Epidemiology of drug resistance: implications for a post-antimicrobial era

In the last several years, the frequency and spectrum of antimicrobial-resistant infections have increased in both the hospital and the community. Certain infections that are essentially untreatable have begun to occur as epidemics both in the developing world and in institutional settings in the United States. The increasing frequency of drug resistance has been attributed to combinations of microbal characteristics, selective pressures of antimicrobial use, and societal and technologic changes that enhance the transmission of drug-resistant organisms. Antimicrobial resistance is resulting in increased morbidity, mortality, and health-care costs. Prevention and control of these infectins will require new antimicrobial agents, prudent use of existing agents, new vaccines, and enhanced public health efforts to reduce transmission.

In an article published in 1982, Walsh McDermott described a typical medical ward in a large city hospital circa 1930. In contrast to the wards of the early 1980s, which were filled with patients with cancer, heart disease, or the complications of diabetes or hypertension, the wards of the pre-antimicrobial era were populated by patients with pneumonia, meningitis, bacteremia, typhoid fever, endocarditis, mastoiditis, syphilis, tuberculosis, and rheumatic fever. There were few effective therapies for most of these conditions. Many of the patients were young, and most would die of the disease or its complications. But within a few years, many of these bacterial infections, and particularly the complications, were rapidly to become memories of the pre-antimicrobial era. The introduction of antimicrobial agents in the mid-1930s "heralded the opening of an era in which literally millions of people-children, adults, and the elderly, all slated for early death or invalidism--were spared..." (1, p. 307).

The development and use of antimicrobial agents was one of the most important measures leading to the control of bacterial diseases in the 20th century. Other medical advances, such as vaccines and effective public health programs, were also instrumental, as were societal improvements in sanitation, hygiene, nutrition, and standard of living, all of which had already led to decreases in many infectious diseases before the advent of antimicrobial therapy. Nevertheless, antimicrobial therapy provided physicians with the ability to prevent some infections, to cure others, and to curtail the transmission of certain diseases. Today, the concept of an untreatable bacterial disease is foreign to most physicians in the developed world. Many bacteria remain fully susceptible to commonly used antimicrobial agents.

Despite this half-century of success, periodic warnings have recurred: the introduction of a new drug was almost always followed by resistance. But there were always newer drugs. Recent events, however, have questioned the continued general effectiveness of antimicrobial agents. The emergence of multiple-drug resistance in Mycobacteriurn tuberculosis, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus, Shigella dysenteriae, and Plasmodium falciparum has made many currently available antimicrobial drugs ineffective and in certain instances is already posing important public health problems. Furthermore, scientists at a recent National Institutes of Health workshop reported that fewer new antimicrobial drugs were under development (2). Such issues have raised the concern that we may be approaching the postantimicrobial era. In this article, I will...