Molecular epidemiology and genomic dynamics of isolates causing relapse infections.

() is one of the leading causes of chronic infections, including reinfection, relapse, and persistent infection, especially in cystic fibrosis patients. Relapse infections are more harmful because of repeated hospitalization and undertreatment of antimicrobials. However, relapse infection in China remains largely unknown. Herein, we performed a 3-year retrospective study from 2019 to 2022 in a tertiary hospital, which included 442 . isolates from 196 patients. Relapse infection was identified by screening clinical records and whole-genome sequencing (WGS). We found that 31.6% (62/196) of patients had relapsed infections. The relapse incidence of carbapenem-resistant infection (51.4%) is significantly higher than that of carbapenem-susceptible infection (20.2%, < 0.0001). These isolates were assigned to 50 distinct sequence types and sporadically distributed in phylogeny, indicating that relapsed infections were not caused by certain lineages. Fast adaptation and evolution of isolates were reflected by dynamic changes of antimicrobial resistance, gene loss and acquisition, and single-nucleotide polymorphisms during relapse episodes. Remarkably, a convergent non-synonymous mutation that occurs in a pyochelin-associated virulence gene (T1056C, M252T) could be a considerable target for the diagnosis and treatment of relapse infection. These findings suggest that integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapsed infections. Continued surveillance of the genomic dynamics of relapse infection will generate further knowledge for optimizing treatment and prevention in the future.IMPORTANCE is a predominant pathogen that causes various chronic infections. Relapse infections promote the adaptation and evolution of antimicrobial resistance and virulence of , which obscure evolutionary trends and complicate infection management. We observed a high incidence of relapse infection in this study. Whole-genome sequencing (WGS) revealed that relapse infections were not caused by certain lineages of isolates. Genomic dynamics of relapse among early and later stages reflected a plasticity scattered through the entire genome and fast adaptation and genomic evolution in different ways. Remarkably, a convergent evolution was found in a significant virulence gene fptA, which could be a considerable target for diagnosis and treatment. Taken together, our findings highlight the importance of longitudinal surveillance of relapse infection in China since cystic fibrosis is rare in Chinese. Integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapse infections.