Penicillin versus ...

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

Difference between Penicillin V and Penicillin G

Penicillin G is sensitive to breakdown by gastric acid, nevertheless it can be given orally in large doses. Penicillin G is available for parenteral administration.

Penicillin V has better acid stability and oral bioavailability than penicillin G. It is available in oral formulations.

Penicillin V and penicillin G have similar antibacterial spectrum, but penicillin V is less active. Penicillin G is the most potent penicillin antibiotic.

Main clinical uses for penicillin G are syphilis, endocarditis, meningitis, and pneumonia.

Main clinical uses for penicillin V are streptococcal pharyngitis, dental infections.

Penicillin vs. Clindamycin

Orofacial infections

Penicillin and clindamycin are both effective in the treatment of orofacial infections 3.

Odontogenic infections

Penicillin is effective as clindamycin in treating odontogenic infection when the level of penicillin resistance among anaerobic bacteria is low1.

Results of prospective double-blind trial of penicillin versus clindamycin for odontogenic infections 1 Penicillin Clindamycin
Successful outcome
22 patients of 27
23 patients of 28
5 patients of 27
5 patients of 28
1 patient
2 patients
Resistance rates for anaerobic isolates

Penicillin vs. Ciprofloxacin (Cipro)

Otitis, Sinusitis

Ciprofloxacin is more effective than penicillin V in the treatment of otitis and sinusitis2.

In comparative randomized study 80 adults suffering from otitis media, sinusitis (maxillaris or frontalis) or peritonsillitis were treated with ciprofloxacin (500 mg 2 times daily) or with penicillin V (2000 mg 3times daily)15. Ciprofloxacin was better than penicillin V: there were fewer resistant strains (one compared to 11), higher eradication rate (57% compared to 43%) and clinical efficacy (60% compared to 48%). Both treatments were well tolerated; side effects were neither reported nor found.


Penicillin vs. Clarithromycin (Biaxin)

Streptococcal pharyngitis

Clarithromycin extended-release is equally effective as penicillin V in the treatment of adolescents and adults with streptococcal tonsillopharyngitis 14.

Results of multicenter, double-blind, randomized comparison of extended-release clarithromycin versus penicillin V for streptococcal pharyngitis/tonsillitis 14 Penicillin V Clarithromycin ER
Regimen 500 mg 3 times daily for 10 days 500 mg once daily for 5 days
Eradication of S. pyogenes at the test-of-cure visit
(139 patients of 154)
(157 patients of 177)
Bacterial eradication at the follow-up visit
(112 patients of 123)
(135 patients of 153)
Clinical cure
> or = 94%

Another study has found that clarithromycin is superior to penicillin in eradicating S. pyogenes 9.

Results of randomized, investigator-blind study of clarithromycin versus penicillin V for streptococcal pharyngitis 9 Penicillin V Clarithromycin
Regimen 13.3 mg/kg 3 times daily for 10 days 7.5 mg/kg twice daily for 5 days
Clinical success (cure + improvement) at the posttreatment evaluation
Clinical success (cure + improvement) at follow-up valuation
Eradication of S. pyogenes
Gastrointestinal complaints
similar and mild

Penicillin vs. Cefuroxime axetil (Ceftin)

Lyme disease (erythema migrans)

Cefuroxime axetil and phenoxymethyl penicillin are equally effective in the treatment of children with erythema migrans4. Side effects occur more frequently with cefuroxime axetil.

Streptococcal pharyngitis

Cefuroxime axetil is at least as effective as penicillin V in the treatment of streptococcal pharyngitis and may be more effective in preventing the carrier state6-8.

Results of prospective, randomized, multi-center study cefuroxime axetil versus penicillin V for streptococcal tonsillopharyngitis 7 Penicillin V Cefuroxime
Regimen 30 mg/kg t.i.d. for 10 days 20 mg/kg/day b.i.d. for 5 days
Bacteriological eradication in group A (1-5 years)
Bacteriological eradication in group B (6-17 years)
Clinical success was 98.30% (CAE) versus 93.25% (PenV)

Results of comparison of cefuroxime axetil and intramuscular benzathine penicillin for streptococcal tonsillopharyngitis 8 Benzathine Penicillin
Clinical cure
Bacteriological cure
Conclusion: intramuscular benzathine penicillin remains an effective treatment for GABHS and oral cefuroxime axetil is also effective.


Penicillin G (intravenous) is as effective as cefuroxime (intravenous) in treating community-acquired pneumonia in children and provide the same rate of recovery 10.

