Not a day goes by without reading or hearing about the seemingly impossible task of finding effective new treatments against "superbugs" that are resistant to existing drugs.

Big Pharma essentially bailed out of antibiotic research several decades ago when chronic disease treatments began to produce significantly better financial returns. While some smaller companies have continued the pursuit of new antibiotics, much of the work continues to be done on known mechanisms or modifications of known chemical structures.

The dearth of prospects for treating these superbugs is often blamed on the lack of investment and market economics (difficult to make a return on investment). Sure, more investment-friendly healthcare market opportunities might lure additional pharma companies and money to the effort, but there is an even bigger factor standing in the way of conquering this medical dilemma.

One of the biggest issues rarely discussed is the tendency of the scientific and medical communities to hold onto and perpetuate what they think are known to be fact. These "established principles" are often dogmatically presented by experts in their scientific rationale and used to support "fact-based" medicine.

This might be fine for establishing best practice guidelines for available products, but this type of thinking makes it difficult to innovate. Think about the medical practice challenges (i.e., fighting with insurers to pay for it) and potential liabilities associated with new off-label uses of prescription drugs. Also, what if we had continued to try to treat viral infections with the same conventional chemistry used for bacterial infections?

Innovation often involves total disregard for "established principles" and ignoring how things are typically done. In order to find truly novel treatments for superbug infections, the medical and scientific communities will have to take a fresh look and be more receptive to radical thinking about these bacterial infections.

We almost need basic science researchers to forget about what they were taught about bacterial resistance and start from scratch. That means academia and NIH also must be more open-minded in grant reviews, supporting more nontraditional research that might even fly in the face of "established principles."

Discovery researchers need to forget about compound structures that have worked in the past and explore new chemistry, mechanisms and perhaps even nondrugable solutions. In terms of drug development, previously predictive preclinical and in vitro lab testing may no longer apply to what we need to discover.

The FDA will have to work with companies to design anti-infective development programs that may not look anything like what has been used in the past for approvals. Most importantly, analyzing drug development or treatment data for new superbug therapies may lead to a completely new statistical paradigm for assessing safety and efficacy.

There is an answer to superbug resistance, but it will not come from traditional thinking or incremental modifications in chemical structures. I just hope conventional thinking doesn't discourage or derail efforts to find truly novel treatments for these difficult-to-treat infections.