Comparing clinical, microbiological and genetic definitions of relapse in patients with subsequent episodes of MRSA bone and joint infection.

Background: Differentiation of a relapse from a new infection is challenging in patients with a recurrent bone or joint infection (BJI). We compared clinical, microbiological, and genomic definitions of relapse among patients with methicillin resistant Staphylococcus aureus (MRSA) BJI.

Methods: All MRSA isolates obtained from BJIs between July 2018 and December 2022 from patients with at least 2 episodes of BJI from two U.S. hospitals underwent whole-genome sequencing. Distinct intrasubject lineages (ISLs) were defined as MRSA genomes from the same individual differing by <100 single nucleotide polymorphisms. Clinical, microbiological, and population genomic criteria were each separately compared to a gold standard for relapse vs. new infection of genomically defined ISLs. The level of agreement was calculated with Cohen's kappa. A multivariable analysis was performed to define factors associated with the occurrence of recurrent episodes with different ISLs.

Results: We included 264 isolates from 80 subjects with a range of 2-5 episodes spanning 16 - 1,403 days. In total, 29 subjects (36%) had >1 ISL. Multilocus sequence type (ST) 8 was the most common (n=147, 55.7%). In multivariable analysis, female sex and antibiotic susceptibility differences in MRSA strains were associated with >1 ISL. Compared to the genomic definition of relapse (same ISL), the level of agreement was poor (Cohen's kappa = -0.16) for the clinical definition, fair for the microbiological definition (Cohen's kappa = 0.29), and substantial for the MLST definition (Cohen's kappa = 0.63).

Conclusions: Clinical and microbiological criteria were not accurate in distinguishing a relapse of BJI from a new infection.