bluuebunny/crossref_metadata_2025 huggingface dataset:
188. Visualizing the Impact of a Wedding Leading to COVID-19 Outbreaks in Healthcare Settings, Washington State, July – August 2020
Authors: Brezak Audrey , Unutzer Anna , Lewis James W , Clark Shauna , Ferro Jessica , Bliesner Siri , Loughran Julie , Kawakami Vance , Deya Ruth , Makayoto Rhodah , Maier Em , Whitney Holly , Bevers Elyse , Templeton Allison A , Burlingham Bonnie , Lewis Larissa , Podczervinski Sara T
Published: December 2021

Background

Large social gatherings during the COVID-19 pandemic have been linked to extensive community transmission. Healthcare workers (HCW) that engage in these social gatherings pose a risk to the vulnerable patients they serve. Public Health—Seattle & King County identified a COVID-19 outbreak associated with a wedding in July 2020 when the 14-day incidence rate was 105 cases per 100,000 residents. HCW who attended the wedding were subsequently linked to 45 outbreaks in healthcare settings across three counties in the next month.

Methods

COVID-19 case interview data was used to identify HCW cases who reported the wedding as their exposure event. The Washington Disease Reporting System (WDRS), the state database in which COVID-19 cases and epi-linkages are tracked, was queried to identify healthcare outbreaks linked to the HCW wedding-attendee cases and the HCW that they infected. NodeXL was used to visualize the resulting chains of wedding-associated healthcare transmission using a Harel-Koren Fast Multiscale layout where the network visualization’s directed arrows represent putative links and direction of transmission. Numbers of associated settings, cases, and deaths were calculated.

Results

Seven HCW wedding attendees were linked to outbreaks in healthcare facilities that they worked at while infectious; HCWs linked to as many as six subsequent healthcare outbreaks. In total, the wedding was connected to 45 healthcare facilities: adult family homes (N=1), hospitals (N=1), supported living agencies (N=7) and associated group homes (N=38), assisted living (N=1), home health services (N=1), behavioral health (N=2), and rehab centers (N=1). Across the settings, 277 cases were identified, including 15 deaths.

Conclusion

A series of COVID-19 healthcare outbreaks was traced back to a wedding. Cases worked in multiple homes, agencies, and other healthcare settings which likely facilitated rapid and wide transmission; the structure of these healthcare settings often do not facilitate a single job providing enough hours and income to support an individual. In terms of public health learnings, addressing these outbreaks require effective contact tracing, multijurisdictional coordination, and for supported living, interventions need to be applied across households sharing staff.

Disclosures

All Authors: No reported disclosures
190. Epidemiology of COVID-19 Breakthrough Infections in Dallas County, Texas, 2021
Authors: Wada Suzanne , Wiegand Jared , Markarian Mary , Hung Victoria , Zhu Christina , Parayil Megin , Shim Kyoo , Serrano Jose , Chung Wendy
Published: December 2021

Background

From March 2020 through May 2021, Dallas County reported a total of 304,056 cases of COVID-19, including 4,073 deaths. During the month of December 2020, a post-holiday surge of cases led to peak daily average case rates of over 50 cases per 100,000. COVID-19 cases and deaths have since declined substantially following the rollout of COVID-19 vaccine delivery. As of June 8, 2021, about 1,831,588 Dallas County residents have received at least one COVID-19 vaccine dose and 910,067 are fully vaccinated. Recent county integration of immunization and case databases enabled identification and analysis of COVID-19 breakthrough infections.

Methods

A COVID-19 breakthrough infection was defined as a positive test (PCR or antigen) collected from an individual ≥ 14 days after receiving the full series of an FDA-authorized COVID-19 vaccine. Nationally, 10,262 vaccine breakthrough infections had been reported from 46 US states and territories, through April 2021. Vaccine breakthrough cases were reviewed and medical records abstracted to collect demographic information, clinical characteristics, and medical conditions. Data analysis was performed using R, version 4.0.2 (2020).

Results

Of the 700 vaccine breakthrough cases reported in Dallas County residents as of June 8, 2021, 304 (43%) were male and 396 (57%) female, with an average age of 53 years. The majority of the vaccine breakthrough cases were White (42%); 25% were Hispanic/Latino; and 20% were Black. Almost all breakthrough cases were confirmed with PCR testing, with 451 (64%) cases receiving the Pfizer vaccine. Of breakthrough cases, 49% were symptomatic; 52% (358) had underlying conditions including: tobacco use, obesity, or immunocompromised state; 68 (10%) were hospitalized; and 11 (1.6%) died. Whole genome sequencing was performed on 51 cases, with 14 (27.5%) variants identified, including: eight B.1.1.7, two B.1.429 and one P.1 variants.

Conclusion

Despite the high levels of vaccine efficacy documented in US vaccine trials, COVID-19 breakthrough infections, though currently uncommon, do occur and are important to investigate. Ongoing close public health surveillance of variants is needed to discern changes in patterns of vaccine efficacy and characteristics of populations at greatest risk of severe disease from COVID-19.

Disclosures

All Authors: No reported disclosures
192. Tolerability Outcomes of Multi-drug Antibiotic Treatment for Pulmonary Nontuberculous Mycobacterial Disease due to Mycobacterium avium Complex in U.S. Medicare Beneficiaries with Bronchiectasis
Authors: Ku Jennifer , Henkle Emily , Carlson Kathleen F , Marino Miguel , Brode Sarah K , Marras Theodore K , Winthrop Kevin L , Winthrop Kevin L
Published: December 2021

Background

Nontuberculous mycobacteria (NTM), most frequently Mycobacterium avium complex (MAC), cause increasingly common pulmonary infections. Treatment interruptions and early discontinuation are common in MAC therapy, but population-based data on treatment outcomes are severely lacking. We examined tolerability outcomes of guideline-based 3-drug therapies (GBT) targeted for pulmonary MAC infection.

