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Less is more: Use the shortest effective duration of antibiotics

Contemporary PEDS Journal, April 2022, Volume 39, Issue 3

Follow best practices when prescribing antibiotics in the pediatric population

Pediatricians tend to be more judicious in prescribing antibiotics than our colleagues in adult medicine, but there remains much room for improvement in ambulatory pediatrics. Reducing therapy to the shortest effective duration may be one of the highest-yield practice changes to decrease unnecessary antibiotic exposure in pediatric patients.

Antibiotic resistance is a growing threat to public health, and antibiotic use (prescribed for a wide variety of pediatric illnesses such as common respiratory disorders) is the primary driving factor that leads to resistance. Many pediatricians may have been taught that not completing a prescribed course could lead to antibiotic resistance. In fact, it is longer exposure to antibiotics that exerts greater selective pressure on bacteria, increasing the risk of resistance.

Adverse drug events (ADEs) are another important consideration in the mission to reduce unnecessary antibiotic use. The findings of one study showed that almost half of all emergency department visits for ADEs in children were due to antibiotics.2 In one study across a large primary care pediatric network, 29% of all antibiotic courses prescribed for acute respiratory tract infection resulted in an ADE.3 In the inpatient setting, each additional day of antibiotic use has been shown to be associated with a 7% increased risk of developing an antibiotic-related ADE.4 Longer duration of therapy is also an important risk factor for Clostridioides difficile infections.5

Therapy should be prescribed for the shortest effective duration. For some indications, that means 0 days. This article discusses several childhood illnesses and recommended durations for antibiotics, which are summarized in the accompanying Table.

Acute otitis media

Acute otitis media (AOM) is the most common indication for antibiotics in children,6 and 95% of children with AOM are prescribed antibiotics.7 However, most children with AOM will improve without antibiotics.8 The number of patients needed to treat for symptomatic benefit after 2 to 3 days is 20,8 whereas the number needed to harm with an antibiotic-related ADE is 4.3 For this reason, the 2013 American Academy of Pediatrics (AAP) clinical practice guidelines recommend watchful waiting for children older than 6 months with mild to moderate unilateral AOM.9 Findings have shown that for most children with AOM given antibiotics, there is no difference in treatment failure between those who receive 5 days and those who receive 7 or more days of therapy.10 When antibiotics are prescribed, high-dose amoxicillin remains the first-line antibiotic treatment for AOM.

Pharyngitis

Group A streptococcal (GAS) pharyngitis is the second most common indication for antibiotics in ambulatory pediatrics. Although the standard recommended antibiotic duration for confirmed GAS pharyngitis remains 10 days,11 the greatest opportunity for antibiotic stewardship in this setting lies in testing for GAS pharyngitis only when indicated; this reduces the likelihood of identifying and treating false positives that represent chronic pharyngeal GAS colonization in patients with viral pharyngitis. Because 20% of healthy, asymptomatic children can be chronic pharyngeal GAS carriers at any given time,12 it is important to test only when there is a high pretest probability for GAS vs viral pharyngitis. This means not testing when a patient has viral upper respiratory infection symptoms including cough, rhinorrhea, congestion, conjunctivitis, and hoarseness or in a child younger than 3 years who has a low likelihood of GAS pharyngitis.11

Community-acquired pneumonia

In the past year, the results of 2 multi-institutional, randomized controlled trials showed no difference in treatment failure or recurrence of infection in children who received short-course (5 days) vs long-course (10 days) antibiotics. High-dose amoxicillin remains the first-line antibiotic treatment for community-acquired pneumonia believed to be bacterial.13,14

Cellulitis

Skin and soft-tissue infections are unique in that clinical improvement is easily visible, so antibiotic duration can easily be tailored based on clinical improvement. Clinical practice guidelines from the Infectious Diseases Society of America recommend 5 days of antibiotics for cellulitis.15 For an extensive case, if evidence of active infection remains after 5 days of therapy, then the course should be extended. On the other hand, for a more minor skin infection, if clinical resolution is shown after 3 days of therapy, then antibiotics could be discontinued. For abscesses without surrounding cellulitis, the guidelines recommend incision and drainage alone, without additional need for antibiotics.15

Urinary tract infections

For simple cystitis (ie, symptomatic urinary tract infection with pyuria and positive urine culture but with- out symptoms suggesting pyelonephritis, such as flank pain, costovertebral angle tenderness, or fever), it has long been known that for adult patients, short courses of antibiotics (1-3 days, depending on antibiotic choice) are sufficient.16 Pediatric guidelines recently adopted these standards to shift recommendations to short courses (3 days).17,18

For pyelonephritis, the AAP’s 2011 guidelines recommend a range of 7 to 14 days. More recent data show that a 7-day course for pyelonephritis results in similar outcomes, including infection recurrence or treatment failure, with lower rates of ADEs compared with longer courses.19

Conclusion

When prescribing antibiotics, the first consideration is whether antibiotics are indicated: How certain is the diagnosis (eg, otitis media with effusion vs AOM, viral vs bacterial pneumonia)? Is this a condition (eg, AOM, sinusitis) for which watchful waiting is a safe option? When antibiotics are definitely indicated, the shortest effective duration must be prescribed to minimize harm to patients.

