The New Bacterial Threat
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For the past decade or more multiple drug resistant strains of bacteria such as methicillin resistant Staphylococcus aureus (MRSA), enterococci and other Gram positive cocci have been highlighted and showcased in the medical and lay press. While the incidence of infections caused by MRSA and other Gram positive cocci has steadily risen, antibacterial drug discovery experts have long known that the greatest disease threat in the future will be from emerging multiple antibiotic resistant strains of Gram negative bacteria including Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa.
Last Spring, in an interview that I conducted with Barry Eisenstein, MD, Senior Vice President of Scientific Affairs at Cubist Pharmaceuticals and an antibacterial drug discovery expert, he indicated that there are currently no drugs in development to treat infections caused by antibiotic resistant Gram negative bacteria. He warned that this, coupled with the loss of interest in antibiotic development by large pharmaceutical companies, will cause infections caused by multiple drug resistant Gram negative bacteria to become a serious unmet medical need in the not so distant future. The appearance of an article in the New York Times this past Saturday chronicling the rise of infections caused by antibiotic resistant Gram negative bacterial suggests that the not so distant future may have already arrived! For the record: would newspaper and television reporters please refrain from identifying bacteria as “germs.” It is an anachronistic term which was coined in the 19th century before bacteria and viruses were conclusively identified as the cause of most infectious diseases.
Despite the media hype about antibiotic resistant Gram positive bacteria, a variety of new drugs have been developed to treat infections caused by these bacteria. Interestingly, because of greater public awareness about MRSA infections and improved hospital infection control and surveillance programs, the incidence of disease caused by MRSA and other Gram positive bacteria is finally beginning to wane. Unfortunately, the same is not true for infections caused by antibiotic resistance Gram negative bacteria.
For those of you who may not know, the cell wall architecture of Gram negative bacteria (and a multitude of antibiotic resistance mechanisms) makes it much more difficult and costly to develop new antibiotics to treat Gram negative infections. Consequently, research in this area has been largely ignored for the past 15 years or so. This means that in the future the morbidity and mortality associated with infections caused by antibiotic resistant Gram negative bacteria is certain to rise. With this in mind, persons at the greatest risk of developing these infections include patients in hospitals and long term care facilities and individuals receiving implantable medical devices.
Because most large pharmaceutical companies abandoned antibiotic drug discovery in the mid to late 1990s, it is unlikely that new Gram negative antibiotics will come from the pharmaceutical sector. While there are several small biopharmaceutical start ups working on antibiotics for Gram negative bacteria (KaloBios Pharmaceuticals, Calixa Therapeutics and Novexel) the increasing regulatory scrutiny and rising development costs suggests that these companies may have trouble bringing new antibiotics to market. Sadly, this places the onus of new Gram negative antibiotic discovery squarely on the shoulders of the US government. To that end, as much as it pains me to say this, it will likely take the death of government official or family member before sufficient resources are allocated to address this rapidly growing unmet medical need. Maybe the Obama Administration ought to think about allocating stimulus monies to begin to address the problem!
Until next time...
Good Luck and Good Job Hunting!!!!!!!
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Rumors are rife that Novartis is going to purchase Lexington, MA-based Cubist for $1.6 billion. Wall Street analysts are speculating that Novartis may announce the deal as early as Monday.
Cambridge, Mass-based Targanta Therapeutics 
