{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:46:55Z","timestamp":1791348415611,"version":"4.3.1"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The detection of\n                      <jats:italic>Tropheryma whipplei<\/jats:italic>\n                      in respiratory specimens has increased with metagenomic next-generation sequencing (mNGS), yet distinguishing colonization from active infection remains challenging. In clinical settings lacking quantitative PCR or pathological confirmation, practical approaches to guide treatment decisions are urgently needed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed nine patients (January 2019\u2013January 2024) with\n                      <jats:italic>T. whipplei<\/jats:italic>\n                      detected by bronchoalveolar lavage fluid (BALF) mNGS. All patients initially received cefoperazone-sulbactam (3.0 g q8h) as empirical therapy for 3\u20135 days without improvement. Targeted therapy (ceftriaxone or meropenem combined with doxycycline or trimethoprim-sulfamethoxazole) was subsequently initiated. We describe clinical characteristics and treatment outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among nine patients (3 male, 6 female; mean age 59 years, range 32\u201379), six (67%) were immunosuppressed. Primary manifestations included fever (67%), cough with sputum (89%), and dyspnea (78%). Common laboratory findings were anemia (67%), lymphocytopenia (67%), hypoalbuminemia (100%), and elevated inflammatory markers (78%). Chest CT predominantly showed patchy ground-glass opacities. Eight cases (89%) had co-infections. All patients showed no improvement after initial cefoperazone-sulbactam therapy. After targeted therapy was initiated, eight patients (89%) achieved defervescence within 3\u20135 days, with resolution of pulmonary infiltrates on follow-up CT within 10\u201314 days. Among these eight responders, one patient (Case 4) underwent repeat BALF mNGS which demonstrated a &amp;gt;99.99% reduction in\n                      <jats:italic>T. whipplei<\/jats:italic>\n                      (from 6,100,499 to 383 reads), reported in the suspected colonizer list rather than the pathogen panel. One non-responder (Case 8) showed a &amp;gt;99% reduction in\n                      <jats:italic>T. whipplei<\/jats:italic>\n                      read count on repeat BALF mNGS after targeted therapy, but ultimately died of polymicrobial sepsis from multidrug-resistant co-pathogens. No relapse occurred during 1-year follow-up.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This retrospective case series suggests that rapid improvement after adding targeted anti-\n                      <jats:italic>T. whipplei<\/jats:italic>\n                      therapy is compatible with possible\n                      <jats:italic>T. whipplei<\/jats:italic>\n                      -associated infection in selected mNGS-positive patients, rather than colonization alone. Sequential mNGS showed marked burden reduction in two cases. These observations require prospective validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1883057","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:40:07Z","timestamp":1782711607000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tropheryma whipplei pneumonia: a retrospective case series of nine patients with treatment response"],"prefix":"10.3389","volume":"13","author":[{"given":"Qiusheng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Fuzhou University Affiliated Provincial Hospital, Fujian Medical University, Fuzhou","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fuzhou University Affiliated Provincial Hospital, Fujian Medical University, Fuzhou","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fuzhou University Affiliated Provincial Hospital, Fujian Medical University, Fuzhou","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fuzhou University Affiliated Provincial Hospital, Fujian Medical University, Fuzhou","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e280","DOI":"10.1016\/S1473-3099(22)00128-1","article-title":"Whipple\u2019s disease and Tropheryma whipplei infections: from bench to 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