Document text
Laur a King, MPH
Advisor y Committ ee o n Immunizatio n Practices
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Disclosures
• Laura King has received consulting fees from Merck for unrelated
work.
• Joseph Lewnard has received consulting fees and grants from Pfizer, Merck, and VaxCyte for related and unrelated work.
• All other authors report no conflicts.
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Overview
• Background and study objective
• Pediatric outpatient visit and antibiotic prescription incidence
• Acute otitis media vaccine serotype attributable proportion and incidence
• Sinusitis and pneumonia vaccine serotype attributable proportion and
incidence
• Summary and conclusions
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Outpatient respiratory infections: a sizeable
burden
• ~1,200 acute respiratory infection (ARI) visits per 1,000 children in a
commercially-insured population in 20181
• ~250 ARI-associated antibiotic prescriptions per 1,000 children issued from doctor’s offices and emergency departments in the US annually (2014-15)
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• Limited knowledge of the proportion of ARI visits and antibiotic 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. 4
Reductions in antibiotic use concurrent with
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. 5
Study objective
Visits and antibiotic prescriptions attributable to additional serotypes in
higher-valency PCVs =
Incidence o f all -caus e
pediatric outpatient visi ts
and antibiotic prescriptions
for AOM , pneumonia, and
sinusitis
Proportio n of outpatient
diseas e caused by S.
pneumoniae PCV15 -13 and
PCV20 -13 serotypes*
*PCV15-13/PCV20-13 serotypes: serotypes in PCV15/PCV20 not in PCV13 6
Visits and antibiotic prescriptions attributable to additional serotypes in
higher-valency PCVs =
Incidence o f all -caus e
pediatric outpatient visi ts
and antibiotic prescription s
for AOM , pneumonia, and
sinusitis Proportio n of outpatient
diseas e caused by S.
pneumoniae PCV15 -13 and
PCV20 -13 serotypes
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All-cause incidence estimation methods
Total incidence = incidence in physician offices and emergency departments +
incidence in all other outpatient settings
8 Setting Data source for number of visits
and antibiotics Data source for - person years
at risk
Physician offices NAMCS 2016, 2018 US Census 2016, 2018
Emergency departments NHAMCS 2016, 2018 US Census 2016, 2018
Alternative outpatient
settings MarketScan Commercial and
Medicaid Databases 2016-2018 MarketScan Commercial and
Medicaid Databases 2016-2018
Condition Outpatient visits per 1000
person-years (95% CI) Antibiotic prescriptions per
1000 person-years (95% CI)
AOM 146 (116, 180) 124 (103, 149)
Sinusitis 40 (27, 58) 39 (24, 60)
Pneumonia 21 (14, 30) 17 (13, 21)
Total 208 (168, 254) 181 (148, 218) All-cause visit and antibiotic prescription
incidence in children by condition
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Incidence of pediatric
outpatient visits and
antibiotic prescriptions fo
AOM, pneumonia, and
sinusitisrVisits and antibiotic prescriptions attributable to additional serotypes in
higher-valency PCVs =
Proportio n of outpatient
diseas e caused by S.
