{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:02:00Z","timestamp":1787781720751,"version":"build-2784847793"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Drug\u2010induced immune hemolytic anemia (DIIHA), a rare complication of beta\u2010lactams, lacks population\u2010level data on subclinical antibody prevalence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To quantify drug\u2010induced antibody incidence and hematologic impact in beta\u2010lactam\u2010treated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective cohort of 4040 patients receiving ceftriaxone, piperacillin\/trizobactam, piperacillin\/sulbactam 2:1 and piperacillin\/tazobactam at a Chinese tertiary hospital (2020.1\u20132020.9). Antibodies were detected via immunoadsorption assays. The primary outcomes were changes in hemoglobin, bilirubin, and lactate dehydrogenase (LDH) levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antibody positivity occurred in 18.07% (730\/4040), highest with piperacillin\/sulbactam 2:1 (24.02% vs. 0.43% Ceftriaxone,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Seropositive patients had a significant hemoglobin decline (\u0394\u2009=\u2009\u22125.00\u2009g\/L, 95% CI \u22126.2 to \u22123.8) and bilirubin elevation (\u0394\u2009=\u2009+0.95\u2009\u03bcmol\/L, 95% CI +0.4 to +1.5), but only 0.2% (2\/730) progressed to severe anemia. Subclinical hemolysis (LDH &gt;\u2009250\u2009U\/L) was prevalent (89.3%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Beta\u2010lactams exhibit high asymptomatic antibody rates (18.07%) with minimal severe hemolysis risk (0.2%). Protocolized monitoring and HLA screening may optimize safety. This first large\u2010scale prospective cohort quantifies the underrecognized epidemic of subclinical antibody formation, challenging traditional pharmacovigilance frameworks that focus solely on overt hemolysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70259","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T04:51:52Z","timestamp":1770094312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Incidence and Clinical Significance of Drug\u2010Induced Antibodies and Hemolytic Anemia Associated With Beta\u2010Lactam Antibiotics: A Prospective Cohort Study"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2283-675X","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Transfusion Medicine Sichuan University West China Hospital  Chengdu 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