Methods

Among beneficiaries with bronchiectasis (ICD-9-CM 494.0 or 494.1) in U.S. Medicare data (01/2006 – 12/2014), we identified first-time MAC GBT therapy users, excluding those with cystic fibrosis, HIV, or a history of organ transplant. MAC GBT was defined as an overlapping prescription of ≥ 28-day supply of a macrolide, ethambutol and rifamycin. Using Cox regression methods, we compared time-to-regimen change or discontinuation within 12 months of therapy start in the following groups: 1) azithromycin-ethambutol-rifamycin vs. clarithromycin-ethambutol-rifamycin; 2) macrolide-ethambutol-rifampin vs. macrolide-ethambutol-rifabutin; and 3) azithromycin-ethambutol-rifampin vs. clarithromycin-ethambutol-rifabutin.

Results

We identified 4,626 GBT therapy users (mean 77.9 years [s.d. 6.1], female [77.7%], and non-Hispanic white [87.2%]). Overall, the rate of regimen change or discontinuation was higher in the clarithromycin-based regimens compared to azithromycin-containing regimens, and in rifabutin-containing regimens compared to rifampin-containing regimens. The rate of drug regimen change or discontinuation was 65% greater in the clarithromycin-ethambutol-rifabutin group compared to the azithromycin-ethambutol-rifampin group (adjusted hazard ratio: 1.64, 95% CI: 1.43, 1.64) (Table 1, Figure 1).

Conclusion

Azithromycin-based regimens and rifampin-containing regimens were less likely to be changed or discontinued within 12 months of therapy compared to clarithromycin-based regimens and rifabutin-containing regimens, respectively. More research is needed to identify factors associated with early treatment change or discontinuation.

Disclosures

Emily Henkle, PhD, MPH, AN2 (Consultant, Advisor or Review Panel member)Zambon (Advisor or Review Panel member) Theodore K. Marras, MD, Astra Zeneca (Speaker’s Bureau)Insmed (Scientific Research Study Investigator)Novartis (Speaker’s Bureau)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Grant/Research Support)Paratek (Consultant)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Research Grant or Support)Paratek (Consultant)RedHill Biopharma (Consultant)Spero (Consultant)
195. Intravenous to Oral Antibiotics Versus Intravenous Antibiotics: A Step-Up or a Step-Down for Extended Spectrum Beta-Lactamase Producing Urinary Tract Infections?
Authors: Gamble Kelly C , Rose Dusten T , Sapozhnikov Julia
Published: December 2021

Background

The treatment of extended-spectrum beta-lactamase (ESBL)-producing urinary tract infections (UTI) may include either intravenous (IV) or oral (PO) antibiotics, according to the Infectious Diseases Society of America guidelines for resistant gram negative infections. The purpose of this study is to evaluate if PO step-down antibiotics, the switch group, compared to continued IV therapy in these UTIs affects clinical outcomes.

Methods

This multicenter retrospective cohort study was conducted in hospitalized patients with an ESBL-producing UTI between July 2016 and March 2020. The control group received a complete antibiotic course with a carbapenem. The switch group was transitioned to an oral agent within five days from initiation of a carbapenem. The primary endpoint was a composite all-cause clinical failure, which was defined as readmission or hospital mortality within 30 days of hospital discharge or a change in antibiotic during hospital admission. The secondary endpoints included individual components of the primary outcome, readmission indication, inpatient length of stay, direct antibiotic costs, and adverse events.

Results

The study included 153 patients: 95 and 58 patients in the control and switch groups, respectively. Demographics between the two groups were similar (Table 1). The mean ± SD duration of therapy was 8.7 ± 3.1 and 7.1 ± 3.3 days, respectively. Four oral agents were used for step-down therapy (Figure 1). The primary outcome occurred in 28% in both groups (27 vs 16 patients, p=0.91). The individual components of the primary outcome and readmission indication were also similar: readmission (93% vs 94%, p=0.95), readmission due to a recurrent UTI (33% vs 25%, p=0.73), hospital mortality (7% vs 6%, p=1.0), and change in antibiotic (0% vs 2%, p=0.38). The median (IQR) length of stay and direct antibiotic cost in the control and switch groups were 8 (6) vs 5 (2) days (p< 0.01) and &278 (&244) vs &180 (&104) (p< 0.01), respectively. Adverse events were similar in both groups except for diarrhea (15% vs 2%, p=0.01).

Table 1. Baseline Demographics. SD: standard deviation, ICU: intensive care unit, qSOFA: quick Sequential Organ Failure Assessment, ESBL: extended spectrum beta-lactamase, UTI: urinary tract infection

Figure 1. Oral Antibiotics. QD: once daily, BID: twice daily, Q2D: every 2 days, Q3D: every 3 days, DS tab: double strength tablet

Conclusion

There was no difference in clinical failure, readmission rate, mortality rate, or change in antibiotic between the control and switch groups; however, the switch group was associated with reduced hospital length of stay and direct antibiotic cost.

