baker Susan , Arrollo David , Gruen Leah , Tetyana Bodnar , Innocentini Nancy , Shulman Stanford
Published: October 2019

Background

Clinical and epidemiologic data support a viral cause of KD, but the etiology has eluded 50 years of study. We previously identified virus-like intracytoplasmic inclusion bodies (ICI) in ciliated bronchial epithelium of KD children but not infant controls, but the antigens within the ICI were unknown. At 1–2 weeks following infection, 75% of peripheral blood plasmablasts (PB) specifically target the infectious agent. We cloned the PB response to KD to identify KD-specific antibodies and their target antigens.

Methods

We isolated single PB from children with KD 1–3 weeks after fever onset by flow cytometry, and amplified immunoglobulin VDJ and VJ genes from each PB by RT-PCR. We sequenced the products and made monoclonal antibodies (Mab) from clonally expanded PB in individual patients. Mab were tested for binding to KD tissues and to a viral peptide array containing 29,939 peptides from known B cell epitopes of animal viruses (www.iedb.org).

Results

We sequenced 1156 PB from 11 KD patients, and identified 44 clonally expanded sets of PB. We prepared 61 Mab from clonally expanded and highly mutated IgA PB, and found that 33/61 bind to KD ICI, 10 strongly and 23 weakly. Of 10 Mab that strongly bind, 2 were VH3-33 (single patient), 2 VH3-23 (single patient), 1 VH3-15, 1 VH3-74, 3 VH1-46 (2 patients), and 1 VH4-59. These Mab CDR3s varied from 11 to 20 aacids, with 4–28 aacid mutations. Mab KD4-2H4 recognized multiple similar peptides from nonstructural protein 4A of hepacivirus C; pt KD4 sera was negative for hepatitis C by fourth-generation ELISA. Amino acid substitution analysis yielded an optimized peptide, and 6 KD Mab recognized this peptide by ELISA. These 6 Mab derived from 3 KD patients, all of whom had coronary aneurysms, and were VH3-74 (n = 1), VH3-33 (n = 2, single patient), VH1-45 (n = 1), and VH3-72 (n = 2, single patient). Strong binding of KD Mab KD4-2H4 and KD6-2B2 to ICI was totally blocked by pre-incubation with optimized peptide. KD but not control sera react with optimized peptide expressed as a glutathione S-transferase fusion protein by western blot.

Conclusion

Children with KD make antibodies to a hepacivirus-like protein, and KD ICI contain this protein. These results strongly suggest that a previously unidentified hepacivirus with a respiratory portal of entry is etiologically related to KD.

Disclosures

All Authors: No reported Disclosures.
1877. Evaluation of Antibiotic Utilization After Introduction of a Dedicated Infectious Diseases-Critical Care Medicine Service in Critical Care Units
Authors: Trachuk Polina , Hemmige Vagish , Chen Victor , Weston Gregory , Cowman Kelsie , Berger Jay , Sarwar Uzma N
Published: October 2019

Background

Infection is a leading cause of admission to intensive care units (ICU), with critically ill patients often receiving a high volume of empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely implemented. An ID-Critical Care Medicine (ID-CCM) pilot program was designed at a large tertiary hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide an ID consult on select patients. We sought to evaluate the impact of this dedicated ID consultation and stewardship program on antibiotic utilization in the ICU.

Methods

This is an IRB-approved single-site retrospective study. We analyzed antibiotic utilization in the ICU during the post-intervention period from January 1, 2017 to December 31, 2017 and compared it to antibiotic utilization in the same ICU during the pre-intervention period from January 1, 2015 to December 31, 2015. Using Poisson regression analysis, we evaluated antibiotic utilization of each agent, expressed as days of therapy (DOT) per 1,000 patient-days, between the two groups.

Results

The six most commonly used broad-spectrum antibiotic agents were included in the final analysis. During the intervention period, statistically significant reductions were seen in cefepime (131 vs. 101 DOT per 1,000 patient-days, P = 0.01), piperacillin-tazobactam (268 vs. 251 DOT per 1,000 patient-days, P = 0.02) and vancomycin (265 vs. 228 DOT per 1,000 patient-days, P = 0.01). The utilization of other antibiotics including daptomycin, linezolid, and meropenem did not differ significantly (Figure 1).

Conclusion

With this multidisciplinary intervention, we saw a decrease in the use of the most frequently administered broad-spectrum antibiotics. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.

Disclosures

All Authors: No reported Disclosures.
1880. Reducing Antibiotic Prescribing for Acute Bronchitis in Outpatient Settings Using a Multifaceted Approach
Authors: Chung Philip , Nailon Regina , Salman Ashraf M , Bergman Scott , Micheels Teresa , Rupp Mark E , Schwedhelm Michelle , Tierney Maureen , Tyner Kate , Van Schooneveld Trevor C , Marcelin Jasmine R , Marcelin Jasmine R
Published: October 2019

Background

Nebraska (NE) ranks among the highest states for per capita antibiotic (AB) use in outpatient (OP) settings. Nebraska Medicine (NM) partnered with NE Antimicrobial Stewardship Assessment and Promotion Program (ASAP), a program funded by NE DHHS via a CDC grant, to reduce AB prescribing for acute bronchitis in OP settings.

