Antibiotic-resistant hypervirulent K. pneumoniae in US patients , a threat

The scientists from Emory Antibiotic Resistance Center have for the first time isolated an hypermucoviscous strain of Klebsiella pneumoniae (from a patient in the U.S.) that is resistant to carbapenems class of antibiotics and exhibits enhanced virulence and colistin heteroresistance.

The research was presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7-11 2018, in Atlanta, Georgia.

Jessie Wozniak, a Microbiology and Molecular Genetics graduate student at Emory University School of Medicine, and colleagues, conducted the study to assess the potential presence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) using isolates collected by Emerging Infections Program's (EIP) Multisite Gram-negative Surveillance Initiative (MuGSI), which collects carbapenem-resistant isolates from 8 states across the country.

"The problem of antibiotic resistance is becoming increasingly alarming. The combination of increased virulence and multidrug resistance makes the situation worse," said Dr. David Weiss, director of the Emory Antibiotic Resistance Center.

For the study, the researchers examined 265 isolates of carbapenem-resistant K. pneumoniae from the MuGSI, using a simple "string test."

In a hospital in Hangzhou, China, a 2016 deadly outbreak of carbapenem-resistant, hypervirulent K. pneumoniae was recently reported in Lancet Infectious Diseases.

Key Findings:

• K. pneumoniae isolate was heteroresistant to the last resort antibiotic colistin, this means that a small subpopulation of cells showed resistance.


• Heteroresistance is more difficult to detect with standard antibiotic susceptibility tests in clinical microbiology labs, and this isolate was classified as susceptible to colistin by standard methods.


• This discrepancy is particularly important, as Weiss' lab has shown that such undetected colistin heteroresistance can cause antibiotic treatment failure in mice.


• The stretchiness observed by the string test is a sign that the bacteria produce more capsule polysaccharide, and has been associated with enhanced virulence previously.


• the isolate was approximately ten times more virulent in mice than other isolates of the same sequence type.


• The U.S. isolate carried several antibiotic resistance genes, along with a new arrangement of virulence genes, but not the same set seen in similar K. pneumoniae isolates from Asian countries.

"The isolate we are studying is not nearly as virulent (able to cause disease) in a mouse model as the bacteria from China," said Dr. Weiss, "However, finding the combination of antibiotic resistance and enhanced virulence from a clinical isolate in the United States (New York) is still alarming." The previously reported hypervirulent forms were largely antibiotic susceptible. Carbapenem-resistant K. pneumoniae, part of the carbapenem-resistant enterobacteriaceae (CRE) superbug family, is considered an urgent (top 3) threat by the CDC.

The researchers are urging more monitoring for this form of bacteria, which have the potential for increased virulence and may be especially worrisome in healthcare settings.

"The string test is very low-tech," Wozniak says. "You take a loop, touch it to the bacterial colony, and pull back. The hypermucoviscous one looks like a string of cheese being pulled from a pizza."