{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:47:55Z","timestamp":1768571275401,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,28]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"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":[[2025,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Recurrence of methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) bacteremia is a high risk complication for patients. Distinguishing persistent lineages from new infections is not standardized across clinical studies.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated factors contributing to recurrence of MRSA bacteremia among subjects in Philadelphia, Pennsylvania. Subject demographics and clinical history were collected and paired with whole-genome sequences of infection isolates. Recurrent bacteremia episodes were recorded and defined as relapse infections (same lineage) or new infections by genomic criteria, where a relapse contains isolates &lt;=25 single nucleotide polymorphisms (SNP) different, and by clinical criteria. All isolates were assessed for pairwise SNP distances, common mutations, and signatures of within-host adaptation using the McDonald-Kreitman test. Clusters of transmission between relapse-associated isolates and other subject lineages were identified.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Among 411 sequential subjects with MRSA bacteremia, 32 experienced recurrent bacteremia episodes, with 24 subjects having exclusively relapse infections, six with infections exclusively from a new strain, and two patients with both relapse and new infections. No concordance between a genomic and a clinical definition of relapse was evident (Cohen\u2019s Kappa = 0.18, CI: -0.41). Recurrence-associated lineages exhibited signatures of positive selection(G- test:&lt;0.01) . Genes with SNPs occurring in multiple relapse lineages have roles in antibiotic resistance and virulence, including 5 lineages with mutations in\n                    <jats:italic>mprF<\/jats:italic>\n                    and 3 lineages with mutations in\n                    <jats:italic>rpoB,<\/jats:italic>\n                    which corresponded with evolved phenotypic changes in daptomycin and rifampin resistance.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Recurrent infections have a diverse strain background. Relapses can be readily distinguished from newly acquired infections using genomic sequencing but not clinical criteria.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.24.25324140","type":"posted-content","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T01:22:51Z","timestamp":1743297771000},"source":"Crossref","is-referenced-by-count":1,"title":["Genomic investigation of MRSA bacteremia relapse reveals diverse genomic profiles but convergence in bacteremia-associated genes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5246-7209","authenticated-orcid":false,"given":"Brooke M.","family":"Talbot","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8295-7951","authenticated-orcid":false,"given":"Natasia F.","family":"Jacko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-2027","authenticated-orcid":false,"given":"Katrina S.","family":"Hofstetter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6395-8668","authenticated-orcid":false,"given":"Tara","family":"Alahakoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2177-4318","authenticated-orcid":false,"given":"Kevin","family":"Bouiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-9680","authenticated-orcid":false,"given":"Timothy D.","family":"Read","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Z.","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"11","key":"2025040102401028000_2025.03.24.25324140v1.1","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1093\/cid\/ciad500","article-title":"Contemporary Management of Staphylococcus aureus Bacteremia-Controversies in Clinical Practice","volume":"77","year":"2023","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am. 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