BioWorld International Correspondent

LONDON - The need for new antibiotics is far greater than realized, with documented antibiotic resistance representing the tip of a fast-growing iceberg and not the true scale of the problem.

But despite huge unmet need, there is little pharma interest in the area, and every antibiotic in the clinic currently is being developed by a biotech company.

In effect, that has left the funding of new antibiotics largely up to the capital markets, noted Tom Schrader, of the investment bank Rodman & Renshaw of New York.

Schrader said that although the issue of antibiotic resistance is widely acknowledged, it is more usually thought of in terms of hospital-acquired infections such as methicillin-resistant Staphylococcus aureus or Clostridium difficile.

Speaking at a satellite event of the American Association for the Advancement of Science Annual Meeting in Boston earlier this month, Schrader pointed out that increasingly resistance is manifest in the community. In that context, the problem not only afflicts the elderly, or those with impaired immune systems. "Athletic abrasions picked up in sports are great breeding grounds," he said.

The increasing need for antibiotics is happening in an environment where - like anti-anxiety drugs - existing antibiotics have been misused. This has generated caution at the FDA. "There's a sense [antibiotic drugs] are hard to get approved, and that's causing tension," Schrader said.

A variety of mechanisms is known to underlay the emergence of antibiotic resistance. The most important are modification of a target so the antibiotic does not bind; the generation of enzymes to degrade the drug; and the development of an impenetrable cell wall that the antibiotic cannot cross, or through which it is expelled immediately.

Lately it has become evident that several mechanisms may be operating at the same time. Patrice Courvalin, director of the French National Reference Center for Antibiotics and the head of the antibacterial agents unit at Institut Pasteur in Paris, referred to this as "combinatorial resistance," adding, "In other words, resistance is infectious and exponential."

Peter Appelbaum, professor of pathology and director of clinical microbiology at the Pennsylvania State University Milton S. Hershey Center, said there is far more resistance to antibiotics than is currently acknowledged. He cited a case of a patient entering his hospital with a S. Aureus infection that was not resistant on admission, but became resistant on treatment.

Few hospitals or nursing homes systematically monitor for resistant infections, and in any case, the most popular current method of testing is not sensitive to many antibiotic resistant bugs, Appelbaum said.

"There's nothing special about our hospital; it's just that we are looking," he added. "The fact is multi-[drug] resistance is already here, and we don't have anything to treat it."

Helen Boucher, assistant professor of medicine and program director of the Infectious Diseases Fellowship and staff physician in the division of geographic medicine and infectious diseases at Tufts University in Medford, Mass., agreed, saying that although at first glance the number of marketed antibiotics appears to be a long list, many of the drugs have toxicities, can only be administered intravenously or are too expensive.

"We don't have enough options," she said. "Every antibiotic has some level of resistance; there are not enough oral options, and we need better PK [pharmacodynamics]."

Robert Moellering, physician-in-chief and chairman of the department of medicine at the Beth Israel Deaconess Medical Center and president and CEO of the Harvard Medical Faculty Physicians at Beth Israel, noted there is some hope on the way in the form of eight antibiotics currently in Phase III development. Beyond that there are nine in Phase I/II trials. Those are based on a variety of different approaches.

"They are all being developed by biotechs. There is no interest at all from pharma," Moellering concluded.