Whole-Genome Sequencing May Pinpoint Treatment of Drug-Resistant Infections Faster

Whole-genome sequencing could help identify drug-resistant bacteria, speeding up the time it takes to pinpoint the best treatment, according to a proof of concept study published in Antimicrobial Agents and Chemotherapy.

The method, which examined several strains of Klebsiella pneumoniae bacteria, used a nanopore DNA sequencer, which measures an electrical signal as DNA passes through a tiny pore. The results suggest the method could help health care providers save about 24 hours in pinpointing the appropriate treatment. The current standard process takes about 96 hours.

"It's important because for critically ill patients every hour could increase their mortality risk," Pranita Tamma, MD, MHS, an associate professor of pediatrics at Johns Hopkins Children’s Center and an author of the study, told Contagion^®.

Dr. Tamma worked with Patricia J. Simner, MSc, PhD, the senior author of the study and an associate professor of pathology and medical microbiology at the John Hopkins University School of Medicine, and others on the work.

The study, which examined bacterial DNA extracted from 40 adult patients hospitalized at The Johns Hopkins Hospital, used two different approaches to predict phenotypic antimicrobial susceptibility testing (AST) profiles. An assembly-based approach identified resistance genes within 14 hours of culture isolates with a a 92 percent accuracy rate. A real-time approach revealed resistance genes within 8 hours of culture isolates with a 77 percent accuracy rate.

"We were definitely very pleased with the accuracy of it," Dr. Tamma told Contagion^®. "It is higher than I thought it would be, which is very exciting."

She said targeted treatment can help prevent bacteria from acquiring new resistance, which is a risk of using the most powerful treatments unnecessarily. It also reduces the likelihood of health care providers choosing ineffective treatments.

"The benefit is ultimately for the patient because you're getting critically ill patients on the right drug earlier," Dr. Tamma told Contagion^®.

More research is expected to test the method on different bacteria strains, and the technology could begin to be used in clinical microbiology laboratories in the next five to 10 years.

"As aggressive as we're working to develop new drugs, I think we need to be equally aggressive in detecting antibiotic resistance earlier than we currently can," Dr. Tamma told Contagion^®.

Antibiotic-resistant microbes infect at least 2 million people in the US each year, and at least 23,000 people die as a result, according to the US Centers for Disease Control and Prevention. By 2050, more people are predicted to die from antibiotic resistance than from cancer, according the Review on Antimicrobial Resistance commissioned by the UK Prime Minister in 2014.

"This is definitely not a problem that's going away anytime soon. It's just going to get worse," Dr. Tamma said. "This kind of research is definitely going to keep being ongoing, and it has to for us to keep up with these resistant bacteria."

Efforts have been ongoing to speed detection and improve treatment of antibiotic resistant bacteria. SeLux Diagnostics recently developed a phenotyping system to help health care providers identify bacteria and determine antibiotic susceptibility to pinpoint targeted antibiotics that will be most effective.

Antimicrobial resistance is recognized as a global crisis, leading to the formation of an international network of study sites to help improve enrollment of patients in interventional studies.