Amoxicillin versus Penicillin

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Difference between Amoxicillin and Penicillin

Drug class Aminopenicillin antibiotic Natural penicillin antibiotic
Formulations • Oral • Oral
• Intramuscular (IM)
• Intravenous (IV)
FDA approved uses • Streptococcal pharyngitis
• Ear, nose, and throat infections
• Skin and skin structure infections
• Genitourinary tract infections
• Lower respiratory tract infections
• Gonorrhea
• Streptococcal pharyngitis
• Skin and soft tissues infections
• Fusospirochetosis (Vincent's gingivitis)
• Infections of the oropharynx
• Syphilis, yaws, bejel, pinta, Rheumatic fever (only penicillin G benzathine)
• Upper respiratory tract infections caused by susceptible streptococci (only penicillin G benzathine)
• Septicemia, empyema, pneumonia, pericarditis, endocarditis, meningitis, disseminated gonococcal infections, syphilis, Listeria infections, actinomycosis (only penicillin G potassium)
Half-life 1 hour 0.5 to 1 hour
Absorption Amoxicillin is better absorbed from the gastrointestinal tract than penicillin.
Amoxicillin is more stable in acid.
Food Food has minimal or no effect on bioavailability of amoxicillin. Food reduces the absorption of penicillin V and may result in lower and delayed peak serum concentrations 4
Protein binding
Antimicrobial spectrum
Gram-positive bacteria Similar activity to penicillin.
Better activity against Enterococcus spp. 1
Streptococcus spp.,
some Enterococcus spp.,
non-beta-lactamase-producing Staphylococci,
Listeria monocytogenes 1
Gram-negative bacteria Enhanced activity against gram-negative bacteria:
Escherichia coli,
Proteus mirabilis
Haemophilus influenza
Neisseria meningitidis 1
Neisseria meningitidis,
some spp. of Haemophilus influenzae 1
Other bacteria Borrelia burgdorferi 1 Treponema pallidum Leptospira spp.,
Clostridia spp. (except C. difficile),
Actinomyces israelii,
Corynebacterium diphtheriae 1
Concentrations Better capacity for reaching effective concentrations  
Pregnancy category B
Suitable for use in infants and children

Amoxicillin advantages over Penicillin

  • Better oral absorption.
  • Longer duration of action and less frequent dosing.
  • Broader antimicrobial spectrum.

Penicillin advantages over Amoxicillin

  • Parenteral penicillin is used to treat serious infections, including syphilis, meningitis, septicemia.

Amoxicillin vs Penicillin V in Streptococcal pharyngitis

Amoxicillin is at least as effective as penicillin V for the treatment of streptococcal pharyngitis in children 2

Results of randomized non-inferiority trial of amoxicillin versus penicillin V in group A beta-haemolytic streptococcal pharyngitis 2
Penicillin V
Regimen 1500 mg once daily for 10 days 500 mg twice daily for 10 days
Treatment failures (including relapses):    
on days 3-6
on days 12-16
on days 26-36
Resolution of symptoms
No significant differences

Results of prospective, comparative, open, randomized, trial of amoxicillin vs. penicillin V for streptococcal tonsillopharyngitis 6
Penicillin V
Regimen 50 mg/kg/day twice daily for 6 days 45 mg/kg/d three times a day for 10 days
Pretreatment GAS eradication rate at 4 day after the completion of treatment
(118 children of 141)
(116 children of 136)
Bacteriologic relapses at one month after the outset of treatment
(11 children)
(6 children)
Conclusion: The efficacy and safety of amoxicillin were not statistically different from those of penicillin in the treatment of GAS tonsillopharyngitis.

Results of prospective observational study of penicillin vs. amoxicillin for streptococcal tonsillopharyngitis in children 5
Penicillin V
Bacteriologic cure
Clinical cure

Amoxicillin vs Penicillin in Pneumonia

Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia in children aged 3-59 months 3.

Amoxicillin vs Penicillin in Dental Infections

Both penicillin and amoxicillin are considered the first line of treatments for odontogenic infections 9. They target most bacteria causing odontogenic infections.

Bacteraemia after dental extraction

Both penicillin V (2 g oral dose) and amoxicillin are effective in reducing the incidence of bacteraemia following dental extraction 7. There is little difference in their antibacterial activity against viridans streptococci and dental anaerobes. However, amoxicillin is preferable to penicillin V for the oral prophylaxis of endocarditis as it can provide much higher serum levels than penicillin V during the 6 to 8 hours following extraction.

Primary teeth abscess

Amoxicillin is as efficacious as penicillin in the treatment of acute abscess of primary teeth 8. Amoxicillin may provide more rapid improvement of swelling.

Dentoalveolar abscess (co-amoxiclav vs penicillin V)

A randomized operator-blind comparative study 10, tested the efficacy of co-amoxiclav and penicillin V for dentoalveolar infections. Both antibiotics provided improvement after drainage. Co-amoxiclav treatment provided significantly greater decrease in toothache during the second and third days after drainage. This may be explained by the eradication of the beta-lactamase producing bacteria with co-amoxiclav that would not be eradicated by penicillin V.


Further reading


  • 1. Alan J. Hauser Antibiotic Basics for Clinicians. LWW; Second edition March 9, 2012, pp.22-24
  • 2. Lennon DR, Farrell E, Martin DR, Stewart JM. Amoxicillin versus Penicillin V in Group A beta -Hemolytic Streprococcus Pharyngitis.Arch Dis Child. 2008 Jun;93(6):474-8. PubMed
  • 3. Addo-Yobo E, Chisaka N, Hassan M, Hibberd P, Lozano JM, Jeena P, MacLeod WB, Maulen I, Patel A, Qazi S, Thea DM, Nguyen NT. Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study. Lancet. 2004 Sep 25-Oct 1;364(9440):1141-8. PubMed
  • 4. Finkel Y, Bolme P, Eriksson M. The effect of food on the oral absorption of penicillin V preparations in children. Acta Pharmacol Toxicol (Copenh). 1981 Oct;49(4):301-4. PubMed
  • 5. Curtin-Wirt C, Casey JR, Murray PC, Cleary CT, Hoeger WJ, Marsocci SM, Murphy ML, Francis AB, Pichichero ME. Efficacy of penicillin vs. amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis. Clin Pediatr (Phila). 2003 Apr;42(3):219-25 PubMed
  • 6. Cohen R, Levy C, Doit C, De La Rocque F, Boucherat M, Fitoussi F, Langue J, Bingen E. Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J. 1996 Aug;15(8):678-82. PubMed
  • 7. Shanson DC, Cannon P, Wilks M. Amoxycillin compared with penicillin V for the prophylaxis of dental bacteraemia. J Antimicrob Chemother. 1978 Sep;4(5):431-6.
  • 8. Paterson SA, Curzon ME. The effect of amoxycillin versus penicillin V in the treatment of acutely abscessed primary teeth. Br Dent J. 1993 Jun 19;174(12):443-9. PubMed
  • 9. Curtis Gregoire. How are odontogenic infections best managed? JCDA April 19, 2010
  • 10. Lewis MA, Carmichael F, MacFarlane TW, Milligan SG. A randomised trial of co-amoxiclav versus penicillin V in the treatment of acute dentoalveolar abscess. Br Dent J. 1993 Sep 11;175(5):169-74. PubMed

Published: July 31, 2014
Last reviewed: October 25, 2017


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