bluuebunny/crossref_metadata_2025_split huggingface dataset:
571. A Report of the Postmarketing Spontaneous Safety Data over 24 Years for GSK’s Measles-Mumps-Rubella (MMR) Vaccine
Authors: Singh Tina , Casabona Giacomo , Abu-Elyazeed Remon , Vetter Volker , Hergibo Fanny 
Published: December 2022

Abstract

Background
GSK’s measles-mumps-rubella (MMR) vaccine is indicated for active immunization of individuals aged 12 months and older against these 3 serious illnesses. It is licensed in &gt; 100 countries worldwide not including the US. In clinical trials, it elicited robust immune responses in children and was well tolerated. Monitoring the vaccine’s real-world safety profile in the general population continues, and rapid collection of data on its real-world use is a strength of passive safety surveillance. We provide an overview of the postmarketing spontaneous safety data over 24 years for GSK’s MMR vaccine.

Methods
Spontaneous adverse events (AE) reports following vaccination with GSK’s MMR vaccine were collected from GSK’s Global Safety Database from 4-December-1997 until 1-March-2022. Annual reporting trends for pyrexia, rashes (commonly reported in the pediatric population), and events of clinical interest like febrile convulsions and neurological conditions were analyzed from 1998 until 2021. The patient exposure was estimated by the number of doses distributed (DD).

Results
Over the reviewed period, ∼445 million doses of GSK’s MMR vaccine were distributed worldwide, and 29,504 cases were spontaneously reported (rate: 6.63 cases reported/100,000 DD). Of all spontaneous AE reports, 9,960 (33.76%) were considered as serious. For the period analyzed, pyrexia and rash were the most frequently reported AEs following vaccination with GSK’s MMR vaccine (Table). Reports of febrile convulsions had a mean frequency of 0.27 cases/100,000 DD (Table); reports of neurological conditions (encephalitis and/or panencephalitis and/or meningitis and/or meningism) had a mean frequency of 0.07 cases/100,000 DD (Table) and did not show a trend of increased incidence over time.

Conclusion
The postmarketing safety data analyzed showed that the safety profile of GSK’s MMR vaccine is consistent with that observed in clinical trials and remains supportive of its overall safety profile in routine use. GSK continues monitoring the safety of its MMR vaccine.

Funding
GlaxoSmithKline Biologicals SA
Acknowledgment: Adina Truta/Julie Mellery provided medical writing/editorial support (Modis c/o GSK)

Disclosures
Tina Singh, MD physician, GSK: Employee of the GSK group of companies and having restricted GSK shares in the GSK group of companies Giacomo Casabona, MD, GSK: I’m an employee of the GSK group of companies and shareholder in the GSK group of companies Remon Abu-Elyazeed, MD, PhD, GSK: Employee of the GSK group of companies and having GSK stocks in the GSK group of companies Volker Vetter, MD, GSK: I’m an employee of the GSK group of companies and hold shares in the GSK group of companies Fanny Hergibo, Pharm.D., GSK: Employee of the GSK group of companies.
572. Adverse Events Following Live Immunization in Patients with DiGeorge Syndrome: A Retrospective, Single Center Study in Korea
Authors: Lim Sung Min , Shin Je Hee , Baek Jee Yeon , Lee Ji Young , Kang Ji-Man , Ahn Jong Gyun 
Published: December 2022

Abstract

Background
DiGeorge syndrome (DGS) is a syndrome accompanied by congenital heart defect, hypoparathyroidism and immunodeficiency of varying severity. Live vaccination is generally contraindicated in patients with DGS. However, in real clinical practice, there are cases in which live vaccines are immunized before the diagnosis of DGS or are incidentally immunized. We collected these cases and investigated adverse events (AEs), especially infections caused by the vaccine strains.

Methods
This retrospective study included all patients diagnosed with DGS at Severance Hospital Seoul, Korea, between November 2005 and June 2021. We extracted patients with ICD-10 code (D82.1) and then excluded subjects without genetic confirm. According to the immune status, subjects were categorized into three groups: group A [CD3 &lt; 500 or CD8 &lt; 200 (cells/mm3)], group B [CD3 ≥500 and CD8 ≥ 200 (cells/mm3)] and group C (unknown).

