Why Do Physicians Unnecessarily Prolong Antibiotics?
Wlodaver, Clifford G. MD*; May, Christopher L. PharmD
From the *College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK; and Department of Pharmacy, Midwest Regional Medical Center, Midwest City, OK.
Correspondence to: Clifford G. Wlodaver, 8121 National Ave, Suite 310, Midwest City, OK 73110. E-mail: email@example.com.
The authors have no funding or conflicts of interest to disclose.
Abstract: The duration of antibiotic therapy is incompletely defined in the literature. In some cases, shorter-than-traditional courses of antibiotics have been shown to be effective and, furthermore, have impacted favorably on the antibiotic resistance and Clostridium difficile epidemics. Despite these facts, we and other antibiotic stewards have frequently observed unnecessary prolongation. In this article, we have elucidated several causes for unnecessary prolongation, commented critically upon these, and proposed solutions.
Antimicrobials cure infections and save lives, yet they are not innocuous. Beyond their commonly appreciated adverse drug reactions such as allergies, they are also responsible for the current multiple drug-resistant organism (MDRO) and Clostridium difficile infection (CDI) epidemics. Evidence-based guidelines and stewardship programs have evolved during the past several years in an attempt to control these epidemics by regulating antibiotic use. These have primarily targeted unnecessary initiation (eg, for the common cold) and de-escalation of empiric regimens once a specific pathogen is identified.1,2 Excessive duration of antibiotic regimens has received considerably less attention. However, duration is nonetheless likely to be a significant source of MDRO and CDI,3 as the risk for dysbiosis is cumulative.4
In recent studies that do address appropriate length of treatment of specific infections, shorter courses are shown to be safer than previously thought and have generated updated guidelines. For example, for community-acquired pneumonia, the Infectious Diseases Society of America (IDSA) and the American Thoracic Society guidelines have recommended a course as short as 5 days.5 However, previous studies document that physicians do not always follow guidelines,6,7 and understanding why may be helpful. In this article, we critically examine patterns and rationales for excessive antibiotic prolongation.
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Perceived Standards of Care
An antibiotic treatment end point is often determined by individual prescribing habits acquired from training and experience, concerns over discontinuing other prescribers orders, continuation until hospital discharge, and by round numbers (ie, 5, 7, 10, and 14 days). These decisions may be more arbitrary than biologic. Moreover, what may not be appreciated is the harm that may result from overtreatment. For instance, a 7.8-fold increased risk for CDI has been demonstrated when antibiotic length increased from less than 4 to greater than 18 days (95% confidence interval, 4.6 13.4).4
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Fear of Relapse
Antibiotics are often prolonged just to be sure that the infection is cured, although, in many cases, there is no evidence that longer courses achieve better outcomes. In fact, recent data suggest that shorter-than-traditional regimens are effective for common infections and that relapses are rare. As examples, for acute uncomplicated cystitis, a single dose of fosfomycin suffices.8 In a study on community-acquired pneumonia, a 3-day course of amoxicillin was shown to be as effective as an 8-day course.9 Furthermore, although pulmonary infiltrates may persist for several days, antibiotics are not necessary beyond clinical cure.5
As a corollary, once a patient has clinically improved on an intravenous antibiotic, switching to an oral agent is a well-founded intervention. However, this may lead to exceeding the recommended length and carries similar risks.
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When a patient s diagnosis is uncertain, infection may be considered in the differential and antibiotics prescribed empirically as a therapeutic trial, based on the reasoning that the potential benefits outweigh the risks. When such trials lack a finite end point, antibiotics may be continued in the absence of improvement or even despite the presence of a documented noninfectious etiology (eg, congestive heart failure rather than pneumonia).
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Misperception That a Shortened Course of Antibiotics Promotes Resistance
There is a common perception, endorsed by some physicians and pharmacists, that shortened courses of antibiotic therapy promote resistance. Yet, as Rice 3 points out, it is, in fact, prolonged courses that are associated with increased resistance. He advises us to get our messages straight.
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Fear of Legal Retribution for Insufficient Antibiotic Treatment
Legal concerns may lead to treatment beyond what is medically sound. However, overtreatment can also lead to litigation, particularly when the drugs are held responsible for the morbidities and mortalities from CDI and MDRO infections.
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In addition to enunciating and critiquing the causes of unnecessary antibiotic prolongation, what else can be done to reduce it? We have drafted an abridged antibiotic-duration table for various bacterial infections and surgical prophylaxis selected from the IDSA guidelines (Table 1). Such a table could be systematically displayed next to the patient s diagnosis, facilitated by electronic medical records. Meeker et al 10 has proposed displaying a poster to nudge guideline-concordant antibiotic prescribing. It focuses on withholding initiation for acute respiratory infections. We suggest adding a warning that, once in use, prolonging antibiotic duration beyond established guidelines does not enhance efficacy and may be harmful. We also suggest applying the concepts of automatic stop orders to antibiotic duration, using the guideline recommendations as their basis. If necessary, based on the patient s clinical course, the prescriber would have the opportunity to challenge and override these orders.
Graphic Table 1
Furthermore, because infections are variable in their intensity, evolution, and response to antibiotics and individual hosts react to them differently, might a therapeutic end point likewise be variable, personalized to a patient s physiological response? A patient s well-being, temperature, pulse, and white blood cell count and inflammatory biomarkers (eg, erythrocyte sedimentation rate, C-reactive protein, procalcitonin (PCT), and neutrophil CD64 expression) are indicators of clinical status and useful for determining antibiotic duration. In particular, elevated PCT levels are reasonably sensitive and specific for bacterial infections and decrease rapidly (T1/2, 24 hours) with their resolution from antibiotics and immune control. The levels are not affected by anti-inflammatory agents or by immune suppression. Studies in respiratory tract infections and sepsis demonstrate that PCT-guided antibiotic discontinuation is effective and safe, and using these values has resulted in shorter-than-standard duration without compromising outcome.11,12 Clinical improvement should give prescribers confidence to follow the guideline recommendations and help overcome the obstacles discussed previously. We believe that customized regimens would likely lead to greater appreciation of the efficacy and safety of shorter durations of therapy and may be an important means of limiting adverse outcomes.
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The authors would like to thank Dr Barbara Trommer, MD, for her critical review of the manuscript and Dr Rob Roy MacGregor, MD, for his comments.
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Key Words: antibiotic stewardship; antibiotic duration; antibiotic resistance; Clostridium difficile