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Interim Results from the PNEUMO Study
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Pneumococcal pNeumonia Epidemiology, Urine serotyping, and
Mental Outcomes study
February 29, 2024
Study Leadership
Wesley H. Self, MD
Vanderbilt UniversityJ. Jackson Resser , MS
Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc.
1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD
Emory University
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PNEUMO study overview
•Adults 18+ years hospitalized with
community acquired pneumonia (CAP)Target
Population
•Multi -country, prospective, population -
based active surveillance studyDesign
•Estimate pneumococcal pneumonia
incidence and serotype prevalence (using
Merck PCV15 and V116 SSUADs), with
longitudinal evaluation of functional status, quality of life and costObjectives►Incidence hospitalized pneumococcal CAP
►Incidence hospitalized PCV15- and
V116 - type pneumococcal CAP
►Direct medical cost
►Work loss
►Functional status
►Cognitive status
►Quality of Life (EQ -5D)Up to 6
months
post -
discharge
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Pneumonia surveillance with prospective, real -time enrollment of
adults hospitalized with CAP (including HCAP)
HCAP, healthcare associated pneumonia US PNEUMO sites: enrollment Sept 2018 - present
Nashville, Tennessee
(2 hospitals) Atlanta, Georgia
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PublicEligibility criteria
Inclusion Criteria
1.Age ≥ 18 years old
2.Hospitalized
3.Clinical signs and/or symptoms of an acute respiratory illness (e.g., new shortness of breath, cough)
4.Clinical signs and/or symptoms of an acute infection (e.g., fever, leukocytosis)
5.Radiologic evidence of pneumonia interpreted by a radiologist (x-ray or CT)
Exclusion Criteria
1.Prior enrollment in this study within the past 30 days (to avoid multiple enrollments for same episode of
pneumonia).
2.Development of pneumonia >72 hours after hospital admission
3.Inability to obtain consent within 72 hours of hospital admission
4.Inability or unwillingness of the patient to provide a urine sample within 72 hours of hospital admission .
5.Non -pneumonia illness completely explains the patient’s acute symptoms. 4
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Tests for S. pneumoniae
•Urine collection from patients at enrollment
(1) BinaxNow pneumococcal urinary antigen test (local testing by research team)
(2) Serotype- specific urinary antigen detection (SSUAD) assays:
•Developed and performed by Merck laboratory
•30 serotypes:
•1, 3, 4, 5, 6A*, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15C#, 16F, 17F, 18C, 19A, 19F, 20A, 22F,
23A, 23B, 23F, 24F, 31, 33F, 35B
•All serotypes in PCV15, PCV20, and V116 included except 15B
•Results of clinically -obtained bacterial cultures:
•Sterile sites: blood, pleural fluid, BAL fluid, CSF, synovial fluid
•Non -sterile sites: high-quality respiratory samples (>25 WBC, <10 epi)
•sputum, endotracheal aspirate
5* assay for serotype 6A has cross- reactivity with serotype 6C
# assay for serotype 15C has mild cross- reactivity with serotype 15B
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Hospitalized adults screened for
eligibility
(n = 5,385)
Enrolled: adults hospitalized with
community acquired pneumonia (CAP)
(n = 3,278)
Analyzed
[All-cause CAP population]
(n = 2,917)
S. pneumoniae detected
[Pneumococcal CAP population]
(n = 352)S. pneumoniae not detected
[Non -pneumococcal CAP]
(n = 2,565)
S. pneumoniae culture positive
from normally sterile site
[Invasive pneumococcal CAP]
(n = 51)S. pneumoniae detected outside
normally sterile site only
[Non -invasive pneumococcal CAP]
(n = 301)Not enrolled (n =2,107)
Enrolled, not analyzed (n = 361)
•No radiographic evidence of pneumonia (n=235)
•Urine not tested by SSUAD (n = 114)
•Patient withdrew (n = 12)Enrolled Patients
12.1%
pneumococcal
prevalence
85.5%
of pneumococcal pneumonia
was non- invasive
PublicPatient Characteristics: Demographics
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Age in years, median (IQR) 60.3 (50.6, 70.2) 60.5 (46.8, 70.2) 0.34
Age category, n (%) 0.01
18-49 years 85 (24.1%) 767/2564 (29.9%)
50-64 years 141 (40.1%) 817/2564 (31.9%)
≥65 years 126 (35.8%) 980/2564 (38.2%)
Female sex assigned at birth, n (%) 167/350 (47.7%) 1147/2558 (44.8%)
Race, n (%) <0.01
White 198 (56.2%) 1771 (69.0%)
Black 145 (41.2%) 703 (27.4%)
Asian 1 (0.3%) 38 (1.5%)
American Indian/Native
Alaskan2 (0.6%) 14 (0.5%)
Native Hawaiian/Pacific Islander2 (0.6%) 6 (0.2%)
Other 6 (1.7%) 54 (2.1%)
Ethnicity, n (%) 0.95
Not Hispanic 328 (93.2%) 2394 (93.3%)
Hispanic 14 (4.0%) 94 (3.7%)
Unknown 10 (2.8%) 77 (3.0%)7