Results
Of a total 94 DGS patients, approximately 40% of subjects (38/94) underwent immunological test, of which 21% (8/38) belonged to group A and 79% (30/38) were in group B. Approximately 80% of study subjects (73/94) had a record of at least one live vaccination. By vaccine type, measles-mumps-rubella accounted for the most at 70% (66/94), followed by varicella, bacillus Calmette–Guérin, rotavirus, and live-attenuated Japanese encephalitis virus vaccine. A total of 50 AEs were observed (Figure 1): fever (n=29), URI (n=9), diarrhea (n=4), rash (n=3), thrombocytopenia (n=3), injection site pus (n=1) and febrile convulsion (n=1). Among them 26% (13/50) occurred in group A and no significant difference in the incidence rate of AEs between group A and B was observed (P = 0.14). Six cases of them turned out to be consistent with live vaccination by WHO 2009 causality analysis. Moreover, there were no serious reactions, including ICU hospitalization or death, and there was no emergence of disease caused by vaccine strains.

Conclusion
Our data show that live vaccines were often given without immunologic screening and generally well tolerated in our study population.

Disclosures
All Authors: No reported disclosures.
580. Influenza, SARS-CoV-2, and routine childhood vaccines – trends in vaccine hesitancy in hospitalized children before and during the COVID-19 pandemic
Authors: Orbea Marisa , Cunningham Rachel , Mary Healy C , Boom Julie A , Bocchini Claire 
Published: December 2022

Abstract

Background
Vaccine hesitancy (VH) is adversely affecting the public health response to the COVID-19 pandemic. Similarly, influenza vaccine uptake is suboptimal. We aimed to monitor trends in VH with respect to influenza, SARS-CoV-2, and routine childhood vaccines.

Methods
We conducted a repeated cross-sectional survey in English and Spanish of caregiver influenza and SARS-CoV-2 knowledge, attitudes, behaviors, and associated VH among hospitalized children 6 mo-18 yrs at a large pediatric medical institution. Caregivers were enrolled over 3 influenza seasons (S); 2019-2020 (S1), 2020-2021 (S2), and 2021-2022 (S3). VH was assessed using the Parent Attitudes about Childhood Vaccines (PACV) survey; PACV score ≥ 50 denoted VH. Descriptive statistics were used.

Results
During 3 influenza seasons, 269/282 (95%), 295/307 (96%), and 384/418 (92%) of approached caregivers were enrolled in S1, S2, and S3 respectively. Most parents (45%) identified as Hispanic/Latino, 35% as White, and 20% as Black/African American. By report, 94% of children in S1, 91% in S2, and 91% in S3 were up-to-date with routine childhood vaccines. Based on PACV score, 13% of parents were VH in 19-20 compared to 17% in 20-21 and 19% in 21-22.
Approximately 70% of caregivers gave or planned to give their child the influenza vaccine across seasons. Following the COVID-19 pandemic, caregivers were less likely to believe that the “flu can be a dangerous infection in children,” and to agree that “all children over 6 months of age should receive the flu shot every year”. Decreased concern persisted or did not recover during the pandemic (Table 1).
Parents were consistently scared of their child getting COVID-19 but fewer (49% versus 38%) were scared of their child getting the SARS-CoV-2 vaccine in S3. More (50% versus 71%) caregivers in S3 were willing to receive the SARS-CoV-2 vaccine themselves and 46% in S2 and 54% of caregivers in S3 had or planned to vaccinate their child against COVID-19 (Table 2). Table 1.Influenza comparison of study population, 2019-2020 versus 2020-2021 versus 2021-2022
Table 2. SARS-CoV-2 comparison of study population, 2020-2021 versus 2021-2022

Conclusion
Our results suggest a trend that VH may be increasing. During the COVID-19 pandemic, caregivers of hospitalized children were less concerned about influenza than pre-pandemic. Intention to vaccinate children against COVID-19 remains suboptimal.

