Problems and dilemmas of antimicrobial resistance.

An important obstacle to the long-term efficacy of an antimicrobial agent is the appearance and spread of resistance to the agent. The fact that many antimicrobials are produced by microorganisms in nature may provide long-term selective pressure for the emergence of resistance in antibiotic-producing as well as -nonproducing organisms. Indeed, the rapidity with which many resistances have appeared after the introduction of a new antibiotic suggests that these resistance genes were already present somewhere in nature prior to clinical use. In the hospital setting, the most recent worrisome resistance traits to emerge include plasmid-mediated resistance to imipenem and to third-generation cephalosporins among nosocomial gram-negative bacteria, and the acquisition of resistance to vancomycin by enterococci. Methicillin-resistant staphylococci continue to be a problem and are increasingly resistant to numerous other agents such as rifampin and the newer fluoroquinolones. The most important resistances seen in community-acquired organisms include beta-lactam resistance in pneumococci and combined ampicillin and chloramphenicol resistance in Haemophilus influenzae. Shigellae resistant to essentially all commonly used oral agents are also a problem, particularly in developing countries. No end is in sight to the problem of antimicrobial resistance, and thus new strategies to prevent infections and control resistant organisms continue to be necessary.