Antibiotics for Pediatrics Infections and Amoxicillin Dosing

Written by Rosy Hao, MD

Edited by Wesley Chan MD

This post was inspired by a post originally in ALiEM [1]. This post aims to demystify amoxicillin treatment for common pediatric infections and look at the evidence behind antibiotic use in some pediatric infections.

What is the evidence behind antibiotic use?

Are antibiotics needed for Acute Otitis Media? 

For acute otitis media: the idea of “watchful watching” with a Safety-Net Antibiotic Prescription (SNAP) has been applied to nonsevere acute otitis media in children > 6 months with observation [2,4, 5]. If a child’s infection worsens or fails to improve within 24 to 48 hours, then parents can fill the SNAP and give antibiotics to the child. This usually does not require a subsequent clinical visit, unless the clinician specifically wants to perform a tympanic membrane exam prior to prescribing antibiotics [2,5].

Cochrane Review Paper “Venekamp et al” included 13 randomized controlled trials from high-income countries with approximately 3400 children receiving either antibiotics (ampicillin, amoxicillin, amoxicillin-clavulanate, and others) or placebo. At 3 months, there was no difference in the number of children with abnormal tympanometry findings (RR = 0.97, 95% CI 0.76 to 1.24). Severe complications such as mastoiditis and meningitis were rare and not different between groups. 

Below is a decision making tree for AOM, summarizing recommendations made by the American Academy of Pediatrics (AAP) and NICE UK for observation versus antibiotic treatment of AOM. The back-up antibiotic prescription (or SNAP) is recommended to reduce subsequent visits should the otalgia persist.

It is important, then, for the clinician to emphasize to the family that symptomatic management should be prioritized for the first two days prior to filling the antibiotic prescription, unless severe symptoms occur [2,6]. 

NICE acute otitis media antibiotic prescribing guidelines [6]

How about Strep Throat?

For streptococcal pharyngitis, there are different styles of management and schools of thought regarding antibiotic treatment. Strep pharyngitis is a self-limited disease that can be treated symptomatically. Some argue antibiotics are used to prevent subsequent complications, including rheumatic heart disease.

The evidence for preventing RF and subsequent rheumatic heart disease (RHD) comes from a series of studies performed in the 1950’s at the Warren Air Force Base [7]. The incidence of RHD is near 0% in industrialized countries, most likely due to improvement in public health rather than antibiotics [8,9]. Based on the current incidence of RF in the US, we would need to treat over 2 million patients with strep throat in order to prevent a single case of RHD [7]. Furthermore, antibiotics have potential adverse effects, and complications of strep pharyngitis without antibiotic treatment are rare. 

Penicillin treatment had no beneficial effect in children on the average duration of sore throat. Penicillin may, however, reduce streptococcal sequelae (such as quinsy, scarlet fever, or impetigo), although this is also debatable [10].

Despite the lack of supporting evidence and controversy surrounding need for treatment, the current recommendations from AAP and IDSA remain to treat confirmed strep pharyngitis with antibiotics. Therefore, it may be worthwhile to include the family in shared medical decision-making regarding symptomatic versus antibiotic treatment.

Amoxicillin Dosing

As a review, amoxicillin is a penicillin derivative antibiotic against susceptible gram-positive and gram-negative bacteria. It has reasonable coverage for most upper respiratory infections and is used as prophylaxis for asplenia and bacterial endocarditis.

Susceptible Bacteria to Amoxicillin

Amoxicillin dosing recommendations and tips

1. Indications for high dose amoxicillin [11]

S. pneumoniae have intermediate to high resistance to penicillin antibiotics as they have penicillin-binding proteins. “High-dose” amoxicillin helps overcome this resistance and should be used in infections commonly seen with S. pneumoniae including the 3 following conditions:

•      • Recommended max dose for suspension: 1000 mg/dose twice daily (max 2000 mg/day) [11]
•      • Recommended max dose for tablet: 875 or 1000 mg/dose [11]

Liquid amoxicillin is available in many concentrations. 

•      • Prescribe higher concentrations to minimize volumes. 
•      • A common concentration is 400 mg/5 mL.

For more information on recommendations regarding observation, surveillance, and safety-net antibiotic prescription, see AAP. [2]

2. Treatment for pediatric community-acquired pneumonia

The most common bacterial pathogen of  CAP is usually S. pneumoniae outside of the immediate neonatal period. However, the most common pathogen for pneumonia up to school age is viral pneumonia, as summarized in the table below. Viral pneumonia can also cause infiltrates on Chest XRay, so it is important to recognize that children <5 years old are unlikely to have bacterial pneumonia. If CAP is suspected, amoxicillin is effective for treatment. 