Disclosures
C. Mary Healy, MD, Dexcom: Stocks/Bonds|Emmes Corporation: Advisor/Consultant|Intuitive: Stocks/Bonds|Quidel Corporation: Stocks/Bonds|Up to Date: Honoraria|Vapotherm: Stocks/Bonds.
596. Anti-Biofilm Activity of Isolated Bacteriophages Targeting Pseudomonas aeruginosa and Staphylococcus aureus
Authors: Brodsky Julia R 
Published: December 2022

Abstract

Background
A rise in the prevalence of antibiotic-resistant infections has prompted a search for alternative methods to combat bacteria in the human body. People with cystic fibrosis are especially vulnerable because their lung environment provides a habitable environment for chronic infection, biofilm formation, and antibiotic-resistant mutations. The difficulty associated with finding bacteriophages targeted to a specific infection is one reason the treatment is used relatively infrequently, even when antibiotics have failed. This study aimed to isolate phage species for strains of Pseudomonas aeruginosa and Staphylococcus aureus, the most common causes of chronic infections in patients with cystic fibrosis.

Methods
Phages targeting multidrug-resistant strains of S. aureus and P. aeruginosa were isolated from samples of fecal matter and soil; stocks were enumerated with the double agar overlay method. The potency of the Pseudomonas-hosted isolates in eradicating biofilms was compared to the efficacy of an antibiotic cocktail and the enzyme cellulase through an in vitro resazurin cell viability assay. Each treatment was performed in sextuplicate. Metabolic reduction of resazurin to resorufin was quantified at 24 and 48 hours of growth using a microplate reader.

Results
Six phage stocks (four targeting Pseudomonas bacteria [from human & feline fecal matter and from soil], two targeting Staphylococcus [from human & feline fecal matter]) contained bacteriophages at concentrations ranging from 3.9x104 pfu/mL to 2.8x107 pfu/mL. The most effective treatments in the assay were found to be cellulase alone and the three inhibitors together.

Conclusion
Feline fecal matter is a potential source of Pseudomonas and Staphylococcus bacteriophages. Enzymes were found to be a critical component of biofilm treatment. The isolated bacteriophages were not the most potent treatment alone, but when combined with cellulase and antibiotics, bacterial growth was markedly slowed.

Disclosures
All Authors: No reported disclosures.
599. Association between Vancomycin AUC and Clinical Failure in Patients with Streptococcal Bacteremia
Authors: Aycock Anna C , Smith Jessica M , Coe Kelci E , Wang Shu-Hua , Reed Erica E 
Published: December 2022

Abstract

Background
Vancomycin (VAN) is an efficacious therapy against Streptococcus. VAN area under the curve to minimum inhibitory concentration (AUC/MIC) is the preferred monitoring strategy for serious methicillin-resistant S. aureus infections but is not well elucidated for other bacterial pathogens such as Streptococcus.

Methods
This was a retrospective cohort study evaluating adult inpatients with streptococcal bacteremia treated with VAN definitive therapy from Jan 1, 2011 to Sept 30, 2021 at a tertiary care academic medical center. VAN AUC was retrospectively calculated using Bayesian software (ClinCalc). The primary outcome was treatment failure, defined as a composite of recurrent or persistent streptococcal bacteremia, 60-day all-cause readmission, or 60-day all-cause mortality. Secondary outcomes included time to bacteremia clearance, hospital length of stay (LOS), and nephrotoxicity. Data collected included demographics; comorbidities; severity of illness; streptococcal species and source; VAN initial trough and duration; and clinical outcomes. Classification and regression tree analysis (CART) was conducted to identify the AUC threshold predictive of clinical failure. Wilcoxon rank sum, Chi Square, or Fisher’s exact tests were utilized as appropriate to compare groups stratified by the CART-identified AUC threshold.

