Outpatient visits and antibiotic use due to higher valency pneumococcal vaccine serotypes.

BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national healthcare surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. PCV15/20-additional serotypes account for 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials.

Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.

Length of antibiotic therapy among adults hospitalized with uncomplicated community-acquired pneumonia, 2013-2020.

OBJECTIVE: The 2014 US National Strategy for Combating Antibiotic-Resistant Bacteria (CARB) aimed to reduce inappropriate inpatient antibiotic use by 20% for monitored conditions, such as community-acquired pneumonia (CAP), by 2020. We evaluated annual trends in length of therapy (LOT) in adults hospitalized with uncomplicated CAP from 2013 through 2020. METHODS: We conducted a retrospective cohort study among adults with a primary diagnosis of bacterial or unspecified pneumonia using International Classification of Diseases Ninth and Tenth Revision codes in MarketScan and the Centers for Medicare & Medicaid Services databases. We included patients with length of stay (LOS) of 2-10 days, discharged home with self-care, and not rehospitalized in the 3 days following discharge. We estimated inpatient LOT based on LOS from the PINC AI Healthcare Database. The total LOT was calculated by summing estimated inpatient LOT and actual postdischarge LOT. We examined trends from 2013 to 2020 in patients with total LOT >7 days, which was considered an indicator of likely excessive LOT. RESULTS: There were 44,976 and 400,928 uncomplicated CAP hospitalizations among patients aged 18-64 years and ≥65 years, respectively. From 2013 to 2020, the proportion of patients with total LOT >7 days decreased by 25% (68% to 51%) among patients aged 18-64 years and by 27% (68%-50%) among patients aged ≥65 years. CONCLUSIONS: Although likely excessive LOT for uncomplicated CAP patients decreased since 2013, the proportion of patients treated with LOT >7 days still exceeded 50% in 2020. Antibiotic stewardship programs should continue to pursue interventions to reduce likely excessive LOT for common infections.

Antibiotic Stewardship in Outpatient Telemedicine: Adapting Centers for Disease Control and Prevention Core Elements to Optimize Antibiotic Use.

The rapid expansion of telemedicine has highlighted challenges and opportunities to improve antibiotic use and effectively adapt antibiotic stewardship best practices to outpatient telemedicine settings. Antibiotic stewardship integration into telemedicine is essential to optimize antibiotic prescribing for patients and ensure health care quality. We performed a narrative review of published literature on antibiotic prescribing and stewardship in outpatient telemedicine to inform the adaptation of the Core Elements of Outpatient Antibiotic Stewardship framework to outpatient telemedicine settings. Our narrative review suggests that in-person antibiotic stewardship interventions can be adapted to outpatient telemedicine settings. We present considerations for applying the Core Elements of Outpatient Antibiotic Stewardship to outpatient telemedicine which builds upon growing evidence describing care delivery and quality improvement in this setting. Additional applied implementation research is necessary to inform the application of effective, sustainable, and equitable antibiotic stewardship interventions across the spectrum of outpatient telemedicine.

Impact of the COVID-19 Pandemic on Inpatient Antibiotic Use in the United States, January 2019 Through July 2022.

Antimicrobial use data reported to the National Healthcare Safety Network's Antimicrobial Use and Resistance Module between January 2019 and July 2022 were analyzed to assess the impact of the COVID-19 pandemic on inpatient antimicrobial use.

Antibiotic Use Among Hospitalized Patients With COVID-19 in the United States, March 2020-June 2022.

We conducted a retrospective study to describe antibiotic use among US adults hospitalized with a COVID-19 diagnosis. Despite a decrease in overall antibiotic use, most patients hospitalized with COVID-19 received antibiotics on admission (88.1%) regardless of critical care status, highlighting that more efforts are needed to optimize antibiotic therapy.

Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.

BACKGROUND: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development. METHODS: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture. RESULTS: Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males. CONCLUSIONS: The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process. CLINICAL TRIALS REGISTRATION: NCT01868464 (ClinicalTrials.gov).

Pediatric outpatient visits and antibiotic use attributable to higher valency pneumococcal conjugate vaccine serotypes.

