bluuebunny/crossref_metadata_2025_split huggingface dataset:
1401. Real-World Effectiveness of Inactivated and Live Attenuated Influenza Vaccines in Children During Three Recent Seasons: 2016–2019
Authors: Bandell Allyn , Mallory Raburn , Ambrose Christopher S 
Published: January 2021

Abstract

Background
Given the substantial burden of influenza in the pediatric population, influenza vaccination with live attenuated influenza vaccines (LAIVs) and/or inactivated influenza vaccines (IIVs) is now recommended for children in an increasing number of countries. In recent seasons, the real-world effectiveness of influenza vaccines has varied substantially. In the 2013/14 and 2015/16 influenza seasons, LAIV demonstrated reduced vaccine effectiveness (VE) against A/H1N1 strains. LAIV and IIVs have also demonstrated variable effectiveness against A/H3N2 strains in recent seasons. This study evaluated LAIV and IIV effectiveness in children between the 2016/17 and 2018/19 seasons.

Methods
Quadrivalent LAIV (LAIV4) and IIV effectiveness studies conducted in the pediatric population from 2016/17 through 2018/19 were identified from published literature, congress presentations, public health websites and personal communication with national investigators. Studies were excluded if they were from countries where Ann Arbor-backbone LAIV was not available for at least one season during the study period, were from randomized, interventional studies, or contained duplicate data from other publications.

Results
For the three seasons, point estimates of all-strain VE for children ranged from 20% to 74% for LAIV4 and from –20% to 68% for IIV (Fig 1A). During the same period, VE against A/H3N2 for children ranged from –76% to 74% for LAIV4 and from 3% to 56% for IIV (Fig 1B). Point estimates of VE against A/H1N1 for children were 50% and 90% for LAIV4 and ranged from 24% to 87% for IIV (Fig 1C). For influenza B, VE for children ranged from 31% to 80% for LAIV4 and from –12% to 80% for IIV (Fig 1D). Statistical comparison of LAIV4 and IIV VE across each season was not feasible due to the multivariate nature of each study cohort.
Figure 1. 2016–2019 Effectiveness of Inactivated and Live Attenuated Influenza Vaccines by Influenza Strain in Children

Conclusion
During three recent seasons, LAIV4 and IIV showed similar moderate effectiveness against all influenza strains, A/H1N1 strains, and B strains. VE against A/H3N2 for LAIV4 and IIV was good in 2016/17, but decreased in the 2017/18 and 2018/19 seasons. VE estimates for LAIV4 and IIV overlapped for all strains and each subtype, demonstrating the general comparability of LAIV4 and IIV VE in the seasons between 2016 and 2019.

Disclosures
Allyn Bandell, PharmD, AstraZeneca (Employee, Shareholder) Raburn Mallory, MD, AstraZeneca (Employee, Shareholder) Christopher S. Ambrose, MD, MBA, AstraZeneca (Employee, Shareholder)
1405. Clinical and laboratory features of fatal dengue fever in children: a case-control study
Authors: Freire Dolores E , Olaya Jeniffer D , Hawkes Michael 
Published: January 2021

Abstract

Background
Dengue fever (DF) is a mosquito-borne illness that causes significant morbidity and mortality in tropical climates. This study compared the clinical features of fatal DF cases to severe non-fatal, and non-severe controls in Ecuador.

Methods
Retrospective case-control study of children (1 month to 15 years) hospitalized with serologically-confirmed DF in Guayaquil, Ecuador from 2013 to 2017. Cases of severe, fatal (SF) DF were compared to two control groups: (1) severe DF survivors (SS); and (2) patients with dengue with warning signs (DWS), matched 3:1 to cases for age, sex, and admission date.
Observational trial profile