Results
Forty-six patients met inclusion criteria during the study timeframe. Eleven patients had a VAN AUC &lt; 329 of which 8 (73%) experienced clinical failure, while 35 patients had a VAN AUC &gt; 329 of which 12 (34%) experienced clinical failure (p=0.04). No significant differences in baseline or clinical characteristics were identified between groups. Median VAN initial trough was higher in the VAN AUC &gt; 329 group (13.2 vs 6.2, p&lt; 0.001). Median hospital LOS was longer in the VAN AUC &gt; 329 group (15 vs 8 days, p=0.05) while median time to bacteremia clearance (29 vs 25 hrs, p=0.15) and nephrotoxicity incidence (13% vs 4%, p=1) were not significantly different.

Conclusion
Vancomycin AUC &lt; 329 was predictive of clinical failure in patients with streptococcal bacteremia. Larger studies are needed before VAN AUC monitoring can be recommended for implementation in the management of streptococcal bacteremia.

Disclosures
All Authors: No reported disclosures.
626. Tebipenem Pharmacokinetics and Soft-Tissue Distribution in Diabetic Patients with Lower Extremity Infections using In Vivo Microdialysis
Authors: Abouelhassan Yasmeen , Fratoni Andrew J , Shepard Ashley , Nicolau David P , Asempa Tomefa E 
Published: December 2022

Abstract

Background
Administration of the oral carbapenem, tebipenem along with its broad spectrum of activity against anaerobic, Gram-positive and Gram-negative pathogens including extended-spectrum β-lactamase-producing Enterobacterales, offers clinicians a potential new option and route to treat a range of infections. Lower extremity infections in diabetic patients are associated with high rates of hospitalization and amputation. Given the microvascular dysfunction and poor peripheral circulation in this population, the aim of this study was to assess tebipenem soft tissue pharmacokinetics (PK) and interstitial fluid distribution among diabetic patients with lower extremity infections using in vivo microdialysis.

Methods
This was a single-center, open-label, observational PK study in diabetic patients with foot infections who were enrolled and received tebipenem (600 mg) orally q8 hrs for a total of 3 doses. A microdialysis catheter was inserted within 4-8 cm of the wound margin to allow for dialysate sampling. Ten concurrent plasma and dialysate samples over an 8 hr period starting immediately prior to the last dose of tebipenem were obtained. Protein binding was determined by ultracentrifugation at 1 hr post-third dose. Plasma and dialysate samples were assayed via a validated LC/MS/MS assay. Non-compartmental analyses for free plasma and soft-tissue concentration were used to obtain PK parameters.

Results
Four male diabetic patients with an age of 70 ± 7 years and a hemoglobin A1C of 10 ± 2% were consented. All patients had an active complicated skin and soft tissue infection as defined by PEDIS Grade 2 or 3. Mean ± standard deviation (SD) plasma protein binding was 50% ± 1%. Mean ± SD tebipenem PK parameters in plasma were: maximum free concentration (fCmax), 2.34 ± 0.94 mg/L; time to Cmax (Tmax), 2.99 ± 1.40 hr; half-life (t1/2), 2.23 ± 1.65 hr and free area under the concentration-time curve (fAUCp(0-8)): 8.37 ± 1.63 mg.h/L. Mean ± SD parameters in tissue were: Cmax, 2.50 ± 1.04 mg/L; Tmax, 2.99 ± 1.40 h; t1/2 1.99 ± 1.42 hr; and AUCt(0-8), 8.01 ± 0.76 mg.h/L.

Conclusion
This study demonstrates that tebipenem has excellent distribution into interstitial fluid and lower extremity tissue of diabetic patients with ongoing foot infections.