Methods

The antimicrobial stewardship (AS) pilot program targeted NM OP clinics during winter 2018. All OP facility clinicians were notified of the availability of online AS educational videos. In addition, 5 primary care clinics (PCC) received clinician-directed interventions that included acute respiratory infection management pocket guides and posters for display in workrooms. Another 5 PCC received both clinician- and patient-directed interventions (examination room patient empowerment posters, Be Antibiotic Aware pledge cards and brochures). We compared AB prescribing rates for acute bronchitis between January and April 2017 and January and April 2018 among the 2 PCC groups and a control group of 5 immediate care clinics/emergency departments (ICC/ED). Clinicians in all 10 PCC were surveyed to assess usefulness of the AS campaign.

Results

A total of 593 acute bronchitis diagnosis encounters were included. AB prescribing rates for acute bronchitis for the 15 sites decreased from 53.7% to 43.6% (P = 0.02). Prescribing rates were unchanged in ICC/ED that received only notification of online educational videos (40.8% vs. 41.5%, P = 1.00) but were reduced in clinics that received clinician-directed (74.5% vs. 33.3%, P < 0.01) and patient-directed (61.1% vs. 48.8%, P = 0.07) interventions. Azithromycin was the most commonly prescribed AB (31.5% in 2017 and 29.8% in 2018). After the AS campaign, only the clinician-directed intervention group saw a reduction in azithromycin prescribing (33.3% vs. 13.9%, P < 0.05). Out of 51 clinicians who completed the survey, 45.1% felt campaign tools facilitated meaningful discussion with patients. Workroom posters and pocket guides were reported by 47.1% and 39.2% to be somewhat or extremely helpful, respectively.

Conclusion

This OP AS campaign led to a significant reduction in AB prescribing. Successful OP AS campaigns need multifaceted approaches but targeted clinician interventions appear most beneficial.

Disclosures

All Authors: No reported Disclosures.
1883. Factors Associated with Stigma Toward Isoniazid-Preventative Therapy in a Rural Community of South Africa
Authors: Foppiano Palacios Carlo F , Kompala Tejaswi , Moll Anthony , Andrews Laurie J , Shenoi Sheela
Published: October 2019

Background

Patients living with HIV should receive isoniazid-preventative therapy (IPT) in order to prevent tuberculosis (TB). In South Africa, IPT implementation has decelerated. Stigma is frequently found to be a barrier to treatment. We sought to understand community members’ perceptions of TB and HIV stigma in order to inform future IPT implementation efforts.

Methods

The study was conducted in the rural KwaZulu Natal province of South Africa. Community members were interviewed anonymously and answers to interview questions were scored to represent stigma. Three different domains of TB knowledge were evaluated: causes, transmission, and treatment and prevention of TB. All three knowledge scores were added to create a total knowledge of TB score. A 7-item scale was used to assess stigma; presence of stigma was defined as 1 or more positive responses on the scale. Descriptive statistics, chi-square tests, linear regression, and Kruskal–Wallis tests were performed.

Results

Among 104 participants, the mean age was 35 ± 9.3 years, 65% were female, and 26% completed secondary school. Overall, respondents had poor knowledge about the causes (mean = 61, SD = 27) and transmission (mean = 46, SD = 21), and good knowledge of the treatment and prevention (mean = 88, SD = 18) of TB. The vast majority of participants identified the presence of stigma (72%), with a mean score of 1.7, SD = 1.4. Participants were less likely to report stigma with excellent TB knowledge, characterized by accurate responses to at least 95% of the knowledge items (P = 0.025). Factors associated with higher levels of stigma included marital status (P = 0.01), being previously screened for TB (P = 0.008), considering mosquitos as a vector for TB transmission (P = 0.005), worrying about being infected with TB (P = 0.0117), and reporting travel to the clinic to be expensive (P = 0.03). Interest in taking IPT exhibited a trend toward significance with lower levels of stigma (P = 0.057). On multivariable linear regression of stigma, marital status (P = 0.0304) and prior TB screening (P = 0.0149) were significant.

Conclusion

HIV-related stigma was prevalent among rural South African community members considering IPT. Stigma decreased with higher knowledge levels. Global expansion and implementation of IPT will require interventions to reduce stigma.

Disclosures

All Authors: No reported Disclosures.
1955. Novel Compound Reverses Vancomycin Resistance in Vancomycin-resistant Enterococci (VRE)
Authors: Onyedibe Kenneth , Dayal Neetu , Sintim Herman
Published: October 2019

Background

Enterococcus causes 14% of all hospital-associated infections (HAIs) according to Centers for Disease Control and Prevention (CDC) data. 35.5% of these HAIs are caused by Vancomycin-resistant Enterococci (VRE) including highly fatal bacteremia, surgical site infections, and urinary tract infections. We present a novel synthetic compound, HSD 03-21 that could make VRE completely susceptible to vancomycin in-vitro.

