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Re: Standard dosage of oral amoxicillin

Dear Editor,

Hazir et al found that amoxicillin 45mg/day is as effective as 90mg/day -- but 24mg/kg/day (8mg/kg tds) is the standard dose mentioned in the British Thoracic Society guidelines (1).

Yours faithfully,

Theo Fenton

Reference:

Send letter to journal:
Re: Re: Standard dosage of oral amoxicillin

Dear Editor,

We appreciate the letter from Dr. Fenton. He expressed concern regarding the dosage of amoxicillin, 15 mg/kg thrice daily, for the treatment of World Health Organization (WHO) defined non-severe pneumonia in children aged 2-59 months. He cited the British Thoracic Society guidelines, which recommend oral amoxicillin in a dose of 8 mg/kg thrice daily (which may be doubled in case of severe infection) for 7-10 days for the treatment of childhood community-acquired pneumonia [1]. WHO ARI guidelines recommended oral amoxicillin dose of 15 mg/kg thrice daily for 5 days for the treatment of childhood pneumonia [2]. Oral amoxicillin is active against S. pneumoniae and H. influenzae, two major bacterial agents that cause childhood pneumonia [3]. Emergence of penicillin resistant pneumococcal infections has raised the concern that lower dose may not be sufficient to overcome the resistance. Reportedly 15% to 40% of S. pneumoniae that had an intermediate resistance to penicillins, were managed with higher dosage of 75mg/kg/day to 90mg/kg/day of amoxicillin [4]. The American Academy of Pediatrics (AAP), recommends empiric initial treatment of acute otitis media with high-dose oral amoxicillin at 80-90 mg/kg daily due to the same concern about pneumococcal resistance. The AAP recommendations mention that based on middle ear fluid and in vitro activity, no currently available oral antibiotic has better activity than amoxicillin against resistant S. pneumoniae [5]. A higher dose, shorter course of oral amoxicillin resulted in significantly lower risk of penicillin-nonsusceptible pneumococcal carriage [6]. The higher dose results in a higher plasma level overcoming the MIC levels of pathogens related to the antimicrobial resistance [7]. Data has shown that for beta- lactam antimicrobial agents, the time that the serum drug concentration exceeds the MIC of the pathogen is a major factor in predicting successful clinical outcome [8]. Thus we believe that besides being efficacious, a short course, high dose outpatient antibiotic therapy is a promising intervention to lessen the impact of antibiotic use on the spread of antimicrobial resistance.

Yasir Bin Nisar

References:

[1] British Thoracic Society of Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in childhood. Thorax. 2002;57(Suppl 1):i1-24.

[2] WHO. Acute Respiratory Infections in Children: Case management in small hospitals in developing countries. A manual for doctors and other senior health workers. Geneva, Switzerland: World Health Organization; 1990.

[3] WHO. Technical bases for the WHO recommendations on the management of pneumonia in children at first-level facilities. Geneva, Switzerland: World Health Organization; 1991.

[4] Steele RW, Thomas MP, Kolls JK. Current management of community- acquired pneumonia in children: An algorithmic guideline recommendation. Infect Med. 1999;16(1):46-54.

[5] American Academy of Pediatrics. Red Book: 2000 Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics 2000.

[6] Schrag SJ, Pena C, Fernandez J, Sanchez J, Gomez V, Perez E, Feris JM, Besser RE. Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: A randomized trial. JAMA. 2001;286(1):49- 56.

[7] Fonseca W, Hoppu K, Rey LC, Amaral J, Qazi S. Comparing pharmacokinetics of Amoxicillin given twice or three times per day to children older than 3 months with pneumonia. Antimicrob Agents Chemother. 2003;47(3):997-1001.