Antibiotic Stewardship in the U.S. Woefully Weak, Experts At Global Conference Say

A confluence of factors including an inflexible regulatory enviroment that discourages research and discovery, a paltry research pipeline for drugs for the most serious illnesses, and a tendency for physicians to unnecessarily prescribe antibiotics for routine aches and pains is largely responsible for the rise of antibiotic-resistant infections in humans, speakers at a major conference on infectious diseases this week announced.

"It is a perfect storm — antibiotic discovery is hard, the return on investment for companies that pursue it is average at best, and the regulatory environment is hostile," said David Shlaes, M.D., an expert in antimicrobial agents, at the biennial International Conference on Emerging Infectious Diseases held in Atlanta.

Singling out the U.S. Food and Drug Administration as the main culprit for the steady increase in antibiotic-resistant diseases, Shlaes said that since 1983 the number of new antibiotic drug approvals granted by the agency has declined eightfold. He said that despite evolving diseases that require individual risk assessment, the FDA often adheres to rigid protocols that have outlived their usefulness.

"FDA guidance requires infeasible trial designs," Shlaes said, speaking at a panel discussing the need for novel therapeutics. He noted that unless the FDA reforms its current approach, "the U.S. will soon be irrelevant. The U.S. market is declining while pharmerging markets are growing."

"Pharmerging" markets are emerging markets that appeal to pharmaceutical companies looking for fresh growth and profitability. They include Brazil, India, and South Korea, but also more recent ones such as Vietnam and the Czech Republic.

Shlaes attributed the slump in antibiotic R&D to the pace of mergers and acquisitions that have occurred over the past several decades. As an example, he showed in a PowerPoint presentation that the pharmaceutical company Aventis is the final result of consolidation between 17 drug companies that existed in the 1980s, when competitive pressure caused many of them to seek partnerships in order to survive. Similarly, Bristol-Myers-Squibb survived through the consolidation of eight other firms.

In order to rejuvenate antibiotic R&D, nothing short of a comprehensive FDA reform is needed, Shlaes said. But while he emphasized that the U.S. offers the starkest example of regulatory inertia, he and others also acknowledged that antibiotic resistance is up globally.

"We have a real issue with antibiotic resistance in Europe," said Mike Sharland, a professor at St. George’s Healthcare NHS Trust and St. George’s University in London. He noted that the high-profile topic of antibiotic resistance at the conference reflects growing worries worldwide.

Sharland added that the European Antibiotic Resistance Surveillance network, which tracks the occurrence and spread of antibiotic resistance across the continent for public health purposes, collects data from 900 microbiology labs at more than 1,400 hospitals.

"Antimicrobial stewardship should occur across the continuum of healthcare, including acute care, long-term care, and ambulatory care," said Ruth Lynfield, a state epidemiologist with the Minnesota Department of Health, who also presented at ICEID.

Lynfield said that according to estimates by the U.S. Centers for Disease Control and Prevention, unnecessary prescriptions for antibiotics given to out-patients for upper respiratory disease account for more than 50 percent of such prescriptions.

Confirming the unfortunate boost antibiotic resistance gets from the dearth of potent new drugs that might prevail over stubborn bacteria, Lynfield said that on average it takes 10 years and $800 million to develop a new antibiotic and bring it to market. "This has led to very few antibiotics being developed in recent years," she said.