bluuebunny/crossref_metadata_2025 huggingface dataset:
1012. Neutrophil Function Enhanced by Recombinant Interferon-Gamma in Newborns
Authors: Castillo-Galvan Ricardo , Soper Nicole , Bennett Monique , Thomsen Isaac
Published: December 2021

Background

Functional differences exist between neonatal and adult neutrophils. The incidence of infection is higher in preterm infants, and the severity of the immune impairment on the neonatal neutrophils is inversely related to gestational age. In order to recognize and combat life-threatening infections, neonates rely predominantly on the innate immune system.Neutrophils are an essential component of innate immunity, and they are the first responders against bacterial and fungal infections. Sepsis continues to be a prominent cause of neonatal mortality, especially among preterm infants. Recombinant interferon-gamma (IFNγ) effects on the immune system have included the upregulation of TLRs expression and stimulation of phagocytosis. They have been shown to reduce severe infections in children with chronic granulomatous disease.

Methods

After the protocol was IRB approved, we enrolled term infants in their first 48 hours of life (Table 1). We then obtained free flow whole-blood samples through venipuncture from the cephalic vein. Samples were incubated with and without IFNγ for 24 hours. Isolation of unperturbed neutrophils using immunomagnetics was performed for a final concentration of 1x106/mL. We then assessed the neutrophil-bacterial interaction using fluorescent GFP-Staphylococcus aureus, and quantified neutrophil killing function on a novel assay involving fibrin matrix as a more physiologic and three-dimensional (3D) environment than standard in vitro or culture-based assays. We evaluated normalized progressive ratios, 20μL/80μL, 30μL/70μL, 40μL/60μL of Neutrophil/GFP-S aureus respectively.Table 1

Results

On the 20 samples, we observed significant differences demonstrating a considerably enhanced phagocytosis on those samples with the addition of IFNγ(p< 0.0001, Table 2 and Figures 1-3).

Conclusion

The phagocytic ability of neonatal neutrophils was greatly enhanced by the addition of IFNγ in term infant blood. Ongoing work will determine whether this remains true for preterm-infant neutrophils and will further delineate mechanisms of these differences. We recognized an opportunity for interferon-based immunomodulation in certain situations on this population at high risk for invasive bacterial infections.

Disclosures

Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Isaac Thomsen, MD, MSCI, Horizon Therapeutics (Consultant)
122. Impact of Infectious Diseases Consultation in Patients with Candidemia at a Large Multi-site Healthcare System Providing Telemedicine Services
Authors: Hammer Katie , Shifflet Andrew , Petteys Megan , Soman Rohit , Williamson Julie E , Medaris Leigh Ann , shahid zainab
Published: December 2021

Background

Candida species are the most common cause of fungemia and are associated with high mortality. Management concordant with the Infectious Diseases Society of America guidelines and infectious diseases consultation (IDC) have been shown to lower mortality in patients with candidemia. The purpose of this study was to compare in-hospital mortality at a large multi-site healthcare system, including sites providing IDC via telemedicine services, in patients with candidemia with and without IDC.

Methods

This was a retrospective, observational cohort study completed at ten sites of Legacy Atrium Health in Charlotte Metro, NC, USA; at five sites, IDC is performed via telemedicine. Adult hospitalized patients identified with candidemia were enrolled May 2018-June 2019. The primary outcome was in-hospital mortality of IDC and non-IDC patients. Secondary outcomes included obtainment of repeat blood cultures, receipt of antifungal treatment, duration of therapy, removal of central venous lines (CVC) when present, and ophthalmological examination. Fisher’s exact, Chi-Square, or two-tailed Student’s t-test were used for demographics, primary and secondary outcomes as appropriate.

Results

A total of 126 patients were enrolled: 103 (82%) in the IDC group and 23 (18%) in the non-IDC group (Table 1). Mortality was significantly lower, and rates of repeat blood culture obtainment and receipt of antifungal treatment were significantly higher in patients with IDC (Table 2). Other outcomes including duration of therapy, removal of CVC, repeat cultures within 48 hours, and ophthalmological examination were not statistically different between groups.

Conclusion

This study is the first multi-site healthcare system providing telemedicine services to evaluate the impact of IDC on candidemia mortality. Ophthalmological examination rates were low in both groups, highlighting a potential area for improvement. IDC had significantly lower mortality, higher rates of antifungal treatment, and higher rates of repeat blood culture obtainment. IDC should be strongly considered in all patients with candidemia.

