bluuebunny/crossref_metadata_2025_split huggingface dataset:
1132. Evaluating an Amoxicillin Dosing Regimen for Community Acquired Pneumonia: A Quality Improvement Initiative Using Clinical and Laboratory Data
Authors: Keeler Emma , Beus Jonathan , Hayes Molly , Zorc Joseph , Metjian Talene , Ku Brandon , Hamershock Rose , Gerber Jeffrey , Chiotos Kathleen 
Published: December 2021

Abstract

Background
Amoxicillin 90 mg/kg/day divided twice daily is recommended for children with mild community acquired pneumonia (CAP). While adequate for fully susceptible Streptococcus pneumoniae isolates, three times daily dosing allows achievement of greater amoxicillin exposure, which may be necessary for isolates with penicillin minimum inhibitory concentrations (MIC) of ≥ 2 μg/mL. We evaluated our current twice daily amoxicillin dosing strategy by characterizing 1) the MIC distribution among S. pneumoniae isolates and 2) the frequency of clinical amoxicillin treatment failures.

Methods
We performed a retrospective cohort study of all S. pneumoniae isolates from sterile and non-sterile sites between 2017-2020. Breakpoints established by the CLSI were used for both meningitis and non-meningitis isolates. Only the first isolate per patient was included. We also evaluated the frequency of amoxicillin treatment failure in patients diagnosed with CAP who were discharged from the ED in 2019. CAP was defined as a discharge diagnosis code for pneumonia and an antibiotic prescription. Treatment failure was defined as an ED or primary care revisit, or admission, within 14 days during which an antibiotic change was made.

Results
28 S. pneumoniae isolates were identified from sterile sites between 2017-2020 and 171 isolates were identified overall. All isolates from sterile sites had penicillin MICs of ≤ 2 μg/mL and 165 (96%) of isolates overall had penicillin MICs of ≤ 2 μg/mL (Table 1). Of these, 10 isolates had MICs of 2 μg/mL, all from non-sterile sites. In 2019, 589 patients were treated for CAP in the ED; 447 (76%) received amoxicillin and 142 (24%) were treated with alternative antibiotics. Treatment failures occurred in 15 amoxicillin-treated patients (3.3%, 95% confidence interval 1.9-5.5%) and in 5 patients (3.5%, 95% confidence interval 1.2-8.0%) treated with alternative antibiotics.

Conclusion
In vitro penicillin resistance was rare at our institution. Further, given that S. pneumoniae is rarely identified by culture, we also demonstrated that clinical amoxicillin treatment failures were infrequent using twice daily amoxicillin dosing. Coupled with provider and family preference, these data supported continuing our current practice of twice daily amoxicillin dosing.

Disclosures
All Authors: No reported disclosures
1133. Opportunities for Antibiotic Discontinuation and De-escalation after Discharge from the Emergency Department in Pediatric Patients with UTI
Authors: Hawkins Stephanie , Gavigan Patrick , Ericson Jessica E , McSherry George 
Published: December 2021

Abstract

Background
In children, urinary tract infection (UTI) represents one of the most common indications for antibiotics. While previous data has demonstrated high rates of misdiagnosis and inconsistencies with empiric antibiotics, the impact and opportunities for antibiotic reduction once final culture and susceptibility data are available, particularly in pediatric patients seen in the emergency department (ED), is unknown.

Methods
This was a retrospective study conducted over a period of 18-months, which included subjects less than 18 years of age who were discharged from the ED with a diagnosis of UTI. Episodes in which urine cultures were negative or grew only mixed urogenital flora were considered possible for discontinuation. De-escalation was considered possible in episodes in which identified bacteria were susceptible to more narrow spectrum agents than the prescribed empiric antibiotic. Rates of discontinuation and de-escalation were calculated as proportions, and excess days of therapy were described. Subjects whose empiric antibiotics were active against isolated bacteria were compared to those with bacteria resistant to empiric therapy.