Methods

HSD 03-21 was synthesized de novo from a hydroxybenzylidene – indolinone backbone in our laboratory. The minimum inhibitory concentration (MIC) of HSD 03-21 and vancomycin against VRE were determined according to clinical laboratory standards institute (CLSI) guidelines. The standard checkerboard assay was used to determine vancomycin-HSD 03-21 interactions against VRE. Briefly, HSD 03-21 and vancomycin at 10 mg/mL were prepared and diluted serially along the ordinate and abscissa of 96-well microtiter plates, respectively. Bacteria was standardized using the 0.5 McFarland standard, diluted (1:100), aliquoted into respective wells and incubated at 37oC for 18–20 hours. All assays were run in triplicates. The fractional inhibitory concentration (FIC) index was calculated for each combination. The FIC of either agent was calculated as: FIC (vancomycin) = MIC of vancomycin in combination/MIC of vancomycin alone and FIC (HSD 03-21) = MIC of HSD 03-21 in combination/MIC of HSD 03-21 alone. The cumulative FIC index ∑FICI was then calculated as: ∑FIC = FIC(vancomycin) + FIC(HSD 03-21). The calculated ∑FIC indices were interpreted as synergistic if ∑FIC: ≤ 0.5.

Results

The MIC of vancomycin for VRE faecalis was 256 μg mL−1 while that of HSD 03-21 was 128 μg mL−1. When vancomycin was combined with HSD 03-21 at 8 μg mL−1 (1/16 MIC), there was a reduction in MIC of vancomycin to 0.5 μg mL−1. The combination showed excellent synergy with ∑FIC of 0.06.

Conclusion

HSD 03-21 reduced the MIC of vancomycin from 256 to 0.5 μg mL−1. This has an immense potential of changing the way we use vancomycin and in the treatment of VRE infections. Translation of this novel compound could save thousands of lives from VRE and the failures and inherent toxicities of current doses of vancomycin.

Disclosures

All Authors: No reported Disclosures.
1957. Impact of β-Lactam Antibiotic Allergy on Antimicrobial Use, Clinical Outcomes, and Costs for Hospitalized Children
Authors: Jones Trahern Wallace , Fino Nora , Olson Jared , Hicks Lauri , Fleming-Dutra Katherine E , Hersh Adam
Published: October 2019

Background

Most β-lactam antibiotic allergies (BLA) are incorrectly diagnosed and could be de-labeled. Adult patients with BLA are more likely to receive broader-spectrum antimicrobials and experience worse health outcomes than nonallergic patients. Similar studies on the impact of BLA on antimicrobial use and clinical outcomes are limited in pediatrics. Our objective was to compare antimicrobial use, and clinical and economic outcomes between hospitalized children with and without BLA.

Methods

This was a retrospective cohort of pediatric patients hospitalized at an Intermountain Healthcare (IH) hospital from 2007 to 2017. IH has 22 hospitals including one children’s hospital. Patients aged 30 days-17 years who received ≥1 dose of an antimicrobial during hospitalization were included. The exposure variable was the presence of BLA (penicillins or cephalosporins) in the allergy field of the medical record. Patients with BLA were matched to nonallergic controls on age, sex, race, clinical service line, admission date, children’s hospital or other hospital, and co-morbid conditions. We used multivariable log-transformed-linear and logistic regression models to compare patients with BLA to controls in terms of antibiotic selection and total antimicrobial days, antimicrobial cost, length-of-stay (LOS) and 30-day readmission. For antibiotic selection we examined the odds of receiving the following broader-spectrum agents individually and in composite: vancomycin, fluoroquinolones, clindamycin, carbapenems, and macrolides.

Results

39,785 patients were identified including 2897 (7%) with BLA. The prevalence of BLA increased with age (Figure 1). 2459 (85%) patients with BLA were matched to a control. Patients with BLA had higher odds of receiving broader-spectrum antibiotics (OR 2.35, 95% CI: 2.07–2.67) and had greater antimicrobial costs (1.21-fold increase, 95% CI: 1.08–1.35) than nonallergic patients (Figure 2). There were no differences in LOS, total antimicrobial days, or 30-day readmission (Figure 2).

Conclusion

Pediatric patients with BLA are more likely to receive broader-spectrum antibiotics and incur higher antimicrobial costs than matched controls. De-labeling interventions could reduce unnecessary exposure to these agents and lower costs.

Disclosures

All Authors: No reported Disclosures.
1962. Renal Outcomes for Participants Taking F/TAF vs. F/TDF for HIV PrEP in the DISCOVER Trial
Authors: Mills Anthony , Workowski Kimberly , Campbell Thomas , Benson Paul , Crofoot Gordon , Salazar Laura , Ogbuagu Onyema , Shalit Peter , Trottier Benoit , Carter Christoph C , Wong Pamela , Brainard Diana M , McCallister Scott , Das Moupali , Doblecki-Lewis Susanne
Published: October 2019

Background

In the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here, we report on the renal outcomes of F/TAF and F/TDF among all DISCOVER participants and in those on baseline F/TDF PrEP who were randomized to F/TAF.

Methods

In total, 5387 men who have sex with men (MSM) and transgender women (TGW) at risk for HIV were randomized 1:1 to receive blinded F/TDF or F/TAF taken once daily (full cohort). Of these, 905 were on F/TDF PrEP at enrollment; of whom, 465 were randomized to F/TAF. Renal function and safety assessments included urinalysis (UA), estimated glomerular filtration rate (eGFRCG), urine protein:creatinine (Cr) ratio (UPCR), markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol-binding protein:Cr ratio [RBP:Cr]) and investigator-reported renal adverse events (AEs). Week 48 data are presented.