Disclosures

All Authors: No reported disclosures
201. Frequency of Pseudomonas aeruginosa (PA) Discrete Inner Colonies and Comparison of Minimal Inhibitory Concentration (MIC) Values between Parent and Inner Colony Isolates Following Fosfomycin Disk Diffusion (DD) Testing
Authors: Zheng Dina , Bixby Morgan L , Smith Elizabeth C , Anderson Jadyn C , Bergen Phillip J , Landersdorfer Cornelia B , Hirsch Elizabeth B
Published: December 2021

Background

Fosfomycin combination therapy is a potential approach for treatment of multidrug-resistant (MDR) PA infections despite a lack of approved susceptibility breakpoints for this organism. While DD testing is commonly used for fosfomycin, growth of discrete inner colonies (IC) within the zone of inhibition has been observed for multiple organisms following DD. Criteria recommended by CLSI and EUCAST are contradictory for interpreting these inner colonies. We therefore sought to determine the frequency of inner colonies and MIC differences between PA parent-inner colony pairs from an international isolate collection.

Methods

A convenience collection of 198 clinical PA isolates from three U.S institutions (n = 82), two Australian institutions (n = 72), and the CDC & FDA Antibiotic Resistance Isolate Bank (n = 44) were included. Fosfomycin MIC values were determined in duplicate on separate days by DD and broth microdilution (BMD) testing. For parent isolates with discrete IC observed during DD, IC isolates were subcultured and MIC values were determined and then compared to their corresponding parent isolates. MIC values were interpreted using CLSI Escherichia coli (EC) breakpoints (susceptible: MIC ≤ 64 μg/mL, intermediate: MIC = 128, resistant: MIC ≥ 256 μg/mL).

Results

Parent isolate BMD MIC values ranged from < 4 to > 256 μg/mL while IC isolate BMD MIC values ranged from 128 to > 1024 μg/mL. MIC50/90 values were 128/256 μg/mL and > 1024/ > 1024 μg/mL for the parent and IC isolates, respectively. A high frequency of 45% (89/198) of parent isolates displayed discrete IC which also demonstrated a higher frequency of resistance (97.8%) compared to the parent isolates (23.7%).

Conclusion

IC MIC values were higher overall compared to parent MIC values, with an average fold difference of ~18 between the parent-inner colony pairs. The frequency of IC found in this study (45%) is considerably higher than previously observed in EC clinical isolates. These data highlight the need to further investigate the importance of these IC and warrant caution for extrapolation of EC breakpoints for fosfomycin susceptibility testing against PA.

Disclosures

All Authors: No reported disclosures
203. Activity of Cefepime in Combination with Taniborbactam (formerly VNRX-5133) Against Pseudomonas aeruginosa from a Global 2018-2020 Surveillance Collection
Authors: Hackel Meredith , Wise Mark G G , Sahm Daniel F
Published: December 2021

Background

Taniborbactam is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor (BLI) with potent and selective inhibitory activity against both serine- and metallo-β-lactamases (MBLs). Taniborbactam restores the activity of cefepime (FEP) against many multidrug resistant organisms, including cephalosporin- and carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa (PA). We evaluated the in vitro activity of the investigational combination cefepime-taniborbactam and comparators against clinical isolates of PA collected during a 2018-2020 surveillance.

Methods

MICs of FEP with taniborbactam fixed at 4 µg/mL (FTB) and comparators were determined against 3,219 PA collected from 221 sites in 52 countries in 2018-2020. Resistant phenotypes were based on 2021 CLSI breakpoints. Acquired β-lactamase (BL) genes were identified via PCR/Sanger sequencing or whole-genome sequencing (WGS) for 516 isolates with meropenem (MEM) MIC ≥8 µg/mL, and for 94 randomly selected isolates with FEP or ceftazidime MIC ≥16 µg/mL. 186 isolates with FTB MIC ≥16 µg/mL, 16 with FTB MIC=8 µg/mL and one with FTB MIC=4 µg/mL were subjected to WGS.

Results

Overall, 28.7%, 26.2% and 20.3% of PA isolates were nonsusceptible (NS) to piperacillin-tazobactam (TZP), MEM or FEP, respectively (Table). FTB demonstrated potent activity (MIC50/90, 2/8 µg/mL; 94.2% inhibited at ≤8 µg/mL) against PA overall and inhibited between 63.4% (ceftazidime-avibactam [CZA] NS) and 82.1% (TZP NS) of isolates in the NS subsets compared to 0% to 69.1% S for comparators. Against the 111 strains carrying VIM or NDM MBL genes, 67.6% had FTB MICs ≤8 µg/mL, with 11.7% having FTB MICs of 16 µg/mL. Plausible explanations for elevated FTB MICs included IMP MBL genes, penicillin binding protein 3 variations, and/or possible efflux pump up-regulation.

Conclusion

FTB demonstrated potent in vitro activity against PA with different resistance profiles, including NS to FEP, MEM, and TZP, and to the BL/BLI combinations CZA, ceftolozane-tazobactam, and meropenem-vaborbactam. FTB was the most active agent tested against PA harboring VIM and NDM MBLs. These findings support the continued development of FTB as a potential new treatment option for challenging infections due to MDR PA.

Disclosures

Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Mark G G. Wise, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
02. Beyond B Antigen Coverage: The Potential of the 4CMenB Vaccine for Cross-protection Against Pathogenic Neisseria Infections
Authors: Garcia Yara Ruiz , Sohn Woo-Yun , Pizza Mariagrazia , Bekkat-Berkani Rafik
Published: December 2021

Background

Two human pathogenic Neisseria species exist: N. meningitidis (Nm) and N. gonorrhoeae (Ng). Although causing disparate clinical syndromes, invasive meningococcal disease (IMD) and gonorrhea, they are genetically similar and share key protein antigens. The 4CMenB vaccine, licensed against meningococcal B disease, comprises 4 antigenic components (factor H binding protein (fHbp), variant 1.1, subfamily B; Neisseria heparin binding antigen (NHBA) peptide 2; Neisserial adhesin A (NadA) variant 3; and Porin A (PorA) P1.4), and potentially protects against non-B invasive meningococcal and gonococcal strains. In this review, we summarize the similarities between these antigens and those in Nm serogroups A, C, W, X and Y and Ng.

