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. 2025 Dec 20;232(6):1338-1350.
doi: 10.1093/infdis/jiaf352.

Methicillin-Resistant Staphylococcus aureus Bacteremia Relapses Show Diverse Genomic Profiles but Convergence in Bacteremia-Associated Genes

Brooke M Talbot  1 , Natasia F Jacko  2   3 , Katrina S Hofstetter  1 , Tara Alahakoon  2 , Kevin Bouiller  2   4 , Timothy D Read  1 , Michael Z David  2   3
Affiliations

Methicillin-Resistant Staphylococcus aureus Bacteremia Relapses Show Diverse Genomic Profiles but Convergence in Bacteremia-Associated Genes

Brooke M Talbot et al. J Infect Dis. .

Abstract

Background: Recurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a high risk complication for patients. Distinguishing persistent lineages from new infections is not standardized across clinical studies.

Methods: 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 contained isolates ≤ 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.

Results: Among 411 sequential subjects with MRSA bacteremia, 32 experienced recurrent bacteremia episodes, with 24 subjects having exclusively relapse infections, 6 with infections exclusively from a new strain, and 2 patients with both relapse and new infections. No concordance between a genomic and a clinical definition of relapse was evident (Cohen κ = 0.18; confidence interval, -0.41). Recurrence-associated lineages exhibited signatures of positive selection (G test, < 0.01). Genes with SNPs occurring in multiple relapse lineages have roles in antibiotic resistance and virulence, including 5 lineages with mutations in mprF and 3 lineages with mutations in rpoB, which corresponded with evolved phenotypic changes in daptomycin and rifampin resistance.

Conclusions: Recurrent infections have a diverse strain background. Relapses can be readily distinguished from newly acquired infections using genomic sequencing but not clinical criteria.

Keywords: antibiotic resistance; genomic epidemiology; hospital epidemiology; infection prevention.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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