References

1. Langford BJ, Morris AM. Is it time to stop counselling patients to “finish the course of antibiotics”? Can Pharm J (Ott). 2017;150(6):349-350. doi:10.1177/1715163517735549

2. Lovegrove MC, Geller AI, Fleming-Dutra KE, Shehab N, Sapiano MRP, Budnitz DS. US emergency department visits for adverse drug events from antibiotics in children, 2011-2015. J Pediatric Infect Dis Soc. 2019;8(5):384-391. doi:10.1093/jpids/piy066

3. Gerber JS, Ross RK, Bryan M, et al. Association of broad- vs narrow-spectrum antibiotics with treatment failure, adverse events, and quality of life in children with acute respiratory tract infections. JAMA. 2017;318(23):2325-2336. doi:10.1001/jama.2017.18715

4. Same RG, Hsu AJ, Cosgrove SE, et al. Antibiotic-associated adverse events in hospitalized children. J Pediatric Infect Dis Soc. 2021;10(5):622-628. doi:10.1093/jpids/piaa173

5. Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile Infection. Clin Infect Dis. 2011;53(1):42-48. doi:10.1093/cid/cir301

6. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315(17):1864-1873. doi:10.1001/jama.2016.4151

7. Frost HM, Becker LF, Knepper BC, Shihadeh KC, Jenkins TC. Antibiotic prescribing patterns for acute otitis media for children 2 years and older. J Pediatr. 2020;220:109-115.e1. doi:10.1016/j.jpeds.2020.01.045

8. Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2015(6):CD000219. doi:10.1002/14651858.CD000219.pub4

9. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131(3):e964-e999. doi:10.1542/peds.2012-3488

10. Kozyrskyj A, Klassen TP, Moffatt M, Harvey K. Short-course antibiotics for acute otitis media. Cochrane Database Syst Rev. 2010(9):CD001095. doi:10.1002/14651858.CD001095.pub2

11. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):1279-1282. doi:10.1093/cid/cis847

12.Tanz RR, Shulman ST. Chronic pharyngeal carriage of group A streptococci. 2007;26(2):175-176. doi:10.1097/01.inf.0000255328.19808.be

13.Williams DJ, Creech B, Walter EB, et al; The DMID 14-0079 Study Team. Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: The SCOUT-CAP randomized clinical trial. JAMA Pediatr. Published online January 18, 2022. doi:10.1001/jamapediatrics.2021.5547

14. Pernica JM, Harman S, Kam AJ, et al. Short-course antimicrobial therapy for pediatric community-acquired pneumonia: the SAFER randomized clinical trial. JAMA Pediatr. 2021;175(5):475-482. doi:10.1001/jamapediatrics.2020.6735

15. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. 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(2):e10-e52. doi:10.1093/cid/ciu444

16. Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257

17. National Institute for Health and Care Excellence. Urinary tract infection (lower): antimicrobial prescribing. October 31, 2018. Accessed March 7, 2022. https://www.nice.org.uk/guidance/ng109

18.Kimberlin DW, ed. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021.

19. Fox MT, Amoah J, Hsu AJ, Herzke CA, Gerber JG, Tamma PD. Comparative effectiveness of antibiotic treatment duration in children with pyelonephritis. JAMA Netw Open. 2020;3(5):e203951. doi:10.1001/jamanetworkopen.2020.3951

20. Wald ER, 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(1):e262-e280. doi:10.1541/peds.2013-1071

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23. Gonzales R, Bartlett JG, Besser RE, et al; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine; Centers for Disease Control; Infectious Diseases Society of America. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann Intern Med. 2001;134(6):521-529. doi:10.7326/0003-4819-134-6-200103200-00021

24. Subcommittee on Urinary Tract Infection. Reaffirmation of AAP clinical practice guideline: the diagnosis and management of the initial urinary tract infection in febrile infants and young children 2-24 months of age. Pediatrics. 2016;138(6):e20163026. doi:10.1541/peds.2016-3026