Disclosures
Yasmeen Abouelhassan, PhD, Pfizer: spouse salary David P. Nicolau, PharmD, Shionogi: Grant/Research Support.
652. Ceftazidime-avibactam Alone or as Combination Therapy? Multicenter Retrospective Cohort Analysis of Clinical Outcomes in Patients with Carbapenem-resistant Gram-negative Infection
Authors: Mishuk Ahmed Ullah , Strich Jeffrey R , Warner Sarah , Sun Junfeng , Malik Seidu , Lawandi Alexander , Kondo Maiko , Satlin Michael J , Chandorkar Aditya , Heil Emily L , Morales Megan K , Mathur Anisha , Timpone Joseph , Wooten Darcy , Sweeney Daniel , Pan Jonathan , Raybould Jillian , Bonne Stephanie , Colindres Roberto , Boucher Helen W , Buckman Sara , Furukawa Daisuke , Uslan Daniel , Hohmann Samuel F , Kadri Sameer S 
Published: December 2022

Abstract

Background
Ceftazidime-avibactam (caz-avi), a novel β-lactam/β-lactamase inhibitor, is commonly utilized for carbapenem-resistant gram-negative infections (CR-GNI). However, the benefits vs risks of combining caz-avi with other agents are unclear.

Methods
In this retrospective cohort study, inpatients with CR-GNI treated with caz-avi were identified at 9 U.S. hospitals. The impact of caz-avi monotherapy (MT) or combination therapy (CT; i.e., any concomitant use of gram-negative-active antibiotics) was studied using logistic regression, controlling for baseline patient and hospital factors. The primary outcome was in-hospital mortality or discharge to hospice (death), and secondary outcomes were length of stay (LOS), resolution of infectious signs and symptoms (clinical response), 90-day recurrent infection and future caz-avi–resistant organism. An adjusted odds ratio (aOR) with 95% confidence interval (CI) was used to assess the primary and secondary outcomes.

Results
328/499 (65.7%) patients received caz-avi as targeted therapy for a CR-GNI. Overall patients treated with MT and CT were similar at baseline and had comparable baseline demographics although patients treated with CT were more likely to be in the ICU and receive a concomitant empiric in vitro-concordant antibiotic (table 1). The most common organism was Klebsiella spp. (44.6%) followed by Pseudomonas aeruginosa (27.7%) (table 2). Concomitant gram-negative agents are shown in table 3. Overall, 92 (28.1%) patients died and CT (vs MT) displayed similar adjusted mortality risk (27.7% vs 28.7%; aOR [95%CI]: 0.67 [0.34-1.33]) and LOS (19 [9, 37] and 20 [9, 42.5] days). CT (vs MT) was associated with greater odds of clinical response (aOR: 2.25 [95%CI:1.15-4.41]). Among survivors, similar rates of 90-day recurrent infection (50/154 (32.5%) were observed in CT vs 18/82 (22.0%) in MT group (p=0.09) and 5 (2.19%) patients had future infection with a caz-avi–resistant pathogen (3 in CT and 2 in MT group).

Conclusion
Compared to patients with CR-GNI treated with caz-avi alone, those who received CT including caz-avy had similar survival and LOS but higher clinical response. The role of CT in the era of novel antibiotics warrants additional study.

Disclosures
Helen W. Boucher, MD, American Society of Microbiology: Honoraria|Elsevier: Honoraria|Sanford Guide: Honoraria.
657. Evaluating Clinical Outcomes of Bacteremic Patients Treated with AmpC-Inducing Versus -Stable Agents
Authors: Barsoum Barbara , Karkenny Gabriel , Donaghy Henry , Doan Thien-Ly 
Published: December 2022

Abstract

Background
AmpC enzymes are β-lactamases that can rapidly hydrolyze penicillins, cephalosporins, and monobactams. When in the presence of β-lactams, inducible pathogens can become derepressed and lead to an overproduction of AmpC. Because of this induction potential, agents that appear susceptible may quickly become resistant, complicating the treatment choices for these infections. The purpose of this study is to assess clinical outcomes in bacteremic patients with an AmpC producing organism based on the antimicrobial agent used.

Methods
This retrospective chart review is approved by Northwell Health IRB and evaluated patients admitted with a positive blood culture from July 2017 to January 2022. The primary objective is outcome of infection (treatment success or failure). Secondary objectives include 30-day readmission related to infection, microbiologic relapse, and in-hospital mortality. Patients were included if they had a positive blood culture demonstrating E. cloacae, E. aerogenes, or C. freundii, cefoxitin resistance, and were treated with a β-lactam antibiotic for at least 72 hours. Patients were excluded if they had polymicrobial cultures or if a resistance gene was detected.