Disclosures

All Authors: No reported disclosures
1061. Clinical Phage Microbiology: Evaluating Phages for Biofilm-associated Prosthetic Valve Endocarditis
Authors: Gelman Daniel , Coppenhagen-Glazer Shunit , Durst Ronen , Nir-Paz Ran , Hazan Ronen
Published: December 2021

Background

Prosthetic valve endocarditis (PVE) is a major treatment challenge associated with biofilm formation. It requires intensive infectious diseases consultations and prolonged therapy. Nevertheless, high mortality rates are reported even with timely diagnosis and optimal management. Bacteriophage (phage) therapy, the use of bacterial viruses as antimicrobial agents, has been suggested as a potential adjunctive treatment for PVE. This is due to the ability of lytic phages to synergize with antibiotics and to destroy biofilms. However, due to their high specificity, it is crucial to match the phages by in-vitro evaluations that simulate the clinical settings.

Methods

In this study we demonstrate this matching using an in-vitro PVE model of vancomycin-resistant Enterococcus faecalis (VRE). We have looked at the ability of the phage EFLK1, alone or in combination with antibiotics, to destroy mature biofilms from a commonly used bioprosthetic valve. In addition, we tried to predict these effects using several in-vitro phage susceptibility assays.

Results

We found that the phage EFLK1 presents a significant inhibitory effect against planktonic cultures of VRE, both alone or in combination with ampicillin or ceftriaxone. We then tested the effect of these combinations on mature biofilm grown on a standard 96-well plates. We found that the phage, or its combination with ceftriaxone, led to a two-log reduction in the bacterial viability. In contrast, the addition of ampicillin to the phage caused interference with this antibacterial effect. When tested against biofilm grown on a pericardial patch, the combination of EFLK1 and ceftriaxone was found most efficient. Finally, when tested on the whole bioprosthetic aortic valve, we found that the phage EFLK1 alone was even more efficient than its combination with ceftriaxone.

Biofilm Eradication from Bioprosthetic Aortic Valve

(A) Representation of E. faecalis biofilm formation on bioprosthetic valves. (B) Following 48-hours of growth, the valves were treated for five days by the phage EFLK1, ceftriaxone or their combination. The valves were then washed from any planktonic cells and the biofilm biomass was established by CFU enumeration.

Conclusion

This study demonstrates that a proper in-vitro matching is essential in the treatment of PVE with phages. As seen here, the phage-antibiotic combination intended for treatment should be drawn according to their efficacy on suitable models, simulating the clinical settings, with the specific pathogen, the valve material, and the used phages taken into consideration.

Disclosures

Ran Nir-Paz, MD, BiomX (Consultant)Technophage (Scientific Research Study Investigator, Advisor or Review Panel member)
1067. Identifying and Assaying New Potential Molecular Targets in Fungi Following a Novel Strategy Based on Binding Site (Dis)Similarities with Proteins of the Human Pharmacolome
Authors: Bedoya-Cardona Johann E , Rubio-Carrasquilla Marcela , Valdes-Tresanco Mario S , Ramirez-Velasquez Iliana M , Moreno Ernesto
Published: December 2021

Background

Invasive fungal infections account for a high burden of morbidity and mortality. This is aggravated because of the toxicity and resistance problems associated to current antifungal drugs, which in whole target only a handful of fungal molecules. In this scenario, new target identification and drug design, together with drug repurposing, represent promising strategies.

Methods

We aim to identify and test in vitro potential new therapeutic targets in fungi. Our strategy consists in identifying fungal proteins with active sites (meaning the set of residues lining the binding pocket) that are similar, but not identical!, to sites of proteins from the human pharmacolome. A high structural similarity with a human counterpart allows validation of the fungal target using cross-reactive inhibitors of the human protein. On the other hand, a few amino acid differences in the binding pocket produce local topological and chemical changes that create a "design space" for new specific inhibitors of the fungal target.

Results

Applying our own bioinformatics approach and taking advantage of the >200 available crystal structures of proteins of the human pharmacolome in complex with inhibitors, we have identified ca. 30 proteins in several fungal species of the genera Histoplasma, Candida, Criptococcus, Aspergillus and Fusarium, whose binding sites share at least 70% amino acid identity with their similar binding pockets in human pharmaceutical targets. So far we have assayed in vitro, in seven different fungal species, ca. 60 known inhibitors of around twenty of the orthologous human proteins. Some of the tested inhibitors have been previously assayed in different species in drug repurposing screenings, while others, to our knowledge, have not been yet tested. Over a dozen of these compounds, targeting eight different protein targets, showed IC50 values in the micromolar order in one or across several species. In general, yeasts were more significantly affected than molds.