Results
A total of 87 episodes of UTI were identified. Pathogenic bacteria were isolated in 51 (59%) of the 78 episodes in which urine cultures were sent, most commonly Escherichia coli (84%). Empiric antibiotic therapy and duration varied and were active against isolated bacteria in 39 (76%) of the episodes. Subjects whose antibiotics were inactive were more likely to be Hispanic and receive cephalexin [Table 3]. Antibiotics were discontinued in 3 of the 27 possible episodes (11%), resulting in 127 extra antibiotic days, median of 6 (IQR=10 days) days per episode. In 20 episodes there was an opportunity for de-escalation, but it was never attempted, leading to 131 extra days of broad-spectrum antibiotics (median 7.5 days, IQR=3).
Table 1. Microbiology and resistance profile of bacteria isolated from urine cultures

Table 2. Empiric antibiotic regimens, including type of antibiotic and duration

Table 3. Comparison of episodes in which empiric antibiotics were active against isolated bacteria versus those in which empiric antibiotics were inactive

Conclusion
Antibiotics are rarely adjusted after discharge from the ED. Lack of adjustment results in unnecessary total and broad-spectrum antibiotic exposures. Initiatives designed to improve antibiotic use post-discharge could result in significant decreases in unnecessary antibiotics, and ultimately reduced rates of antibiotic resistance.

Disclosures
All Authors: No reported disclosures
1146. Lactococcus species Catheter-Related Bloodstream Infections in Pediatrics: A Case Series
Authors: Firmani Sarah E , Maples Holly , Balamohan Archana 
Published: December 2021

Abstract

Background
Central venous catheters (CVC), may lead to central line-associated blood stream infections (CLABSIs). In the past, Lactococcus species have seldom been considered pathogenic. However, clinically significant infections have been reported, of which few are pediatric cases, all outside the United States.

Methods
We retrospectively identified pediatric patients with bacteremia secondary to Lactococcus spp. admitted to a tertiary pediatric hospital from January 2018 - December 2020. We reviewed the PubMed database for cases of pediatric Lactococcus spp. infections in English, peer-reviewed literature.

Results
We identified 3 patients with Lactococcus spp. bacteremia. The average patient was 17 months old (range, 6–24 months). All had a CVC; two had short bowel syndrome and 1 had nephrotic syndrome. None received probiotics. Empiric treatment for all included vancomycin. Two of 3 patients were de-escalated to ceftriaxone. All isolates were susceptible to penicillin. Duration of treatment was 10-14 days. Two of 3 were managed with CVC retention and none had recurrence of infection.
A literature review revealed 9 additional cases (Table 1). The most common source of infection was blood (33%), with 66% (2/3) occurring in patients with central lines. Other sources included liver abscess (11%), brain abscess (11%), cerebrospinal fluid (11%), urine (11%), and endocarditis (22%). Median patient age was 12 months (range, 14 days-14 years). Five of 9 patients had an underlying risk factor. Duration of therapy ranged from 7-40 days. Most definitive treatment regimens consisted of a third-generation cephalosporin (44%). Of bacteremia, 2/3 received vancomycin as part of their definitive therapy. Five of 9 reported quantitative antimicrobial sensitivity testing (AST) or interpretation of AST to beta-lactam antibiotics; 80% (4/5) were susceptible.

Conclusion
To the best of our knowledge, these are the first reported pediatric cases of Lactococcus infections in the United States and suggests Lactococcus spp. should be considered pathogenic in the appropriate circumstances. This series adds to the limited literature, including AST. Continued accrual of susceptibility data may raise the possibility of using a 3rd generation cephalosporin as empiric therapy for Lactococcus bacteremia.

Disclosures
All Authors: No reported disclosures
1156. Pneumococcal Colonization in Children with Persistent Asthma and without Asthma
Authors: Olarte Liset , Banerjee Dithi , Swanson Douglas S , Tabakh Jennifer E , Lee Brian R , Harrison Christopher J , Selvarangan Rangaraj 
Published: December 2021

Abstract

Background
The most common underlying medical condition among children ≥ 5 years of age with invasive pneumococcal disease is asthma. How asthma affects pneumococcal colonization is not fully understood. Our objective was to compare pneumococcal colonization rates in children with persistent asthma vs. without asthma.