Methods

Published data in humans were analyzed to conduct a narrative literature review of the potential extent of meningococcal vaccine-induced protection against non-B meningococcal strains and Ng. Techniques applied to indirectly measure this effect are based on genotype-phenotype modelling, strain coverage, bactericidal killing and direct impact on disease reduction.

Results

Data were identified from countries in America, Europe, Africa and Oceania. The genes encoding for fHbp and NHBA are also present in strains belonging to the five non-B serogroups, while NadA is present in several strains of serogroups C, W and Y, and PorA P1.4 mainly in serogroup W. At the genome level, Ng and Nm share up to 90% homology. Most of the outer membrane vesicle antigens, like PilQ, Omp85 (BamA), NspA, MtrE, MetQ, LbpA, PorB, FetA, OpcA and NHBA, are highly conserved in Ng. In addition, a synergistic effect might enhance immunogenicity against non-B serogroups as shown against serogroup B.

Conclusion

4CMenB components are present and conserved in several Ng and Nm strains. Recent results demonstrate that 4CMenB reduces MenW disease incidence in infants and might generate cross-protection against other non-B serogroups. In addition, 4CMenB has been proven to be effective in reducing gonococcal infections in adolescents. Research on future genomic and proteomic characterizations of IMD and gonorrhea strains will provide information on the molecular basis of the underlying broad strain coverage, while informing decisions regarding prevention and immunization programmes.

Disclosures

Yara Ruiz Garcia, MSc, PhD, GSK group of companies (Employee) Woo-Yun Sohn, MD, GSK group of companies (Employee, Shareholder) Mariagrazia Pizza, Biological Sciences, PhD, GSK group of companies (Employee, Shareholder) Rafik Bekkat-Berkani, M.D, GSK group of companies (Employee, Shareholder)
03. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster Dose in Adults and Adolescents Vaccinated Against Meningococcal Disease 3 - 6 Years Earlier
Authors: Peterson James , Deseda Carmen , Julien Katie , Zambrano Betzana , Áñez Germán , Jiayuan Sue , Pan Judy , Arroum Habiba , Varghese Kucku , Jordanov Emilia , Dhingra Mandeep S
Published: December 2021

Background

Booster doses of meningococcal conjugate vaccines may induce long-term protection against invasive meningococcal disease. MenACYW-TT [MenQuadfi®] is a quadrivalent meningococcal conjugate vaccine, licensed for use in ages 2 years and older in USA. The vaccine is also licensed in ages 12 months and older in EU and other countries.

Methods

A phase IIIb study (NCT04084769) was conducted to evaluate the persistence of immune response in adults and adolescents primed 3-6 years earlier with either MenACYW-TT or MCV4-CRM (Menveo®) and, safety and immunogenicity of MenACYW-TT when administered as a booster dose with or without concomitant administration with MenB vaccines (Bexsero® and Trumenba®). Serum bactericidal assays with human complement (hSBA) and baby rabbit complement (rSBA) were used to measure antibodies against vaccine serogroups at baseline (Day 0 [D0]), D06 (in a subset) and 30 days post-vaccination (D30). Safety data were collected up to 6 months post-vaccination.

Results

At D0, the GMTs were higher in subjects primed with MenACYW-TT vs MCV4-CRM for serogroups C, Y and W, and were comparable for serogroup A. At D0, all hSBA GMTs were higher than those observed pre-priming dose, suggesting persistence of immunity. Sufficiency of hSBA seroresponse ( >75%) was demonstrated following administration of MenACYW-TT booster dose regardless of the priming vaccine administered 3-6 years earlier. Vaccine seroresponse in a subset of participants at D06 ranged from 77.8% (95%CI 62.9%; 88.8%) for serogroup A to 97.8% (88.5%; 99.9%) for serogroup W suggesting a quick onset of immune response post-booster. Post-vaccination (D30) hSBA GMTs were comparable for serogroups A, Y and W regardless of the nature of the priming vaccine and were higher for serogroup C in subjects primed with MenACYW-TT vaccine. The MenACYW-TT booster dose was well-tolerated and had similar safety profiles regardless of the priming vaccine. The safety profiles were comparable regardless of the MenB vaccine co-administered with MenACYW-TT vaccine.

Conclusion

MenACYW-TT used as priming vaccine was able to demonstrate persistence of immune response 3-6 years later. MenACYW-TT elicits robust booster responses in adults and adolescents primed with MenACYW-TT or MCV4-CRM

Disclosures

Betzana Zambrano, MD, Sanofi Pasteur (Employee) Germán Áñez, MD, Sanofi Pasteur (Other Financial or Material Support, Former employee) Sue Jiayuan, MSc, Sanofi Pasteur (Independent Contractor) Judy Pan, PhD, Sanofi Pasteur (Employee) Habiba Arroum, MD, Sanofi Pasteur (Employee) Kucku Varghese, PhD, Sanofi Pasteur (Employee) Emilia Jordanov, MD, Sanofi Pasteur (Employee, Shareholder) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee, Shareholder)
05. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Updates from Year 3 of Multi-Site Trial
Authors: Burgess Timothy , Richard Stephanie A , Collins Limone , Colombo Rhonda E , Ganesan Anuradha , Geaney Casey , Hrncir David , Lalani Tahaniyat , Markelz Ana E , Maves Ryan C , Maves Ryan C , McClenathan Bruce , Mende Katrin , Modi Jitu , Montgomery Jay R , Schofield Christina , Seshadri Srihari , Skerrett Catherine , Spooner Christina , Utz Gregory , Warkentien Tyler , Williams Alan , Coles Christian L
Published: December 2021

