Change to Resistance

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Once hailed as miracle drugs, antibiotics are in peril.

Antibiotics have fallen victim to their own success.

Evidence of bacterial resistance to antibiotics continues to mount at alarming levels. Studies cited by the Centers for Disease Control and Prevention (CDC) indicate that nearly 50 percent of antimicrobial use in hospitals is unnecessary or inappropriate. The agency warns that “Failure to improve use will mean an empty medicine cabinet for sick patients in the relatively near future.”

Enter Arjun Srinivasan, M.D. ’92. “What has changed and is changing is the awareness that we must work hard to change how we use antibiotics,” he says. As medical director of the CDC’s “Get Smart for Healthcare” campaign, which focuses on appropriate antibiotic stewardship in in-patient facilities, Srinivasan is on the front line of the fight against antimicrobial resistance.

Srinivasan, who also serves as the associate director for healthcare-associated infection prevention programs in the Division of Healthcare Quality Promotion at CDC’s National Center for Emerging and Zoonotic Infectious Diseases in Atlanta, researches infection control, multi-drug resistant gram-negative pathogens and antimicrobial use, and conducts outbreak investigations.

Srinivasan knows antimicrobial stewardship protocols. The issue has been the focus of his work for more than a decade. Beginning in 2007, he led a CDC outbreak team that uncovered problems in hospitals, compounding pharmacies, nursing homes, dialysis facilities and doctor’s offices. Earlier, at the Johns Hopkins School of Medicine, he was a staff physician, associate hospital epidemiologist and founding director of the Johns Hopkins Antibiotic Management Program. While there, he garnered the staff teaching award, and later at CDC his career work resulted in the Society for Healthcare Epidemiology of America’s 2008 Investigator Award.

“The reasons we started the program at Hopkins are even more compelling today,” Srinivasan says.

Applied Learning

Note his use of the word “we.” A big part of Srinivasan’s professional success and happiness stems from his very personal approach to the work and the people doing it—the researchers, doctors, policy-makers and patients. Srinivasan also is a man who is keen to know something of a wide range of subjects and to think critically about them, the better to see patterns and connections.

Both these attributes he traces to his education in the liberal arts and sciences at Davidson. He took the Humanities program, worked at the public radio station WDAV, participated in College Bowl and, his senior year, studied Shakespeare while working on his biology honors thesis as a pre-medical student.

“I graduated having taken exactly the same number of science and non-science classes,” Srinivasan says of his well-rounded academic life. “At Davidson, you don’t end up narrow. That’s why I went there.”

Social lessons of life on campus were at least as important. He and his best friend, Brent Leviner ’92, butted heads hard and often.

“The only thing we agreed on was that we were great, great friends who had knock-down drag-outs about every kind of social and political issue,” Srinivasan says. “It taught me that you can have common goals and common interests and, really, a common view of the world, and still be just diametrically opposed on how to get there. It taught me that just because someone opposes what you do or how you do it doesn’t mean they’re a bad person. Oftentimes, when you frame the discussion in that way, you find out that you’re more similar than you are different.”

That’s not a bad viewpoint to hold in the high-stakes and often fractured and politicized world of American public health care.

The United States in many ways trails the efficacy of more centralized policy-making and record-keeping in Europe. That disparity was just one of the points that Srinivasan and others made last fall on PBS’s Frontline in “Hunting the Nightmare Bacteria.”

During the hour, they delved into the complexities of “gram-negative” bacteria, a class of fast-evolving bacteria whose defensive “armor” has rendered many antibiotics wholly ineffective. Ironically, in some cases, clinicians have had to turn to older and more toxic antibiotics to use against new strains of bacteria—bringing full-circle the empirical observation of Alexander Fleming that drug resistance was already in play even as his 1928 discovery, penicillin, was being hailed as a miracle drug.

Perfect Storm

From the start, bacteria have been evolving as fast as they can to resist antibiotics. It’s what they do. Now, they can do it a lot faster, thanks to everything from global air travel to the plastic-ball pit at your local hamburger emporium.

Two recent cases in point, according to Frontline: Since the National Institutes of Health’s Clinical Center in Bethesda, Md. went into crisis mode a little over two years ago to contain a deadly outbreak of an organism called KPC, some 44 states have reported the infection. Likewise instances of infection by another antibiotic-resistant bacteria called NDM-1 doubled in 2013, and it has now been reported in 48 countries.

Frontline examined the broadest implications of antibiotic use. Because resistant bacteria can spread from one patient to another, patients who are not even exposed to antibiotics can still suffer the consequences of infections with resistant bacteria. In this regard, antibiotics are a unique class of drugs, and the considerations for good antibiotic stewardship are likewise unique and different from drugs for cancer, cholesterol management, arthritis, dementia or diabetes.

There’s an “economic paradox” of antibiotics to consider, as well: limited, short-term use of a drug is not as appealing to shareholders as one that is to be taken daily for the rest of a patient’s life. That hard reality directly affects research and development funding. The precarious economics of the antibiotic development pipeline, which began to slow as far back as the 1980s, is no small factor in the current crisis of bacterial resistance.

Still, the evolutionary forces of nature cited by Fleming himself present the biggest challenges. To meet those challenges will require a multi-pronged response, antibiotic stewardship that is both defensive and offensive, including high-tech genomics, big-data statistical analysis, vigorous hygiene protocols in hospitals, national policy debates, research and development funding, public-private partnerships and public awareness.

Srinivasan notes encouraging signs of research and development in the pharmaceutical industry, as well as the bipartisan Generating Antibiotic Incentives Now (GAIN) act recently passed by congress and signed into law by the president. And the Food and Drug Administration has issued “guidance rules” to farmers, considered the first step to phase out non-treatment based uses of antibiotics in agriculture. A forthcoming Frontline program for which Srinivasan also interviewed is slated to look at the use of antibiotics in animals.

“There are always new challenges,” says Srinivasan. “Good antibiotic stewardship—the right antibiotic at the right time in the right dose for the right duration—is a win for clinicians, for patients, for health care institutions, and for better, more cost-effective care. It’s a challenge for everyone. No one is rolling around in extra money right now, but an investment in the short run pays off hugely in the long run.”

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About Author

John Syme '85

Senior Writer John Syme graduated from Davidson with a French degree in 1985. After gigs in newspaper, advertising, translation in France and cross-country travel writing in the United States, he returned to alma mater in 2001. He has no immediate plans to graduate again.

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