Big data targets drug resistance

Daly, who, before becoming dean directed the pediatric bone marrow program at Boston Children’s Hospital and the Dana-Farber Cancer Institute, said physicians there — concerned about infection because bone marrow transplants weaken the immune system — could see that the tools they had at their disposal were weakening.

“The fact is that the diminishing potency of our prophylactic armamentarium really was quite frightening. There were lots of diseases and infections that, once they set in, despite our efforts at prophylaxis, it became very, very challenging,” Daly said. “In virtually every medical context, the physicians’ arsenal of antimicrobial therapies has become a rapidly dwindling set. New therapies are just not being developed fast enough.”

The problem is alarming enough, Daly said, that in 2016 the World Health Organization declared it one of the greatest threats to global health and made it a top priority.

Though improper use of drugs — for the wrong microbes, or in regimens that don’t completely eradicate the infection, leaving the hardiest surviving microbes alive to multiply — can increase resistance, it’s also a natural process, part of an ongoing arms race between microbe and host, Daly said. Research has found mechanisms of drug resistance in 30,000-year-old microbes frozen in permafrost, indicating that it is a natural phenomenon and not a result of poor prescribing practices and patient adherence.

“What it says is that the constant battle between pathogen and host … has been an ancient battle. It’s now playing out in the human body,” Daly said.

While Daly said that new antibiotic drugs are needed, progress in fighting resistance will come from other sources as well, including leveraging insights about bacteria gleaned by analyzing the large data sets newly available. One potentially fruitful area, Daly said, is the vast amount of genomic data now available that can provide a better understanding of a microbe’s weaknesses.

Thousands of tuberculosis genomes have been analyzed, for example, as researchers look to better understand patterns of drug resistance in a bacterium that ranks high on a global list of the most worrisome drug-resistant infections.

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