Cultural and Economic Factors That (Mis)Shape Antibiotic Use: The Nonpharmacologic Basis of Therapeutics

Since the dawn of therapeutics, the prescribing of medications and their use by patients has been marked by substantial variability in both rationality and effectiveness. Drug use historically has reflected the highest principles of science as well as strikingly irrational behavior. This heterogeneity has been particularly vivid in the case of antibiotics. Antibiotics are among the most commonly used therapeutic agents, accounting for 12% of ambulatory care prescriptions (1). Their use ranges from treatment of minor self-limited outpatient symptoms to potentially fatal conditions in critically ill patients. Antibiotics loom large economically as well, accounting for approximately 15% of the nearly $100 billion in annual medication expenditures in the United States (2). Because of their role in treating infections, antibiotics tap into some of our most deeply held beliefs about bodily integrity and invasion. Furthermore, other than certain vaccines, antibiotics are the only drug class whose use influences not just the patient being treated but the entire ecosystem in which he or she lives, with potentially profound consequences. The determinants of antibiotic use and misuse are thus of particular importance. They include factors as diverse as the physicianpatient relationship, clinical microbiology, health economics, and the most basic definitions of illness and therapy (3). Factors Leading to Antibiotic Misuse In their psychosocial dimension, medications can have properties that transcend pharmacology and may take center stage in some clinical situations. Social scientists and wise clinicians have long been aware that providing a patient with a drug is an interpersonal as well as a biochemical intervention (4); this is particularly true of antibiotics. The writing of a prescription signifies that the physician has made a diagnosis and that treatment is possible. A prescription officially (and tangibly) assigns the patient to the sick role, with all of its benefits and responsibilities (5). It can also act as a termination strategy for an office visit, a sign that the visit has been consummated, the encounter is complete, and it is time for the patient to move on. This strategy creates a paradoxical outcome in the current environment, which is so preoccupied with throughput. A prescription for an antibiotic is often seen as the quickest way to end the visit of a patient with possible infectious symptoms. The number of patients seen per hour is increasing, and such increased productivity is frequently commended in the same management memorandum that criticizes out-of-control drug expenditures. Ironically, managers' desire to reduce the use of diagnostic tests (cultures) and prevent return visits also creates pressures that favor heavy antibiotic use. Through the alchemy of the pharmacy, the paper prescription and its inscrutable ritualistic writings are transformed into a container of tablets or capsules. In a real sense, the drug prescription prolongs the physicianpatient encounter by enabling the patient to ingest a dose of the doctor several times a day. As Sir William Osler noted, The desire to ingest medicines is one of the principal features which distinguish man from the animals (6). This perspective helps to explain the drug hunger that many symptomatic patients bring to the physician visit, in which they feel satisfied only by receiving a prescription (7). Such demands are not based on clinical data as we know it (8-10). Patient expectations have been further intensified by the advent of direct-to-consumer advertising of antibiotics by pharmaceutical manufacturers. Unlike the situation of depression, incontinence, or impotence, for which undertreatment is common, no logic exists for increasing the public's demand for antibiotics. These advertisements serve primarily to persuade patients to demand newer, more costly antibiotics in clinical situations in which older, generic products, or no drug at all, would often work just as well. They are skillfully constructed to promote the ease or effectiveness of the target product and, of course, do not mention cost or note the similar effects of older therapies (11). Two trends have intensified the effect of direct-to-consumer promotion of antibiotics. First, the credibility of many once-respected sources of authority is waning, taking a toll on physicians' professional sovereignty (12, 13). Related to this trend is the parallel rise of consumer activism; worried that their health maintenance organization will deny them needed therapy to reduce expenditures, patients demand treatments that they fear might otherwise be withheld. Taken together, these trends turn therapeutic decision making into more of a dialogue (at best) or a tug-of-war (at worst) between patient and physician, a phenomenon that would have been unthinkable a generation ago. Add to this a growing if belated concern over patient satisfaction, the