Pediatric Outpatient Antimicrobial Stewardship: Minimizing Antibiotic Duration

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Avoiding prolonged duration of therapy when possible should be a stewardship goal in the outpatient setting.
Avoiding prolonged duration of therapy when possible should be a stewardship goal in the outpatient setting.

Antimicrobial stewardship is essential to prevent overuse of antibiotics and the development of antibiotic-resistant organisms.1 A core antimicrobial stewardship strategy is to encourage discontinuation of therapy as soon as possible when active infection is no longer suspected. In many situations, shorter durations of therapy may achieve the same clinical outcomes with lower cost, fewer adverse events, less disruption of the microbiome, and less selection of antibiotic-resistant organisms.2

Historically, professional medical organizations have recommended antibiotic courses to include substantial days of therapy after clinical recovery. The primary goal was to eradicate the organism at the infection site prior to development of resistance and transmission to others. This is particularly relevant for pathogens such as Mycobacterium tuberculosis or Salmonella typhi. However, most infections are caused by bacteria that are normally commensal organisms (eg, Escherichia coli) and episodically become opportunistic pathogens. Resistance among commensals may develop during antibiotic treatment of other infections, and this resistance may be shared with other bacteria in the microbiome.

Approximately 60 million courses of antibiotics are prescribed each year in the United States in outpatient settings for patients under 20 years old.3 There is considerable variation in duration of prescribed antibiotic therapy for common diagnoses in pediatric patients.4 Drivers of this variation include lack of pediatric data for minimum effective duration of therapy, concern for relapse by treating pediatricians, or simple provider preference. Nonetheless, we believe opportunities exist to shorten duration of therapy for common pediatric infections, thus reducing pressure on flora to develop resistance. When published recommendations provide a range of duration for an infection (eg, 7-14 days), a pragmatic approach would be to prescribe the lower range value for most children and reserve the more prolonged duration for children with more severe presentations, slow clinical response, young age, immunodeficiency, comorbidities, or infections without source control (eg, an undrained abscess).

Urinary Tract Infections

In a meta-analysis of randomized clinical trials of urinary tract infections in children, short-course therapy (1-3 days) was found to be inferior to long-course therapy (7-14 days).5 Evidence for specific treatment duration of 7, 10, or 14 days is lacking, although longer courses may be appropriate for children with slower recovery, increased risk for renal scarring, or in young infants. The SCOUT study (Short Course Therapy for Urinary Tract Infections in Children; ClinicalTrials.gov identifier: NCT01595529), an ongoing multicenter clinical trial comparing 5 vs 10 days of therapy, may provide additional guidance.6

Community-Acquired Pneumonia

For duration of treatment of community-acquired pneumonia (CAP), an important consideration is whether the pneumonia is simple or complicated (with empyema or systemic infection involving other organs), the latter requiring more prolonged therapy tailored for each patient. The 2011 Infectious Diseases Society of America (IDSA) guideline states that 10-day courses have been best studied for uncomplicated CAP, but also suggests that shorter courses may be just as effective, particularly for more mild disease.7 In developing countries, the World Health Organization recommends 3 days of therapy with high-dose amoxicillin (in areas of low HIV prevalence) if tachypnea alone is present and 5 days of therapy if retractions are present.8 However, in a recent double-blind randomized controlled trial of ambulatory CAP in children 6 to 59 month old, 5 days of therapy with high-dose amoxicillin was found to be equivalent to 10 days of therapy, but 3 days of treatment was associated with increased need for rescue treatment and/or hospitalization.9

Skin and Soft Tissue Infections

IDSA recommends 7 days of therapy for treatment of skin and soft tissue infection, but also suggests that 5 days is sufficient for nonpurulent cellulitis, with extension of duration if the infection has not improved.10 Incision and drainage of cutaneous abscesses often is sufficient for cure, although the addition of antibiotics can reduce recurrence. For deeper infections, duration of therapy may need to be prolonged if adequate surgical drainage is not achieved.