Methods
This is a single center retrospective cohort study. We used salvage mid-turbinate samples testing negative for influenza per routine care from 5-18 year-olds with upper respiratory symptoms or febrile illness during 2017-18 and 2018-19 northern hemisphere respiratory seasons (November to April). Analyzed groups were those with persistent asthma or those without asthma. Samples were evaluated for pneumococcal colonization by real-time PCR using CDC lytA primers (positive Ct ≤ 35). Positive samples were further tested with multiplex serotype-specific PCR assays to determine pneumococcal serotype.

Results
Of 363 children (120 with persistent asthma and 243 without asthma), 87.6% were 5-10 years old; and 49.9% were male. Fifty percent of samples were from January-February. Pneumococcal colonization rate was lower in children with persistent asthma (10%) vs. without asthma (18.9%) (p=0.03). The odds of colonization were lower in children with persistent asthma (OR 0.4 [95%CI 0.2-0.9]) after adjusting for age, sex, clinic site, smoking exposure, and number of pneumococcal vaccine doses. Colonized patients without asthma were younger than the other groups (Table 1). Pneumococcal serotype/serogroup was assigned in 45 (77.6%) positive samples; 16 (36%) samples corresponded to PCV13 serotypes and 29 (64%) samples to non-PCV13 serotypes. The most common serotypes were: 19F (n=7), 3 (n=6), 6C/6D (n=5), 23B (n=4), 33F/33A/37 (n=4), 35B (n=3), 22F/22A (n=3), 23A (n=3).
Table 1

Conclusion
Patients with persistent asthma had lower rates of pneumococcal colonization than patients without asthma during respiratory season.

Disclosures
Liset Olarte, MD, MSc, GSK (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)Sanofi (Research Grant or Support) Douglas S. Swanson, MD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Sanofi (Research Grant or Support) Brian R. Lee, PhD, MPH , Merck (Grant/Research Support)Pfizer (Grant/Research Support) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)
1158. Pediatric Group A Streptococcal Peritonitis: A Single-Center Eleven Patient Case Series
Authors: Pershing Nicole L , Eldredge Scott , Burgeson Jack E , Dansie David , Russell Katie , Korgenski Kent , Ampofo Krow , Vukin Elizabeth 
Published: December 2021

Abstract

Background
Pediatric group A streptococcal peritonitis (GASP) is a rare but serious infection, with few cases reported in the literature. Utah has an unusually high incidence of invasive GAS (iGAS) disease, but the frequency and characteristics of pediatric GASP are unknown.

Methods
We performed a retrospective chart review to identify GASP in Utah children from 2000-2019. GASP was defined as isolation of GAS from peritoneal fluid or blood and clinical signs of peritonitis.

Results
: Eleven children with GASP were identified, with slight female predominance (n=6). Median age was 6 years; males were significantly younger than females (1.4 versus 7.2 years, p=0.01). GAS was isolated from 4 of 8 blood and 8 of 11 peritoneal cultures obtained. Peritoneal fluid PCR was positive for GAS in one patient. Ten patients underwent laparotomy. Peri-appendiceal inflammation prompted appendectomy in 7 patients; only one had pathologic findings of acute appendicitis. Four patients developed streptococcal toxic shock syndrome and 7 required intensive care. Non-white race (n=4) and lack of appendectomy (n=5) were associated with more severe outcomes. Median antibiotic duration was 27 days. Median hospitalization was 8 days. All patients survived.
Figure 1. Schematic representation of GAS peritonitis patient clinical course.

Each patient is represented by a single line. Duration of symptoms prior to hospitalization, as well as duration of hospitalization (day 0 representing admission), intensive care, antibiotic administration, and timing of procedural interventions are noted. Duration of antibiotics after discharge for patient 3 was unable to be verified, as indicated by a question mark. Hospitalization, general pediatric hospital care. PICU, pediatric intensive care unit. IR, interventional radiology.

Conclusion
We present the largest pediatric case series of GASP to date. Diagnostic hallmarks included gastrointestinal symptoms, fever, systemic inflammation, and peritoneal enhancement without an abdominal source. Peri-appendiceal inflammation was common, although acute appendicitis was rare, and appendectomy was associated with a less severe course. GASP should be considered in patients with acute abdominal processes given increasing incidence of iGAS infections.

