Study Compares Hypervirulent Infections

The study, “Genomically Defined Hypervirulent Klebsiella Pneumoniae Contributed to Early-Onset Increased Mortality,” was published in Nature Communications on March 1.  

This study builds on researchers’ long investigations of hypervirulent Klebsiella pneumoniae, or hvKp, Russo says. He explains that, in the 1980s, a new hypervirulent pathotype of Klebsiella pneumoniae emerged in Taiwan that behaved differently from what’s now called classical Klebsiella pneumoniae.  

Classical K. pneumoniae, or cKp, infections typically occur within hospitals and health care settings, most often among patients with comorbidities. But hvKp is capable of infecting young, healthy people in the community, not just patients in health care settings, causing meningitis, infection of the eyes, necrotizing fasciitis, abscesses, and other serious infections, including multiple sites of infection, which is unusual for cKp.  

“Young, otherwise healthy people are at risk for infections due to hvKp, whereas the people who get cKp infections usually have underlying disease, and these infections are primarily health care-associated,” Russo says. 

Russo and colleagues later identified five genes that could be used as biomarkers to identify hvKp versus cKp strains with 95 percent accuracy.  

Further research indicated that all five genetic biomarkers must be present to classify a Klebsiella pneumoniae strain as hypervirulent. This finding, Russo says, needed emphasis after some researchers began classifying strains as hypervirulent if they contained only one or some — but not all five — of the biomarkers.  

In the current paper, the researchers conducted a longitudinal cohort study to compare several groups of patients with Klebsiella pneumoniae infections to better understand virulence, mortality rates, and other clinical outcomes. 

The study, which included data collected from 2017 to 2023, focused on patients in China because of that region’s high hvKp prevalence. “hvKP infections occur around the world but are much more common in the Asian Pacific Rim for reasons that are not clear,” Russo says. “This study used the presence of all five biomarkers to rigorously define the hvKp group so that we have greater confidence in the data,” Russo says.  

The team analyzed data and compared outcomes of people infected with K. pneumoniae strains that possessed none of the genetic hypervirulent biomarkers, those infected with strains containing only one to four of the five biomarkers, and those containing all five biomarkers. They further used propensity score matching, a statistical matching technique, to ensure these groups had similar comorbidities. 

The results indicated that hvKp clearly causes more severe disease and increased mortality. The mortality rate in the hvKp cohort was 17.0 percent at 14 days compared to 7.4 percent in the cKp cohort. 

The analysis also revealed that hvKp strains are less likely to acquire antimicrobial resistance than previously believed, Russo says, adding that strains previously misclassified as hypervirulent may have inflated antimicrobial resistance figures within the medical literature.  

While cKp infection often leads to pneumonia, the study results indicated that hvKp strains caused pneumonia more commonly than previously thought, in addition to their ability to cause abscesses, meningitis, and other infections often associated with hvKp.  

Another surprising finding, Russo notes, is that many cases of hvKp infection originated in health care settings. “hvKp, which was originally described as primarily a cause of community-acquired infection, is now, at least in China, infecting patients in health care settings,” Russo says.  

That finding is of particular concern, Russo says. hvKp is known to cause serious disease in healthy individuals. However, it can be especially severe and deadly when infecting hospitalized, more vulnerable patients.  

Currently there are no approved clinical lab tests to differentiate between cKp and hvKp strains. The genomic analysis, which looks for the five biomarkers, while highly reliable, is imperfect, Russo adds; it’s possible for a strain to possess all five biomarkers but still lack hypervirulence. Further, the genomic analysis is validated using mouse models, a process that can take 14 days. 

Nonetheless, Russo says that approval of an accurate, pragmatic test to differentiate hvKp from cKp, such as an assessment for the five biomarkers, is needed for optimal patient care, infection control, and surveillance.

In the meantime, it’s important that clinicians remain vigilant and consider the clinical context when suspecting hvKp infection, Russo says. “We now need to be cognizant that hypervirulent strains can also get into hospitals and cause infections in these settings,” he says. 

Additional study authors include researchers from Peking University Third Hospital and Capital Medical University, both in Beijing, China. This study was supported by the National Institutes of Health, the Department of Veterans Affairs, and several organizations in China.