R-plasmids in hospitals — Implications for antibiotic use

Most physicians are aware of the fact that bacteria resistant to antibiotics exist, but few may be aware of the reasons for their existence or the means that may be taken to overcome them. One of the most convincing demonstrations of the principle of Darwinian evolution (survival of the fittest) has been the appearance of antibioticresistant bacteria in response to the tremendous selection pressure of antibiotic usage in medicine and agr!culture. If one were to calculate the quantity of antibiotics released into the environment (hospitals, farms, etc.) since the first introduction of antimicrobial agents in the late 1930s, the figures would probably be staggering and one would wonder how the microbial world could possibly have survived this onslaught. For example, it is estimated that several million pounds are used in the U.S., alone, everyyear. However, microorganisms still exist and continue to cause infection. The biological basis of this amazing survival is the capacity of microorganisms to inherit and to exchange genetic information in small packets known as plasmids, and the fact that plasmids can encode resistance mechanisms to almost all of the antimicrobials in clinical use. The existence of resistance plasmids, and their consequences for therapy is something that all physicians must take into consideration; it is less important for the clinician to be able to recognize the presence of resistance plasmids in bacteria as such. Nonetheless, the advent of rapid screening techniques for the detection of resistance plasmids in bacterial isolates has created a new field molecular epidemiology that allows one to chart the nature of the spread of resistance mechanisms in a hospital environment. This is a highly interesting and illuminating field of study since it shows that resistance plasmids, by some mechanism or another, can pass between different genera and species of bacteria and can be disseminated in all parts of a hospital under the selective pressure of antibiotic usage. In general (and not surprisingly) one finds the highest incidence of antibiotic resistance and R-plasmids in surgical and intensive-care wards. This much is known, what can be done about it? There is constant pressure on microorganisms to survive the onslaught of antimicrobial agents and, in another sense, there is constant pressure on physicians to use more and more, and newer and newer agents. In a recent survey in the United States it was concluded that about half of the prescibed use of antibiotics was "inappropriate"; this is a nice way of saying that they should (probably) not have been used! Since it is recognized that resistant strains and R-plasmids only flourish when the antibiotic selection pressure is maintained, an uncontestable solution is to prompt more appropriate use of antibiotics by applying the principles and practice of infectious disease treatment, allied with good microbiological study. The latter identifies, not so much R-plasmids, but those organisms that contain R-plasmids and their distribution within a given environment. The choice of antimicrobial agent is a complex and heavy responsibility which must take many factors into consideration: the illness, the patient, availability and pattern of use of drug, the microorganism, and also the bacterial population of the environment or hospital in which treatment is to take place. The latter may be an important guideline and the prudent physician will keep himself informed as to current microbiological and resistance problems before deciding on the antimicrobial agent to be used. Although each patient is an individual case, the existence of Rplasmids and resistant organisms create a background against which the choice of drug must be made. The newest and most advanced drugs are not always the best choice when all factors are taken into consideration for a given patient or outbreak. As a case in point, due to the distribution of certain R-plasmids kanamycin is in some instances a more effective drug than gentamicin against the resistant organisms. However, the physician may be under pressure to use more expensive and less welljustified third-generation cephalosporins or other antibiotics that should be conserved for more appropriate use. In the future, the physician will be ably assisted in his choice of the most appropriate antibiotic by modern advances in microbiology and clinical biochemistry that will permit more rapid isolation, identification, and characterization of pathogens; one can predict much closer collaboration between the infectious disease specialist and microbiologist, with advantages for the patient and disadvantages for the microbial population. It is worth emphasizing again that R-plasmids and resistant organisms are present because of the use of antimicrobial agents and that one significant act that can be taken to reduce this distribution is the more carefully considered use of antimicrobial agents. In this context, the extensive (and often inappropriate?) use of antibiotics in agriculture has also created a large reservoir of Rplasmids and resistant organisms. Although there is no convincing evidence that such extensive agricultural use has contributed to the microbial antibiotic resistance problems in humans, the presence of this large collection in our environment is disturbing and could be reduced.