Results

In the full cohort, F/TAF was associated with more favorable changes in eGFRCG, β2M:Cr, and RBP:Cr compared with F/TDF (Table 1). Treatment-emergent proteinuria by UA was more common with F/TDF than F/TAF (24.3% vs. 21.3% P = 0.009), as were treatment-emergent elevations in UPCR >200 mg/g (35 [1.5%] vs. 16 [0.7%], P = 0.005). Compared with F/TDF, participants taking F/TAF had numerically fewer study drug-related renal AEs, severe study drug-related renal AEs, and discontinuations due to renal AEs (Table 2). Proximal renal tubulopathy (Fanconi syndrome) was reported in one participant in the F/TDF arm and none in the F/TAF arm. In participants on F/TDF PrEP at enrollment who were randomized to F/TAF, statistically significant increases in eGFRCG were apparent as early as week 4 (Table 1 and Figure 1), as were decreases in tubular proteinuria (Table 1). Renal biomarker changes in PrEP-naïve participants mirrored those in the full cohort.

Conclusion

Through 48 weeks, MSM and TGW taking F/TAF for PrEP had significantly better measures of renal function and fewer study-drug-related renal AEs compared with those taking F/TDF; switching from F/TDF to F/TAF was associated with improvements in eGFRCG and tubular function biomarkers. F/TAF for PrEP is effective and has a superior renal safety profile compared with F/TDF.

Disclosures

All Authors: No reported Disclosures.
2845. Oral Antibiotic Use and Risk of Colorectal Cancer in the UK, 1989–2012: A Matched Case–Control Study
Authors: Zhang Jiajia , Haines Charles , Watson Alastair , Hart Andrew , Jane Platt Mary , Pardoll Drew , Cosgrove Sara E , Cosgrove Sara E , Gebo Kelly , Sears Cynthia
Published: October 2019

Background

Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and CRC risk is lacking.

Methods

A matched case–control study (incident CRC cases and up to 5 matched controls) was conducted in the Clinical Practice Research Datalink (CPRD; 1989–2012). The CRPD is validated as 92% and 99% sensitive and specific for CRC detection (98% PPV). Antibiotic exposure [categorical and continuous terms (spline)] was investigated for risk pattern, stratified by tumor location, using conditional logistic regression and adjusting for known confounders.

Results

In total, 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use increased risk of colon cancer in a dose-dependent fashion (Ptrend < 0.001), but effects differed by anatomic location. Colon cancer risk was greatest in the proximal colon and with antibiotics with anti-anaerobic activity (Figure 1). In contrast, an inverse association was detected between antibiotic use and rectal cancers (Ptrend = 0.003), particularly with length of antibiotic exposure >60 days (adjusted odds ratio [AOR], 0.85, 95% CI 0.79–0.93) when compared with no antibiotic exposure. Nonlinearity models showed significantly increased colon cancer risk after minimal antibiotic use, but decreased rectum cancer risk with cumulative use of over 30 days (Figure 2). Penicillins, particularly ampicillin/amoxicillin, increased risk of colon cancer (AOR,1.09, [1.05–1.13]) whereas tetracyclines reduced risk for rectal cancer (AOR, 0.90, [0.84–0.97]). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, Pinteraction < 0.001). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (AOR, 1.17, [1.06–1.31]).

Conclusion

We conclude that oral antibiotic use associates with increased colon cancer risk, particularly in the right colon, but a reduced risk for rectal cancer. This effect heterogeneity suggests unabsorbed antibiotics impact gut microbiota in the right colon to enhance carcinogenesis whereas antibiotic anti-inflammatory or anti-proliferative actions may yield an inverse effect on carcinogenesis in the rectum.

Disclosures

Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.
2855. Respiratory Syncytial Virus Neutralizing Antibodies in Cord Blood and Serum from Infants up to 2 Years of Age in a Multinational Prospective Study
Authors: Domachowske Joseph B , Bianco Veronique , Ceballos Ana , Cousin Luis , D’Andrea Ulises , Dieussaert Ilse , Englund Janet A , Gandhi Sanjay , Haars Gerco , Jose Lisa , Klein Nicola , Marie. Langley Joanne , Leach Amanda , Madhi Shabir A , Maleux Koen , Lien-Anh Nguyen Thi , Puthanakit Thanyawee , Silas Peter , Stoszek Sonia K , Tangsathapornpong Auchara , Teeratakulpisarn Jamaree , Virta Miia , Zaman Khalequ
Published: October 2019

Background

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during infancy worldwide. High cord blood (CB) concentrations of anti-RSV neutralizing antibody (nAb) may attenuate, delay, or prevent infant infection. We report RSV A and B nAb concentrations in CB and serum from a birth cohort at different time points through 2 years of age.

Methods

Between 2013 and 2017, newborns from 8 countries were studied prospectively from birth to 2 years of age (NCT01995175). CB was collected at birth for the entire cohort. A subcohort of children was randomly assigned to have one blood sample collected again at either 2, 4, 6, 12, 18, or 24 months of age. Sera were analyzed for RSV A and B nAb concentrations by serum neutralization assay. Active surveillance was used to identify LRTIs during the 2-year follow-up as previously reported.

