Resistant infections spur hunt for new strategies

For Russell Bird, MD, bacteria resistant to methicillin has become so firmly entrenched in his community that he considers it a fair bet that most of the skin infections he sees will fall into this category.

"Over the summer, we were seeing two cases [of methicillin-resistant Staphylococcus aureus] a day. Last year, we saw none," said Dr. Bird, a family physician working at Baptist Urgent Care in Louisville, Ky. "It's very scary. I've almost stopped culturing because of the antibiotic pressure in the community. It's all MRSA."

As a result, many antibiotics are off the table. He can still use the sulfa drugs. But, in an age of shrinking options to treat infectious disease, he's afraid that someday soon he'll lose those too.

Dr. Bird is by no means alone in this concern.

MRSA's jump from its traditional hospital-setting bunker to the general community where it has been causing death and serious illness among otherwise healthy people represents the dangers that can arise when the war against antibiotic resistance suffers a setback. It has since given physicians and scientists increasing motivation to look outside the box for new defenses. Last month, for instance, the National Research Council's two committees on New Directions in the Study of Antimicrobial Therapeutics issued a roadmap toward such solutions.

"We used to have great antibiotics. What are we going to do?" said Arturo Casadevall, MD, PhD, chair of one of the committees and professor of infectious diseases at Albert Einstein College of Medicine in New York. "We are in real danger."

The report, "Treating Infectious Diseases in a Microbial World," urged the use of several scientific strategies to develop new compounds. These include shifting focus from bacterial metabolism to other possible drug targets such as blocking the bacteria's means of communication. Another promising path is to revisit old files for promising drugs that may have been abandoned for corporate rather than scientific reasons. Research that puts greater emphasis on harnessing the power of the body's own immune system as well as "friendly" bacteria should also be considered.

"It's become harder and harder to discover new antibiotics because we've mined to the bottom of the usual targets," said Carl F. Nathan, MD, a member of one of the committees and chair of the microbiology and immunology department at Weill Medical College of Cornell University in New York. "We feel that society needs a sustained, planned, organized approach to developing anti-infectives."

The committees noted, though, that the long talked about "gorillacillin" -- a sought-after super drug that would fight all infectious agents -- is actually not a worthy pursuit.

"It's not going to happen and it's not even a good idea to wish for," said Dr. Nathan. "We cannot actually survive without [many forms of bacteria]."

The panels also called for more rapid tests that would enable physicians to assess infections as well as patients' immune systems. The hope is that this would allow physicians to use narrower spectrum antibiotics that knock out the target while being less likely to engender resistance in other organisms.

But until science makes more headway, many suggest there may still be more that can be done to preserve the effectiveness of currently available antibiotics. Overuse has gone down, though not enough. A study in the Nov. 9 issue of the Journal of the American Medical Association found that prescribing antibiotics for children with sore throats had decreased from 66% of visits in 1995 to 54% in 2003. But it also concluded that physicians were increasingly using broad-spectrum versions that are not recommended.

Adding positive momentum to the situation will take an enormous amount of effort.

"Changing physician behavior is a science unto itself," said Charles P. Mouton, MD, chair of the community and family medicine department at Howard University College of Medicine in Washington, D.C. "In some areas, we have done a great job, and physicians are more aware of the problem. But you explain to some patients that they don't need antibiotics and they think that you're trying to shortchange them."

A systematic review published in the Cochrane Library last month found that effective interventions were multipronged, tailored for the local environment and targeted to both physicians and patients. Lectures and pamphlets had a minimal effect while those that were interactive and one-on-one had the greatest impact.

"You need to figure out what you need in your community," said Sandra Arnold, MD, lead author and assistant professor of pediatrics at the University of Tennessee Health Sciences Center and LeBonheur Children's Hospital in Memphis. "Almost everything works to some degree, but the more complex, the better the result. It's hard to keep them up. The durability of the effect is also a big remaining question."

The paper also found that it may be better to tell physicians to prescribe a narrow-spectrum antibiotic over one with more power rather than none at all. Doctors agreed this may be a good middle ground, particularly in light of the preferences of many patients.

"When treating the antibiotic-demanding patient, I often make the rationalization as I pen the word 'amoxicillin' that since most antibiotics prescribed for [upper respiratory infections] are at par with placebo, I might as well do the least damage as possible," said Dr. Bird.