Background

The SARS-CoV-2 pandemic has spotlighted respiratory infections and the value of effective vaccines. The SARS-CoV-2 vaccine has been remarkably effective; however, influenza vaccine effectiveness has been reported to be lower among active duty military populations than in the general public (18% vs 36%). The Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study compares 3 FDA-licensed influenza vaccine types (egg-based, cell-based, and recombinant) to assess differences in immunogenicity and effectiveness in adults.

Methods

Participants in the 3rd year of PAIVED (2020/21 influenza season) were enrolled from October 2020 through January 2021. Participants received weekly surveys about influenza-like-illnesses (ILI) experienced in the past week; if they reported an ILI, they were queried about symptom duration and severity, and asked to self-collect a nasal swab and dried blood sample. Four weeks later, more information about symptom duration and illness burden was obtained via telephone interview, and the participant collected a second blood sample.

Results

PAIVED year 3 enrolled 3,269 participants (Table 1). 278 participants reported 1 ILI , while 60 reported 2 ILIs, and 18 reported 3 ILIs. No pathogen was identified for most processed ILI samples (78%); the most common viruses were SARS-CoV-2 (25, 12%), rhinovirus (24, 12%), and seasonal coronaviruses (4, 2%). No influenza has been identified thus far. Among those participants who had convalescent ILI visits (275), the median duration of the reported ILIs was 9 days (IQR 5, 15), with a median of 4 days (IQR 2, 7) of limited activity, and 2 days (IQR 0, 3) with fever. Three individuals were hospitalized.

Conclusion

There have been relatively low rates of ILI identified in this study during this season, with only 11% of the participants reporting an ILI so far, consistent with low rates of non-COVID-19 ILI reported elsewhere during the current pandemic. We anticipate some influenza cases may be identified as more samples are processed. Planned analyses include calculating comparative influenza vaccine effectiveness to inform future vaccine purchasing decisions, as well as comparing serological response to the different vaccines.

Disclosures

Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Jitu Modi, MD, GSK (Speaker’s Bureau)
06. United States Healthcare Provider Preferences for Adult Pneumococcal Vaccine Recommendations
Authors: Vietri Jeffrey , Meyers Kelley , Poulos Christine , Chilson Erica , Sweeney Carolyn , Davis Kimberly , Snow Vincenza
Published: December 2021

Background

Pneumococcal vaccine recommendations for US adults are complex, varying by age and underlying conditions, and include both 23-valent polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine. The Advisory Committee on Immunization Practices (ACIP) will vote on new recommendations in October after the 15- (PCV15) and 20-valent (PCV20) conjugate vaccines are approved. Stakeholder acceptability is part of ACIP’s evidence to recommendation framework, but few data are available on health care providers’ (HCPs) preferences for potential recommendations.

Methods

752 HCPs (300 physicians, 150 nurse practitioners, 150 physician assistants, & 152 pharmacists) were surveyed. Object case best-worst scaling (BWS) was used to elicit preferences for hypothetical recommendations for 1) adults 19-64 years with chronic conditions and 2) immunocompetent adults ≥65 years. Presented recommendations included combinations of PCV15/PCV20 either as routine or after shared clinical decision making (SCDM), and PPSV23 as routine, SCDM, or no recommendation. Following BWS, HCPs were asked to assume ACIP was considering implementing both of their preferred recommendations for the age/risk groups. HCPs were then given the opportunity to change their selections and propose recommendations not included in the BWS exercise. Additional information was collected using conventional survey items.

Results

Routine use of higher-valent PCVs in sequence with PPSV23 was most often preferred for both adults 19-64 with chronic conditions (40%) and immunocompetent adults ≥65 (49%) when elicited separately for each age/risk group. Most respondents (63%) revised their recommendations after considering implementation, which resulted in most (59%) favoring recommendations harmonized across the age/risk groups, and 75% favoring routine use of PCV15 or PCV20 among immunocompetent adults ≥65. When asked directly, HCPs generally approved of the idea of simplifying adult pneumococcal vaccine recommendations, harmonizing the interval between vaccines, and lowering the cutoff for age-based recommendations below 65 years.

Conclusion

US HCPs generally prefer simplification of the adult pneumococcal recommendation, favoring broad routine use of both higher-valent PCVs and PPSV23.

Disclosures

Jeffrey Vietri, PhD, Pfizer Inc (Employee, Shareholder) Kelley Meyers, PhD, RTI Health Solutions (Independent Contractor) Christine Poulos, PhD, Pfizer Inc (Other Financial or Material Support, Employee of RTI-HS, which received funds from Pfizer to conduct the study) Erica Chilson, PharmD, Pfizer, Inc (Employee, Shareholder) Vincenza Snow, MD, Pfizer Vaccines (Employee)
07. Recombinant Zoster Vaccine (RZV) Second-Dose Completion in Adults Age 50‒64 Years in the United States
Authors: Leung Jessica , Gray Elizabeth B , Anderson Tara , Sharkey Sarah M , Dooling Kathleen L
Published: December 2021

Background

In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV, Shingrix) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥50 years, with the 2nd dose recommended 2–6 months after the 1st dose. Among Medicare beneficiaries, 2-dose series completion 6 months and 12 months post initiation was 78% and 86%, respectively. Here we estimate the proportion of adults age 50–64 years who completed the 2-dose RZV series within 6 or 12 months after receiving their 1st dose, by using two administrative claims databases.