Conclusion

Our results point to new potential fungal targets that can be exploited for the design of new antifungal agents. Ongoing work by our group aims to identify, by virtual screening, specific inhibitors for several of these potential targets.

Disclosures

All Authors: No reported disclosures
1110. In Vivo Pharmacodynamics of Vancomycin Against Staphylococci in Young Infants
Authors: Gwee Amanda , Duffull Stephen , Zhu Derek
Published: December 2021

Background

Coagulase-negative staphylococci are the predominant pathogen causing late onset sepsis in young infants, however, the pharmacodynamic target for vancomycin therapy is unknown. This study aimed to determine the pharmacodynamic target of vancomycin in young infants with staphylococcal infections.

Methods

Retrospective data were collected for infants aged 0-90 days with methicillin-resistant Staphylococcus aureus (MRSA or coagulase-negative staphylococci (CoNS) bacteraemia over a 4-year period at the Royal Children’s Hospital Melbourne, Australia. Vancomycin broth microdilution minimum inhibitory concentrations (MIC) were determined. A published pharmacokinetic model was externally validated using the study dataset and a time-to-event pharmacodynamic model developed using non-linear mixed effects modelling, with the event being the first negative blood culture. Simulations were performed to determine the 24-hour trough vancomycin concentration correlating with a 90% probability target attainment (PTA) of the area under the curve in the first 24-hours (AUC0-24) exceeding the identified target.

Results

Thirty infants, 28 with CoNS and two with MRSA bacteraemia, who had 165 vancomycin concentrations determined were included. The vancomycin broth microdilution MIC was determined for 24 CoNS and one MRSA isolate, both with a median MIC of 1 mg/L (CoNS range 0.5 to 4). An AUC0-24 ≥3 00 mg/L·h was associated with a 7.8-fold increase in the chance of bacteriological cure for all staphylococci at any time point compared to an AUC0-24 < 300 mg/L·h (hazard ratio 95% CI: 3.21-18.8). The 24-hour trough concentrations associated with a 90% PTA of achieving this target were > 13-16 mg/L and > 8-12 mg/L for 6 and 12-hourly dosing, respectively.

Conclusion

Our study found that an AUC0-24 ≥ 300 mg/L·h was associated with a 7.8-fold increase in bacteriological cure in young infants with staphylococcal bloodstream infections.

Disclosures

All Authors: No reported disclosures
1117. Tazobactam Pharmacokinetic/Pharmacodynamic Target Attainment in Healthy Volunteers and Critically-Ill Hospitalized Patients
Authors: Kalaria Shamir N , Pogue Jason M , Heil Emily , Heil Emily
Published: December 2021

Background

Pharmacokinetic/pharmacodynamic (PK/PD) targets and attainment are well described for beta-lactams; however, are rarely considered for beta-lactamase inhibitors. Recent evidence suggests that tazobactam (TAZ) target exposures to restore piperacillin bacteriostatic and 1 log 10 bactericidal activity against Enterobacterales are fT> the piperacillin/tazobactam (TZP) MIC of 64% and 77%, respectively. The aim of this study was to evaluate TAZ probability of target attainment (PTA) of a 500 mg every 6-hour dose of tazobactam using population PK data in both healthy volunteers and hospitalized patients.

Methods

PK exposures in 1,000 patients with varying degrees of renal function were simulated using a previously described TAZ PK model developed with data from critically ill infected patients. An identical one-compartment structural model describing TAZ PK using mean population parameters observed in phase 1 PK studies was also used to simulate exposures in healthy volunteers. All simulated patients received 500 mg of TAZ as an intravenous infusion over 30 minutes or as a 3-hour extended-infusion.

Results

The table displays PTA results for patients with an estimated creatinine clearance of 60 mL/min. Based on healthy volunteer data, the highest TZP MIC where ~90% PTA was achieved for bacteriostasis was 1 mg/L and was 0.25 mg/L for bactericidal activity. These were only achieved with extended infusion administration of TAZ. In the cohort of hospitalized patients, >90% PTA of TAZ exposures associated with both bacteriostasis and 1 log kill were achieved up to a MIC of 2 for intermittent infusion and up to 4 mg/L for extended infusion, due to decreased TAZ clearance in hospitalized patients. These values are significantly lower than the CLSI TZP susceptibility breakpoint of 16 mg/L, and PTA rates were lower at increased creatinine clearances.

Conclusion

fT>TZP MIC target attainment is poor with maximal package insert tazobactam doses given with piperacillin, even when administered as an extended infusion. These findings have serious implications for the role of TZP in beta-lactamase producing Enterobacterales, including ESBLs, and suggest the current susceptibility breakpoints are 4-32 fold higher than those supported by PK/PD data.

