Por què médicos prolongan uso de antibiòticos?

Why Do Physicians Unnecessarily Prolong Antibiotics?
Wlodaver, Clifford G. MD*; May, Christopher L. PharmD € 
Author Information
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: cliff_wlodaver@yahoo.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.
Back to Top
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
Back to Top
Fear of Relapse

Antibiotics are often prolonged €œjust 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.
Back to Top
Diagnostic Uncertainty

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).
Back to Top
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 €œget our messages straight. €
Back to Top
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.
Back to Top

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 €œnudge 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.
Back to Top

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.
Back to Top

1. Dellit TH, Owens RC, McGowan JE Jr, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007; 44 (2): 159 €“177. Buy Now [Context Link]
2. Wlodaver CG, May C. Antibiotic Stewardship: using clinical guidelines to control antibiotic overuse and deter microbial adaptation. Infect Dis Clin Pract. 2012; 20: 12 €“17. Ovid Full Text [Context Link]
3. Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and Clostridium difficile. Clin Infect Dis. 2008; 46 (4): 491 €“496. Buy Now [Context Link]
4. Stevens V, Dumyati G, Fine LS, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011; 52 (5): 42 €“48. [Context Link]
5. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 (suppl 2): S27 €“S72. [Context Link]
6. Cabana MD, Rand CS, Powe NR, et al. Why don €™t physicians follow clinical practice guidelines? A framework for improvement. JAMA. 1999; 282: 1458 €“1465. Buy Now [Context Link]
7. Pronovost PJ. Enhancing physicians €™ use of clinical guidelines. JAMA. 2013; 310: 2501 €“2502. Buy Now [Context Link]
8. Falagas ME, Vouloumanou EG, Togias AG, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010; 65 (9); 1862 €“1877. [Context Link]
9. el Moussaoui R, de Borgie CA, van den Broek P, et al. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia; randomized double blind study. BMJ. 2006; 332: 1355 €“1358. [Context Link]
10. Meeker D, Knight TK, Friedberg MW, et al. Nudging guideline-concordant antibiotic prescribing: a randomized clinical trial. JAMA Intern Med. 2014: 174 (3): 425 €“431. Buy Now [Context Link]
11. Soni NJ, Samson DJ, Galaydick JL, et al. Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis. J Hosp Med. 2013; 8 (9): 530 €“540. Buy Now [Context Link]
12. Schuetz P, Chiappa V, Briel M, et al. Procalcitonin algorithms for antibiotic therapy decisions. Arch Intern Med. 2011; 171 (15): 1322 €“1331. [Context Link]
Key Words: antibiotic stewardship; antibiotic duration; antibiotic resistance; Clostridium difficile


Publicado en Sin categoría |

Deja una respuesta

Tu dirección de correo electrónico no será publicada. Los campos obligatorios están marcados con *