Methods

We used medical and pharmaceutical claims data from October 2017‒March 2020 IQVIA® PharMetrics Plus and October 2017‒October 2020 IBM® MarketScan® databases. RZV vaccination was defined using Current Procedural Terminology and National Drug Codes. We allowed for sufficient follow-up time by examining 1st doses given at least 6 or 12 months prior to the end of the study period in both databases. Place of administration was available in IQVIA data.

Results

Among persons age 50‒64 years, in IQVIA and MarketScan, 70% and 68% received their 2nd RZV dose within 6 months, respectively, and 79% and 81% received their 2nd dose within 12 months, respectively. The median age of 1st dose of RZV vaccination was 60 years and ~60% were female [Table 1]. When the 2nd dose was administered within 12 months, the median interval between 1st and 2nd doses was 104 and 98 days in the IQVIA and MarketScan databases, respectively. Characteristics by age, sex, or region were similar in persons who received 1 RZV dose vs. 2 RZV doses [Table 1]. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 55% of vaccinations occurred at ambulatory medical provider offices and 40% at pharmacies; among 2 doses recipients, 33% of vaccinations occurred at provider offices and 62% at pharmacies.

Conclusion

Among 50‒64-year-olds, 2-dose RZV series completion was ~70% within 6 months and 80% within 12 months of initiation. The findings were similar across two administrative claims databases. Availability of RZV at pharmacies has potentially helped to increase RZV 2nd dose completion rates.

Disclosures

All Authors: No reported disclosures
11. People Living with HIV During the COVID-19 Pandemic: Who Did (or Did Not) Receive Annual Influenza Vaccination?
Authors: Kahal Deborah A , Wharton Brian , James Christopher , Caplan Richard , Arlene Bincsik K
Published: December 2021

Background

Nationally, younger adults and racial minorities have lower levels of influenza vaccination (influenza vaccination = vaccine) than non-Hispanic White adults. During the 2015-16 season, most vaccine decliners in our program were male, black, and 45-66 years of age. As part of a quality improvement (QI) initiative to increase 2020-21 vaccine coverage amongst PLWH, we sought to compare patient characteristics between vaccine recipients and non-recipients.

Methods

Our program cares for 60% of Delawareans with HIV. The largest site in Wilmington was the QI site. IRB exemption was received, and pre-defined sociodemographic and HIV-specific variables were extracted from the EMR and CareWare from 1 Oct 2020 through 31 March 2021. Patient reports of external vaccine required confirmation. All PLWH ≥ 18 years of age, including those newly establishing care, met eligibility criteria. Comparisons between vaccinated and unvaccinated PLWH were performed using Wilcoxon rank sum tests for continuous variables and chi-squared tests for categorical variables. A multivariable logistic regression model, including age, sex, race, insurance, poverty level, HIV status, and virologic suppression, was used to predict vaccine.

Results

780 patients met study inclusion criteria and 86% (667/780) received vaccine. Characteristics of PLWH with and without vaccine are presented in Table 1. Older age, lower HIV viral load, and virologic suppression had a statistically significant (p< 0.05) association with vaccine receipt in unadjusted analysis. Only older age (p< 0.01) was significantly associated with vaccine in logistic regression modeling (Table 2), however this relationship was non-linear.

Table 1. Characteristics of patients living with HIV during the 2020-2021 Influenza vaccination season

Table 2. Multivariable Analysis of Baseline Characteristics

Conclusion

A very high rate of PLWH received vaccine, far exceeding local and national benchmarks, with EMR data unlikely to have fully captured all vaccines. The role of the COVID-19 pandemic in vaccine amongst PLWH is not yet known. While older age was associated with vaccine in adjusted analysis, the number of unvaccinated patients was small, confidence intervals wide, and associations consequently weak. Larger studies are needed to further investigate factors associated with vaccine receipt amongst PLWH.

Disclosures

Deborah A. Kahal, MD,MPH, FACP, Gilead (Speaker’s Bureau)Viiv (Speaker’s Bureau)
12. Modeled Impact of the COVID-19 Pandemic and Associated Reduced Adult Vaccinations on Herpes Zoster in the United States
Authors: La Elizabeth M , Curran Desmond , Salem Ahmed , Singer David , Lecrenier Nicolas , Poston Sara
Published: December 2021

Background

During the COVID-19 pandemic, adult vaccination in the United States (US) decreased substantially in 2020. Unlike other vaccine-preventable diseases where individuals may have experienced reduced risk due to COVID-related mitigation efforts (e.g., lockdown restrictions, use of face masks), individuals remained at risk of herpes zoster (HZ). This study projects the impact of reduced recombinant zoster vaccine (RZV) use on HZ cases and complications in the US.

Methods

A multi-cohort Markov model estimated the impact of missed RZV vaccinations, by comparing scenarios with and without missed vaccinations between Apr-Dec 2020, on cases of HZ, postherpetic neuralgia (PHN), and quality-adjusted life-years (QALYs) among US adults aged ≥ 50 years. Epidemiology, RZV efficacy, and utility inputs were obtained from standard US sources, clinical trial data, and published literature. Missed doses were estimated using data on RZV doses and an assumed 43% reduction in RZV vaccinations during the pandemic, based on publicly available data. Deterministic sensitivity and scenario analyses were conducted.

