New antibiotic class battles resistant infections

The healthcare community faces an increasing clinical challenge in preventing and controlling the growing emergence of resistant organisms. Tigecycline (Tygacil, Wyeth) is one of a slim list of new antibiotics in development that shows substantial promise as a broad-spectrum agent with activity against many resistant gram-positive bacteria and, to a lesser extent, gram-negative bacteria.

Tigecycline, a derivative of minocycline, belongs to a new class of tetracyclines known as glycylcyclines. It is being developed as a broad-spectrum agent for parenteral use. Wyeth is seeking approval for tigecycline for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections (cSSI) caused by gram-negative and -positive pathogens, anaerobes, and both methicillin-susceptible and -resistant strains of Staphylococcus aureus.

At the 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C., Wyeth presented new phase III data based on a clinical trial in patients with complicated intra-abdominal infections. This study compared tigecycline with a current empiric combination treatment, Primaxin (imipenem and cilastatin for injection) for intra-abdominal infections. Overall, in patients with a positive culture, the microbiologic eradication rate was 91.3% for tigecycline as a monotherapy treatment versus 89.9% for imipenem/cilastatin, with a similar safety and tolerability profile in the two groups. Additional data were also presented comparing tigecycline with vancomycin/aztreonam in the treatment of cSSI. A total of 21 abstracts on tigecycline were presented at the meeting.

In July of 2004, the African American Heart Failure Trial (A-HeFT) was halted early due to the significant survival benefit seen in patients on BiDil. Investigators reported that adding BiDil to standard heart failure therapy provided a 43% improvement in survival compared with patients taking standard therapy plus placebo. BiDil also resulted in significant benefit for the primary endpoint, a composite score of death, first hospitalization, and quality of life.

Researchers believe that African Americans may be more prone to nitric oxide deficiency than other populations. Isosorbide dinitrate is a nitric oxide donor. Hydralazine, by reducing oxidative stress, may enhance the effects of nitric oxide derived from nitric oxide donors, as well as from endogenous sources.

If approved for use in the African American subset of congestive heart failure patients, BiDil would carry patent protection until 2020. But approval for the general heart failure population would limit patent life until 2007, according to NitroMed.

Novel drug for hormone-refractory prostate cancer Abbott Laboratories has filed for Food & Drug Administration approval of a novel compound, atrasentan (Xinlay), for the treatment of metastatic hormone-refractory prostate cancer. Atrasentan is an orally bioavailable endothelin receptor antagonist and represents the first in its class to be tested clinically in prostate cancer. Because treatment options for patients with prostate cancer who no longer respond to hormone therapy are limited, the FDA has granted the new drug fast-track status.

Results from the recently reported phase III trial evaluating the 10-mg dose of atrasentan vs. placebo in patients with metastatic androgen-independent prostate cancer continued to show beneficial results in favor of atrasentan, although the primary end point of disease progression (i.e., new lesions, clinical symptoms, skeletal complications, or pain) did not reach statistical significance in the intent-to-treat analysis. Nevertheless, increases in bone alkaline phosphatase, total alkaline phosphatase, and PSA were significantly reduced in patients treated with atrasentan, suggesting that this agent delays disease progression.

Quality-of-life parameters were also significantly improved with atrasentan, most notably in the pain component of the prostate cancer subscore.