Results
1051 patients were admitted with suspected DF and 552 were IgM-positive. Patients were classified as SF (n=11), SS (n=30), or DWS (n=511) (Figure1). Among SF cases, median age was 9.6 years (IQR 5.5-11), 7 (64%) were male, and median time to death was 1.5 days (IQR 0.8-4.0). (Table 1) SF cases had a median of 3 (Range 0-5) encounters with healthcare providers prior to presentation, compared to 2 (Range 0-5, p=0.02) for SS and 2 (Range 0-3, p=0.02) for DWS. Physical findings more common in SF cases than controls included: higher weight, tachycardia, tachypnea, delayed capillary refill, and hepatomegaly (p&lt; 0.05 for all comparisons). Neurological manifestations were more prevalent in the SF group: 9/11 (82%) patients compared to 15/30 (50%, p=0.09) in SS and 7/33 (21%, p&lt; 0.01) in DWS. Total leukocyte count (7.8x103/µL versus 4.5x103/µL, p=0.03) and absolute neutrophil count (5.1x103/µL versus 2.1x103/µL, p=0.03) were higher in SF cases than DWS controls. Fewer SF patients received intravenous dextrose than SS controls (27% versus 70%, p=0.03) (Table 2).

Admission characteristics of children with dengue fever

Management and outcome

Conclusion
Delayed recognition by healthcare workers, higher weight, vital sign abnormalities, hepatomegaly, neurological symptoms, leukocytosis, neutrophilia, and lack of dextrose in intravenous solutions were associated with mortality in children with DF. These findings have implications for optimizing the diagnosis and management of severe pediatric dengue infection.

Disclosures
All Authors: No reported disclosures
1407. Cytomegalovirus (CMV) infection in the first year of life in a cohort of infants in rural Guatemala
Authors: Munoz Flor M , Lamb Molly , Waggoner Jesse , Paniagua-avila alejandra , Bauer Desiree , Connery Amy , Olson Daniel , Natrajan Muktha , Anderson evan , Calvimontes Mirella , Bolanos Guillermo , El Sahly Hana , Asturias Edwin J 
Published: January 2021

Abstract

Background
Little is known about the epidemiology of Cytomegalovirus (CMV) infection in low resource countries. We evaluated the frequency and effects of post-natal CMV infection in infants from a prospective cohort study designed to assess the effects of post-natal Zika on neurodevelopment (ND) in rural Guatemala.
Infants with CMV infection (blue bars) were older compared CMV-negative (red bars) infants.

Methods
Infants were evaluated for CMV infection by PCR using urine samples collected at 0-3 months of age. ND testing was conducted by local psychologists using a culturally adapted Mullen Scales of Early Learning (MSEL). We explored associations between CMV infection and microcephaly, neurological, visual and hearing deficits, malnutrition and ND outcomes at 1 year of age.

Results
The infant cohort (N = 469) had a mean age at enrollment of 1.5 (SD 0.75) months; 47% were female and 71% were breastfeeding at 1 year. A total of 103 (22%) were CMV positive and the majority of these (97%) were &gt; 4 weeks of age at testing. Infants &gt; 4 weeks of age were more likely to be CMV positive (P &lt; 0.0001) (Figure). Gender was not correlated with CMV positivity. Among children with head circumference (HC) measurements, microcephaly (HC &lt; 2 SD) was present in 9/87 (10.3%) CMV positive and 35/338 (10.4%) CMV negative infants at 0-3 months of age (p =0.99). Among 438 infants who underwent screening for hearing deficits and a complete ophthalmologic evaluation, none of the CMV positive children had abnormal vision or hearing. Abnormal neurological exams in the first year of life occurred in 50/100 (50%) CMV positive and 166/365 (45.5%) CMV negative infants (p =0.56). There was no association between CMV infection at 0-3 months and MSEL overall or subdomain scores at 1 year (overall Relative risk (RR) 1.02, 95% CI 0.99-1.05, p=0.16). Malnutrition at 0-3 months (RR: 1.53, 95% CI 0.89-2.66, p = 0.13) and 1 year (RR: 1.10, 95% CI 0.77-1.58, p=0.59) was not associated with CMV infection at 0-3 months.

Conclusion
In a cohort of Guatemalan infants, postnatal CMV infection was common (22%) and more likely to occur after the neonatal period. There was no correlation between CMV infection and microcephaly at 0-3 months or at 1 year of age, nor with abnormal nutritional, neurologic, ophthalmologic, hearing or ND deficits at 1 year of age. This is the first epidemiologic report on CMV infection in early life in rural Guatemala.

