Clinical and genomic characteristics of hypervirulent Klebsiella pneumoniae isolated from throat culture suggesting an emerging causative agent of pharyngitis
摘要
Hypervirulent Klebsiella pneumoniae (hvKp) is rarely implicated in non-invasive infections. We report eleven cases of pharyngitis with whole genome sequencing of throat culture isolates identifying hvKp. Most cases (64%) occurred in the summer months of June to September. Cases were geographically diverse and only one patient reported recent travel outside of the continental US. No patients were diabetic or immunosuppressed, though five patients (45%) were prescribed inhaled or intranasal corticosteroids. Clinical presentation was indistinguishable from viral or streptococcal pharyngitis. All isolates were string-test positive. Genetic serotyping and multi-locus sequence typing identified four unique strains: K2–ST3252 (n = 4 cases), K1–ST23 (n = 3 cases), K2–ST66 (n = 3 cases), and K2–ST2039 (n = 1). Virulence biomarkers iucA, iroB, peg-344, and rmpA were present in all isolates, with rmpA2 only in ST23 isolates. Four hypervirulence-associated plasmids were identified, with ST23 isolates additionally harboring antimicrobial resistance associated plasmids. All isolates carried fluoroquinolone-resistance genes oqxA and oqxB, and ST23 isolates expressing beta-lactamase (blaSHV-187-like) and fosfomycin-resistance genes (fosA6). Despite the presence of genetic resistance markers, all isolates were phenotypically susceptible to common antibiotics. Single nucleotide polymorphism (SNP) analysis revealed high genetic similarity (<2 SNPs) among three ST3252 isolates from the same family, while other isolates showed greater diversity. All patients received oral antibiotics with resolution of symptoms, and post-treatment throat culture showed eradication of hvKp in three of four patients tested. Invasive disease did not develop in any patients. Our study proposes a causative association between hvKp and symptomatic pharyngitis as it circulates endemically in the community.