Antimicrobial use on Campylobacter revealed by next-generation sequencing in patients with common variable immunodeficiency

Quentin Jehanne¹Anne Conrad²Raphaële Nove Josserand²Nicolas Benech²Paul Marie Schatz²Lucie Bruhl¹Astrid Ducournau¹Johanna Aptel¹Moeava Martin^1,3Marine Jauvain¹Olivier Dauwalder²PHILIPPE Lehours^1,3*

• ¹CNR des Campylobacters et des Hélicobacters, Bordeaux, France
• ²Hospices Civils de Lyon, Lyon, France
• ³Université de Bordeaux, Bordeaux, France

Because few studies have focused on recurrent Campylobacter bacteremia, we investigated two clinical cases of patients with common variable immunodeficiency and repeated Campylobacter bacteremia over a period of 6 to 10 years. We analyzed and compared genomes from isolates obtained from both patients during follow-up. For patient #1, 18 isolates of Campylobacter coli and 17 isolates of Campylobacter jejuni were obtained from 2014 to 2024. For patient #2, 10 isolates of C. coli were obtained from 2019 to 2024. Next-generation sequencing was used to identify species, characterize antimicrobial resistance, perform multilocus sequence typing, and analyze core-genome single-nucleotide polymorphisms, as well as to uncover potential sources of contamination. For patient #1, all 18 C. coli isolates obtained from 2022 to 2024 were from the same clonal complex and source of contamination (chicken) and exhibited high levels of genomic resemblance based on core-genome single-nucleotide polymorphism analysis. Each C. coli isolate probably originated from the same initial strain. However, two clusters of C. jejuni were identified: one consisting of isolates from 2014 and the other consisting of the remaining isolates from 2022 to 2024. A 16S rRNA mutation in position A1387G was present in four C. coli isolates from 2022 and 2023, and this was associated with gentamicin resistance. One C. coli isolate was also resistant to ertapenem and exhibited an amino acid duplication within the PorA protein sequence. For patient #2, each C. coli isolate was from the same clonal complex, which was of porcine origin. Similar to patient #1, three of the isolates from 2023 had an A1464G 16S rRNA mutation and were gentamicin resistant. Retrospective analyses of antimicrobial use for both patients highlighted an association between antimicrobial selection pressure and the emergence of resistance markers, suggesting in vivo selection.