A Novel Antimicrobial Agent Joins the Battle against Resistant Bacteria

• Drug resistance, microbial
• chemistry, pharmaceutical
• Drug design
• Linezolid
• Antibiotics

Lately, the medical news has featured a disturbing number of reports of the inexorable development of bacterial resistance to almost all available antimicrobial agents (1, 2). Whereas resistant gram-negative bacteria were a major problem in the 1970s, the past decade has seen a crescendo of problems with multidrug-resistant gram-positive bacteria, including methicillin-resistant staphylococci, penicillin-resistant pneumococci, and vancomycin-resistant enterococci (3). The latter are particularly vexing because several strains of vancomycin-resistant enterococci (especially Enterococcus faecium) are resistant to all available antibiotics (4). In the past, the solution to the problem of bacterial resistance has depended primarily on the development of novel antimicrobial agents. However, this approach is quickly proving to be less than totally efficacious, and the number of new classes of antimicrobial agents being developed has markedly decreased in recent years (5). The obvious bacterial targets for selective inhibition or killing have largely been discovered, it seems, making it increasingly difficult to find new agents that are effective and nontoxic (5). Indeed, no novel class of antimicrobial agents has been developed since the early 1980s. The “new” macrolides and fluoroquinolones, for example, are simply chemically modified variants of agents known since the 1950s and 1960s, respectively.

The advent of resistant gram-positive bacteria has not gone unnoticed by the pharmaceutical, biotechnology, and academic communities. All of these groups are making concerted efforts to find novel antimicrobial agents to meet this need. In one instance, this involves dusting off an old agent, everninomicin, which was discovered decades ago but was shelved because of potential toxicity and problems with formulation (6). A new formulation of this drug is now in phase II and III trials against infections with resistant gram-positive bacteria. In another instance, the approach has involved retrofitting an old streptogramin antimicrobial agent, pristinamycin, to administration of …