Results

In 2020, approximately 21 million (M) RZV distributed doses were expected, including an estimated 9.2M RZV series initiations in Apr-Dec. An estimated 3.9M RZV series initiations were missed, resulting in 31,945 projected HZ cases, 2,714 PHN cases, and 610 lost QALYs projected over a 1-year follow up. If individuals with missed RZV initiations remain unvaccinated in 2021, avoidable HZ cases will increase to 63,117 over 2 years. Further, if the same number of RZV initiations are missed in 2021, 95,062 avoidable HZ cases are expected. In a sensitivity analysis assuming 30% RZV reduction, 18,020 avoidable HZ cases and 1,531 PHN cases were observed over 1 year.

Conclusion

Adding to the substantial COVID-19 infection-related morbidity and mortality, reduced RZV use during the pandemic resulted in further burden from avoidable HZ cases. Health care providers should continue to emphasize the importance of vaccination against HZ and other preventable diseases during the pandemic.

Funding

GlaxoSmithKline Biologicals SA (GSK study identifier: [VEO-000222]).

Acknowledgement

Business & Decision Life Sciences c/o GSK (Coordination: Quentin Rayée).

Disclosures

Elizabeth M. La, PhD, The GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder) Ahmed Salem, MSc, The GSK group of companies (Employee) David Singer, PharmD, MS, The GSK group of companies (Employee) Nicolas Lecrenier, Ing, PhD, The GSK group of companies (Employee, Shareholder) Sara Poston, PharmD, The GSK group of companies (Employee, Shareholder)
13. The Efficacy and Effectiveness of Pneumococcal Vaccines against Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis
Authors: Childs Lana , Kobayashi Miwako , Farrar Jennifer Loo , Pilishvili Tamara
Published: December 2021

Background

Two pneumococcal vaccines are currently recommended for use in U.S. adults: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Recommendations for adult PCV13 use were supported by a large randomized-controlled trial (RCT) demonstrating PCV13 efficacy against pneumococcal pneumonia (PnPn) and vaccine-type (VT) PnPn in older adults. New pneumococcal conjugate vaccines are expected to be licensed for adults in late 2021 and recommendations for use among adults will be reviewed and revised, as needed. We conducted a systematic review to summarize evidence on the vaccine efficacy and effectiveness (VE) of PPSV23 and PCV13 against PnPn among adults.

Methods

We conducted a search of literature published from 1998 to February 2021 on PCV13 and PPSV23 VE studies using eight reference databases. Studies targeting adults with immunocompromising conditions were excluded. VE results with 95% confidence intervals (CI) were abstracted and stratified by vaccine product, outcome evaluated (PnPn and VT PnPn), study design, and effect measure. When applicable, random effects models were used to estimate pooled VE and I-squared statistic was reported to assess heterogeneity.

Results

Of 3,422 screened studies, we included 15 studies: three on PCV13 and 12 on PPSV23 (Table 1). In addition to the RCT, we identified two observational studies for PCV13 (Table 1); however, pooled VE of the observational studies was not estimated due to differences in methods for reporting results. Pooled PPSV23 VE against PnPn from two RCTs was 63% (95% CI: 31, 80 I2=0%). Pooled VE of PPSV23 against VT PnPn from three observational studies was 18% (95% CI: -35, 35 I2=38%). PPSV23 effectiveness against PnPn was limited with a pooled VE of 25% (95% CI: 7, 39 I2=78%) from nine observational studies.

Conclusion

Findings from observational studies supported PCV13 VE against VT PnPn reported in the RCT. Differences in the study design made the magnitude of PPSV23 effectiveness against PnPn and VT PnPn difficult to assess; however, findings from recent observational studies suggest PPSV23 provides limited protection against VT PnPn.

Disclosures

All Authors: No reported disclosures
14. Postmarketing Safety Experience With MenACWY-TT
Authors: Serra Lidia , Mather Susan , Burman Cindy , Webber Chris
Published: December 2021

Background

MenACWY-TT (Nimenrix®), a quadrivalent meningococcal tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in 82 countries but not in the United States. MenACWY-TT is administered in infants as a 2 + 1 (6 weeks to < 6 months of age) or 1 + 1 (6 to < 12 months of age) schedule with the booster dose at 12 months of age, and from 12 months of age as a single dose. In addition to its widespread use to protect against meningococcal serogroups A, C, W, and Y, MenACWY-TT is a constituent of an investigational pentavalent meningococcal (MenABCWY) vaccine currently undergoing clinical development.

Methods

Using the MenACWY-TT Periodic Safety Update Report (PSUR) with format and content in accordance with Good Pharmacovigilance Practice Module VII and International Council for Harmonisation Guideline E2C, for data up to April 19, 2020, postmarketing safety experience with MenACWY-TT is considered. The PSUR data included herein are spontaneous adverse events (AEs) from the Pfizer safety database. AEs were coded by system organ class (SOC) and preferred term (PT) using MedDRA v.22.1J.

Results

The cumulative estimated exposure of MenACWY-TT was nearly 26 million doses, with the majority administered in 0- to 16-year-olds and in the Western European Union (Figure 1). Over the reporting period, 13,301 cumulative AEs occurred. The most common SOCs in the reporting period were general disorders and administration site conditions (n=5169; 39%); nervous system disorders (n=1986; 15%); injury, poisoning and procedural complications (n=1266; 10%); and gastrointestinal disorders (n=1031; 8%) (Figure 2). By PT, the most common AEs were pyrexia (n=1613; 12%), headache (n=738; 6%), and vaccination site pain (n=394; 3%) (Figure 3). Of the 3299 serious AEs reported, the most common were pyrexia (n=317; 10%) and headache (n=209; 6%).

