{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T12:05:54Z","timestamp":1783253154909,"version":"3.54.6"},"posted":{"date-parts":[[2025,4,7]]},"group-title":"Epidemiology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    We aimed to estimate the burden of antibiotic-nonsusceptible non-bacteremic pneumonia and sinusitis due to\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    (pneumococcus) in US adults (\u226518 years).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We estimated antibiotic-nonsusceptible pneumococcal sinusitis and non-bacteremic pneumonia incidence as products of non-bacteremic pneumococcal pneumonia and sinusitis incidence rates, serotype distribution, and serotype-specific antimicrobial nonsusceptibility prevalences by antibiotic class and guideline-recommended agents from 2016-2019. We derived pneumonia and sinusitis incidence rates from national healthcare utilization surveys and administrative datasets; pneumococcal-attributable attributable percents and serotype distributions from published data; and serotype-specific nonsusceptibility estimates from Active Bacterial Core surveillance data. We evaluated nonsusceptibility for all serotypes and those targeted by 15-, 20- and 21-valent pneumococcal conjugate vaccines (PCV15\/20\/21).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>An estimated 16.4% (95% confidence interval 12.8-21.4%) of non-bacteremic pneumococcal pneumonia and 19.0% (14.8-24.9%) of sinusitis cases were nonsusceptible to \u22653 antibiotic classes, translating to 243,521 (179,673-333,675) and 1,844,726 (1,070,763-2,904,089) outpatient visits for pneumonia and sinusitis, respectively, and 10,155 (7,542-13,803) pneumonia hospitalizations annually. An estimated 31.2% (26.6-36.3%) of non-bacteremic pneumococcal pneumonia and 10.5% (9.4-12.0%) of pneumococcal sinusitis cases were nonsusceptible to \u22651 outpatient first-line antibiotic agent. Cases attributable to serotypes targeted by PCV15, PCV20, and PCV21 that were nonsusceptible to \u22653 antibiotic classes accounted for 7.4% (4.7-11.1%), 8.5% (5.8-12.1%), and 12.6% (9.2-17.5%) of all non-bacteremic pneumococcal pneumonia cases, and 8.4% (5.3-12.5%), 9.4% (6.2-13.4), and 14.4% (10.4-20.0%) of all pneumococcal sinusitis cases.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We demonstrated high proportions of antibiotic nonsusceptibility in non-bacteremic pneumococcal pneumonia and sinusitis in US adults. PCVs and antibiotic stewardship may mitigate antibiotic nonsusceptibility in pneumococcal disease.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.04.25325277","type":"posted-content","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T01:01:08Z","timestamp":1744074068000},"source":"Crossref","is-referenced-by-count":1,"title":["Acute respiratory infections due to antibiotic-nonsusceptible\n                  <i>Streptococcus pneumoniae<\/i>\n                  in United States adults"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-4712","authenticated-orcid":false,"given":"Laura M","family":"King","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin L","family":"Andrejko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwako","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Lewnard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025041001101276000_2025.04.04.25325277v1.1","unstructured":"Centers for Disease Control and Prevention. 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