"The drastically increased use of antibiotics has certainly accelerated the appearance of resistant strains. Yet there is another aspect of this issue that deserves mention. A reader of the popular press is likely to carry away the impression that the emergence of antibiotic-resistant bacteria is a recent phenomenon. That is not the case. The first published report of a penicillin-resistant strain appeared in the 1940s, shortly after penicillin began to be used clinically. In the intervening years, there have been many reports of resistant bacteria, and surveys have shown a steady increase in the number of resistant strains. Even during the 1960s, reports of bacterial strains resistant to multiple antibiotics were becoming commonplace. Yet most physicians and medical policymakers dismissed such reports as unimportant because new antibiotics were constantly appearing on the market, and these new antibiotics allowed physicians to keep ahead of the resistant strains.
"A major contributor to the current crisis was the widespread attitude during the 1970s that bacterial resistance to antibiotics was not a serious medical problem, nor was it likely to become so, because new antibiotics would continue to appear in time to replace those made obsolete by bacterial resistance mechanisms. Unfortunately, there was a serious flaw in this rosy projection. Already in the 1970s, it was becoming more and more difficult to find new antibiotics. Development of a new one therefore has become increasingly expensive for the pharmaceutical companies.
New requirements for more and larger clinical trials prior to licensing of an antibiotic further increased the cost of bringing a new drug to market. The result was that the companies began to cut back on their antibiotic discovery programs and to focus instead on more profitable drugs. It now takes at least 10 years to bring an antibiotic from the discovery stage to the market, so decisions made during the 1970s and 1980s are having their most profound effect on today's medical treatment. Few new antibiotics are now in the pipeline, whereas antibiotic resistance among bacteria is increasing faster than ever. So the current perception of a crisis in antibiotic resistance is not just a matter of an increase in multiply resistant strains of bacteria but also of the reduced availability of new antibiotics to take care of resistant strains.
"Overuse and abuse of antibiotics by physicians is the main cause of the antibiotic resistance crisis. Understandably, however, physicians do not wish to take all the blame for what could become a major public relations disaster--if fears about the impending 'loss of antibiotics' prove to be justified. This has led to the search for others to share the blame. A popular candidate is the patient who demands antibiotics even when they are inappropriate or the patient who does not take antibiotics as prescribed.
"It is true that failure of tuberculosis patients to take antibiotics as prescribed has played a major role in the emergence of multiply resistant strains of the bacterium that causes tuberculosis. In this case, patients were taking the antibiotics sporadically over long periods, a practice that led to chronic exposure of bacteria to doses of antibiotics too low to eradicate them--a prime selective environment for resistant strains. Therapeutic regimens of antibiotics are designed to expose the bacteria to high doses of antibiotics that eradicate the bacteria from the body, either by killing them directly or by helping the immune system to clear them. If a patient stops taking an antibiotic prematurely and there are still bacteria in the body, the period during which the concentration of antibiotic in circulation falls gradually to zero allows bacteria to experience the sublethal concentrations of antibiotic that tend to select for resistant strains.
"This type of patient misuse of an antibiotic is not, however, the one most conducive to selection of resistant strains. It is the sporadic use of antibiotics--for example, taking one pill a day instead of the prescribed three or four--that provides the optimum setting for the development of resistant strains. Most people agree that failure of patients to take antibiotics as prescribed is probably a minor factor in the development of resistant strains compared with the overuse of antibiotics in crowded settings such as modern hospitals, where selective pressure for resistance is constant and where transmission of resistant strains to staff members and patients is most likely to occur.