Disclosures
Molly Lamb, PhD, BioFire (Grant/Research Support)
1411. Risks and Outcomes of Adenovirus Disease in Pediatric HSCT Recipients –Comparison of Current Antiviral Treatment Options
Authors: Thomas Sanya J , Young Rebecca R , Steinbach William , Lugo Debra J 
Published: January 2021

Abstract

Background
Adenovirus can cause multi-organ dysfunction in hematopoietic stem cell transplant recipients (SCTr). It accounts for 22% of infection-associated mortality in umbilical cord transplant recipients (UCTr). This study determines whether transplant characteristics are associated with risk of adenovirus disease (ADVd), and compares time to resolution of ADVd between patients who received antiviral therapy.

Methods
We conducted a retrospective single center cohort study of pediatric patients undergoing stem cell transplant at Duke University between 2005 and 2016. We identified cases of single end-organ and disseminated ADVd (2 or more organs) using a classification tool defined a priori. We used a Cox proportional hazards (CPH) regression model to compare the hazard of ADVd between SCTr differing by type of transplant and type of conditioning regimen. We also used CPH to compare the hazard of time to resolution of ADVd between SCTr differing by absence or presence of antiviral therapy (cidofovir, brincidofovir or both).

Results
There are 830 subjects, including 93 subjects with ADVd post-SCT. UCTr had 3.30 times the hazard of developing ADVd compared to non-cord blood allogeneic transplants and 7.30 times the hazard compared to autologous transplants (Figure 1). No difference in hazard of ADVd was detected between patients who received myeloablative vs non-myeloablative conditioning. Twenty-seven percent of the subjects received antiviral therapy; these patients had higher mortality (38%). The majority (87%) of diseased subjects had resolution of disease. Subjects that did not receive antiviral therapy experienced earlier resolution of ADVd compared to subjects who received antiviral therapy even after adjusting for subjects with disseminated disease (HR (95% CI): 3.75 (1.57, 8.93), p=0.003). Subjects with single end organ disease had earlier resolution of ADVd compared to disseminated disease (HR (95% CI): 2.24 (1.22, 4.10), p=0.009).
Figure 1a. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of transplant.

Figure 1b. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of conditioning regimen.

Conclusion
This is the first pediatric cohort study to report risk factors and clinical outcomes of ADVd, irrespective of ADV-DNAemia. UCTr recipients have a higher hazard of ADVd compared to other SCTr. Contrary to previous reports studying ADV-DNAemia, our study noted an earlier resolution of ADVd in the absence of antiviral therapy.

Disclosures
All Authors: No reported disclosures
1417. Clinical Features and Outcomes of raoultella terrigena Infections. A Single-Center Experience from Karachi, Pakistan
Authors: Ahmed Ishfaque , Nasir Nosheen , Ali Bushra Jamil , Mahmood Syed Faisal 
Published: January 2021

Abstract

Background
Raoultella terrigena (formerly Klebsiella terrigena) is an environmental gram-negative rod, occasionally causing infections in humans, especially in elderly, immunosuppressed patients. Moreover, this organism tends to be multi-drug resistant, limiting treatment options. Evidence on clinical presentation and outcomes of this infection is limited; we conducted a cross-sectional study to get a better insight into these infections.

Methods
We conducted a cross-sectional study on all adult patients with clinical specimen positive for Raoultella terrigena at a 700-bedded tertiary care hospital in Karachi, Pakistan, between January 2013 to December 2018.

Results
A total of 58 patients with R. terrigena were identified. The median age was 61.5 years, and the male to female ratio was (60.9% vs. 39.1%). The most common site of infection was respiratory tract 28.3%, followed by urinary tract infections 26%, and central line-associated infections 15.2%. In 12 patients 22.6%, R. terrigena was a colonizer. Amongst infected cases, 23.6% were in shock, and of which 18.1% required vasopressors. 29.2% had respiratory failure requiring non-invasive ventilation in 13.9%, and mechanical ventilation in 15.3%. The previous history of multidrug-resistant organisms was present in 67.4% cases and the history of prior antibiotics use within the last six months was present in 78.3%. 91.3% of isolates were resistant to piperacillin-tazobactam and meropenem, 65.2% were resistant to colistimethate. However, tigecycline susceptibility maintained in 30.4% checked in n=31, 67.4% and fosfomycin sensitivity in 15.2% cases, checked in n=29, 63% cases. Eight patients lost to follow up. Majority of patients were treated with combination therapy n=31, 81.6% and meropenem plus colistemethate was the most commonly used combination n=11, 44%. The overall mortality rate was 44.7%. Among all recorded co-morbid conditions, chronic kidney disease was strongly associated with mortality (p= .029), as also the use of vasopressors (p= .005).Persons who had high (greater or equal to three) Charlson comorbidity index had high mortality (p=0.002).

