New drugs: tigecycline, ziconotide, and clofarabine.

The extent to which microorganisms have developed resistance to antimicrobial agents to which they were initially susceptible is an ongoing concern. The approval of tigecycline (Tygacil—Wyeth) represents an important step in the development of new antibiotics active against certain bacteria resistant to many of the previously marketed antibiotics. Designated by some as the first of a new class of glycylcycline antibiotics, tigecycline is closely related structurally to minocycline (e.g., Minocin), shares many of the actions and risks of minocycline and other tetracyclines, and may be considered the newest addition to the tetracycline class of antibiotics. However, tigecycline is not apparently affected by the two major tetracycline resistance mechanisms, ribosomal protection and efflux, and crossresistance between tigecycline and other antibiotics has not been observed. Tigecycline has a broad spectrum of action that includes numerous gram-positive and -negative aerobic and anaerobic bacteria, some of which (e.g., methicillin-resistant Staphylococcus aureus) have not been demonstrated to be susceptible to other tetracyclines. Its action is usually bacteriostatic. The broad spectrum of action of the new agent permits its use as monotherapy for certain infections for which the use of a combination of antibiotics has previously been necessary. Tigecycline is administered by intravenous infusion and is indicated for the treatment of complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) caused by susceptible strains of the bacteria identified in Table 1. It has also demonstrated activity in vitro against many other organisms including problematic bacteria such as vancomycin-resistant Enterococcus faecalis and E. faecium; however, the clinical effectiveness of tigecycline in the treatment of infections caused by these bacteria has not yet been demonstrated. In the treatment of cSSSI, tigecycline was compared with a combination regimen of vancomycin and aztreonam (e.g., Azactam) in management of complicated deep soft tissue infections including wound infections, cellulitis, major abscesses, infected ulcers, and burns. The clinical cure rates were 86% and 88%, respectively, and the two regimens were considered to be comparable in their effectiveness. For treatment of cIAI such as appendicitis, cholecystitis, diverticulitis, gastric/duodenal perforation, intraabdominal abscess, perforation of intestine, and peritonitis, tigecycline was compared with imipenem/cilastatin (Primaxin). The clinical cure rates were 86% among patients treated with either of the antibiotics. The treatment of serious infections, which are frequently mixed infections caused by more than one organism, must often be initiated before causative organisms have been identified and their susceptibility determined. Tigecycline may be used as empiric monotherapy before results of these tests are known, and its broad spectrum of action, which includes bacteria such as staphylococci, streptococci, enterococci, and Bacteroides species, provides effective treatment for many infections that otherwise may have required the use of two or more antibiotics. However, to reduce the development of drug-resistant bacteria, tigecycline should be used only to treat infections that are documented or strongly suspected to be caused by susceptible bacteria. The adverse events most frequently reported with the use of tigecycline are nausea (30%) and vomiting (20%) that are usually mild to moderate in severity and generally occur in the first 1 to 2 days of therapy. Other commonly experienced adverse events include diarrhea (13%), local reactions (9%), infection (8%), fever (7%), and abdominal pain (7%). Because antibiotic-associated colitis has been reported with the use of almost all antibacterial agents, this possibility should be considered in patients who experience diarrhea while being treated with tigecycline. In the clinical studies with