pneumoniae PCV15 -13 and
PCV20 -13 serotypes
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Challenges in estimating the proportion of
outpatient disease caused by S. pneumoniae
• Children frequently colonized with pneumococcus
• Samples not regularly obtained from infection site in outpatient
disease
• Few studies conducted for non-AOM ARIs in pediatric outpatients
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cc cii idd dee enn ncc cee eoo off foo ouu utt tpp paa att tii iee enn ntt tAA AOO OMM M PP Prr roo opp poo orr rtt tii ioo onn naa ann ndd d
cc caa auu uss see edd dbb byy yPP PCC CVV V11 155 5-- -11 133 3aa ann ndd dPP PCC CVV V22 200 0-- -11 133 3ss see err roo ott tyy ypp pee ess siinn Proportion and incidence of outpatient AOM
caused by PCV15-13 and PCV20-13 serotypes in
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AA AOO OMM MThree approaches to estimating PCV15-13 and
PCV20-13 attributable proportions in AOM
1. Vaccine probe: use vaccine effectiveness against disease associated
with all etiologies to estimate attributable proportion
2. Pneumococcal prevalence and serotype distribution from middle ear fluid in children with AOM
3. Differential nasopharyngeal (NP) carriage between sick and healthy children and NP carriage serotype distribution in children with AOM
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AA AOO OMM MAOM pneumococcal and vaccine serotype
attributable percents
AOM attributable percent (95% CI)
Method All pneumococcal
serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 16.7 (4.3, 41.9) 0.9 (0.2, 2.3) 4.5 (1.1, 11.5)
Middle ear fluid 22.3 (17.1, 27.5) 1.0 (0.7, 1.4) 5.1 (3.9, 6.4)
Differential NP
carriage 14.0 (2.0, 26.0) 0.7 (0.1, 1.5) 3.7 (0.5, 7.1)
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vv vii iss sii itt tss s Estimated pediatric outpatient visits for AOM
attributable to PCV15-13 and PCV20-13 serotypes
Incidence per 1000 person-years (95% CI) Annual number in thousands* (95% CI)
Method PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 1.3 (0.3, 3.5) 6.5 (1.6, 17.1) 92 (23, 257) 477 (121, 1,251)
Middle ear fluid 1.5 (1.0, 2.2) 7.4 (5.2, 10.2) 109 (72, 161) 543 (381, 747)
Differential NP
carriage 1.0 (0.1, 2.2) 5.4 (0.8, 10.7) 76 (11, 165) 397 (56, 787)
*Estimated using 2018 census estimate for children <18 years 15
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pp prr ree ess scc crr rii ipp ptt tii ioo onn nss sEstimated pediatric outpatient antibiotic
prescriptions for AOM attributable to PCV15-13 and PCV20-13 serotypes
Incidence per 1000 person-years (95% CI) Annual number in thousands* (95% CI)
Method PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 1.1 (0.3, 3.0) 5.6 (1.4, 14.5) 79 (19, 217) 408 (104, 1,065)
Middle ear fluid 1.3 (0.9, 1.8) 6.3 (4.5, 8.5) 93 (63, 135) 464 (333, 626)
Differential NP
carriage 0.9 (0.1, 1.9) 4.6 (0.7, 9.1) 65 (9, 139) 340 (48, 666)
*Estimated using 2018 census estimate for children <18 years 16
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aa ann ndd dss sii inn nuu uss sii itt tii iss scc caa auu uss see edd dbb byy yPP PCC CVV V11 155 5-- -11 133 3aa ann ndd dPP PCC CVV V22 200 0-- -11 133 3
ss see err roo ott tyy ypp pee ess sProportion and incidence of outpatient pneumonia
and sinusitis caused by PCV15-13 and PCV20-13
serotypes
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pp pnn nee euu umm moo onn nii iaa a
ss sii inn nuu uss sii itt tii iss sTwo approaches to estimating PCV15-13 and
PCV20-13 attributable proportions in pneumonia
and sinusitis
1. Vaccine probe: use vaccine effectiveness to estimate attributable
proportion
2. Differential NP carriage between sick and healthy children and NP carriage serotype distribution in children with AOM
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Method All pneumococcal
serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 18.2 (12.5, 27.3) 0.9 (0.5, 1.5) 4.4 (2.9, 6.7)
Differential NP carriage 11.8 (1.0, 22.7) 0.6 (0.0, 1.2) 2.8 (0.2, 5.5) PP Pnn nee euu umm moo onn nii iaa a Pneumonia pneumococcal and vaccine
serotype attributable percents
Pneumonia attributable percent (95% CI)