Results

In total, 2,401 newborns were enrolled and followed up. >99% of infants had detectable CB RSV A and B nAb. Geometric mean antibody titers (GMTs) varied by country, but were overall higher for RSV B than for RSV A (327 vs. 251; Figure 1). The lowest GMTs were seen from CB sera collected from South African newborns (197 RSV A, 255 RSV B); Canadian newborns had the highest RSV A GMT (383), while Hondurans had the highest RSV B GMT (460). 1380 infants provided follow-up serum nAb results as part of the subcohort (Figure 2). Dramatic waning of GMTs was evident, with a ~3-fold drop in GMTs at 2 months of age, and an additional ~2-fold drop between 2 and 4 months of age. At 6 and 12 months of age, 71% and 50% of infants had RSV A nAb and GMTs were at a nadir of 14. At 6, 12, and 18 months of age, RSV B nAb was detected in 98%, 69%, and 63% of infants, respectively. The RSV B nAb nadir GMT of 20 was observed at 12 months of age, while the 6- and 18-month RSV B nAb GMTs were 30 and 31, respectively. A total of 1,017 LRTIs were identified during the 2-year study period; of which, 94 (9%) were caused by RSV A and 132 (13%) by RSV B. Associations between CB nAb levels and RSV infection will be presented.

Conclusion

Neutralizing Ab to RSV A and B was present at birth in infants from 8 countries, and waned over time. GMTs were at a nadir at 6 to 12 months of age.

Funding. GlaxoSmithKline Biologicals SA.

Disclosures

All Authors: No reported Disclosures.
2886. Retrospective Case–Control Study of the Performance of the Karius Test, a Plasma Microbial Cell-free DNA Next-generation Sequencing test, to Detect Invasive Mold Infections in Hematopoietic Cell Transplant Recipients with Pneumonia
Authors: Hill Joshua A , Hong David K , Dalai Sudeb , Ho Carine , Hollemon Desiree D , Blair Lily , Stevens-Ayers Terry , Boeckh Michael , Fisher Cynthia E
Published: October 2019

Background

Pulmonary invasive mold infections (IMI) cause significant morbidity and mortality after hematopoietic cell transplant (HCT). Noninvasive diagnostic options are limited, particularly for non-Aspergillus (non-Asp) molds. Given differences in activity and toxicities of antifungals, early diagnosis and targeting of specific IMI is important. We evaluated the performance of the Karius Test, a plasma microbial cell-free DNA next-generation sequencing (NGS) test, for detecting IMI in HCT recipients.

Methods

We conducted a retrospective case–control study of 24 HCT recipients with proven non-Asp pulmonary IMI, 51 probable/proven Aspergillus pulmonary IMI, and 20 controls with nonfungal pulmonary infections. All subjects had plasma obtained within 14 days of diagnosis. Workup included bronchoalveolar lavage (BAL) and/or biopsy, with fungal stains/culture and galactomannan testing of BAL and serum. Plasma cell-free DNA was extracted and NGS performed (Karius, Redwood City, CA). Human reads were removed and remaining sequences aligned to a curated database including over 300 fungi. Organisms present above a predefined significance threshold were reported. A higher sensitivity research-use only pipeline was also used. Analysis of sequencing data was blinded to all clinical data.

Results

We identified pathogenic molds in 19/24 (79%) of subjects with proven non-Asp IMI, including Mucor, Rhizomucor, Scedosporium, Rhizopus, and Cunninghamella spp. In Aspergillus proven/probable IMI, A. fumigatus was identified in 13.7% (7/51) of subjects. In 3 other subjects with proven/probable aspergillosis, we also identified Rhizomucor miehei and R.pusillus, and Cunninghamella, consistent with clinical findings. The use of an optimal-sensitivity pipeline identified an additional 9 subjects with Aspergillus spp. and other pathogenic molds, increasing detection of molds to 37.3% (19/51). Specificity for molds in negative samples was 100% (20/20).

Conclusion

The Karius plasma NGS test is a noninvasive means of detecting IMI with high sensitivity for non-Aspmolds in HCT recipients with pulmonary disease. Further assay optimization may increase sensitivity for Aspergillus. This may be a useful adjunctive test for diagnosing IMI, and larger studies should be conducted.

Disclosures

All Authors: No reported Disclosures.
2890. Antibiotic Overuse at Discharge in Hospitalized Patients with Bacteriuria or Treated for Pneumonia: A Multi-Hospital Cohort Study
Authors: Vaughn Valerie M , Petty Lindsay A , Ratz David , Malani Anurag N , Mclaughlin Elizabeth , Patel Twisha S , Bernstein Steven J , Hsaiky Lama , Dumkow Lisa , Pogue Jason M , Flanders Scott A , Gandhi Tejal N
Published: October 2019

Background

Antibiotics prescribed at hospital discharge account for half of antibiotic use related to hospitalization for urinary tract infection or bacterial pneumonia. It is unclear how much antibiotic use at discharge represents overuse, and thus, could potentially be improved through antibiotic stewardship.

