Nunes, AlexandraOleastro, MónicaAlves, FredericoLiassine, NadiaLowe, David M.Benejat, LucieDucounau, AstridJehanne, QuentinBorges, VítorGomes, João PauloGodbole, GauriPhilippe, Lehours2024-01-122024-01-122023-08-17Microbiol Spectr. 2023 Aug 17;11(4):e0107023. doi: 10.1128/spectrum.01070-23. Epub 2023 Jun 26.2165-0497http://hdl.handle.net/10400.18/8898Erratum in: Microbiol Spectr. 2023 Dec 12;11(6):e0312123. doi: 10.1128/spectrum.03121-23. Epub 2023 Oct 10.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10434052/We present two independent cases of recurrent multidrug-resistant Campylobacter jejuni infection in immunocompromised hosts and the clinical challenges encountered due to the development of high-level carbapenem resistance. The mechanisms associated with this unusual resistance for Campylobacters were characterized. Initial macrolide and carbapenem-susceptible strains acquired resistance to erythromycin (MIC . 256mg/L), ertapenem (MIC . 32mg/L), and meropenem (MIC . 32mg/L) during treatment. Carbapenem-resistant isolates developed an in-frame insertion resulting in an extra Asp residue in the major outer membrane protein PorA, within the extracellular loop L3 that connects b-strands 5 and 6 and forms a constriction zone involved in Ca21 binding. The isolates presenting the highest MIC to ertapenem exhibited an extra nonsynonymous mutation (G167AjGly56Asp) at PorA’s extracellular loop L1. IMPORTANCE Carbapenem susceptibility patterns suggest drug impermeability, related to either insertion and/or single nucleotide polymorphism (SNP) within porA. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.Importance: Carbapenem susceptibility patterns suggest drug impermeability, related to either insertion and/or single nucleotide polymorphism (SNP) within porA. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.engCampylobacter jejuniRecurrent InfectionHigh-level Carbapenem Resistanceimmunocompromised PatientsMacrolide ResistanceMajor PorinInfecções GastrointestinaisRecurrent Campylobacter jejuni Infections with In Vivo Selection of Resistance to Macrolides and Carbapenems: Molecular Characterization of Resistance Determinantsjournal article10.1128/spectrum.01070-23