The 5 most promising antibiotic treatments in the industry's pipeline all have something in common: Not one was developed by Big Pharma. John LaMattina, former head of R&D at Pfizer ($PFE), pointed out in Forbes that companies like Cubist ($CBST), Basilea ​Pharmaceutica ($BSLN) and Otsuka are doing most of the late-stage heavy lifting in antibiotics, and, excluding Roche's ($RHHBY) recent re-entry to the field, most of the world's largest drugmakers are standing on the sidelines as so-called superbugs become all the more common

 Concerns have arisen over the fact that major pharmaceutical companies years ago had abandoned R&D in the search for new antibiotics, yet we are now at a point in time when “superbugs”, bacteria that are resistant to existing drugs, are beginning to proliferate. One big company, Roche, has gotten back into this area of research. However, other major companies like Pfizer PFE +0.23% and Merck Merck remain on the sidelines. If that doesn’t change, where will the needed life-saving agents emerge?

Recently, Infectious Disease News highlighted five antibiotics currently in the pipeline that offer some promise.
1) Ceftobiprole (Basilea) for hospital-acquired pneumonia
2) Delamanid (Otsuka) for tuberculosis in patients who are resistant to other anti-TB drugs
3) Oritavancin (The Medicines Company) for acute bacterial skin and skin structure infections (ABSSSIs)
4) Ceftolozane/Tazobactam (Cubist) for urinary tract and intra-abdominal infections
5) Tedizolid (Cubist) for ABSSSIs

What is notable about this list is that all of these drugs come from small companies. While the potential financial returns from a drug in this area don’t necessarily appeal to big pharma, smaller companies clearly see opportunities. One company that has staked its future in this area is Cubist, the innovator behind the last two entrants on the Infectious Disease News list. (Since the list was published, Cubist received FDA approval for tedizolid, which is being marketed under the trade name Sivextro.) Cubist’s Chief Scientific Officer, Dr. Steve Gilman, a former Pfizer colleague, recently told me that 75% of their scientists are focused on novel antibiotics and they will spend over $400 million this year in this area. Gilman is proud of the fact that they have a broad research program looking for treatments for both gram negative and gram positive infections.

The Cubist commitment and others like it are encouraging in that progress is being made on fighting the superbugs. However, many would hope that the big companies will also enter the fray. A limiting factor for the reentry of the big players is the dearth of new targets that scientists can attack that address the issue of why bacteria develop resistance in the first place. Most of the drug discovery work that is occurring these days is centered on altering the structure of existing antibiotics. While this offers a rational starting point, the focus on existing classes of drugs leads to compounds for which bacterial resistance can more easily emerge.

What is needed is more basic research on bacterial drug resistance. This is where the NIH can play a big role. The total 2014 NIH budget for infectious diseases is $5 billion.  However, this is spread across all infectious diseases like HIV/AIDS, as well as biodefense work. Perhaps the time has come for the NIH to make understanding the mechanisms of bacterial resistance a national health priority and invest accordingly.