Revisiting mutational resistance to ampicillin and cefotaxime in Haemophilus influenzae

Autor: Margo Diricks, Sabine Petersen, Lennart Bartels, Thiên-Trí Lâm, Heike Claus, Maria Paula Bajanca-Lavado, Susanne Hauswaldt, Ricardo Stolze, Omar Jiménez Vázquez, Christian Utpatel, Stefan Niemann, Jan Rupp, Inken Wohlers, Matthias Merker
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Genome Medicine, Vol 16, Iss 1, Pp 1-17 (2024)
Druh dokumentu: article
ISSN: 1756-994X
DOI: 10.1186/s13073-024-01406-4
Popis: Abstract Background Haemophilus influenzae is an opportunistic bacterial pathogen that can cause severe respiratory tract and invasive infections. The emergence of β-lactamase-negative ampicillin-resistant (BLNAR) strains and unclear correlations between genotypic (i.e., gBLNAR) and phenotypic resistance are challenging empirical treatments and patient management. Thus, we sought to revisit molecular resistance mechanisms and to identify new resistance determinants of H. influenzae. Methods We performed a systematic meta-analysis of H. influenzae isolates (n = 291) to quantify the association of phenotypic ampicillin and cefotaxime resistance with previously defined resistance groups, i.e., specific substitution patterns of the penicillin binding protein PBP3, encoded by ftsI. Using phylogenomics and a genome-wide association study (GWAS), we investigated evolutionary trajectories and novel resistance determinants in a public global cohort (n = 555) and a new clinical cohort from three European centers (n = 298), respectively. Results Our meta-analysis confirmed that PBP3 group II- and group III-related isolates were significantly associated with phenotypic resistance to ampicillin (p
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