Methicillin Resistant Staphylococcus aureus: A Growing Link between MRSA Infections and Pigs

That methicillin resistant Staphylococcus aureus (MRSA) is in the news again is not surprising. However, to my knowledge, Nicholas Kristof‘s article in today’s New York Times may be the first Op-Ed piece written by a non-scientist about the growing threat and seriousness of MRSA infections. Mr. Kristof apparently became aware of MRSA when he was contacted by Tom Anderson, MD, a Camden, Indiana physician who was experiencing “phenomenal levels of MRSA infections" in his community.

Beginning in the early 1990s, Dr Anderson noticed a rapidly rising incidence in the number of community acquired skin infections caused by MRSA among his patients. Most of Dr Anderson’s patients were swine farmers—the predominant industry in Camden. At first puzzled by the growing incidences of MRSA outbreaks, Dr. Anderson began to suspect that his patient’s pigs may be the source of growing number of cases of MRSA skin infections. He was reluctant to alert public health officials about his suspicions because any hint livestock-related health issues might jeopardize the livelihood of many of his neighbors and friends. By last fall, however, Camden’s MRSA epidemic had grown so large that Dr. Anderson could no longer remain silent. Rather than alert the authorities himself, he decided to invite Mr. Kristof, an investigative reporter, to visit him in Camden and break the story. Unfortunately, before Mr. Kristof could visit, Dr. Anderson died abruptly at age 54. There was no autopsy, but a blood test suggested he may have died from a heart attack or aneurysm. And—this is where the story gets interesting—a recent Dutch study has linked porcine MRSA isolates to a case of human endocarditis. Dr. Anderson had himself suffered at least three bouts of MRSA infections.

In another Dutch study conducted in 2004, MRSA strain ST398 (which caused the endocarditis in the more recent study) was isolated from three family members, three farm workers and 8 of 10 pigs from a single farm. Since then, strain ST398 has spread rapidly through the Netherlands — especially in swine-producing areas— and pig farmers there are 760 times more likely than the general population to carry MRSA. More recently, a study conducted by public health officials in Ontario, Canada showed that 20% of pig farmers were colonized by strains of MRSA genetically identical to those isolated from European pigs. Finally, a 2008 study conducted in Iowa, reported that strain ST398 was isolated from 45 percent of pig farmers and 49 percent of hogs that were tested. Together, these studies suggest that colonization of swine by MRSA and pig farmers is very common and that swine (and possibly other agricultural animals) could become an important reservoir for strains of MRSA.

While not conclusive, most infectious diseases experts believe that the emergence of MRSA and antibiotic resistant bacteria can be directly linked to the widespread and rampant use of antibiotics as growth enhancers in livestock feed. Despite the alarming emergence of multiple antibiotic resistance bacteria, livestock producers in the US and elsewhere continue to add antibiotics to livestock feeds. This led Mr. Kristof to lament that “we as a nation have moved to a model of agriculture that produces cheap bacon but risks the health of all of us.” Not surprisingly, as is frequently the case, big business has chosen to place profits before the health and safety of society.

Until next time...

 

Good Luck and Good Reading (look for Mr. Kristof’s Sunday column on the emergence of antibiotic resistant "superbugs")

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Another Antibiotic Discovery And Development Company Is Downsizing

Targanta Therapeutics, a Cambridge, MA-based biopharmaceutical company, announced that it will lay off 85 of its 115 employees or almost 75% of its workforce. The news follows the FDA’s rejection of its application for oritavancin, an antibiotic it is developing to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic resistant bacteria. The agency wants Targanta to conduct another Phase III clinical trial to further assess of oritavancin’s safety and efficacy.

The company estimates that the new clinical trial will cost about $20 million. Targanta CEO Mark Leuchtenberger said “We are no longer a pre-commercial company. We are back to being a Phase three company, and that requires us to right-size and to streamline our operations.”

Things are not going well for companies in the antibacterial drug discovery and development space. Late last month, FDA rejected Swiss-based Arpida’s NDA for iclaprim an antibiotic it was developing to treat complicated skin and soft infections caused by MRSA. Shortly after receiving the news, Arpida layed off roughly 72% of its employees and is down to about 30 employees like Targanta.

It is unfortunate that big pharma decided to abandon antibacterial discovery and development research about eight years ago. Consequently, development of  new, much-needed antibiotics has been relegated to financially-strapped, small biopharmaceutical companies whose likelihood of success is questionable.

Until next time…

Good Luck and Good Job Hunting!!!!!!!!

FDA Delays Approval of Ceftobiprole to treat MRSA

U.S. regulators have delayed a decision on approval of an antibiotic from Johnson & Johnson and Basilea saying they need further audits of clinical sites, the two companies said on Wednesday.

Ceftobiprole, a broad-based spectrum antibiotic targeted mainly against infections caused by methicillin-resistant Staphylococcus aureus (MRSA), is Basilea's lead product and the news hit the Swiss biotech shares, which plummeted 27 percent.

In a so-called complete response letter on the drug's approval application, for complicated skin and skin structure infections, the Food and Drug Administration (FDA) said it was unable to review the clinical data submitted with the NDA until issues of data integrity had been resolved. The FDA has asked J&J to conduct additional audit work of clinical investigator sites and to address specific questions related to site monitoring."

Ceftobiprole is approved in Canada and Switzerland and has been recommended for approval in the European Union. A new application in the United States is planned within a year.

Late last week, FDA rejected an NDA for another antibiotic, iclaprim, being developed by Arpida, another Swiss company. It has been a bad two weeks at FDA for approval of new antibiotics—drugs that we desperately need.