The German Society for Pediatric Infectious Diseases (DGPI) undertook a large study of culture-proven tonsillopharyngitis involving several agents and included a 1 year follow-up to establish the effect on complications. In one arm of this study, cefuroxime was compared with penicillin V. Cefuroxime axetil was more effective than penicillin V in eradicating group A beta-haemolytic streptococci (GABHS) at the assessment 2-4 days post-treatment (441/490 (90%) patients versus 1196/1422 (84%) patients). Clinically, the two agents were equivalent in efficacy, and carriage rates were similar (11.1% and 13.8%, respectively) in patients 7-8 weeks post-treatment. One case of glomerular nephritis occurred in a patient given penicillin V. There were no post-streptococcal complications confirmed for patients treated with cefuroxime axetil. The findings confirm the previously reported efficacy of short-course (4-5 day) of cefuroxime axetil and indicate that short-course is comparable to the standard oral penicillin V regimen in preventing post-streptococcal sequelae.

Recurrent Streptococcal pharyngitis

Cefuroxime axetil is more effective than penicillin V for the treatment of recurrent tonsillopharyngitis5.

Results of comparative randomized blind study of cefuroxime axetil and phenoxymethylpenicillin in children with tonsillopharyngitis 5. Phenoxymethylpenicillin Cefuroxime
Eradication rate at day 2-5 post treatment
(61 patients of 109)
(99 patients of 114)
Clinical cure rate at day 2-5 post treatment
(73 patients of 109)
(98 patients of 114)
Treatment failures or recurrence/reinfection of GAS tonsillopharyngitis at up to 21-28 days post-treatment
(37 patients of 109)
(9 patients of 114)
Received additional antibiotics during the study period
(50 patients of 109)
(2 patients of 114)
Adverse events rate

Further reading


  • 1. Gilmore WC, Jacobus NV, Gorbach SL, Doku HC, Tally FP. A prospective double-blind evaluation of penicillin versus clindamycin in the treatment of odontogenic infections. J Oral Maxillofac Surg. 1988 Dec;46(12):1065-70. PubMed
  • 2. Falser N, Mittermayer H, Weuta H. Antibacterial treatment of otitis and sinusitis with ciprofloxacin and penicillin V. Infection. 1988;16 Suppl 1:S51-4. PubMed
  • 3. von Konow L, Kondell PA, Nord CE, Heimdahl A. Clindamycin versus phenoxymethylpenicillin in acute orofacial infections. Eur J Clin Microbiol Infect Dis. 1992 Dec;11(12):1129-35. PubMed
  • 4. Arnez M, Radsel-Medvescek A, Pleterski-Rigler D, Ruzic'-Sabljic' E, Strle F. Comparison of cefuroxime axetil and phenoxymethyl penicillin for the treatment of children with solitary erythema migrans. Wien Klin Wochenschr. 1999 Dec 10;111(22-23):916-22. PubMed
  • 5. Holm S, Henning C, Grahn E, Lomberg H, Staley H. Results from a comparative randomized blind study of cefuroxime axetil and phenoxymethylpenicillin in children. Scand J Infect Dis. 1995;27(3):221-8. PubMed
  • 6. Gooch WM 3rd, Swenson E, Higbee MD, Cocchetto DM, Evans EC. Cefuroxime axetil and penicillin V compared in the treatment of group A beta-hemolytic streptococcal pharyngitis. Clin Ther. 1987;9(6):670-7. PubMed
  • 7. Scholz H. Streptococcal-A tonsillopharyngitis: a 5-day course of cefuroxime axetil versus a 10-day course of penicillin V. results depending on the children's age. Chemotherapy. 2004 Apr;50(1):51-4. PubMed
  • 8. Uysal S, Sancak R, Sunbul M. A comparison of the efficacy of cefuroxime axetil and intramuscular benzathine penicillin for treating streptococcal tonsillopharyngitis. Ann Trop Paediatr. 2000 Sep;20(3):199-202. PubMed
  • 9. McCarty J, Hedrick JA, Gooch WM. Clarithromycin suspension vs penicillin V suspension in children with streptococcal pharyngitis. Adv Ther. 2000 Jan-Feb;17(1):14-26. PubMed
  • 10. Amarilyo G, Glatstein M, Alper A, Scolnik D, Lavie M, Schneebaum N, Grisaru-Soen G, Assia A, Ben-Sira L, Reif S. IV Penicillin G is as effective as IV cefuroxime in treating community-acquired pneumonia in children. Am J Ther. 2014 Mar-Apr;21(2):81-4. PubMed
  • 14. Takker U, Dzyublyk O, Busman T, Notario G. Comparison of 5 days of extended-release clarithromycin versus 10 days of penicillin V for streptococcal pharyngitis/tonsillitis: results of a multicenter, double-blind, randomized study in adolescent and adult patients. Curr Med Res Opin. 2003;19(5):421-9. PubMed

Published: March 31, 2008
Last updated: February 22, 2017


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