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

Abstract

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.

Figure 1.. Estimation framework.

Framework to derive estimates of visits and antibiotic prescriptions attributable to pneumococcal serotypes included in 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20) not included in PCV13. All-cause incidence estimation methods are detailed in eMethods 1. Primary attributable fraction analysis methods are detailed in eMethods 2 (AOM) and eMethods 3 (pneumonia, sinusitis) and supplemental analysis methods are detailed in eMethods 5.

Figure 2.. Distribution of PCV13, PCV15-additional, and PCV20-additional serotypes among children with outpatient ARIs.

We illustrate the proportions of isolates belonging to serotypes across studies included in the meta-analysis of pneumococcal serotype distributions in ARIs (eMethods 4; eTable 5) by serotype and PCV inclusion category (PCV13: serotypes 1, 3, 4, 5, 6A, 6B, 7A, 9V, 14, 18C, 19A, 19F, 23F; PCV15-additional: 22F, 33F; PCV20-additional: 22F, 33F, 8, 10A, 11A, 12F, 15B). Only serotypes representing ≥ 1% of isolates presented. Related aggregated serotypes denoted by (*); see eTable 6 for detailed serotype categorization. Data presented here are pooled directly from studies in eTable 5; Markov chain Monte Carlo estimates by PCV inclusion category are presented in eTable 9.