Importance: Streptococcus pneumoniae is a known etiology of acute respiratory infections (ARIs), which account for large proportions of outpatient visits and antibiotic use in children. In 2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15, PCV20) were recommended for routine use in infants. However, the burden of outpatient healthcare utilization among U.S. children attributable to the additional, non-PCV13 serotypes in PCV15/20 is unknown. Objective: To estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional serotypes (non-PCV13 serotypes) to quantify potential impacts of PCV15/20 on outpatient visits and antibiotic prescriptions for these conditions. Design: Multi-component study including descriptive analyses of cross-sectional and cohort data on outpatient visits and antibiotic prescriptions from 2016-2019 and meta-analyses of pneumococcal serotype distribution in non-invasive respiratory infections. Setting: Outpatient visits and antibiotic prescriptions among U.S. children. Participants: Pediatric visits and antibiotic prescriptions among children captured in the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medicare Care Survey (NHAMCS), and Merative MarketScan, collectively representing healthcare delivery across all outpatient settings. Incidence denominators estimated using census (NAMCS/NHAMCS) and enrollment (MarketScan) data. Main outcomes and measures: Pediatric outpatient visit and antibiotic prescription incidence for acute otitis media, pneumonia, and sinusitis associated with PCV15/20-additional serotypes. Results: We estimated that per 1000 children annually, PCV15-additional serotypes accounted for 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. Projected to national counts, PCV15/20-additional serotypes account for 173,000 (118,000-252,000) and 968,000 (722,000-1,318,000) antibiotic prescriptions among U.S. children each year, translating to 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of all outpatient antibiotic use among children. Conclusions and relevance: PCV15/20-additional serotypes account for a large burden of pediatric outpatient healthcare utilization. Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. These higher-valency PCVs, especially PCV20, may contribute to preventing ARIs and antibiotic use in children.

Health Equity and Antibiotic Prescribing in the United States: A Systematic Scoping Review.

We performed a scoping review of articles published from 1 January 2000 to 4 January 2022 to characterize inequities in antibiotic prescribing and use across healthcare settings in the United States to inform antibiotic stewardship interventions and research. We included 34 observational studies, 21 cross-sectional survey studies, 4 intervention studies, and 2 systematic reviews. Most studies (55 of 61 [90%]) described the outpatient setting, 3 articles were from dentistry, 2 were from long-term care, and 1 was from acute care. Differences in antibiotic prescribing were found by patient's race and ethnicity, sex, age, socioeconomic factors, geography, clinician's age and specialty, and healthcare setting, with an emphasis on outpatient settings. Few studies assessed stewardship interventions. Clinicians, antibiotic stewardship experts, and health systems should be aware that prescribing behavior varies according to both clinician- and patient-level markers. Prescribing differences likely represent structural inequities; however, no studies reported underlying drivers of inequities in antibiotic prescribing.

Characteristics of patients associated with any outpatient antibiotic prescribing among Medicare Part D enrollees, 2007-2018.

The 2007-2018 National Health Interview Survey data linked with Medicare claims were used to examine older adults' characteristics and assess their associations with receiving an antibiotic prescription. This analysis shows variation in antibiotic prescribing among adults enrolled in Medicare Part D by race and ethnicity, sex, geography, and health status.

Comparison of outpatient antibiotic prescriptions among older adults in IQVIA Xponent and publicly available Medicare Part D data, 2018.

The distributions of antibiotic prescriptions by geography, antibiotic class, and prescriber specialty are similar in the US Centers for Medicare and Medicaid Services (CMS) Part D Prescriber Public Use Files and IQVIA Xponent dataset. Public health organizations and healthcare systems can use these data to track antibiotic use and guide antibiotic stewardship interventions for older adults.

Using machine learning to examine drivers of inappropriate outpatient antibiotic prescribing in acute respiratory illnesses.

Using a machine-learning model, we examined drivers of antibiotic prescribing for antibiotic-inappropriate acute respiratory illnesses in a large US claims data set. Antibiotics were prescribed in 11% of the 42 million visits in our sample. The model identified outpatient setting type, patient age mix, and state as top drivers of prescribing.

Urgent-care antibiotic prescribing: An exploratory analysis to evaluate health inequities.