Conclusion
R.terrigena is a highly drug-resistant organism with high mortality rate, and causes hospital-acquired respiratory tract infections in majority of patients.

Disclosures
All Authors: No reported disclosures
115. Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Test on Antimicrobial Prescribing for Extended-spectrum Beta-lactamase and Carbapenemase-producing Bacteria in Bloodstream Infections
Authors: Coyne Ashlan Kunz , Casapao Anthony , Isache Carmen , Morales James , McCarter Yvette , Jankowski Christopher 
Published: January 2021

Abstract

Background
Molecular rapid diagnostic tests (mRDT) may help expedite the time to optimal antimicrobial therapy (TTOT) for extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing bacteria in bloodstream infections (BSI). The greatest impact of mRDT appears to occur when combined with antimicrobial stewardship program (ASP) intervention. The purpose of this study was to evaluate if mRDT + ASP influences the TTOT for patients with ESBL- and carbapenemase-producing E. coli and K. pneumoniae in BSI compared to conventional microbiological methods with ASP (CONV + ASP).

Methods
Multicenter, retrospective, cohort study evaluating five years of patients that had a positive E. coli or K. pneumoniae blood culture determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Patients were excluded if they had polymicrobial BSI, transferred–in with previously identified positive blood cultures, were immunosuppressed, or died before culture results.
Primary outcome was TTOT defined as time from blood culture draw to start of carbapenem therapy for ESBL-producing BSI and ceftazidime-avibactam, meropenem-vaborbactam, or at least one drug active in-vitro with the most-narrow spectrum for carbapenemase-producing BSI. Secondary outcomes were time to microbial clearance (TTMC) defined as the time from index blood culture draw to the time of first negative blood culture or hospital discharge, all-cause hospital mortality, 30-, 60- and 90-day readmission rates, and Clostridioides difficile rates.

Results
A total of 378 patients were included for analysis. Baseline characteristics were balanced between mRDT + ASP (n=164) and CONV + ASP (n=214). Infectious diseases consults were significantly greater for CONV + ASP compared to mRDT + ASP (82.2% vs 34.8%; p&lt; 0.001). The mRDT + ASP demonstrated a statistically significant decrease in TTOT (20.5 hrs [(IQR 17.0–42.2 hrs)] vs 50.1 hrs [(IQR 27.6–77.9 hrs)]; p&lt; 0.001) and TTMC (71.9 hrs [(IQR 54.1–108.5 hrs)] vs 91.2 hrs [(IQR 64.6–134.3 hrs)]; p=0.007). Other secondary endpoints were similar between groups.
Table 1. Comparison of baseline characteristics for the mRDT+ASP and CONV+ASP groups

Graph 1. Kaplan Meier time to optimal antimicrobial therapy

Graph 2. Kaplan Meier time to microbial clearance

Conclusion
Our study supports the additional benefit of mRDT to ASP on shortening the TTOT and TTMC in patients with ESBL- or carbapenemase-producing E. coli and K. pneumoniae in BSI compared to CONV + ASP.

Disclosures
All Authors: No reported disclosures
1420. A One Health Approach Examining the Potential Linkage between Agricultural Livestock and Human Antibiotic Resistance at the Watershed Level
Authors: Donner Linsey M , Li Xu , Snow Daniel D , Sangster Jodi L , Staley Zachery R , Amandus Loralee J , Mathews Wayne A , Bartelt-Hunt Shannon 
Published: January 2021

Abstract

Background
Antibiotic resistance is a significant public health threat and widespread use of antibiotics in agriculture is increasing the concern about agricultural contributions to the dissemination of antibiotic resistant bacteria. Of concern is the level of exposure to antibiotics and antibiotic-resistant bacteria in the watershed. Consequently, adopting a One Health approach to measure antibiotic levels and identify antibiotic resistance gene (ARG) transfer at the human, animal and environmental interfaces is essential to better understand how antibiotic resistance is spread.

