Darwin Chronicles

August 2005

FDA withdrawals support for enrofloxacin in animals

ROCKVILLE, Md. – Bayer cannot market enrofloxacin (Baytril) for the treatment of bacterial infections in poultry, according to the FDA.

The FDA’s Center for Veterinary Medicine (CVM) began proceedings to withdraw use of this fluoroquinolone in poultry. Scientific data showed that use of enrofloxacin led to resistance in Campylobacter, which causes foodborne illness in humans. Poultry harbors Campylobacter in the gastrointestinal (GI) tracts without becoming ill. Enrofloxacin does not completely eliminate Campylobacter from the bird’s GI tract. As a result, the surviving organisms develop resistance to fluoroquinolones, the drugs used to treat foodborne illnesses, according to the FDA.

The most recent CDC data show that Campylobacter resistance to ciprofloxacin, another fluoroquinolone used in humans, has risen to 21% as of 2002. When the FDA first approved the fluoroquinolone class of drugs for use in poultry in 1995, such resistance was negligible.

“This is a very important decision because it is the first time the FDA has cited antibiotic resistance as the reason for banning use of a drug,” said Margaret Mellon, PhD, JD, director of the Food and Environment Program at the Union of Concerned Scientists.

The decision takes effect Sept. 12, 2005, unless Bayer appeals.

In related news, 90% of the 26.5 million pounds of antibiotics estimated to be used in the United States as feed additives are used in 23 states, according to a report released by Environmental Defense.

The report, “Resistant Bugs and Antibiotic Drugs: State and County Estimates of Antibiotics in Agricultural Feed and Animal Waste,” is the first study to provide state and county level estimates of the quantities of antibiotics used as feed additives for chicken, hogs and beef cattle, along with estimates for antibiotics in animal waste.

North Carolina and Iowa are each estimated to use 3 million pounds of antibiotics as feed additives annually, the same quantity of antibiotics estimated to be used each year in human medicine nationwide. Seven other states – Georgia, Arkansas, Texas, Alabama, Minnesota, Mississippi and Missouri – use at least 1 million pounds of antibiotics as feed additives. On a per square mile-adjusted basis, Delaware is estimated to be the most intensive user of all antibiotic feed additives, using three times as many antibiotics per thousand square miles (187,000 pounds) as the next closest state, North Carolina (64,000 pounds). Two other small states join the ranks of the top 10 states on a per square mile basis: Maryland (4th) and Indiana (9th).

Overuse of antibiotics in agriculture is widely regarded as contributing to the spread of antibiotic-resistant bacteria that threaten human health. It is common practice to add antibiotics to animal feed in order to promote faster growth or prevent disease that could result from the crowded, stressful conditions, rather than treat sick animals.

The report urges swift enactment of The Preservation of Antibiotics for Medical Treatment Act (S. 742/H.R. 2562) to phase out use of medically important antibiotics as feed additives.

More than 380 organizations, including the American Medical Association, the American Academy of Pediatrics and the American Public Health Association, endorsed nearly identical legislation last year.

The Environmental Defense report can be accessed at www.environmentaldefense.org/go/antibiotic.estimates.

Mouse studies of oseltamivir show promise against H5N1 influenza virus

Mouse studies of oseltamivir (Tamiflu, Roche), show promise against H5N1 influenza virus. Experiments in mice show that oseltamivir, a neuraminidase inhibitor, can suppress the avian influenza virus strain H5N1.

Oseltamivir dramatically boosted the survival rate of mice infected with this avian influenza strain circulating in Asia, according to a recent study in the Journal of Infectious Diseases.

Public health experts fear that the avian flu virus could lead to a deadly flu pandemic.

In its study, the St. Jude research team gave oseltamivir or placebo to mice infected with H5N1 influenza virus. The highest dosage level, adjusted for weight, was equivalent to the recommended dose for humans with “run of the mill” influenza. Of 80 mice infected with H5N1 virus, 20 received placebo, 30 received oseltamivir at one of three dosage levels for five days and 30 received the drug at one of three dosage levels for eight days.

None of the mice that received placebo survived. Only five of 10 mice that received the highest daily dose of oseltamivir for five days survived. Although oseltamivir suppressed the virus in the mice, the virus continued to grow if researchers stopped the drug after five days.

Mice that received oseltamivir for eight days fared better. Survivors included one of 10 mice given the lowest daily dose, six of 10 given the middle-range daily dose, and eight of 10 given the highest daily dose. The eight-day dose of oseltamivir allowed more time for virus levels to fall and less chance for avian flu to rebound after researchers stopped the drug, according to a National Institutes of Health press release.

In addition to testing the efficacy of oseltamivir against H5N1 virus in mice, the St. Jude researchers compared the virulence of the new Vietnam virus with a 1997 variant of H5N1 that killed six people in Hong Kong. Researchers found that the 2004 H5N1 virus circulating in Vietnam is more virulent than its 1997 predecessor. A longer course of antiviral treatment may be required to conquer the aggressiveness of the new antigenic variant of H5N1 virus, according to the researchers.

“The H5N1 avian flu viruses are in a process of rapid evolution. We were surprised at the tenacity of this new variant,” said Elena A. Govorkova, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., in a release. “Our results provide baseline information that will be needed for further studies on preventing and treating avian flu with antiviral drugs.”

The National Institute of Allergy and Infectious Diseases sponsored the research.

In related news, Russia has reported bird flu in wild flocks located in several Siberian districts. The flu started in wild waterfowl.

West Nile vaccine using DNA technology approved for horses

The Department of Agriculture (USDA) recently licensed a vaccine that protects horses from West Nile virus (WNV).

The technology used in the vaccine, which the CDC and Fort Dodge Animal Health developed, could serve as a basis for human vaccines against WNV, according to a release from the CDC.

DNA vaccines present several advantages over traditional vaccine approaches. They offer a quick turn around during emerging epidemics because, once developed, they can be adapted easily for similar organisms. DNA vaccines, unlike the traditional vaccine model, are less vulnerable to changes in temperature, and they allow for multiple vaccine candidates to be combined in a single vaccination. Finally, horses vaccinated with a DNA vaccine can be differentiated from those that have been naturally infected, an important factor for public health disease monitoring activities.

The vaccine should be commercially available to veterinarians through Fort Dodge Animal Health in early 2006. In addition, the DNA technology used to develop the vaccine is serving as the foundation for a small human WNV vaccine.

Since 1999, there have been more than 16,000 reported cases of WNV in humans and more than 650 deaths. In addition, more than 21,000 West Nile cases in horses have been reported since 1999.

Fort Dodge Animal Health is a distributor of animal health care products.