Methods

From July 2017 to December 2018, trained abstractors at 46 Michigan hospitals collected detailed data on a sample of adult, nonintensive care, hospitalized patients with bacteriuria or treated for community-acquired or healthcare-associated pneumonia (discharge diagnosis of pneumonia plus antibiotic treatment). Antibiotic prescriptions at discharge were assessed for overuse using a guideline-based hierarchical algorithm: evaluating first for unnecessary antibiotics (noninfectious/nonbacterial syndrome), then excess duration (antibiotics needed, but prescribed for longer than necessary), and finally avoidable fluoroquinolones (safer alternative antibiotic available) (Figure 1). For each disease state, descriptive results are shown with comparisons by t- or Fisher’s exact tests.

Results

Of 17,157 patients (7,283 with bacteriuria; 9,874 treated for pneumonia), 30.1% of patients with bacteriuria had asymptomatic bacteriuria and 11.4% of patients treated for pneumonia did not meet diagnostic criteria for pneumonia. The most common antibiotics prescribed at discharge were fluoroquinolones. Nearly half (43.6%) of patients had antibiotic overuse at discharge (33.8% bacteriuria, 50.9% pneumonia), with a median 4 days of overuse after discharge (Table 1). For bacteriuria, 45.0% of overuse days at discharge were due to unnecessary antibiotics; for pneumonia, 61.2% were due to excess antibiotic duration (Figure 2). Patients with community-acquired pneumonia and those with sepsis on admission had the highest rates of antibiotic overuse at discharge (Table 2).

Conclusion

In the largest assessment of antibiotics at discharge to-date, antibiotic overuse at discharge was extremely common. Specific targets for discharge stewardship vary by disease state. Notably, interventions may be more effective at reducing fluoroquinolone prescribing at discharge indirectly by stopping treatment for asymptomatic bacteriuria and reducing excess duration in pneumonia.

Disclosures

All Authors: No reported Disclosures.
2899. Decreased Hepatitis C Virus-Associated Mortality in the US 2014–2017 After New Oral Direct-Acting Antiviral Era
Authors: Wasti Zainab , Coppock Dagan , Chou Edgar , Heun Lee Dong
Published: October 2019

Background

Due to the ease of use and low side effect profile of new direct-acting antivirals (DAA), cure rates for hepatitis C virus (HCV) infection have increased in recent years. However, limited data exist addressing the mortality associated with HCV infection since the advent of DAAs. This study examines multiple-cause-of-death (MCOD) data from 2014 to 2017 to describe changes in HCV-associated mortality in the United States.

Methods

We examined death certificate information from public use MCOD data obtained from the National Center for Health Statistics. All-cause mortality associated with HCV, as defined by ICD-10 codes (B17.1 and B18.2), was evaluated. The age-adjusted crude mortality rate was calculated. Overall HCV-associated mortality, stratified by race and gender, was analyzed.

Results

From 2014 to 2017, the number of deaths associated with HCV, as listed in death certificates decreased from 19,613 to 17,253. This represents an average of 4% decrease in mortality each year. Crude age-adjusted mortality decreased from 5.01 (95% CI 4.93–5.08) deaths per 100,000 people in 2014 to 4.13 (95% CI 4.07–4.20) deaths per 100,000 people in 2017. Males had age-adjusted mortality of 6.82 (95% CI 6.76–6.88) and females had age-adjusted mortality of 2.59 (95% CI 2.55–2.63). African Americans had age-adjusted mortality of 7.50 (95% CI 7.37–7.63), and whites had age-adjusted mortality of 4.39 (95% CI 4.35–4.42) during the three-year period.

Conclusion

After the introduction of DAAs in 2014, mortality associated with HCV significantly decreased in the United States. There were differences in mortality rates by gender and race, which may reflect differences in HCV seroprevalence. With the availability of effective, well-tolerated HCV treatment, aggressive HCV screening and linkage to care is warranted, especially in high-risk populations.

Disclosures

All Authors: No reported Disclosures.
2902. Pertussis Antibody Levels in Preterm Infants After Maternal Tdap Immunization During Pregnancy
Authors: Healy C Mary , Rench Marcia , Swaim Laurie , Rajam Gowrisankar , Havers Fiona , Hariri Susan , Schiffer Jarad , Baker Carol J
Published: October 2019

Background

Maternal immunization with tetanus, diphtheria, acellular pertussis vaccine (Tdap) in the third trimester reduces infant pertussis, but data are lacking on how this strategy impacts pertussis antibody levels in large cohorts of preterm infants

Methods

We collected paired maternal delivery-cord sera from infants of women who received Tdap ≥7 days before birth. IgG to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by Luminex assay (IU/mL). Geometric mean concentrations (GMC) with 95% confidence intervals (CI) for pertussis antibodies were calculated. Four infant groups were compared by weeks of gestation: very (<32), moderate (32–33) and late preterm (34–36), and term (≥37).

