Laura King, MPH

Advisory Committee on Immunization PracticesFebruary 22, 2023

Pediatric outpatient ARI visits and antibiotattributable to serotypes in higher valency 
Disclosures

• Laura King has received consulting fees from Merck for un

work.

• Joseph Lewnard has received consulting fees and grants fr

Merck, and VaxCyte for related and unrelated work. 

• All other authors report no conflicts.
Overview

• Background and study objective• Pediatric outpatient visit and antibiotic prescription incidence • Acute otitis media vaccine serotype attributable proportion an• Sinusitis and pneumonia vaccine serotype attributable proport

incidence

• Summary and conclusions
Outpatient respiratory infections: a siz

burden• ~1,200 acute respiratory infection (ARI) visits per 1,000 ch

commercially-insured population in 2018

1

• ~250 ARI-associated antibiotic prescriptions per 1,000 chi

from doctor’s offices and emergency departments in the U(2014-15)

2

• Limited knowledge of the proportion of ARI visits and ant

prescriptions attributable to Streptococcus pneumoniae

1. King LM, et al. Antimicrob Steward Healthc Epidemiol. 2021;1(1):1-8. doi: 10.1017/ash.2021.230.

2. Hersh AL, et al. Clin Infect Dis. 2021;72(1):133-137. doi: 10.1093/cid/ciaa667.
Reductions in antibiotic use concurren

PCV uptake

US outpatient oral antibiotic prescriptions per 1,000 persons, 2011-2016

King et al., Clin Infect Dis. 2020; 70(3):370-377). doi: 10.1093/cid/ciz225.
Study objective

Incidence of all-cause 

pediatric outpatient visits 

and antibiotic prescriptions 

for AOM, pneumonia, and 

sinusitis

Proportion of outpatient 

disease caused by S. 

pneumoniae PCV15-13 and 

PCV20-13 serotypes*

Visits and antibiotic prescriptions attributable to additional ser

higher-valency PCVs =

*PCV15-13/PCV20-13 serotypes: serotypes in PCV15/PCV20 not in PCV13 
Incidence of all-cause 

pediatric outpatient visits 

and antibiotic prescriptions 

for AOM, pneumonia, and 

sinusitis

Proportion of outpatient 

disease caused by S. 

pneumoniae PCV15-13 and 

PCV20-13 serotypes

Visits and antibiotic prescriptions attributable to additional ser

higher-valency PCVs =
All-cause incidence estimation method

Setting Data source for number of visits 

and antibiotics

Data source foat risk

Physician offices NAMCS 2016, 2018 US Census 201Emergency departments NHAMCS 2016, 2018 US Census 201Alternative outpatient settings

MarketScan Commercial and Medicaid Databases 2016-2018

MarketScan CoMedicaid Data

Total incidence = incidence in physician offices and emergency de

incidence in all other outpatient settings
All-cause visit and antibiotic prescripti

incidence in children by condition 

Condition Outpatient visits per 1000 person-years (95% CI) Antibiotic prescrip

1000 person-year

AOM 146 (116, 180) 124 (103, 1Sinusitis 40 (27, 58) 39 (24, 60Pneumonia 21 (14, 30) 17 (13, 21Total 208 (168, 254) 181 (148, 2
Incidence of pediatric 

outpatient visits and 

antibiotic prescriptions for 

AOM, pneumonia, and 

sinusitis

Proportion of outpatient 

disease caused by S. 

pneumoniae PCV15-13 and 

PCV20-13 serotypes

Visits and antibiotic prescriptions attributable to additional ser

higher-valency PCVs =
Challenges in estimating the proportio

outpatient disease caused by S. pneum• Children frequently colonized with pneumococcus• Samples not regularly obtained from infection site in outp

disease

• Few studies conducted for non-AOM ARIs in pediatric out
Proportion and incidence of outpatient 

caused by PCV15- caused by PCV15-13 and PCV20 13 and PCV20 13 and PCV20-13 ser

13 ser
Three approaches to estimating PCV15-13 

PCV20-13 attributable proportions in AOM1. Vaccine probe: use vaccine effectiveness against disease 

with all etiologies to estimate attributable proportion

2. Pneumococcal prevalence and serotype distribution fro

ear fluid in children with AOM

3. Differential nasopharyngeal (NP) carriage between sick 

children and NP carriage serotype distribution in childre
AOM pneumococcal and vaccine serot

attributable percents

AOM attributable percent (95% CI)

Method

All pneumococcal 

serotypes PCV15-13 serotypes PCV20

Vaccine probe 16.7 (4.3, 41.9) 0.9 (0.2, 2.3) 4.5 Middle ear fluid 22.3 (17.1, 27.5) 1.0 (0.7, 1.4) 5.1 Differential NP carriage 14.0 (2.0, 26.0) 0.7 (0.1, 1.5) 3.7 
Estimated pediatric outpatient visits for AO

attributable to PCV15-13 and PCV20-13 se

Method

Incidence per 1000 person-years (95% CI) Annual number in 

PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes 

Vaccine probe 1.3 (0.3, 3.5) 6.5 (1.6, 17.1) 92 (23, 257) Middle ear fluid 1.5 (1.0, 2.2) 7.4 (5.2, 10.2) 109 (72, 161) 