Results
A total of 71 patients were included in analysis, with 40 patients in the carbapenem or cefepime group (Group A), 18 patients in the piperacillin/tazobactam group (Group B), and 13 patients in the ceftriaxone or aztreonam group (Group C). The most frequently isolated pathogen was E. cloacae and the most common source of infection was genitourinary. Treatment failure was seen in 16.7% of Group B patients, 15.4% of Group C patients, and 12.5% of Group A patients (p=0.901). Microbiologic relapse was experienced in 5.6% of patients in Group B and 2.5% of patients in Group A (p=0.686). In Group C, 15.4% of patients were readmitted within 30 days related to infection, compared to 11.1% in Group B and 2.5% in the Group A (p=0.23). In-hospital mortality was 16.7% in Group B, compared to 15% in Group A (p=0.341).

Conclusion
Although not statistically significant, patients who received piperacillin/tazobactam had numerically more treatment failure, microbiologic relapse, and 30-day readmission related to infection when compared to the patients who received a carbapenem or cefepime.

Disclosures
All Authors: No reported disclosures.
667. Real-world Experience of Cefiderocol with Pseudomonas aeruginosa in the PROVE (Retrospective Cefiderocol Chart Review) Study
Authors: Marcella Stephen , Carr Amy L , Kobic Emir , Nguyen Sean , Zhou Anan 
Published: December 2022

Abstract

Background
Gram-negative (GN) bacterial resistance is an urgent global health problem. Cefiderocol (CFDC) is active against many resistant GN pathogens, including Pseudomonas aeruginosa (PA). PROVE is an ongoing international, retrospective study assessment of CFDC use for Gram-negative infections (GNI).

Methods
Patients were eligible if they received ≥ 72 hours of CFDC. Patient and pathogen characteristics, hospital course, and antibiotic treatment patterns were described. All-cause mortality (ACM) at 14 and 30 days and clinical cure were examined as outcomes, overall, and by key characteristics such as pathogen susceptibility (determined at the local level), patient demographics, infection site, and severity of illness. Serious adverse drug reactions (SADR) were recorded.

Results
To date, 123 patients treated with CFDC at 12 sites were included. Sixty-five patients had PA as a pathogen, either alone (N=45) or in combination with another pathogen (N=20) attributed to starting CFDC. The median age was 54 years; 68% were male. The most prevalent comorbidity was diabetes with end stage organ damage (N=15, 23%). CFDC was given in an ICU setting in 54 (82%) patients. Vasopressors and mechanical ventilation were required in 42% and 62%, respectively. Most (91%) PA were carbapenem resistant. The median time from a positive culture to start of CFDC was 6 days. CFDC monotherapy was used in 75%. The most common GN antibiotic class used concurrently with CFDC was aminoglycosides (N=7). Targeted therapy with CFDC against pathogens of known susceptibility with or without prior GN antibiotics accounted for 80% of use. The remainder was used for salvage (15%) or empirically (2%). Susceptibility testing to CFDC, available for 54 cultures (54 patients), showed 94% (51/54) were susceptible. Post-CFDC initiation 14- and 30-day all-cause mortality (ACM) was 9% (95% CI: 3%-19%) and 23% (95% CI: 14%-35%) respectively. Clinical resolution was achieved in 66% (95% CI: 53% -77%). Thirty-day ACM for susceptible pathogens was 25% (13/51).
Cefiderocol Use Patterns in Pseudomonas aeruginosa

Conclusion
Real-world use of CFDC for PA demonstrated that most patients had multiple comorbidities and were severely ill. These data suggest that CFDC is being used appropriately with little empirical use in patients with few treatment options.

Disclosures
Stephen Marcella, MD, MPH, Shionogi: Shionogi employee|Shionogi, Inc: Employee Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board Sean Nguyen, n/a, Shionogi: Employee Anan Zhou, MPH, Shionogi, Inc: contracting work for Shionogi, Inc.