Landmark Developments in Infectious Diseases

A 20-Year Look-Back: Two Steps Forward, One Step Back

Ingrid G. Hein


October 20, 2015

In This Article

Antibiotics, Resistance, and the Human Microbiome

"A new class of antibiotics—the fluoroquinolones—are among the most important to hit the field in the past 20 years," said John Bartlett. These drugs are well tolerated intravenously or by mouth, and quickly became the standard of treatment for several conditions (such as pneumonia). Bartlett commented, "We use those drugs like candy."

That has to change, he says. New antibiotics and new treatments are needed. "The understanding that we might be facing infections that can't be treated [with the antibiotics we have] is a relatively new and scary understanding."

"We're now close to 70 years into the antibiotic era," says Dr Martin Blaser, director of the Human Microbiome Program, New York University Langone Medical Center. "For the first 50-60 years, we could come up with new antibiotics—but the pipeline is dry. Resistance is gaining on antibiotics. We're losing ground."

Antibiotic stewardship has become one of the most important root issues in the fight against infectious diseases. Moreover, it's a widespread problem, because antibiotic use isn't limited to hospitals. Farmers use antibiotics in animals raised for human consumption, and traces of antibiotics are appearing in river water, worsening the problem of resistance through increased exposure to antibiotics.

"We need to create a generation of new narrow-spectrum antibiotics and better diagnostics," says Blaser. "The economics are all wrong. Prescribing the inexpensive broad-spectrum antibiotic is costing us more."

Advocacy for antibiotic stewardship has only been on the forefront for about 10 years. IDSA's 2004 report, Bad Bugs, No Drugs was one of the first to raise the red flag on the problem of antibiotic resistance, and the lack of new antibiotics. "Antibiotics are unique among medicines because drug resistance causes them to become less effective postapproval. Antibiotics are not as profitable as drugs that treat chronic conditions, cancer, or lifestyle issues, owing to their short durations of use (often 7-14 days) and current pricing policies."

IDSA's Stephen Calderwood says "Antibiotic resistance has received some attention, but not much action. The next report, in 2010, was the "10 × '20" initiative. The idea was to develop 10 new antibacterial drugs by 2020.[30]

Calderwood says that since then, seven new antibiotics have been approved for use in people, all in the past year or two. "Momentum is now building, but it needs coordinated levels of support."[31]

In September 2014, the US President's Council of Advisors on Science and Technology released its report on combating antibiotic resistance. The report labeled the situation an "antibiotic-resistance crisis" and called for surveillance, new clinical trials, and stewardship of current antibiotics.

C difficile Infection

C difficile infection is a good example of the consequences of an altered microbiome, says Martin Blaser. "You develop C difficile infection because you have taken antibiotics, but the only way to treat it is with other antibiotics."

We need new ways to treat infection, he says, pointing to a 2013 study on the effectiveness of fecal transplant—the process of transferring a donor's feces, by colonoscopy or enema into the patient's colon, to treat C difficile.[32] "This process restores order to the human ecosystem. It turns out to be very effective."

Blaser says that overuse of antibiotics is not limited to causing infection resistance. His hypothesis is that overuse of antibiotics is also contributing to increases in autism, allergies, obesity, juvenile diabetes, and asthma.[33]

John Bartlett says it will be fascinating to find out the impact of fecal transplant on these conditions, on the basis of health features of fecal transplant donors. He says that it's a new, potentially exciting, era for infectious disease. "But for now, we have no practical application, except fecal transplant—which has in fact been a popular treatment for about 5-10 years, predating what we know about the microbiome."

"We choose to take specimens from people who have a normal body mass index and other target characteristics, but we don't know the full impact," he said. "Are there any consequences?"


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