Results

344 preterm and 688 term mother-infant pairs were included. Among preterm infants, mean maternal age was 31.2 years (range 15.1–39.3); 37% were white, 37% Hispanic, 17% Black, 8% Asian and 1% other. Fifty-six were very preterm infants (16%, mean gestation 30.5 weeks), 82 moderate (24%, 33.1 weeks), and 206 late (60%, 35.4 weeks); 17 (5%) were born at <30 weeks. For preterm infants, Tdap was administered at a mean gestation of 29.9 weeks (very 27.9; moderate 29.7; late 30.4; [P < .001]), and at a mean interval of 29.3 days before delivery (very 17.9; moderate 24; late 34.5 [P <.001]). Eleven (3%) women received Tdap during the second trimester (8 very, 2 moderate, 1 late). GMCs (95% CI) of pertussis-specific IgG at birth varied by gestation (table). Infant antibody levels as a proportion of maternal antibodies increased from 24 to 32% in infants < 30 weeks to 117 to 132% in those ≥37 weeks (P<.001).

Conclusion

Although levels are lower than in term infants, maternal immunization with Tdap results in substantial pertussis-specific antibodies in most preterm infants, especially late preterm infants.

Disclosures

All Authors: No reported Disclosures.
1143. Measuring Up! Benchmarking Antimicrobial Use in Canadian Children’s Hospitals
Authors: Blackburn Julie , Bowes Jennifer , Harrison Mary-Ann , Barrowman Nick , Roy Hélène , Science Michelle , Timberlake Kathryn E , Tse-Chang Alena , Roberts Ashley , Paquette Vanessa C , Kwan Natasha , Vayalumkal Joseph V , Constantinescu Cora , Dersch-Mills Deonne , Mertz Dominik , Khan Sarah , Al Matawah Yameen , Thibeault Roseline , Gosselin Louise , Lefebvre Marie-Astrid , Fanella Sergio , Walus Ashley N , Barton Michelle , Harris Venita , Comeau Jeannette L , Slayter Kathryn , Foo Cheryl , McConnell Athena , Seifert Blair , Leifso Kirk , Viel-Thériault Isabelle , Le Saux Nicole
Published: October 2019

Background

Inappropriate antimicrobial use (AU) is recognized as a leading cause of antimicrobial resistance. However, quantifying AU in hospitals is challenging due to variability in information systems. Point prevalence surveys (PPS) provide a means to quantify AU in a cross-sectional manner within and between institutions. The aim of the study was to describe and compare the prescription patterns of AU across pediatric hospitals in Canada using PPS.

Methods

Two PPS (November 2018 and February 2019) were conducted at each of the 15 Canadian pediatric hospitals. For each PPS, AU data were collected for all inpatients ≤ 18 years (excluded mental health and birthing units) on the survey date. Data, including admitting diagnosis, age, comorbidities, Infectious Diseases consult, admitting service, documented pathogen(s), and antimicrobial(s) prescribed, was collected and entered into a RedCap database.

Results

In total, we surveyed 3826 patient-days. The mean proportion of children receiving at least one antimicrobial was 35.2% [range 25.1% to 42.9%]. Of the 1951 antimicrobials prescribed, the most common were third-generation cephalosporins [3GC] (16%; 321), aminopenicillins (15%; 297), TMP-SMX (11%; 207), piperacillin–tazobactam (10%; 193) and first-generation cephalosporins (9%; 181). Overall, the frequency of carbapenems, quinolones and vancomycin use was 4% (79), 3% (65) and 8% (151), respectively. Of the antimicrobials used for targeted or empiric therapy (n = 1541), 373 (24.2%) were for pneumonia, 278 (18%) for intra-abdominal infections and 251 (16.3%) for fever without a source. For the treatment of community-acquired pneumonia (CAP) (n = 178), aminopenicillins and 3GC use was 31% and 37%, respectively.

Conclusion

Our study used a standardized approach to assess AU to obtain benchmarking data for Canadian pediatric hospitals. About one-third of children hospitalized in Canadian pediatric hospitals are prescribed at least one antimicrobial. Of patients on treatment for CAP, only 31% were prescribed aminopenicillins. More detailed analysis of the rationale for AU, and assessment of appropriateness is required to fully understand antimicrobial prescribing practices in pediatric hospitals and develop stewardship initiatives.

Disclosures

All authors: No reported disclosures.
1162. An Evaluation of Metrics for Catheter-Associated Urinary Tract Infections (CAUTIs): A Statewide Comparison
Authors: Pepe Dana , Maloney Meghan , Leung Vivian , Harizaj Adora , Banach David , Dembry Louise , Dembry Louise , Advani Sonali D
Published: October 2019

Background

The Standardized Infection Ratio (SIR) is a metric used to gauge catheter-associated urinary tract infection (CAUTI) prevention, both locally and nationally. The device utilization ratio (DUR) is a process metric that captures catheter harm. More recently, the cumulative attributable difference (CAD) was introduced, which identifies the number of excess infections that need to be prevented to reach the desired goal. Our objective was to evaluate these metrics across all acute care hospitals in Connecticut (CT) by facility size.

Methods

A CAUTI Targeted Assessment for Prevention (TAP) Report for acute care hospitals across CT was generated from 1/1/2018 to December 31/2018, using the National Healthcare Safety Network (NHSN) database. CAUTI events, SIR, DUR, and CAD were compared across all hospitals. The SIR goal of 0.75 was used to calculate the CAD. Hospitals were stratified into large ( >425 beds), medium (250 to 424 beds), and small ( <249 beds) based on the Healthcare Cost and Utilization Project NIS Description of Data Elements, Agency for Healthcare Research and Quality for urban hospitals in the northeast region.