Disclosures
All Authors: No reported disclosures
1171. Measles and Rubella Seroprevalence among HIV-infected and uninfected Children and Adults in Zambia
Authors: Yang Yangyupei , Mutembo Simon , Carcelen Andrea , Hayford Kyla , Mwansa Francis , Moss William J 
Published: December 2021

Abstract

Background
Despite the availability of safe and effective vaccines, measles and congenital rubella syndrome remain important causes of morbidity and mortality. HIV-infected individuals may be more vulnerable to measles because of poor immune responses to vaccination. Population-level estimates and comparisons of measles and rubella seroprevalence between HIV-infected and uninfected children and adults in sub-Saharan Africa are needed to guide vaccination policy and control strategies.

Methods
This cross-sectional study was performed by analysing a selected and weighted subsample from the Zambia Population HIV Impact Assessment survey (ZAMPHIA). ZAMPHIA was conducted in 2016 to estimate national HIV incidence and prevalence in Zambia. Dried blood spots and plasma samples were tested for IgG antibodies to measles and rubella viruses using a commercial enzyme immunoassay. We estimated national age-specific measles and rubella seroprevalence by HIV infection status using hierarchical generalized additive models.

Results
Specimens from 9521 HIV-uninfected (3840 children age under 10 years, 3981 youth age 10-19 years, and 1700 adults age 20-49 years) and 331 HIV-infected (53, 107, and 171 respectively) individuals were included in the study. Measles seroprevalence was lower among HIV-infected children (46.4%) compared to HIV-uninfected children (76.4%, p &lt; 0.001). In both HIV-uninfected and HIV-infected individuals, measles seroprevalence increased steadily with age but more rapidly in the HIV-infected until about the age of 20 years when the seroprevalence was similar between the two groups. Above 20 years, measles seroprevalence was similar between HIV-infected and uninfected adults. There was no significant difference in rubella seroprevalence between HIV-infected and HIV-uninfected individuals.
Figure 1. Measles and Rubella Age-specific Seroprevalence

The lines represent generalized additive model fits for the mean (solid) and 95% confidence intervals (dashed). Data are grouped by age in years and year 0 includes only specimens from children 9-11 months. Rubella-containing vaccine was not available in the public sector prior to the serosurvey.

Conclusion
Measles seroprevalence was lower among HIV-infected than uninfected children and youth. HIV-infected children would likely benefit from revaccination. Many children were susceptible to rubella before the introduction of the combined measles and rubella vaccine in Zambia.

Disclosures
Kyla Hayford, PhD, MA, Pfizer, Inc. (Other Financial or Material Support, KH conducted the study and analyses while working at the Johns Hopkins School of Public Health but is an employee at Pfizer, Inc. as of 26 October 2020.)
1173. Changes in Invasive Pneumococcal Disease Incidence Following Introduction of PCV10 and PCV13 Among Children &lt; 5 Years: The PSERENADE Project
Authors: Bennett Julia C , Knoll Maria Deloria 
Published: December 2021

Abstract

Background
Higher valency pneumococcal conjugate vaccines (PCV10 and PCV13) replaced PCV7, and an updated global analysis of PCV impact on invasive pneumococcal disease (IPD) incidence is needed. We aimed to estimate the change in vaccine-type (VT), non-VT type and all-serotype (ST) IPD incidence following introduction of PCV10/13 among children &lt; 5 years of age.

Methods
IPD ST-specific incidence or cases and population denominators were obtained directly from surveillance sites. IPD incidence rate ratios (IRRs) for each site were estimated comparing the pre-any PCV incidence to each post-PCV10/13 year using Bayesian multi-level, mixed effects Poisson regressions. All-site weighted average IRRs were estimated using linear mixed-effects regressions. Results were stratified by product (PCV10 vs. PCV13) and years of prior PCV7 use (none, some [1-3 years or 4-5 years if &lt; 70% PCV uptake], or many [≥ 4 years with ≥ 70% uptake]).