Differential NP carriage 1.0 (0.1, 2.2) 5.4 (0.8, 10.7) 76 (11, 165) *Estimated using 2018 census estimate for children <18 years
Estimated pediatric outpatient antibiotic antibiotic 

prescriptions for AOM attributable to PCV1

prescriptions

and PCV20-13 serotypes

Method

Incidence per 1000 person-years (95% CI) Annual number in 

PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes 

Vaccine probe 1.1 (0.3, 3.0) 5.6 (1.4, 14.5) 79 (19, 217) Middle ear fluid 1.3 (0.9, 1.8) 6.3 (4.5, 8.5) 93 (63, 135) Differential NP carriage 0.9 (0.1, 1.9) 4.6 (0.7, 9.1) 65 (9, 139) 

*Estimated using 2018 census estimate for children <18 years
Proportion and incidence of outpatient pne

and sinusitis caused by PCV15- caused by PCV15-13 and PCV2

13 and PCV213 and PCV2

serotypes
Two approaches to estimating PCV15-13 a

PCV20-13 attributable proportions in pneuand sinusitis1. Vaccine probe: use vaccine effectiveness to estimate att

proportion

2. Differential NP carriage between sick and healthy childr

carriage serotype distribution in children with AOM
Pneumonia pneumococcal and vaccine 

serotype attributable percents

Pneumonia attributable percent (95% CI)

Method

All pneumococcal 

serotypes PCV15-13 serotypes PCV20

Vaccine probe 18.2 (12.5, 27.3) 0.9 (0.5, 1.5) 4.4 Differential NP carriage 11.8 (1.0, 22.7) 0.6 (0.0, 1.2) 2.8 
Estimated pneumonia pediatric outpatient 

and antibiotic prescriptions attributable to 13 and PCV20-13 serotypes

Outcome Method

Incidence per 1000 person-years 

(95% CI)

Annual nu

PCV15-13 

serotypes

PCV20-13 

serotypes

PCV15-13 

serotypes

Outpatient visits

Vaccine probe 0.2 (0.1, 0.4) 0.9 (0.5, 1.6) 14 (7, 26) Differential NP carriage 0.1 (0.0, 0.3) 0.6 (0.1, 1.3) 9 (1, 21) 

Antibiotic prescriptions

Vaccine probe 0.1 (0.1, 0.3) 0.7 (0.5, 1.2) 11 (6, 19) 

Differential NP carriage 0.1 (0.0, 0.2) 0.5 (0.0, 1.0) 7 (1, 15) 

*Estimated using 2018 census estimate for children <18 years
Sinusitis pneumococcal and vaccine se

attributable percents

Sinusitis attributable percent (95% CI)

Method

All pneumococcal 

serotypes PCV15-13 serotypes PCV20

Vaccine probe 30.6 (21.0, 45.8) 1.5 (0.9, 2.5) 7.3 Differential NP carriage 11.8 (1.0, 22.7) 0.6 (0.0, 1.2) 2.8 
Estimated sinusitis pediatric outpatient vis

antibiotic prescriptions attributable to PCVand PCV20-13 serotypes

Outcome Method

Incidence per 1000 person-years 

(95% CI)

Annual nu

PCV15-13 

serotypes

PCV20-13 

serotypes

PCV15-13 

serotypes

Outpatient visits

Vaccine probe 0.6 (0.3, 1.2) 2.9 (1.7, 5.2) 44 (23, 85) 

Differential NP carriage 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 17 (1, 40) 

Antibiotic prescriptions

Vaccine probe 0.6 (0.3, 1.2) 2.9 (1.5, 5.2) 43 (21, 85) 

Differential NP carriage 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 16 (1, 39) 

*Estimated using 2018 census estimate for children <18 years
Summary and conclusions
Point estimate ranges: attributable percen

number visits, number antibiotic prescript

Condition

PCV15-13 serotypes PCV20-13 s

Attributable 

percent of 

outpatient 

disease

Annual no., in thousands Attributable 

percent of 

outpatient 

disease

Annu

Outpatient 

visits

Antibiotic 

prescriptions

Outpat

visit

AOM 0.7–1.0 76–109 65–93 3.7–5.1 397–5Pneumonia 0.6–0.9 9–14 7–11 2.8–4.4 43–6Sinusitis 0.6–1.5 17–44 16–43 2.8–7.3 82–2Total* 1.9–3.4 103–168 90–148 9.4–16.8 527–8

*Individual condition ranges may not sum to total ranges due to simulation methods and rounding
Study limitations

• Pneumococcal attributable percent, serotype distribution

vaccine effectiveness estimates based on published data

• Limited data for attributable proportion and serotype dist

sinusitis and pneumonia 

• All-cause incidence data from 2016-2018• Assumed healthcare utilization constant across serotypes
Conclusions

• Additional serotypes included in higher-valency PCVs acco

~100–830 thousand outpatient visits and ~90–730 thousa

antibiotic prescriptions for AOM, pneumonia, and sinusitichildren annually. 

• PCV15-13 serotypes: 103–168K visits and 90–148K antibiotic pr• PCV20-13 serotypes: 527–831K visits and 458–731K antibiotic p

• The estimated incidence of pediatric outpatient visits and 

prescriptions attributable to PCV20-13 serotypes is 4 – 5 tincidence attributable to PCV15-13 serotypes.
Project team

UC Berkeley• Laura King, MPH• Joe Lewnard, PhDCDC Respiratory Diseases Branch• Miwako Kobayashi, MD, MPH• Kristin Andrejko, PhD• Adam Cohen, MD, MPH

CDC Office of AntibioStewardship• Sarah Kabbani, MD, • Lauri Hicks, DO