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pp pnn nee euu umm moo onn nii iaa a Estimated pneumonia pediatric outpatient visits
and antibiotic prescriptions attributable to PCV15 -
13 and PCV20-13 serotypes
Incidence per 1000 person-years
(95% CI) Annual number in thousands*
(95% CI)
Outcome Method PCV15-13
serotypes PCV20-13
serotypes PCV15-13
serotypes PCV20-13
serotypes
Vaccine probe 0.2 (0.1, 0.4) 0.9 (0.5, 1.6) 14 (7, 26) 68 (39, 118)
Outpatient visits
Differential NP
carriage 0.1 (0.0, 0.3) 0.6 (0.1, 1.3) 9 (1, 21) 43 (4, 95)
Antibiotic prescriptions Vaccine probe
Differential NP
carriage 0.1 (0.1, 0.3)
0.1 (0.0, 0.2) 0.7 (0.5, 1.2) 0.5 (0.0, 1.0) 11 (6, 19)
7 (1, 15) 53 (34, 86)
34 (3, 70)
*Estimated using 2018 census estimate for children <18 years 20
SSSSiinininnuuuussssiiiittttiiiis ss s pneumococcal an d vaccine serotype
attributable percents
Sinusitis attributable percent (95% CI)
Method All pneumococcal
serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 30.6 (21.0, 45.8) 1.5 (0.9, 2.5) 7.3 (4.9, 11.2)
Differential NP carriage 11.8 (1.0, 22.7) 0.6 (0.0, 1.2) 2.8 (0.2, 5.5)
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ss sii inn nuu uss sii itt tii iss s Estimated sinusitis pediatric outpatient visits and
antibiotic prescriptions attributable to PCV15-13
and PCV20-13 serotypes
Incidence per 1000 person-years Annual number in thousands*
(95% CI) (95% CI)
PCV15-13 PCV20-13 PCV15-13 PCV20-13
Outcome Method serotypes serotypes serotypes serotypes
Vaccine probe 0.6 (0.3, 1.2) 2.9 (1.7, 5.2) 44 (23, 85) 216 (122, 381)
Outpatient visits
Differential NP 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 17 (1, 40) 82 (7, 180) carriage
Vaccine probe 0.6 (0.3, 1.2) 2.9 (1.5, 5.2) 43 (21, 85) 209 (112, 384)
Antibiotic
prescriptions Differential NP 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 16 (1, 39) 79 (7, 181) carriage
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*Estimated using 2018 census estimate for children <18 years
SS Suu umm mmm maa arr ryy yaa ann ndd dcc coo onn ncc cll luu uss sii ioo onn nss s Summary and conclusions
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Point estimate ranges: attributable percent,
number visits, number antibiotic prescriptions
PCV15-13 serotypes PCV20-13 serotypes
Condition Attributable
percent of
outpatient
disease Annual no., in thousands
Outpatient Antibiotic
visits prescriptions Attributable
percent of
outpatient
disease Annual no., in thousands
Outpatient Antibiotic
visits prescriptions
AOM 0.7–1.0 76–109 65–93 3.7–5.1 397–543 340–464
Pneumonia 0.6–0.9 9–14 7–11 2.8–4.4 43–68 34-53
Sinusitis 0.6–1.5 17–44 16–43 2.8–7.3 82–216 79–209
Total* 1.9–3.4 103–168 90–148 9.4–16.8 527–831 458–731
*Individual condition ranges may not sum to total ranges due to simulation methods and rounding 24
Study limitations
• Pneumococcal attributable percent, serotype distribution, and
vaccine effectiveness estimates based on published data
• Limited data for attributable proportion and serotype distribution in sinusitis and pneumonia
• All-cause incidence data from 2016-2018
• Assumed healthcare utilization constant across serotypes
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Conclusions
• Additional serotypes included in higher-valency PCVs account for
~100–830 thousand outpatient visits and ~90–730 thousand antibiotic prescriptions for AOM, pneumonia, and sinusitis among US children annually.
• PCV15-13 serotypes: 103–168K visits and 90–148K antibiotic prescriptions
• PCV20-13 serotypes: 527–831K visits and 458–731K antibiotic prescriptions
• The estimated incidence of pediatric outpatient visits and antibiotic prescriptions attributable to PCV20-13 serotypes is 4 – 5 times the
incidence attributable to PCV15-13 serotypes.
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Project team
UC Berkeley
• Laura King, MPH
• Joe Lewnard, PhD
CDC Respiratory Diseases Branch
• Miwako Kobayashi, MD, MPH
• Kristin Andrejko, PhD
• Adam Cohen, MD, MPH CDC Office of Antibiotic
Stewardship
• Sarah Kabbani, MD, MS
• Lauri Hicks, DO
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