Of note, because of the routine vaccinations against both Streptococcus pneumoniae and H influenzae, viral pathogens including RSV, human rhinovirus have become more common culprits in children who are vaccinated. [12]

The first-line treatment is with high-dose amoxicillin for 7 days. [13] If the patient does not improve 48 hours after initiating amoxicillin, consider broadening coverage to include atypical pneumonia, penicillin-resistant S. pneumo, or S. aureus. Replace amoxicillin with a macrolide, such as azithromycin.

•      • Azithromycin dosing: 10 mg/kg/dose PO on day 1 (max 500 mg/dose), then 5 mg/kg/dose PO daily on days 2-5 (max 250 mg/dose)
•      • Duration: 5 days

Also consider other etiologies, such as:

•      • Viral pneumonia
•      • Aspiration pneumonia
•      • Asthma
•      • Foreign body aspiration
•      • Complications of pneumonia (pleural effusion, empyema, and necrotizing pneumonia)

3. Treatment for strep pharyngitis

A serious possible sequelae of strep pharyngitis is rheumatic heart disease, although incidence is very low in high-resourced countries. The cause of this is unclear, and a systematic review in 2014 found that “large scale randomized controlled trials are necessary to assess the value of antibiotics for GAS pharyngitis in high-resource countries, in order to achieve uniform and evidence-based guidelines” [14].

Streptococcal pharyngitis itself is usually self-limited and can be managed symptomatically; complications are rare [7]. Given the possible adverse effects of amoxicillin, it is reasonable for clinicians to discuss benefits and risks with families for shared medical decision making [7].

Recent evidence favors once-daily amoxicillin dosing in patients aged 3 years and older [15].

•      • Amoxicillin dose: 50 mg/kg once daily (max 1000 mg/dose/day) for age ≥3 years
•      • Duration: 10 days

Indications to prescribe amoxicillin-clavulanate instead of amoxicillin alone

Amoxicillin-clavulanate is the antibiotic of choice when AOM treatment fails or recurs despite amoxicillin [16].  

•      Amoxicillin may fail because:
  •             • Beta-lactamase resistance
  •             OR
  •             • AOM is due to non-typeable Haemophilus influenza and Moraxella catarrhalis. 

The clavulanate irreversibly inhibits bacterial beta-lactamase, increasing the effectiveness of amoxicillin. The amoxicillin component remains “high”-dose (80-90 mg/kg/day) [14].​

Indications for prescribing amoxicillin-clavulanate include:

1.      1. AOM treated with amoxicillin within the last 30 days: There is increased risk of beta-lactamase resistance or AOM due to non-typeable Haemophilus influenza and Moraxella catarrhalis (which produce beta-lactamase).
2.      2. Recurrent AOM: This is defined as having ≥3 episodes of AOM in a period of 6 months, or ≥4 episodes in 12 months [16].​​  Non-typeable Haemophilus influenza is common in recurrent episodes.
3.      3. AOM with concomitant purulent conjunctivitis: Typically seen with non-typeable Haemophilus influenza

Amoxicillin-clavulanate prescribing:

• Amoxicillin-clavulanate dose: 80-90 mg/kg/day, divided into 2 doses daily
• Duration:
  • < 2 years of age = 10 days
  • ≥ 2 years of age = 5-7 days

Take-Home Points

Although the benefit is questionable in many cases, amoxicillin is used to treat a variety of conditions in pediatrics, most commonly acute otitis media, community-acquired pneumonia, and streptococcal pharyngitis.

•      • CAP: High-dose amoxicillin (to overcome bacterial resistance) is prescribed 80-90 mg/kg/day divided into 2 doses for 7 days
•      • Group A Strep pharyngitis: Low-dose amoxicillin is 50 mg/kg/day, once a day (to prevent rheumatic fever)
•      • Amoxicillin-clavulanate: Use if AOM treated in last 30 days, AOM with purulent conjunctivitis, 3+ episodes of AOM in 6 months, or 4+ episodes of AOM in 12 months
•      • AOM is usually self-limited and complications are rare. It is appropriate for non-severe cases of AOM to watch for 48 hours without giving antibiotics.
  •            • If > 6 months with only unilateral AOM, observe for 48 hours and SNAP
  •            • If > 2 years, regardless if uni/bilateral, observe for 48 hours and SNAP
•      • If treating AOM with antibiotics: High-dose amoxicillin (to overcome bacterial resistance) is prescribed 80-90 mg/kg/day divided into 2 doses. Duration depends on age.
•      • Group A Strep pharyngitis: No treatment, or low-dose amoxicillin (50 mg/kg/day) once a day (to prevent rheumatic fever)
  •            • However, using antibiotic to prevent RF is theoretical
•      • Amoxicillin-clavulanate: Use if AOM treated in last 30 days, AOM with purulent conjunctivitis, 3+ episodes of AOM in 6 months, or 4+ episodes of AOM in 12 month