Conclusion

Based on cumulative safety data in conjunction with existing efficacy and effectiveness data, the benefit-risk profile of MenACWY-TT remains favorable and is consistent with the safety profile of MenACWY-TT established in clinical studies.

Disclosures

Lidia Serra, MS, Pfizer Inc (Employee, Shareholder) Susan Mather, MD, Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Chris Webber, MD, Pfizer (Employee, Shareholder)
16. An Ambulatory Quality Improvement Initiative to Optimize Influenza Vaccination Amongst Adults Living with HIV During the COVID-19 Pandemic
Authors: Kahal Deborah A , James Christopher , Wharton Brian , Eaddy Sherine , Gaines Elizabeth , Henry Karen , Juarez Luis , Arlene Bincsik K
Published: December 2021

Background

Seasonal influenza vaccination decreases individual and population-level morbidity and mortality, mitigates risk of acquiring influenza-like illness, and prevents healthcare system overburdening. Vaccination is important for people living with HIV (PLWH) who have increased risk for severe disease, hospitalization, and poor outcomes. Moreover, influenza vaccination has been associated with decreased COVID-19 mortality in older patients. Historical annual adult influenza vaccinations rates at the study site were 65%, exceeding local and national benchmarks. Amidst COVID-19, we recognized a need to increase influenza vaccination rates.

Methods

A multifaceted, bundled quality improvement (QI) initiative aimed to achieve ≥ 80% influenza vaccination coverage for the 2020-21 season in PLWH ≥18 years of age at our Wilmington site (N=750). Stakeholders were identified, and a voluntary multidisciplinary team formed to lead the initiative (Fig. 1). Fishbone diagram outlined clear, rapidly implementable, and reproducible levers for change (Fig. 2). Physical and virtual space changes included: diverse clinical displays (visuals, patient materials), phone messaging, and virtual platform use. Staff education and updates were consistently provided by the team. Institutional Review Board exemption was received, and electronic medical record and CareWare data were extracted from 1 Oct 2020 through 31 March 2021. All external vaccinations were confirmed. Overall and eligible in-clinic vaccination rates were updated and displayed weekly.

Results

86% vaccination coverage was achieved (Fig. 3) with a median weekly in-clinic vaccination rate of 67% (Fig. 4).

Conclusion

A QI project to improve 2020-21 influenza vaccination rates exceeded our goal in adult PLWH at an urban mid-Atlantic HIV clinic during the COVID-19 pandemic. A multidisciplinary approach that engaged stakeholders was vital to success. Rapid roll-out of changes was challenging, requiring flexibility and clear communication. Data collection was consistent, albeit imperfect, and needs enhancement. Elucidating the effects of each change and the COVID-19 pandemic on vaccination rates is not yet known. Lessons learned may be applicable to other ambulatory settings and will inform future vaccination efforts.

Disclosures

Deborah A. Kahal, MD,MPH, FACP, Gilead (Speaker’s Bureau)Viiv (Speaker’s Bureau)
17. A Retrospective Cohort Study of Influenza Infected Multiple Myeloma Patients Comparing Clinical Outcomes Between Vaccinated and Unvaccinated
Authors: Wilson Taylor D , Leffert Jacob , Crescencio Juan Carlos Rico , Jenkins Mitchell , Burgess Mary J
Published: December 2021

Background

The current standard of care for multiple myeloma (MM) patients is to administer the influenza vaccine (InfV) annually. While in immunocompetent patients, the influenza vaccine is associated with significant benefit in morbidity and mortality, the inherent immunodeficiency from MM and its treatments reduce the InfV efficacy but it is thought to have some benefit. The effect on morbidity and mortality in MM patients has not been evaluated. Our study aims to investigate whether InfV vaccination status affects outcomes of MM patients diagnosed with Influenza A or B (FluA, FluB).

Methods

This was a retrospective study, using Arkansas Clinical Data Repository, which identified all MM patients diagnosed with FluA or FluB during five consecutive flu seasons from September 1st to April 30th, 2015-2020. Those with hospital-acquired influenza were excluded. The outcome data were collected for 30 days following the initial diagnosis. Fisher Exact test was used to compare categorical variables, and Mann Whitney U test to compare continuous variables.

Results

We identified 194 MM patients diagnosed with FluA or FluB. Sixty-five (34%) were vaccinated and 129 (66%) were not vaccinated. A total of 87 (45%) were admitted to the hospital. Twenty-five (38%) of the vaccinated vs. 62 (48%) of the unvaccinated group were hospitalized (p=0.22), and 4/65 vaccinated vs. 12/129 unvaccinated required ICU treatment (p=0.59). Two patients in the vaccinated and 3 in the non-vaccinated group were intubated (p=1). The mean length of stay (LOS) for the vaccinated and unvaccinated was 10 days and 14 days, respectively, which was not significantly different (p=0.197). Two (3%) patients died within 30 days of diagnosis in the vaccinated group while four (3%) died in the unvaccinated group (p=1).

Conclusion

The InfV status of MM patients had no effect on outcomes including the need for hospital admission, ICU stay, mechanical ventilation, LOS, and death. Hospitalization was common, but severe illness requiring ICU care and intubation were less common. Six patients died within 30 days of influenza diagnosis. Vaccination strategy, including high-dose and repeat doses, should be examined in MM patients.

Disclosures

All Authors: No reported disclosures