Epidemiological, Phylogenetic, and Resistance Heterogeneity Among in a Large U.S. Deep South Healthcare system.

BACKGROUND

() disease in the United States is commonly attributed to outbreaks of 1 or 2 monophyletic carbapenem resistance (CR) lineages that vary by region. However, there is limited knowledge regarding CR epidemiology and population structures in the U.S. Deep South, and few studies compare contemporary CR and carbapenem-susceptible (Cs) , despite relative prevalence of the latter.

METHODS

We performed a multiyear analysis of 2462 cases in a large healthcare system in Birmingham, AL, and 89 post-2021 isolates were sequenced and phenotyped by antibiotic susceptibility tests.

RESULTS

Although the cumulative CR rate was 17.7% in our cohort, rates regularly increased in winter months as result of seasonal changes in case incidence of Cs, specifically. Genotyped CR belonged to clonal group (CG) 1, CG2, CG108, CG250, or CG499, with local clones of CG108, CG250, and CG499 persisting over multiple months. There was no clonal expansion of any Cs lineage. Among CR isolates, levels of β-lactam antibiotic resistance and the repertoire of related genetic resistance determinants, which included the novel CR-conferring FtsI A515V polymorphism, differed according to CG. CG108 and CG499 isolates displayed specific heteroresistance to sulbactam and trimethoprim/sulfamethoxazole, respectively, which resulted in discrepant susceptibility results in microbroth versus agar-based antibiotic susceptibility tests modalities.

CONCLUSIONS

We report an unusually high degree of CR phylogenetic diversity principally driven by emergent U.S. lineages harboring novel resistance elements that must be incorporated into diagnostic, surveillance, and preclinical research efforts.