Disclosures

Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Emily Heil, PharmD, MS, BCIDP, Nothing to disclose
1127. Validation of an Adult and Pediatric Beta-Lactam Allergy Risk Stratification Tool
Authors: Jaffa Rupal K , Ton Minh-Thi , Forrester Jeanne , Patel Rupal , Brantley Courtney W , Campbell Jamie , Carlson Travis J , Morris Lee , Patel Niraj C , Shah Ekta , Boger Michael S , Davidson Lisa
Published: December 2021

Background

Penicillin allergies are commonly reported, yet more than 95% of these patients can tolerate β-lactams. A comprehensive allergy history is essential when determining which patients can safely receive a β-lactam but is rarely obtained. When available, interpretation of the history is often limited by lack of comfort in determining risk of an allergic reaction. Our antimicrobial stewardship and allergy team created a standardized allergy history questionnaire and risk stratification tool. The purpose of this study was to validate this tool by comparing risk levels assigned by various clinicians to that assigned by an allergist.

Methods

We prospectively identified 50 adult and 50 pediatric patients hospitalized between July 1, 2020 and March 31, 2021 with an allergy to penicillin, amoxicillin, ampicillin, or cephalexin. Patients with severe non-IgE mediated reactions were excluded. All patients (or caregivers) were interviewed by the same pharmacist using the allergy questionnaire. Clinicians from various subspecialties, including an adult and pediatric allergist, an adult and pediatric infectious diseases (ID) physician, an adult and pediatric hospitalist, and an adult and pediatric ID pharmacist, received anonymized completed questionnaires and the risk stratification tool, but were blinded to other clinicians’ responses. The primary endpoint was overall concordance in risk stratification between non-allergists and allergists.

Results

Overall concordance was 66% (33/50) in adult and 90% (45/50) in pediatric patients (Table 1). Concordance between individual clinicians and the allergist are shown in Figure 1. In adults, anaphylaxis, difficulty breathing, and angioedema were associated with less severe stratification by non-allergists than allergists. No clinicians stratified any pediatric patient into a lower risk category than the allergist.

Table 1. Clinician Agreement with Allergist

Figure 1. Risk Stratification Severity Compared to Allergist

Conclusion

Use of a β-lactam allergy risk stratification tool led to agreement with allergist assessment in the majority of patients. Variation in risk assignment was greater in adult patients; however, non-allergist pediatric providers assigned all patients at the same or more severe level as the allergist, indicating safety in this population.

Disclosures

All Authors: No reported disclosures
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

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

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

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

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

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

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 < 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 < 5 Years: The PSERENADE Project
Authors: Bennett Julia C , Knoll Maria Deloria
Published: December 2021

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 < 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 < 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 < 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 <5>

* 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 < 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

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
1204. Assessing Perceptions and Efficacy of COVID-19 Case and Contact Investigations – Dallas County, Texas, 2020
Authors: Serrano Jose , Clouston Harper R , Wiegand Jared , Shim Kyoo , Popper Nathan , Maaraoui Kayla , Limsenben Joshua , Hum Maxwell , Roseman Robert , Gomez Ivorry , Chung Wendy
Published: December 2021

Background

During 2020, a total of 193,318 cases of COVID-19 were reported in Dallas, with daily average case rates exceeding 50 per 100,000 for over 7 weeks. An adaptable survey functionality within a newly implemented COVID-19 surveillance system provided an opportunity to assess case knowledge and attitudes about isolation and contact tracing efforts.

Methods

COVID-19 illnesses were classified using the 2020 CSTE case definitions. Cases were interviewed and records reviewed for exposures and illness characteristics. Supplemental questionnaires assessing knowledge of public health recommendations were given to a convenience sample of 987 cases during the month of December 2020. Fishers exact and chi-square analyses were performed using SAS 9.4.

Results

Of the 987 respondents, 99% reported beginning isolation on or before receipt of test results, and 1% were not in isolation at the time of public health interview. Of cases reporting contacts, 92% had advised household members to quarantine prior to interview, and 91% did not want public health to call their household. Of cases reporting non-household close contacts, 75% had advised these contacts to quarantine prior to interview, and 91.3% did not want the health department to call these persons. Cases ≥ 65 years were less likely to have notified their own close contacts (OR: 0.2; 95% CI=0.1-0.8) of their test results, and more likely to prefer the health department to notify their household contacts of their positive result (OR: 4.1; 95% CI=1.3-12.5). Compared with White cases, Hispanic cases were less likely to be aware that their test was positive at the time of interview (OR: 0.3; 95% CI=0.1-0.7). Non-White cases were less likely to be aware of resources for food, rent and utility assistance prior to interview (OR: 0.25; 95% CI=0.1-0.7). All respondents perceived the public health interview to have been of some value to them, most often to answer their questions about retesting (51%) and duration of isolation (48%).