Healthcare disparities and inequities exist in a variety of environments and manifest in diagnostic and therapeutic measures. In this commentary, we highlight our experience examining our organization's urgent care respiratory encounter antibiotic prescribing practices. We identified differences in prescribing based on several individual characteristics including patient age, race, ethnicity, preferred language, and patient and/or clinician gender. Our approach can serve as an electronic health record (EHR)-based methodology for disparity and inequity audits in other systems and for other conditions.

An Oil-in-Water adjuvant significantly increased influenza A/H7N9 split virus Vaccine-Induced circulating follicular helper T (cTFH) cells and antibody responses.

BACKGROUND: Unadjuvanted A/H7N9 vaccines are poorly immunogenic. The immune response is improved with the addition of MF59, an oil-in-water adjuvant. However, the cellular immunologic responses of MF59-adjuvanted A/H7N9 vaccine are not fully understood. METHODS: 37 participants were vaccinated with 2 doses of 2013 influenza A/H7N9 vaccine (at Days 1 and 21) with or without MF59 and enrolled in an immunology substudy. Responses were assessed at multiple timepoints (Days 0, 8, 21, 29, and 42) for hemagglutination inhibition (HAI) and neutralizing antibody (Neut) assays, memory B cell responses by enzyme-linked ImmunoSpot; circulating follicular helper T cells (cTFH) and CD4 + T cells by intracellular cytokine staining. RESULTS: MF59-adjuvanted influenza A/H7N9 vaccine induced significantly higher hemagglutination inhibition (HAI) and neutralizing antibody (Neut) responses when compared to unadjuvanted vaccine. The adjuvanted vaccine elicited significantly higher levels of Inducible T-cell Co-Stimulator (ICOS) expression by CXCR3+CXCR5+CD4+ cTFH cells, compared to unadjuvanted vaccine. The magnitude of increase in cTFH cells (from baseline to Day 8) and in IL-21 expressing CD154+CD4+ T cells (from baseline to Days 8 and 21) correlated with HAI (at Day 29) and Neut antibody (at Days 8 and 29) titers. The increase in frequency of IL-21 expressing CD154+CD4+T cells (from baseline to Day 21) correlated with memory B cell frequency (at Day 42). CONCLUSION: cTFH activation is associated with HAI and Neut responses in recipients of MF59-adjuvanted influenza A/H7N9 vaccine relative to unadjuvanted vaccine. Future studies should focus on optimizing the cTFH response and use cTFH as an early biomarker of serological response to vaccination. This trial was registered at clinicaltrials.gov, trial number NCT01938742.

Identifying Higher-Volume Antibiotic Outpatient Prescribers Using Publicly Available Medicare Part D Data - United States, 2019.

Antibiotic prescribing can lead to adverse drug events and antibiotic resistance, which pose ongoing urgent public health threats (1). Adults aged ≥65 years (older adults) are recipients of the highest rates of outpatient antibiotic prescribing and are at increased risk for antibiotic-related adverse events, including Clostridioides difficile and antibiotic-resistant infections and related deaths (1). Variation in antibiotic prescribing quality is primarily driven by prescribing patterns of individual health care providers, independent of patients' underlying comorbidities and diagnoses (2). Engaging higher-volume prescribers (the top 10% of prescribers by antibiotic volume) in antibiotic stewardship interventions, such as peer comparison audit and feedback in which health care providers receive data on their prescribing performance compared with that of other health care providers, has been effective in reducing antibiotic prescribing in outpatient settings and can be implemented on a large scale (3-5). This study analyzed data from the Centers for Medicare & Medicaid Services (CMS) Part D Prescriber Public Use Files (PUFs)* to describe higher-volume antibiotic prescribers in outpatient settings compared with lower-volume prescribers (the lower 90% of prescribers by antibiotic volume). Among the 59.4 million antibiotic prescriptions during 2019, 41% (24.4 million) were prescribed by the top 10% of prescribers (69,835). The antibiotic prescribing rate of these higher-volume prescribers (680 prescriptions per 1,000 beneficiaries) was 60% higher than that of lower-volume prescribers (426 prescriptions per 1,000 beneficiaries). Identifying health care providers responsible for a higher volume of antibiotic prescribing could provide a basis for additional assessment of appropriateness and outreach. Public health organizations and health care systems can use publicly available data to guide focused interventions to optimize antibiotic prescribing to limit the emergence of antibiotic resistance and improve patient outcomes.