Staphylococcus pettenkoferi : an underrecognized species with clinically relevant antimicrobial resistance. A comprehensive genomic European study

Staphylococcus pettenkoferi has increasingly been reported as a human pathogen, with virulence potential recently confirmed in vivo. However, its genomic diversity and antimicrobial resistance remain insufficiently characterized. This study, conducted within the PETTENK-OS project of the ESCMID Study Group for Staphylococci and Staphylococcal Diseases (ESGS), aimed to characterize the genomic diversity and resistome of this underrecognized coagulase-negative staphylococcus (CoNS). Whole-genome sequencing was performed on 61 European clinical isolates (mainly bloodstream infections and osteomyelitis) from 17 hospitals in five countries, plus two reference strains. Antimicrobial susceptibility profiles were determined by disk diffusion and broth microdilution (2025 EUCAST breakpoints). Phylogenetic analyses clustered the 63 isolates into two major clades: Clade I (n = 51; subclades I-A, n = 47, and I-B, n = 4) and Clade II (subclades II-A, n = 8, and II-B, n = 3). Susceptibility rates were below 70% for cefoxitin, erythromycin, and levofloxacin, whereas high susceptibility (>90%) was observed for vancomycin, teicoplanin, dalbavancin, aminoglycosides, oxazolidinones, trimethoprim-sulfamethoxazole, fusidic acid, and tetracycline. Nearly all isolates (92.1%) were fosfomycin-resistant. Daptomycin MIC50/90 values (1/2 mg/L) were elevated, including eight resistant isolates carrying mutations in walKR, cls1, and/or cls2 genes. Twenty-two isolates (35.4%) were multidrug-resistant, and 18 (28.6%) were methicillin-resistant, all in subclade I-A and mecA-positive within SCCmec type IV. This study provides a comprehensive genomic and phenotypic assessment of antimicrobial resistance in S. pettenkoferi, revealing widespread multidrug-resistant lineages, including ceftobiprole- and daptomycin-resistant isolates across distinct clades. These findings underscore the need for continued surveillance and improved diagnostics for this increasingly encountered CoNS species.