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Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Type of home before illness, n (%) 0.27
Community dwelling 320 (90.9%) 2382 (92.9%)
Nursing Home 6 (1.7%) 43 (1.7%)
Assisted Living 6 (1.7%) 33 (1.3%)
Rehabilitation hospital 1 (0.3%) 13 (0.5%)
School housing 0 (0.0%) 0 (0.0%)
Homeless/shelter 12 (3.4%) 40 (1.6%)
Other 3 (0.9%) 33 (1.3%)
Unknown 4 (1.1%) 21 (0.8%)
Ever regularly smoked tobacco, n (%) 205/349 (58.7%) 1232/2554 (48.2%) <0.01
Alcohol use >3 days/week, n (%) 30/348 (8.6%) 145/2543 (5.7%) 0.03
Use of opioids at least weekly, n (%) 68/339 (20.1%) 438/2462 (17.8%) 0.31
Interacts with child <5 years old at
least once per week, n (%)122/340 (35.9%) 682/2468 (27.6%) <0.01
Lives with children, n (%) 83/346 (24.0%) 517/2534 (20.4%)Patient Characteristics: Social History
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Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Chronic medical conditions, n (%)
Dementia 11/349 (3.2%) 65/2528 (2.6%) 0.362
COPD 97/346 (28.0%) 487/2510 (19.4%) <0.001
Asthma 72/346 (20.8%) 474/2518 (18.8%) 0.413
Heart failure 61/340 (17.9%) 446/2509 (17.8%) 0.824
Prior MI 37/344 (10.8%) 231/2525 (9.1%) 0.359
Prior stroke 38/347 (11.0%) 255/2516 (10.1%) 0.651
End stage kidney disease with
chronic kidney replacement14/342 (4.1%) 125/2515 (5.0%) 0.424
Diabetes mellitus 82/348 (23.6%) 684/2525 (27.1%) 0.159
Chronic liver disease 30/343 (8.7%) 173/2508 (6.9%) 0.254
Immunosuppression 72/343 (21.0%) 529/2499 (21.2%) 0.983
Solid organ cancer 80/348 (23.0%) 589/2501 (23.6%) 0.981
Hematologic cancer 30/346 (8.7%) 193/2511 (7.7%) 0.598
Solid organ transplant 25/347 (7.2%) 205/2528 (8.1%) 0.545
Pregnant 0/348 (0.0%) 22/2533 (0.9%) 0.081
Obesity with body mass index
>30 kg/m289/355 (25.9%) 1009/2479 (40.7%) <0.001Patient Characteristics: Chronic Medical Conditions
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Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Received antibiotics for current illness before
hospitalization, n (%)71/328 (21.6%) 613/2297 (26.7%) 0.05
Duration of acute illness prior to hospital admission [days], median (IQR)2.6 (1.3, 5.0) 2.7 (1.1, 5.7) 0.36
CURB- 65* score at hospital admission, n (%) 0.17
0 (low risk) 123/345 (35.7%) 943/2523 (37.4%)
1 (low risk) 126/345 (36.5%) 869/2523 (34.4%)
2 (moderate risk) 60/345 (17.4%) 547/2523 (21.7%)
3 (high risk) 31/345 (9.0%) 150/2523 (5.9%)
4 (high risk) 5/345 (1.4%) 14/2523 (0.6%)
5 (high risk) 0/345 (0.0%) 0/2523 (0.0%)
Timing of Enrollment <0.01
Before COVID- 19 in US (October 2018 –
February 2020)231/345 (67.0%) 1249/2519 (49.6%)
After COVID- 19 in US (March 2020 –
October 2022)114/345 (33.0%) 1270/2519 (50.4%)Patient Characteristics: Acute Illness
10* CURB -65: pneumonia severity scoring system, consisting of the following variables: confusion, uremia, respiratory rate, blood pressure, age >65
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BinaxNOW
125 patients positive
Cultures
56 patients positive44 53 SSUAD
283 patients positive 199
1117523352 Patients with ≥1 Positive Pneumococcal Test
12Percentage of Pneumococcal Serotype Detections
14.6%
9.8%
7.0%
6.0%5.7%5.4%5.1%4.7%4.1%3.5%3.2%2.8%2.2%1.9%1.6%1.3%0.9% 0.3% 0.0%
n=46 n=31 n=22 n=19 n=18 n=17 n=16 n=15 n=13 n=11 n=10 n=9 n=7 n=6 n=5 n=4 n=3n=1n=0
3 22F 19A 35B 9N 19F 23A 11A 23B 7F, 8,
17F, 316A/C 16F,
20A1, 5 9V, 15C 15A 33F 4, 6B,
24F14, 10A,
12F18C,
23F
Serotype316 serotypes detected by SSUAD (denominator) among 283 unique patients
13Vaccine Category Pneumococcal serotypes% of serotypes in adults
hospitalized with CAP
(n=2917)
V116 (21 serotypes) 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B 9.3%
PCV20 (19 serotypes; serotype 15B not tested) 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 18C, 19A, 19F, 22F, 23F, 33F 6.7%
PCV15 (15 serotypes) 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F 5.8%
V116 and not PCV15 or PCV20 (11 serotypes) 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B 4.1%8.0%11.3%
8.7%
4.7%8.4%
6.9%
4.0%7.3%
5.8%
4.0%4.8%
3.1%
0%2%4%6%8%10%12%
18-49 years old (n=852) 50-64 years old (n=958) 65+ years old (n=1107)% of patients with ≥1 serotype in categoryV116 PCV20 PCV15 11 unique V116 serotypesPercentage of Pneumococcal Serotype by Vaccine in Adults Hospitalized with CAP
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Conclusions
•Pneumococcal CAP remains a major cause of adult hospitalizations
•SSUAD assays greatly increase S. pneumoniae detection over traditional testing
•Among adults hospitalized with CAP:
•12.1% with S. pneumoniae detected
•9.3% with a pneumococcal serotype in V116
•4.1% with a serotype unique to V116 (not PCV15 or PCV20)
•Most commonly detected serotypes unique to V116: 35B, 9N, 23A, 23B
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