Brad Spellberg, MD


November 02, 2011

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Skyrocketing Resistance and Declines in New Antibiotic Development

Hello. This is Dr. Brad Spellberg, Associate Professor of Medicine at the Los Angeles Biomedical Research Institute and the Harbor UCLA Medical Center and the David Geffen School of Medicine at UCLA. I am currently in Boston, Massachusetts, at the Infectious Diseases Society of America (IDSA) 2011 meeting.

I would like to give you an update on a critical issue that all infectious disease practitioners understand well: the lack of new antibiotics to treat resistant infections.

We are dealing with 2 converging public health crises. We are seeing skyrocketing antibiotic resistance and dramatic declines in new antibiotic development. These trends are becoming worse over time. Numerous abstracts at this year's IDSA meeting describe increasing encounters with extreme drug-resistant gram-negative bacilli, which are in some cases pan-resistant (resistant to all available antibiotics).

Unfortunately, a new survey presented here, led by Helen Boucher[1] and other members of the Antimicrobial Availability Task Force at the IDSA, found a continued decline in antibiotic development. We are still not seeing sufficient new antibiotics for gram-negative bacteria.

The IDSA has strongly attempted to support new antibiotic development, and as part of its 10 x '20 Initiative is calling for the development of 10 new systemic antibiotics by the year 2020. Thus far, we have only had 1 systemic antibiotic, ceftaroline, approved, so we are still a long way from meeting that goal.

Generating Antibiotic Incentives Now

There is some good news. Recently introduced into both the House of Representatives and the Senate is a new piece of legislation called the Generating Antibiotic Incentives Now (GAIN) Act. We need to thank the lead sponsor, Representative Phil Gingrey, for taking the bull by the horns with this issue.

Representative Gingrey's bill has numerous cosponsors. This is a bipartisan piece of legislation that seeks to economically incentivize companies to get back into the business of antibiotic development. This is a good first step, and hopefully it will be strengthened and then passed within the next year.

The GAIN Act also calls for the development (and seeks to incentivize the development) of new rapid diagnostics, which of course are a cornerstone in our efforts to improve antibiotic stewardship and the accuracy of antibiotic prescriptions.

Improvements in Antibiotic Stewardship: More Than Nagging Docs

We have talked about incentivizing new antibiotic development. We need to continue to improve our antibiotic stewardship. We need to prolong the useful lives of these drugs. We need to think of antibiotics as a precious limited resource, just like forestry, fisheries, and energy, which must be both renewed and conserved.

For 65 years, the cornerstone of stewardship has been physician nagging. We nag physicians to avoid overprescribing antibiotics, but we haven't gotten very far with that strategy. We know that Alexander Fleming, the discoverer of penicillin, warned the public and physicians about the overuse of penicillin in 1945. So this is a 65-year-old conversation and we need to start moving it to the next level.

To do that, we need rapid diagnostics so that we are more accurate when we prescribe antibiotics. We also need to work on giving shorter courses of antibiotic therapy. Why are we giving 10-14 days of antibiotics for skin infections when we know you only need 7 days to treat ventilator-associated pneumonia?

We also should avoid overly broad therapy. It's not appropriate for us to be using antibiotics that have broad gram-negative activity when we are treating skin infections and community-associated pneumonias that are caused by gram-positive organisms. We don't have any oral gram-negative drugs in the pipeline, so we really need to try to preserve the fluoroquinolones and should not be using them to treat simple skin infections.

In 1981, Dr. Walsh McDermott wrote that it is not too much to state that the introduction of antibiotics has represented a force for change in the 20th century of the same general kind as James Watt's modification of the steam engine in the 18th century. This was an awesome acquisition of power.

If we want to preserve that power, we have to mobilize grassroots efforts and political support to reverse the regulatory and economic barriers that continue to prevent new antibiotic discovery and development. We must improve the science and technology of infection prevention and antibiotic stewardship to prolong the useful lives of antibiotics.

Thank you. This is Brad Spellberg for IDSA and Medscape.

Web Resources

Antibiotic Development: The 10 x '20 Initiative


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