Until next time….

Happy Thanksgiving

 

Optimer's New Carbohydrate-Based Antibiotic May Be a Winner

Optimer, a San-Diego, CA-based biopharmaceutical company, reported positive Phase III clinical trial results for OPT-80, its lead treatment for Clostridium difficile gastroenteritis. C. difficile gastroenteritis is caused by exotoxins secreted by clostridia that have colonized the colon following prolonged antibiotic treatment for other bacterial infections. If left untreated, patients can die from a pseudo-membrane that forms in the colons of C. difficile-infected people. The incidence of C. difficile gastroenteritis has drastically increased over the past decade because of prolonged treatments with multiple antibiotics that are often necessary to eradicate infections caused by multiple drug resistant bacteria.

Historically, CHO-based drugs (with a few notably exceptions like heparin) have not fared well as therapeutic agents. To my knowledge, OPT-80 is the first synthetic carbohydrate (CHO)-based antibiotic to demonstrate anti-bacterial efficacy in a Phase III clinical trial. Having worked for Transcell Technologies (now defunct) and Alchemia,Pty—both of which attempted to develop CHO-based antibiotics—Optimer’s clinical success with OPT-80 is certainly noteworthy. I wish the company continued success in the future—mostly because I have always thought that carbohydrates would make good antibiotics!

 

Until next time…

 

Good Luck and Good Job Hunting!!!!!!

 

 

Another US Biotechnology Company Bites the Dust: Japan's Takeda Pharmaceuticals to Buy Millennium Pharmaceuticals

Takeda Pharmaceutical Co., Japan’s largest pharmaceutical manufacturer, announced that it has agreed to buy Cambridge MA-based Millennium Pharmaceuticals for $8.8 billion. Millennium, founded in 1993 by high profile MIT researchers and once heralded as one the most innovative American biotechnology companies, never lived up to analyst’s expectations. That said, the company did develop and win regulatory approval for an anti-cancer drug, Velcade, which is expected to garner additional approval for wider use in oncology later this year.

Velcade, which is used to treat relapsed multiple myeloma after other drugs fail generated more than $800 million last year. Millennium anticipates U.S. approval by June to promote Velcade as an initial therapy to treat these disorders. Millennium markets Velcade in the US and shares revenue with Johnson & Johnson which markets Velcade in 85 other countries. Analysts predict that the Takeda acquisition will help to propel Velcade to blockbuster status.

The Takeda-Millennium deal follows Eisai Co.’s (another Japanese company) agreement in December to buy the U.S.'s MGI Pharma Inc. for $3.9 billion as Japanese companies, aided by a weak dollar against the yen, seek growth abroad. Japanese companies have been hampered by government-ordered price cuts, weak pipelines and a lack of new products  As one financial analyst put it ``There's no doubt the weak dollar against the yen is making U.S. biotech very attractive right now to potential Japanese buyers,''

Takeda’s best seller is the diabetes drug Actos which is slated to lose patent protection in the near future. Acquisition of Millennium provides Takeda with an entrée into the oncology and cardiovascular markets both of which are poised for expansive growth in the next five years. Analysts also believe that the Millennium acquisition will boost Takeda’s drug discovery and development flow. Millennium is conducting human trials with experimental drugs for cancer, heart disease, gastrointestinal disorders and rheumatoid arthritis.

The ongoing acquisition of American biotechnology companies by Japanese pharmaceutical companies reminds me of  the Japanese foray into the US real estate market in the early 1990s. Only time will tell whether the Japanese will be able to hang on to their acquisitions this go around (they weren’t the last time).  Earlier this week, Switzerland's Novartis AG agreed to buy 77 percent of eye-care company Alcon Inc. in a two-step transaction totaling $39 billion. Does anybody else see a troubling trend developing here as a result of the recession that we are in or heading into?

Don’t be surprised to see some “asset reallocation” and downsizing at Millennium. The Japanese are well recognized for increasing efficiency and work output with smaller numbers of employees.

Until next time….

Good Luck and Good Job Hunting (not in Cambridge MA)!!!!!!!!

Tysabri: A Drug Snatched from the "Jaws of Defeat"

You gotta give Biogen/IDEC and Elan credit for winning regulatory approval for a product that was previously pulled from the market because of serious and potentially life-threatening side effects. On Monday, the US Food and Drug Administration granted regulatory approval for Tysabri as a treatment for patients with severe Crohn’s disease who do not respond to more conventional biotechnology treatments like Humira (Abbott Laboratories) and Remicade (Johnson & Johnson). About 500,000 patients in the US suffer from Crohn’s disease (an autoimmune disease) and usually causes diarrhea, fever and severe intestinal inflammation and bleeding. Currently, there is no known cure for the disease.

As many of you may recall, Tysabri, a treatment for multiple sclerosis, was temporary pulled from the market in 2005 after three patients treated with the drug developed a rare and sometimes fatal nervous disorder called multifocal leukoencephalopathy (MFL). FDA allowed the drug back on to the market in 2006 but only under a restricted distribution program. Tysabri is used by more than 12,000 Americans with multiple sclerosis . Since its reintroduction, there have been no new reports of MFL or other serious side effects. Because of its past safety record, patients with Crohn’s disease who use the drug must also enroll in a distribution program similar to the one required for MS patients treated with Tysabri.

The approval of Tysabri for a new therapeutic indication may make Biogen/IDEC a more attractive  takeover candidate. As many of you may know, Biogen/IDEC put itself up for sale about 3 months ago and was unable to find a buyer.

Until next time….

Good Luck and Good Job Hunting!!!!!!!!