Conclusion

The aversion of a majority of COVID-19 cases for health department notification of their contacts is a significant deterrent to name-based contact tracing approaches. Acknowledgement of this limitation could better focus existing resources on the delivery of expedited notifications and information to contacts by proxy.

Disclosures

All Authors: No reported disclosures
140. Antibiotic Prophylaxis for Upper Gastrointestinal Bleed in Liver Cirrhosis: Less May Be More
Authors: Mansoor Armaghan-e-Rehman , Hadi Yousaf B , Naqvi Syeda Fatima Z , Khan Ali Y , Khan Raja S , Singal Ashwani , Kupec Justin
Published: December 2021

Background

Antibiotics in patients with cirrhosis and upper gastrointestinal bleeding are shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics, with 7 days of therapy generally recommended. Antibiotic duration has not been compared to outcomes in current scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on outcomes.

Methods

This was a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010-2018. Patients were divided into three cohorts based on duration of antibiotic administration: 1-3 days, 4-6 days, and 7 days or more. Rates of infection within 30 days, time to infection, rebleeding and mortality were compared between the three groups. Multivariable analysis was conducted to evaluate independent risk factors for infection.

Results

Medical charts of 943 patients with cirrhosis and upper GI bleed were reviewed. 303 patients did not have concomitant confirmed or suspected infection on presentation, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients >6 days. The groups were well matched in demographic & clinical variables. 27 patients developed infections within 30 days of bleed. High MELD score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the antibiotic groups (p= 0.78). In the 30 days following GI bleed, pneumonia was the most diagnosed infection (11 patients) followed by UTI (8 patients). Four patients developed spontaneous bacterial peritonitis and 3 were diagnosed with bacteremia. There was no difference in time to infection (p= 0.75), early re-bleeding (p=0.81), late re-bleeding (p= 0.37) and in-hospital mortality (p= 0.94) in the three groups. Six patients developed C. Difficile infection, none of whom were in the short antibiotic group.

Conclusion

Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding if bleeding has abated and there is no active infection.

Disclosures

All Authors: No reported disclosures
1215. A Mixed Methods Study on Severe Bacterial Infections in People Who Inject Drugs
Authors: Hrycko Alexander , Eckhardt Benjamin , Mateu-Gelabert Pedro , Ciervo Courtney
Published: December 2021

Background

Severe bacterial infections (SBI) associated with intravenous drug use have been increasing in frequency in the U.S. over the last decade. This mixed methods study aims to identify the risk factors associated with SBI in hospitalized individuals with recent injection drug use.

Methods

We conducted 34 quantitative and 15 qualitative interviews between August 2020 and June 2021 at Bellevue Hospital in New York City. Eligible participants were (1) >/= 18 year of age, (2) admitted with a SBI, and (3) reported injection drug use within the 90 days prior to admission. Quantitative and qualitative data was obtained using a quantitative survey and in-depth, semi structured interviews of participants respectively. Analysis was performed to examine trends and explore common themes potentially contributing factors to SBI.

Results

Of the 34 participants included, the median age was 37.5, 85% were male, 53% white, and 65% reported being homeless within the past 3 months. Endocarditis was the most common primary diagnosis (65%). Median length of hospital stay was 24 days and 35% required ICU level care during admission. A causative microorganism was identified in 85% of participants and 50% had Staphylococcus aureus as the sole organism. Discharges against medical advice occurred in 35%. Daily injection drug use in prior 30 days was 95% with a median of 10 injections per day. In the 30 days prior to admission, 50% reported an increase in injection frequency, 80% reported reusing needles and/or syringes, 75% reused cookers, 65% reused cottons. Analysis of qualitative interview data revealed high risk injection behaviors. Participants were not practicing and unaware of strategies to reduce their risk of drug injection-related SBI. Prior hospitalizations for SBI did not impact on this knowledge deficit on what constitutes bacterial infection risk and how to prevent it.

Conclusion

Study findings highlight the complexity of the injection drug use process and the potential social and physiological pathways leading to SBI. Multiple domains at the structural, network, and individual level that impact drug injection practices and provide context by which these factors predispose and lead to physiological tissue damage and the development of SBI among PWID.

Disclosures

Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support)