Hypervirulent, hyper-resistant pneumonia superbug kills 5 in China hospital

A fatal pneumonia outbreak in five patients in a hospital in China has led to the discovery of a hyper-resistant, hypervirulent, and highly transmissible Klebsiella pneumoniae superbug, scientists reported in the journal The Lancet Infectious Diseases.

The new and emerging superbug is a double threat because it combines the hypervirulence of one K. pneumoniae strain with the hyper-resistance of another one. Because it can cause untreatable and fatal infections even in relatively healthy individuals, it poses an enormous danger to human health, according to scientists at Hong Kong Polytechnic University (PolyU), in Kowloon, China.

The outbreak began in February 2016 in the intensive care unit at the Second Affiliated Hospital of Zhejiang University, in Hangzhou, China. All five patients were on mechanical ventilation following surgery for multiple trauma. They all developed severe pneumonia, had poor responses to antibiotic treatment, and eventually died of severe lung infection, septicemia, and/or multiple organ failure.

To investigate, Chen Sheng, PhD, professor of Applied Biology and Chemical Technology at PolyU, collaborated with Rong Zhang, PhD, of the Department of Clinical Laboratory Medicine at the Second Affiliated Hospital. They found that the causative agent was a carbapenem-resistant K. pneumoniae (CRKP) strain of the ST11 type, which is the most prevalent and transmissible carbapenem-resistant K. pneumoniae type in China.

But further analysis showed that the samples from the five patients also contained several antibiotic resistance genes, allowing it to resist to carbapenem antibiotics. In addition, lab tests indicated that the bacteria were unusually hypervirulent, which is not typical for ST11 strains.

This new strain—named ST11 CR-HvKP (ST11 carbapenem-resistant hypervirulent K. pneumoniae)—is a “real superbug,” the investigators noted, because it simultaneously exhibits hyper-resistance, hypervirulence, and high transmissibility.

“Due to its hypervirulence and phenotypic resistance to commonly used antibiotics, ST11 CR-HvKP strains may cause untreatable and fatal infections in relatively healthy individuals with normal immunity,” the investigators warned.

They noted that ST11 CR-HvKP has an outer mucoid layer, making it easy to stick to surfaces such as medical devices and tubing. “The transmission route is not clear yet, but our data suggest that medical equipment, such as ventilators and different catheters, might be transmitting these new superbug strains,” the authors wrote. As a result, the superbug can cause opportunistic infections in clinical settings, such as ventilator-associated pneumonia.

“The ST11 CR-HvKP strains do not only infect lungs and cause pneumonia, but also invade the bloodstream and other internal organs,” they added. “Novel strategies must be devised to prevent ST11 CR-HvKP from proliferating extensively in the human intestinal tract where they were detected.”

The investigators tried treating the superbug with colistin—the drug of last resort for carbapenem-resistant enterobacteriaceae infections—both alone and in combination with other drugs, but found the drug was ineffective against ST11 CR-HvKP infections.

Although it’s not approved for use in China, eftazidime/avibactam (Avycaz^® made by Allergan) might be effective against the superbug, the researchers speculated. However, “ST11 CR-HvKP may develop resistance to this antibiotic very quickly, based on the clinical data from the USA,” they noted.

For now, heightened infection prevention and control measures appear to have averted further transmission of the superbug in the hospital ICU, the investigators reported.

But if the superbug spreads, it has the potential to cause a global epidemic.

“Because of the genetic similarity between ST11 and ST258 types of K. pneumoniae, ST258 hypervirulent K. pneumoniae strains might have emerged and become transmissible in the USA and in European countries,” the authors wrote.

“Future research should focus on the development of intervention measures to prevent further dissemination of such organisms in hospital settings,” they advised.