drive to shorten outpatient encounters as much as possible, and aggressive marketing directed at physicians, and the stage is set for the demand and receipt of astoundingly large quantities of unnecessary antibiotics. Viewed in this context, it is not surprising that the small voice of therapeutic restraint and concern about microbial resistance is so difficult to hear above the din. The movement favoring adoption of clinical guidelines for rational antibiotic use often runs headlong into the pressures on the primary care physician as the proprietor of a small business, just trying to get through the day and satisfy his or her customers. For example, in focus groups designed to reveal physicians' knowledge about, attitudes toward, and motivations for prescribing, some clinicians presented with clinical vignettes that were constructed to sound compellingly viral in cause still favored use of antibiotics to improve symptoms and reduce the likelihood of superinfection (14). However, a larger group argued that even if antibiotics were not indicated, they often felt obliged to prescribe them because of patient demand. This problem is still more acute in the developing world, although a full discussion is beyond the scope of this paper. In the inpatient setting, a different set of forces conspires to encourage excessive antibiotic use. In teaching hospitals, prescribing decisions frequently are made by those with the least clinical experience (interns and residents); at the same time, each year hospitalized patients become more acutely ill and their cases increasingly complex. These factors, combined with the ubiquitous pressure to keep length of stays short (the inpatient equivalent of the shrinking office visit), make it difficult to pursue a course of watchful waiting in managing a fever of unknown origin. Such temperance is particularly difficult if the prescribing physician has been in practice for only a few months. The first priority becomes the prevention of disaster within the next 24 hours, a goal often thought to be met best by broad-spectrum antibiotics or a cacophony of narrower-spectrum agents used in combination. Evidence for Antibiotic Misuse The perspective outlined above helps explain why analyses of antibiotic use patterns have consistently documented that prescribing is suboptimal (15). Many randomized, placebo-controlled trials of acute bronchitis, cough, and upper respiratory illnesses have found that outcomes are no better in typical patients taking antibiotics than in those given placebo (8-10). However, of the 51 million visits for colds, upper respiratory tract infections, and bronchitis in the United States in one recent year, 50% to 66% culminated in an antibiotic prescription (16, 17). Clinical factors often seem to play a minor role in antibiotic decision making in these illnesses. Diagnostic uncertainty also plays a role; a recent study of patients with sore throats found that two thirds of antibiotic prescriptions were written for patients whose cultures came back negative (18). A large current survey of antibiotic use in treating infectious symptoms in children revealed widespread disregard of commonly recommended diagnostic strategies and therapeutic guidelines and frequent overuse of antibiotics in upper respiratory tract infections (65%) (19). Several patient demographic factors have been found to increase the likelihood that antibiotics will be prescribed. These include being female, young, and white and living in a rural area (15). In the developing world, social and economic factors as well as suboptimal drug use have driven the emergence and spread of multidrug-resistant tuberculosis (20). In hospitalized patients, incorrect dosing or poor choice of drug occurs often. In a study performed at one teaching hospital (21), we found that physicians usually ordered inappropriate doses or intervals for clindamycin, metronidazole, and cefazolin. At another large hospital, antibiotic prophylaxis before surgery was found to be correctly timed in only 40% of cases (22). At the same institution, physicians did not respond correctly to 25% of instances in which culture and sensitivity data were available (23). Overuse of such antibiotics as vancomycin raises concern about the emergence of resistant organisms as well as cost. One recent study found that only 40% of orders at several hospitals were compatible with Centers for Disease Control and Prevention (CDC) guidelines (24). Overuse of vancomycin is probably an important factor in the spread of resistance (25); during a period when vancomycin use was rapidly increasing, resistance rates increased from 0.8% to 4.0% (26). Antibiotic Resistance and Costs The total costs associated with antibiotics come from multiple sources: medication, adverse events, and the often hidden cost of antimicrobial resistance (2). Adverse events occur in a small proportion of antibiotic courses, but because of the frequency of antibiotic use, they accounted for 23% of all adverse events recorded at one h