References

1. 1. Hao R, Tat S. PEM Pearls: 5 Tips to Demystify Amoxicillin in Pediatric Infections. AliEM blog, August 23, 2019. Available at: https://www.aliem.com/pem-pearls-5-tips-amoxicillin-pediatric-infections/.
2. 2. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media [published correction appears in Pediatrics. 2014 Feb;133(2):346. Dosage error in article text]. Pediatrics. 2013;131(3):e964-e999. doi:10.1542/peds.2012-3488
3. 3. Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2015;2015(6):CD000219. Published 2015 Jun 23. doi:10.1002/14651858.CD000219.pub4
4. 4. Sakulchit T, Goldman RD. Antibiotic therapy for children with acute otitis media. Can Fam Physician. 2017;63(9):685-687
5. 5. Le Saux N, Robinson JL; Canad ian Paediatric Society, Infectious Diseases and Immunization Committee. Management of acute otitis media in children six months of age and older. Paediatr Child Health. 2016;21(1):39-50. doi:10.1093/pch/21.1.39
6. 6. NICE (2018). Otitis Media (acute): antimicrobial prescribing guidance [PDF] https://www.nice.org.uk/gOtitis media (acute): antimicrobial prescribinguidance/ng91/resources/visual-summary-pdf-4787282702
7. 7. Anand Swaminathan, “Do Patients with Strep Throat Need to Be Treated with Antibiotics?”, REBEL EM blog, January 5, 2015. Available at: https://rebelem.com/patients-strep-throat-need-treated-antibiotics/.
8. 8. Chad Hayes, “The secret reason we treat strep throat”, Chad Haydes MD Blog, January 11, 2015, Avaiable at http://www.chadhayesmd.com/infection-confessions-2-strep-throat/.
9. 9. Watkins DA, Johnson CO, Colquhoun SM, et al. Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015. N Engl J Med. 2017;377(8):713-722. doi:10.1056/NEJMoa1603693
10. 10. Zwart S, Rovers MM, de Melker RA, Hoes AW. Penicillin for acute sore throat in children: randomised, double blind trial. BMJ. 2003;327(7427):1324. doi:10.1136/bmj.327.7427.1324
11. 11. High dose amoxicillin: Rationale for use in otitis media treatment failures. Paediatr Child Health. 1999;4(5):321-323. doi:10.1093/pch/4.5.321
12. 12. Katz SE, Williams DJ. Pediatric Community-Acquired Pneumonia in the United States: Changing Epidemiology, Diagnostic and Therapeutic Challenges, and Areas for Future Research. Infect Dis Clin North Am. 2018;32(1):47-63. doi:10.1016/j.idc.2017.11.002
13. 13. Bradley JS, Byington CL, Shah SS, et al. 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(7):e25-e76. doi:10.1093/cid/cir531
14. 14. Van Brusselen D, Vlieghe E, Schelstraete P, De Meulder F, Vandeputte C, Garmyn K, Laffut W, Van de Voorde P. Streptococcal pharyngitis in children: to treat or not to treat? Eur J Pediatr. 2014 Oct;173(10):1275-83. doi: 10.1007/s00431-014-2395-2. Epub 2014 Aug 12. PMID: 25113742.
15. 15. Andrews M, Condren M. Once-daily amoxicillin for pharyngitis. J Pediatr Pharmacol Ther. 2010;15(4):244-248.
16. 16. Granath A. Recurrent Acute Otitis Media: What Are the Options for Treatment and Prevention?. Curr Otorhinolaryngol Rep. 2017;5(2):93-100. doi:10.1007/s40136-017-0151-7

The following two tabs change content below.

• Bio
• Latest Posts

Wesley Chan

EM/IM Resident Class of 2024

Latest posts by Wesley Chan (see all)

• Altitude Sickness: Is it the Altitude or Are You Just Out of Shape? - February 18, 2021
• Triage Systems in Resource Limited Settings - February 12, 2021
• Staying Sufficiently Salty: Avoiding Exercise-associated Hyponatremia - November 24, 2020