Results
Analyses included 45 surveillance sites from 31 countries, primarily high-income (80%). Thirty surveillance sites had pre- and post-PCV data (PCV10: no prior PCV7=5 sites, some=2, many=2; PCV13: no prior PCV7=3, some=5, many=13). Five years after PCV10/13 introduction, the all-site IRRs in children &lt; 5 years were generally similar across products and prior PCV7 use strata for all-serotype IPD (range 0.23-0.41), PCV7 STs (0.01-0.13), PCV10non7 STs (1, 5, and 7F; 0.05-0.20), and ST6A (0.01-0.18). IRRs for ST19A were lower for PCV13 sites (range by PCV7 use: 0.09-0.31) than for PCV10 sites (1.1-1.4). ST3 IRRs were dynamic, differing by product at year 5 (range for PCV13 sites=0.86-1.02; PCV10 sites=1.55-1.78), but converging by year 7. NonPCV13 STs increased across all strata (range 1.9-2.6), except one strata with a single African site that declined.
Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children &lt;5&gt;

* Total sites indicates number of sites with incidence rate data included and pre/post sites indicates number of sites with both pre- and post-PCV data to estimate IRRs for each outcome. ** Year 0 indicates the year of PCV10/13 introduction and year -1 indicates the last year of PCV7 use prior to PCV10/13 introduction.

Conclusion
All-serotype IPD in children &lt; 5 years declined following both PCV10 and PCV13 use, driven by substantial declines in VT serotypes and offset by increases in nonPCV13 STs. ST19A decreased among PCV13-sites, mitigating replacement disease occurring after PCV7 use, but increased, on average, among PCV10-sites. Changes in ST3 were heterogeneous, increasing in some sites and no change from baseline in others. Data from low-income and high-burden settings were limited.

Disclosures
Julia C. Bennett, MSPH, Pfizer (Research Grant or Support) Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)
1183. Serum Bactericidal Activity Induced by Live Attenuated Pertussis Vaccine BPZE1 is Comparable to Boostrix™
Authors: Keech Cheryl A , Gorringe Andrew , Cavell Breeze , Goldstein Peter , Rubin Keith 
Published: December 2021

Abstract

Background
In a Phase 2b, multi-center, placebo-controlled, randomized study, intranasal BPZE1 induced mucosal and serum antibodies to pertussis antigens and protected against subsequent colonization following attenuated challenge with BPZE1 3 months later. BoostrixTM also induced serum but not mucosal antibodies and did not protect against BPZE1 challenge. We have evaluated the induction of serum bactericidal activity (SBA) for Bordetella pertussis by BPZE1 or Boostrix vaccination. A previous study showed that Boostrix induction of SBA is dependent on Prn whereas B. pertussis infection induces SBA targeting Prn and other antigens.

Methods
A convenience set of subjects who had a broad range of Prn and PT IgG serum concentrations from treatment groups who received BPZE1+BPZE1 or Boostrix+Placebo (Day 1 and 85 vaccination) were randomly selected to assess SBA using B. pertussis strain B1917. Three timepoints (baseline, 28 days following first and second vaccination) were analyzed and interpolated 50% killing titers determined. The relationship to Prn IgG concentration was assessed.

Results
BPZE1 and Boostrix elicited similar and significant increases in SBA following vaccination. BPZE1 and Boostrix elicit anti-Prn IgG, with Boostrix eliciting higher concentrations. A greater SBA response relative to PRN IgG was observed for BPZE1 compared to Boostrix. SBA-Prn correlations were high post-Boostrix (0.74) as previously reported; correlation was lower (0.35) following BPZE1, suggesting the involvement of broader antigenic protection beyond Prn alone.
Table of GMT and GMFR in SBA and Prn IgG

Conclusion
In this exploratory investigation, the novel intranasal live-attenuated pertussis vaccine BPZE1 induced SBA titers that were similar to Boostrix using a B. pertussis strain representative of current disease isolates. SBA-Prn correlations were high post-Boostrix, consistent with prior reports showing Prn is the acellular vaccine antigen that mediates SBA. In contrast, BPZE1 bactericidal antibodies appear broader than Prn which may be important given the global rise of Prn-deficient B. pertussis strains.

Disclosures
All Authors: No reported disclosures