Acute Otitis Media

Recent evidence has shown that treatment with 10 days of therapy remains the standard of care for pediatric acute otitis media. In a recently published randomized controlled trial of 520 children, those treated with amoxicillin-clavulanate for 5 days were more likely to have clinical failure than those who were treated for 10 days (77 of 229 children [34%] vs 39 of 238 [16%]), were more likely to have failure defined as lack of resolution, or to have worsening of symptoms or otoscopic signs of infection.11 There were no significant between-group differences in recurrence rates, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. It should be remembered that most acute otitis media is viral, and that in children older than 2 years without severe symptoms, pediatricians may delay antibiotics for 48 to 72 hours.

Group A Streptococcus Pharyngitis

Streptococcal pharyngitis is a common pediatric infection requiring antibiotic therapy. As detailed in the 2012 IDSA pharyngitis guidelines, selective swabbing of throats, limited to pharyngitis lacking overt viral features (mouth ulcers, worsening rhinorrhea, cough) is important in the identification of those with bona fide streptococcal pharyngitis.12 When group A streptococcus is identified, 10 days of therapy with penicillin or amoxicillin is clearly superior to shorter courses for eradication and prevention of rheumatic fever.

Acute Sinusitis

The 2013 American Academy of Pediatrics guidelines for management of acute bacterial rhinosinusitis do not make a recommendation for treatment duration.13 Some experts have recommended treatment for 1 week after clinical improvement (minimum duration 10 days). Of note, the recommended duration of therapy for uncomplicated acute bacterial sinusitis in adults is 5 to 7 days.

Conclusions

Avoiding prolonged duration of therapy when feasible should be a stewardship goal in the outpatient setting. Practice or institutional guidelines that include duration, combined with education and feedback to prescribers, can lead to safe sustained decreased durations of therapy for common pediatric infections. Opportunities to decrease duration of antibiotic therapy should be reviewed regularly. Response Adjusted for Duration of Antibiotic Risk is a pragmatic strategy that incorporates competing risks and adverse events to examine the impact of antibiotic use.14 Further comparative effectiveness studies in children are needed to determine the efficacy and safety of short-course therapy for various common infections.

Reference

  1. Centers for Disease Control and Prevention. Core Elements of Hospital Antibiotic Stewardship Programs. Updated February 23, 2017. Accessed October 1, 2017.
  2. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. Updated April 10, 2017. Accessed October 1, 2017.
  3. Centers for Disease Control and Prevention. Outpatient Antibiotic Prescriptions — United States, 2014.
  4. Vaz LE, Kleinman KP, Raebel MA, et al. Recent trends in outpatient antibiotic use in children. Pediatrics. 2014;133:375-385.
  5. Keren, R. Chan E. A meta-analysis of randomized, controlled trials comparing short- and long-course antibiotic therapy for urinary tract infections in children. Pediatrics. 2002;109(5):E70-0.
  6. ClinicalTrials.gov. stance The SCOUT Study: Short Course Therapy for Urinary Tract Infections in Children (SCOUT). https://clinicaltrials.gov/ct2/show/NCT01595529. Accessed October 16, 2017.
  7. Bradley JS, Byington CL, Shah SS, et al; Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53:e25-76.
  8. World Health Organization. Revised WHO Classification and Treatment of Pneumonia in Children at Health Facilities: Evidence Summaries. Geneva, Switzerland: World Health Organization; 2014. https://www.ncbi.nlm.nih.gov/books/NBK264162/
  9. Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J, Dagan R. Short-course antibiotic treatment for community-acquired alveolar pneumonia in ambulatory children: a double-blind, randomized, placebo-controlled trial. Pediatr Infect Dis J. 2014;33:136-142.
  10. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Executive summary: practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:147-159.
  11. Hoberman A, Paradise JL, Rockette HE, et al. Shortened antimicrobial treatment for acute otitis media in young children. N Engl J Med. 2016; 375:2446-2456.
  12. Shulman ST, Bisno AL, Clegg HW, et al. Executive summary: clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 uUpdate by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55:1279-1282.
  13. Wald E, Applegate KE, Bordley C, et al; American Academy of Pediatrics. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics. 2013;132:e262-280.
  14. Evans SR, Rubin D, Follmann D, et al. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015;61:800-806.
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