Methods
In this project, antibiotic levels were measured using passive organic chemical integrative samplers (POCIS) for 30-day periods from August – November 2018 from Elkhorn River and Shell Creek watersheds in Nebraska (Figure 1). In addition, whole genome sequences of bacterial isolates cultured from the watersheds were assessed to identify ARGs present on mobile genetic elements (MGE) that had &gt;95% similarity to mobile ARG present in isolates recorded in the NCBI GenBank database was identified using ResFinder.
Figure 1. Sampling locations within the two watersheds.

Results
The study demonstrated significant antibiotic levels present throughout the watershed, with five of them associated with human usage (Table 1). In addition, seasonally based drug-resistant bacterial species was associated with specific antibiotic levels in the watershed (Figure 2). Mobile ARGs were detected in 87.5% of isolates collected from the Elkhorn River and 80.0% within Shell Creek (Figure 3).

Table 1. Pharmaceutical levels in the watershed

Figure 2. Antibiotic levels and drug-resistant bacteria in the watershed

Figure 3. Antibiotic resistance observed from each isolate at every sampling date and site. A colored bar denotes that resistance to that antibiotic was observed.

Conclusion
These results present evidence of transfer of highly mobile ARGs between environment, clinical, and animal-associated bacteria and highlight the need for a One Health perspective in assessing the spread of antibiotic resistance. The presence of significant levels of antibiotics persisting in this agricultural watershed points out the need for ongoing monitoring of compliance with the Food and Drug Administration (FDA) recommendation of veterinarian oversight of the use of antibiotics in the use of veterinary feed directive applications.

Disclosures
All Authors: No reported disclosures
1421. Assessing Serious Infections Common in Persons Who Inject Drugs in the United States and Tennessee
Authors: Lowry Michael , Fiske Christina , Rebeiro Peter F 
Published: January 2021

Abstract

Background
The opioid crisis is a public health emergency in the United States (US) and Tennessee (TN), and injection drug use predisposes users to a variety of serious infections. We therefore examined infection rates among persons who inject drugs (PWID) from 2001-2014 in the US and TN.

Methods
We conducted an ecological study using publicly available data including discharge diagnosis codes: the Healthcare Cost and Utilization Project (HCUP). We identified all persons from 2001-2014 with ICD-9 codes for bacterial infections common among PWID: endocarditis (IE), osteomyelitis (OM), septic arthritis (SpA), and skin/soft tissue infections (SSTI). We calculated rates of substance use and infection among all hospital discharges. Spearman’s rank correlation quantified the relationship between infection and reported hepatitis C seropositivity (HCV), Substance Abuse (SA) and opioid use disorder (OUD) rates. Poisson regression yielded incidence rate ratios (IRR) and 95% confidence intervals [-], and restricted cubic splines were fit to assess annual trends flexibly.

Results
Unadjusted rates of both substance use and infection among those discharged from hospitals were higher in the US overall than in TN from 2001-2014 (p&lt; 0.05) (Figure 2,3). Overall infections, HCV (IRR=1.14 [1.12-1.17]), SSTI, OM, and SpA increased annually in the US; overall infections, HCV (IRR=1.14 [1.10-1.15]), and SSTI increased in TN. OUD (IRR=0.96 [0.94-0.98]) and IE (IRR=0.97 [0.97-0.98]) decreased in the US (Table 1). In the US, there were strong positive correlations between any other infection and HCV (ρ=0.87), IE and OUD (ρ=0.7), SSTI and HCV (ρ=0.9), OM and HCV (ρ=0.69), and SpA and HCV (ρ=0.68); IE was negatively correlated with HCV (ρ=-0.84). In TN, overall infections (ρ=0.68), and specifically SSTI (ρ=0.62), were correlated with HCV (Figure 1).
Table 1

Figure 1

Figure 2

Conclusion
Serious infections common in PWID are increasing in TN and the US; they correlate with HCV rates, which have risen significantly in hospitalized patients. Interestingly, opioid use disorder incidence from discharge data declined from 2001-2014 for both TN and the US, which may be due to coding lapses or shifts in type of opioid use with no well-known billing code. However, we must continue monitoring and mitigating both substance use and its sequelae.

Disclosures
All Authors: No reported disclosures