Results

A comparison of CAUTI metrics for 29 acute care hospitals across CT is shown in Table 1. Median SIR and DUR were 0.97, 1.02, 0.77, and 22%, 14%, 14.5% for large, medium and small hospitals, respectively. Of the 20 small hospitals, SIR could not be calculated for 5 hospitals, while 2 hospitals had an SIR = 0, as they had no reported infections. Median CAD for large, medium and small hospitals was 6.17, 1.3 and 0.25, respectively. Of note, 40% of small hospitals (J – CC, as in Table 1) had a negative CAD. Interestingly, 5 of these 8 hospitals with a negative CAD had a DUR higher than 16%.

Conclusion

Based on CT hospital data, metrics like CAD and SIR may be more suitable for larger hospitals or hospitals with higher CAUTI events, whereas DUR may be a more useful metric for smaller hospitals or hospitals with rare events. Hospitals with high SIR and low DUR may represent a population with high-risk catheter use, poor catheter care or higher rates of urine culturing. On the other hand, hospitals with high DUR and low SIR may represent low-risk populations, better catheter care practices or lower rates of urine culturing. Ultimately, we need a combination of metrics to measure preventable catheter harm.

Disclosures

Louise Dembry, MD, MS, MBA, ReadyDock: Consultant, Stock options.
1165. Risk Factors for Bloodstream Infections During Extracorporeal Membrane Oxygenation (ECMO)
Authors: In Hong Sun , You Shinae , Ryu Byung-Han , Hong Kyung-Wook , Cho Oh-Hyun , Bae In-Gyu
Published: October 2019

Background

Although bloodstream infections (BSIs) are important complications of ECMO, data on clinical characteristics of ECMO-associated BSIs remain limited. This study aimed to investigate clinical characteristics of ECMO-associated BSIs and evaluate the role of routine active surveillance cultures (ASCs) in predicting subsequent BSIs.

Methods

We reviewed the medical records of adult patients who received ECMO for >48 hours in 2 teaching hospitals between January 2013 and March 2019. ECMO-associated BSIs were defined as bacteremia occurring from 48 hours after ECMO initiation. ASCs for multidrug-resistant organisms were obtained from nasal, axillary, inguinal, and rectal swabs when patients were admitted to the ICUs.

Results

Overall, 28 of 110 (25.4%) patients had BSIs within the median 7 days after ECMO initiation. Table 1 shows the clinical characteristics of patients with ECMO-associated BSIs. Among BSI cases, the most common pathogens were Candida spp. (25%). Longer ECMO days (P < 0.01), steroid use (P = 0.02), and more blood transfusions (P < 0.01) were associated with BSIs. However, there was no association between the results of ASCs and subsequent pathogens of BSIs.

Conclusion

BSIs during ECMO were associated with longer ECMO duration, steroid use and blood transfusion. The pathogens of BSIs could not be related to ASCs.

Disclosures

All authors: No reported disclosures.
1167. Dialysis-Related Bloodstream Infections: A Pre- and Post-ClearGuard HD Cap Conception Study
Authors: Li William , Otto Caitlin , Nakeshbandi Mohamed , Augenbraun Michael
Published: October 2019

Background

25% of patients on hemodialysis receive therapy via a tunneled dialysis catheter (TDC). Bacteremia is one of the most feared complications with an all-cause mortality rate of 12–25%, Medicare spending costs amounting nearly $600 million annually and average hospital length of stay of 12 days per episode. The ClearGuard HD chlorhexidine impregnated catheter (ClearGuard cap) has recently shown potential to significantly reduce rates of bacteremia.

Methods

Retrospective review of 150 patients receiving hemodialysis at a single outpatient center in Brooklyn, NY from January 1, 2015 to January 31, 2019. As of February 1, 2019, the ClearGuard cap was implemented for all patients. Poisson regression was used to estimate crude event rate for both pre- and post-intervention periods, with 95% Wald-based confidence intervals (CI). Follow-up for pre-intervention cases terminated at the date the intervention was introduced. A likelihood ratio test of difference in incidence pre vs. post-intervention was conducted. A Kaplan–Meier (K-M) plot of time from the first dialysis since January 2015 to first infection was constructed (pre-intervention cases only). Subsequent subgroup analyses distinguished TDC vs. other patients. The log-rank test was used to test differences between subgroups; Bonferroni corrections to P-values were applied to address the multiple testing problem.

Results

Median total tracking period (including post-infection follow-up) was 1.75 years (range 0.02–4.26) for pre-intervention cases; 0.19 years (range 0.08–0.21) for post-intervention cases. Event rate was estimated as 9.7 events per 100 person-years (95% CI 6.7, 14.1) for pre-intervention cases; zero (95% CI 0.0, infinity) for post-intervention cases (P = 0.318 for pre- vs. post-comparison) with a clear limitation being lack of power given recent implementation date. We found a statistically significant risk for infection in patients with TDC (P < 0.001).

Conclusion

In an underserved, poorly health literate, largely foreign-born, socioeconomically challenged population such as ours, we not only established a significant risk of bacteremia with TDC’s but preliminary post-ClearGuard cap conception data currently being followed is promising for a significant reduction in catheter-related bacteremia.

Disclosures

All authors: No reported disclosures.