An extremely virulent (hypermucoviscous) strain of Klebsiella pneumoniae (K pneumoniae) that is resistant to carbapenem and colistin has been isolated for the first time from a patient in the United States.
“Although the news is bad, it’s not as bad as it could be. This isolate is about 10 times more virulent than the K pneumoniae strains already circulating in the United States; however, it is less virulent than the isolate from China,” said Jessie Wozniak, a third-year PhD graduate student at Emory University in Atlanta, Georgia, who presented the findings today at the 2018 ASM Microbe Meeting and spoke with Contagion®.
The isolate that was the source of an outbreak last year in a hospital in Hangzhou, China, is the scary stuff of Hollywood movies. It killed 5 people despite the aggressive use of antibiotics. The isolate found by the Emory University investigators can withstand the polymyxin antibiotic colistin, which is being pressed back into service as a last resort to thwart hospital-acquired infections in the era of multidrug resistance.
The investigators were able to show that the isolate was heteroresistant to colistin. Heteroresistance is a phenomenon where only a small number of cells in the total population possess the resistance. This makes them hard to detect. But, given the right selection pressure—in this case, the use of colistin—the small number of cells can burgeon into an infection.
“K pneumoniae may be inching towards prevalence in an already very drug-resistant background of K pneumoniae,” speculates Dr. Wozniak. “So, with time, what has transpired in China is conceivable here.
Adding to the concern, experiments in mice conducted by the Emory University researchers have indicated that colistin heteroresistance that is flying under the detection radar can be setting the stage for the failure of antibiotic treatment when the infection is finally recognized.
Dr. Wozniak was part of the team that examined 265 isolates of carbapenem-resistant K pneumoniae collected by the US Centers for Disease Control and Prevention (CDC) as part of its Emerging Infections Program Multisite Gram-negative Surveillance Initiative. Carbapenem is one of the “last resort” antibiotics. If it proves ineffective, few treatment options are left.
The detection strategy was decidedly low-tech, but effective. By touching an inoculating loop to a colony and withdrawing the loop, hypermucoviscous colonies could be revealed, much like the thread of a triple-cheese pizza as a slice is retrieved. “All the work is done in a fume hood since the capsule string can be up to a foot long,” said Dr. Wozniak.
More in-depth analyses of the isolate detected by this “string test” revealed it to be markedly more virulent in mice than its K pneumonia brethren. Whole-genome sequencing ferreted out several antibiotic resistance genes, including a new arrangement of virulence genes that differ from the K pneumoniae isolates from Asian countries. A key to the virulence appears to be the expression of genes that control the ability of the bacteria to acquire iron. This capability is very important in governing the severity of infection. The isolate also contains an armada of genes that when expressed, bestow resistance to silver, copper, beta-lactamases, fluoroquinolones, and aminoglycoside antibiotics.
The antibiotic resistance of the isolate is broad and includes amikacin, ampicillin/sulbactam, aztreonam, cefazolin, cefepime, ceftazidime, ceftriaxone, gentamicin, ertapenem, levofloxacin, meropenem, piperacillin/tazobactam, tetracycline, tigecycline, tobramycin, nitrofurantoin, and trimethoprim/sulfamethoxazole.
“Taken together, our research supports the conclusion that the emergence of hypermucoviscous, carbapenem-resistant K pneumoniae could be a concern that necessitates further study and surveillance,” the researchers wrote in the poster.