Despite the reported virulence of hypermucoviscous Klebsiella pneumoniae strains, these organisms may be associated with good prognoses, according to a study published in the Journal of Antimicrobial Chemotherapy.

K pneumoniae is a frequent causative micro-organism for bloodstream infection. Early mortality rates of K pneumoniae bloodstream infection are still high, despite improvements in clinical practice. Risk factors for early mortality include the underlying comorbidities of patients, initial severity of the disease, and primary site of infection. In addition, bacterial pathogenic factors, such as virulence factors and antimicrobial susceptibility are crucial elements affecting clinical outcomes of people with bloodstream infection.

K pneumoniae strains are grouped in >160 capsular types by serotyping. Hypervirulent-K pneumoniae, including K1 and K2 strains, usually exhibits hypermucoviscous phenotypes and the presence of these strains has been reported to be a risk factor for mortality in patients with this infection. The global spread of multidrug-resistant (MDR) strains are another concern regarding K pneumoniae. However, the effects of the hypervirulent-K pneumoniae and each virulence factor on early mortality from K pneumoniae bloodstream infection in human patients have not yet been demonstrated. Therefore, this study conducted a comprehensive analysis to investigate risk factors in patients with K pneumoniae bloodstream infection with a focus on antimicrobial resistance and virulence factors.

Over a 1-year period, all people with K pneumoniae bloodstream infection (n=579; median age, 71 years) from 6 general hospitals were included. The risk factors for hosts and causative K pneumoniae isolates were assessed by multivariate Cox hazards modelling to determine associations with 30-day mortality in patients with K pneumoniae bloodstream infection. The Charlson comorbidity index was used to evaluate underlying conditions in patients, and the sequential organ failure assessment (SOFA) score was used to determine initial disease severities.

The 30-day mortality rate for patients with K pneumoniae bloodstream infection was 16.9%. Results showed that pks carriage by a causative strain was an independent risk factor for 30-day mortality in those with K pneumoniae bloodstream infection, especially when accompanied by MDR strains of the bacteria. K pneumoniae strains with wzi50 genotype were associated with increased 30-day mortality. In K pneumoniae isolates, the pks gene cluster was observed more frequently in hypervirulent-K pneumoniae, including K1, K2, and K20. This genotoxin has been demonstrated to induce DNA damage in host cells by DNA double-strand breaks, resulting in cell cycle arrest and apoptosis of injured cells. Conversely, hypervirulent-K pneumoniae is associated with invasive liver abscess syndrome, and hypervirulent‑K pneumoniae isolates showed an inverse association with 30‑day mortality. Further, host-associated risk factors strongly associated with increased 30-day mortality included an increased SOFA score and leukopenia status.

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Overall, the study authors concluded that, “Importantly, carriage of the pks gene cluster, which is responsible for the synthesis of colibactin, was a relevant marker of early mortality. Therefore, clinicians should carefully manage patients with [bloodstream infection] caused by MDR K pneumoniae strains carrying the pks gene cluster.”

Reference

Kim D, Park BY, Choi MH, et al. Antimicrobial resistance and virulence factors of Klebsiella pneumoniae affecting 30 day mortality in patients with bloodstream infection [published online October 5, 2018]. J Antimicrob Chemother. doi: 10.1093/jac/dky397