Risk Perception and Inappropriate Antimicrobial Use: Yes, It Can Hurt

Received 3 February 2009; accepted 3 February 2009; electronically published 10 April 2009. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. Reprints or correspondence: Dr. John H. Powers, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700B Rockledge Dr., Rm. 1123, Bethesda, MD 20892 (powersjohn@mail.nih.gov). Clinical Infectious Diseases 2009; 48:1350–3 2009 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2009/4810-0003$15.00 DOI: 10.1086/598184 One of the first principles of medicine since the time of Hippocrates has been to first do no harm. All medical interventions—drugs, biologics, and devices— have the potential to cause unwanted harm, which accompanies the potential for benefit. The safe use of medical interventions relies on using them in situations in which there is substantial evidence of effectiveness to justify any potential harm. In the absence of evidence of benefit, even low-frequency or non-serious harm is not justifiable. However, it seems that various providers sometimes give antimicrobials to patients using the maxim “it can’t hurt”—in other words, even if it does not work as intended, the risk of harm is vanishingly low. This is based on a mistaken assumption that the use of antimicrobials comes at no cost to the patient or to society. However, not only can antimicrobials cause direct toxicity to patients, including serious adverse events, such as anaphylaxis, but inappropriate use spreads antimicrobial resistance to both the persons who receive the drug and those who do not, without providing benefits to either group. Using antimicrobials properly entails an accurate diagnosis, timely administration of the drug, and use at the optimal dosage and duration. Amazingly, after 80 years of antimicrobial use, we still are not clear on some of these points, such as the appropriate duration of antimicrobial treatment for some diseases (e.g., pneumonia). On the other side of the coin, appropriate use entails avoiding the use of antimicrobials when the harm outweighs the benefits, such as situations in which studies have not reliably and reproducibly demonstrated the benefits of antimicrobials. Appropriate use also entails not using antimicrobials as a substitute for timely follow-up, that is, just in case “something bad might happen.” Learning from history. Appropriate conditions of use for anti-infective agents is an issue that dates back to the use of serum therapy to treat pneumococcal pneumonia in the early 1900s. Serum therapy decreased mortality, but only in the cases of disease due to the same pneumococcal type against which the serum was directed [1]. Serum therapy caused serious adverse events, such as allergic reactions with attendant hypotension, so it was important to make an appropriate diagnosis by typing organisms prior to administering the serum. With the introduction of sulfa drugs, typing of organisms became less necessary, but this led to use of the drugs in situations in which their benefits did not outweigh their risks in cases of inappropriate diagnosis. The issue of adverse events with antimicrobials also has a long history. Deaths attributable to the mixing of sulfanilamide with diethylene glycol spurred the passing of the Food, Drug, and Cosmetic Act in the United States in 1938. Theodore Klummp of the US Food and Drug Administration pointed to the importance of appropriate use in the findings of his investigation of the sulfanilamide tragedy: “I think you would be interested in some of the implications that arise from the observations recorded. I refer particularly to the 105 deaths associated with consumption of the drug...In a hundred instances the drug was administered on a physician’s prescription [for] Bright’s disease [nephritis], bichloride and mercury poisoning, renal colic and backache [2, p. 82].” Based on cases such as these, H. Corwin Hinshaw in 1939 urged that, “For the most