This injectable is the first in new class of antibiotics

July 11, 2005

For more than a decade now, pharmacists have seen an escalating incidence of resistance to currently used antibiotics. At an alarming rate, antibiotics have become less effective against bacterial infections. Moreover, resistance once seen only in the hospital environment is now being acquired in the community.

Thus the approval of Wyeth Pharmaceuticals' Tygacil (tigecycline) for injection, the first drug in a new class of antibiotics called the glycylcyclines, gives health professionals another weapon in their war against drug resistance. The drug was developed by adding a glyco-amino acid chain to the familiar drug minocycline. The result is a new, more potent compound that is likely to become the newly restricted drug on many drug formularies.

According to Wyeth, of the nearly 90,000 people killed annually by a hospital-acquired infection, about 70% of the infections are resistant to at least one antibiotic. In fact, resistance is estimated to cost the United States between $4 billion and $5 billion annually due to longer hospital stays and treatment with multiple drugs.

In clinical trials, monotherapy with tigecycline showed comparable cure rates to combination treatment with vancomycin and aztreonam for skin and skin structure infections; the rate was 86.5% for tigecycline and 88.6% with the combination. The clinical cure rate for methicillin-resistant Staphylococcus aureus was 78.4% for tigecycline, compared with 76.5% for the combination treatment.

"Broad-spectrum agents are particularly useful infections involving more than one pathogen or in the setting of empiric therapy, when the pathogen might not be identified at the start of treatment," said Richard H. Drew, Pharm.D., M.S., BCPS, professor at Campbell University School of Pharmacy.

Due to tigecycline's structural similarity to the tetracyclines, similar adverse events may be seen, including the potential for discoloration during tooth development. This includes women in the second half of pregnancy and children up to age eight years. Tigecycline is classified as Pregnancy Category D and may cause fetal harm if administered to pregnant women. The drug should also be used with caution in patients with known hypersensitivity to the tetracycline class.

Wyeth stresses that tigecycline should be used to treat only infections proven or strongly suspected to be caused by susceptible bacteria, and that culture and susceptibility information be considered when available. (A table listing the bacterial strains that tigecycline is active against can be found in the on-line version of this article on Drug Topics' Web site.)

"Unfortunately, this may be unlikely to occur in the real-world setting unless institutional restrictions are set forth on the use of this agent," said Blair Capitano, Pharm.D., an infectious diseases clinical R.Ph. at the University of Pittsburgh Medical Center. She feels we should use any means necessary to aid in optimizing therapy. However, in vitro testing does not always reflect the interaction between the drug and the pathogen that occurs in vivo.

Financial experts said that tigecycline could be a big seller, with $750 million in sales by 2008.

"Agents that target resistant pathogens are always welcome," concluded Drew, who is also an assistant research professor of infectious diseases at Duke University School of Medicine. "The introduction of a new antibiotic also threatens to contribute to new resistance unless used prudently," noted Capitano. With the limited number of broad-spectrum agents on the horizon, tigecycline should be used judiciously, she suggested.