Prevalence of Hypervirulence-Associated Pathogenicity Loci Among Klebsiella pneumoniae Bloodstream Isolates at a United States Hospital

BackgroundKlebsiella pneumoniae (K. pneumoniae) strains have been divided into two major categories: classical K. pneumonia, which are frequently multidrug-resistant and cause hospital-acquired infections in patients with impaired defenses, and hypervirulent K. pneumoniae, which cause severe disseminated community-acquired infections in immunologically normal hosts. Both types of infections may lead to bacteremia and are associated with significant morbidity and mortality. The relative burden of these two types of K. pneumoniae among bloodstream isolates within the United States is not well understood. MethodsWe examined consecutive K. pneumoniae isolates cultured from the blood of hospitalized patients at Northwestern Memorial Hospital (NMH) in Chicago, Illinois April 2015 - April 2017. Bloodstream isolates underwent whole genome sequencing, and clinically relevant data (sequence type [ST], capsule loci, virulence factors, and antimicrobial resistance genes) were inferred from the genome using the bioinformatic tools Kleborate and Kaptive. Patient demographic, comorbidity, and infection information, as well as phenotypic antimicrobial resistance of the isolate were extracted from the electronic medical record. Candidate hypervirulent isolates were tested in a murine model of pneumonia. Complete genome sequences of these candidate hypervirulent isolates were obtained and plasmid content was evaluated. ResultsK. pneumoniae bloodstream isolates (n=104) from NMH were highly diverse consisting of 75 distinct STs and 51 unique capsule loci. The majority of these isolates (n=58, 55.8%) were susceptible to all tested antibiotics except ampicillin, but 17 (16.3%) were multidrug-resistant. A total of 32 (30.8%) of these isolates were STs of known high-risk clones, including ST258 and ST45. In particular, 18 (17.3%) were resistant to ceftriaxone, 17 harbored extended-spectrum beta-lactamases, and 9 (8.7%) were resistant to meropenem. Four (3.8%) of the 104 isolates were hypervirulent K. pneumoniae, as evidenced by hypermucoviscous phenotypes, high levels of virulence in a murine model of pneumonia, and the presence of large plasmids similar to characterized hypervirulence plasmids. Of particular concern, several of these plasmids contained tra conjugation loci suggesting the potential for transmission. Two of these hypervirulent strains belonged to the well characterized ST23 lineage and one to the emerging ST66 lineage. ConclusionsWhile NMH K. pneumoniae bloodstream infections are caused by highly diverse strains, the most prevalent STs were those of multidrug-resistant high-risk clones. A small number of hypervirulent K. pneumoniae were observed in patients with no recent travel history, suggesting that these isolates are undergoing community spread in the United States.