Microbial Resistance: Bacteria and More

Reprints or correspondence: Dr. Robert C. Moellering, Jr., Harvard Medical School, Dept. of Medicine, Beth Israel Deaconess Medical Center, 110 Francis St., Suite 6A, Boston, MA 02215 (rmoeller@caregroup.harvard.edu). Clinical Infectious Diseases 2003; 36(Suppl 1):S2–3 2003 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2003/3602S1-0002$15.00 The 20th century saw a series of remarkable discoveries that changed the face of medical practice. Among the most important was the discovery of antimicrobial agents, beginning with the synthesis of arsphenamine by Paul Ehrlich as the century dawned [1]. With this discovery, the dreaded scourge of syphilis was brought under control, although not eradicated. However, the toxicity of the drug made it less than ideal as an antimicrobial agent. Shortly thereafter, optochin (ethyl cupreine) was tried for therapy of pneumococcal pneumonia, but it too was toxic and was not effective enough to be successful. Moreover, pneumococci with resistance to this drug were isolated from patients who failed to respond to treatment—one of the first observations of antimicrobial resistance! The middle of the century saw an even more remarkable set of discoveries: the development of the first true antibiotics, beginning with the sulfonamides and penicillin and progressing through a whole series of effective antimicrobials that attacked the bacterial cell at numerous vulnerable points. The discovery of effective antituberculous agents and antifungal agents soon followed. Viral infections provided a greater challenge, but even these have now yielded, at least in part, to the science of chemotherapy. The luster of the antimicrobial era soon began to show evidence of tarnish, however, as first bacteria, then fungi, and then viruses began to develop resistance to the antimicrobial agents directed against them [1]. Microbial ingenuity and resilience have never been more evident than in their remarkable ability to develop resistance to chemotherapeutic agents. This is especially true of bacteria that have modified their DNA by chromosomal mutation and by acquiring resistance genes via conjugation, transformation, and even transduction. There are seemingly no boundaries to the capabilities of some microorganisms to develop resistance. The recent acquisition of vancomycin resistance in enterococci by the assembly of multiple foreign genes into transposable elements and the demonstration of transferable fluoroquinolone resistance genes in Klebsiella pneumoniae are 2 vivid examples of this [2, 3]. Antimicrobial resistance has been fueled by inappropriate use of antimicrobial agents—especially those directed against bacteria. Widespread industrial and agricultural use of antimicrobials has played a role, but the unwillingness of the medical profession to accept measures for the restraint or control of indiscriminate prescribing and inappropriate dosing of antibiotics needs to be addressed. Clinicians have failed to deal with a potentially solvable problem, and others are taking up the challenge. The inexorable spread of antimicrobial resistance is now of concern to agencies of numerous governments and health agencies worldwide, including the World Health Organization, which has attempted to bring order to chaos and provide rational solutions to the problem. The 5 articles in this symposium provide insight regarding a number of important aspects of antimicrobial resistance. The first article, by Howard et al. [4], discusses the global impact of drug resistance. They note that although a number of previous studies have focused on costs, morbidity, and mortality related to infections caused by resistant microorganisms, most of these studies concentrate primarily on the infected patient. The authors emphasize that this is not the whole story and make the important observation that the true cost of antimicrobial resistance goes far beyond the individuals infected with resistant bacteria, fungi, or viruses. When the rates of resistance become high enough, physicians and others determining therapeutic policy change empiric therapy for a variety of common infections, including respiratory tract infections, malaria, and tuberculosis. The authors note that in some cases, the overall costs of these changes exceed those related to treatment failure. Livermore [5] focuses on resistance in bacteria and discusses the plethora of mechanisms involved, including several that have only recently been discovered. He also notes that there are a number of elements in the epidemiology of bacterial resistance that are not fully understood. For instance, we do not know why certain