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Penicillin versus Other Antibiotics

Penicillin vs. Amoxicillin

Amoxicillin achieves higher blood levels, has longer plasma half-life and lower protein binding activity.

Streptococcal pharyngitis

Amoxicillin is at least as effective as penicillin V for the treatment of streptococcal pharyngitis in children10.

Randomised non-inferiority trial10 was conducted to test the non-inferiority of once-daily amoxicillin to the recommended twice-daily penicillin V in streptococcal pharyngitis. 353 children with positive throat swabs for GABHS were randomised to amoxicillin 1500 mg once-daily (n=177) or penicillin V (n=176) 500mg twice-daily for 10 days. Eradication of GABHS was determined with follow-up throat cultures on days 3-6, 12-16 and 26-36. Treatment failures (including relapses) occurred at each visit in 5.8%, 12.7% and 10.7% of amoxicillin recipients and 6.2%, 11.9% and 11.3% of penicillin V recipients respectively. No significant differences in resolution of symptoms were noted between groups. In this adequately-powered study, once-daily amoxicillin is not inferior to twice-daily penicillin V for the treatment and eradication of GABHS in children with pharyngitis.

Penicillin vs. Amoxicillin/Clavulanic acid

Dental Abscess

A dentoalveolar abscess is an acute lesion characterized by localization of pus in the structures that surround the teeth. Amoxicillin/clavulanic acid is as effective as penicillin in the treatment of acute dentoalveolar abscess.

In a randomised, operator-blind, comparative clinical trial1, the efficacy of co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid, eight-hourly) was compared to that of penicillin V (250 mg phenoxymethylpenicillin, six-hourly) in the treatment of acute dentoalveolar abscess. Symptoms improved in all patients, however those receiving amoxicillin/clavulanic acid recorded a significantly greater decrease in toothache during the second and third days of the treatment. Only one patient reported a significant adverse effect associated with therapy, and this was in the penicillin group.

Streptococcal pharyngitis

Amoxicillin/clavulanic acid and penicillin V are similarly effective for the first treatment of strep throat. There is no evidence that amoxicillin/clavulanic acid is better than penicillin V2.

One hundred and sixty-five consecutive patients ( > 2 years of age) with acute group A streptococcal (GAS) pharyngitis randomly received co-amoxiclav (79 patients) or penicillin V (86 patients). After 7 days, tonsillar cultures from seven patients (9.6%) in the penicillin V group grew group A streptococcus; three of these patients had tonsillitis symptoms. In the co-amoxiclav group these figures were three (3.8%) and two respectively. Within the 12 month follow up period, there were 4 clinical recurrences (6.1%) in the penicillin V group and 7 (9.3%) in the co-amoxiclav group. There is no evidence that co-amoxiclav is better for the first treatment of acute GAS pharyngitis, but bacteriological failure and clinical recurrence are strongly associated with the presence of beta-lactamase activity in commensal flora.

Recurrent Streptococcal tonsillitis

Amoxicillin/clavulanic acid may be more effective than penicillin V for prevention of recurrent infection.

The failure of penicillin to eradicate Group A beta-haemolytic streptococcal tonsillitis may be caused by beta-lactamase producing bacteria in the tonsillar tissue. A prospective randomized clinical study13 comparing penicillin-V potassium with amoxicillin plus clavulanate potassium in the treatment of acute episodes of recurrent streptococcal tonsillitis was conducted. Twenty children were included in each group. Surface tonsillar cultures were obtained before therapy, 10 days after termination of therapy, and then once every two months for up to one year. beta-Lactamase producing aerobic and anaerobic bacteria were present in 34 of the 40 (85%) tonsillar cultures prior to treatment. Group A beta-haemolytic streptococci were eradicated in 14 of 20 (70%) patients treated with penicillin and in all those treated with amoxicillin/clavulanate potassium. In a one-year follow-up, 11 of the 19 patients treated with penicillin and two of the 18 treated with amoxicillin/clavulanate potassium had recurrent streptococcal tonsillitis. This study demonstrates that amoxicillin/clavulanate potassium is better for the prevention of recurrent infection.

Otitis media

Amoxicillin-clavulanate is superior to penicillin V in the treatment of middle ear infection.

A prospective, double-blind, randomized study12 compared two different antimicrobial agents. Children (aged 1-10 years, n=360) with secretory otitis media of at least 3 months' duration were evenly distributed among 4 treatment groups: penicillin V for 14 and 28 days, and amoxicillin/clavulanate potassium for 14 and 28 days. Criteria for improvement was a change in tympanometric findings to type C1 or type A. The success rates were in favor of amoxicillin-clavulanate treatment for 28 days (rates for respective 14- and 28-day groups: penicillin V, 23% and 19%; amoxicillin-clavulanate, 31% and 44%). Antimicrobial therapy was more efficient in unilateral vs bilateral disease. Amoxicillin-clavulanate provides superior improvement to penicillin V.

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.

Multicenter, double-blind, randomized study14 compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes. A total of 539 patients, aged 12-75 years, were randomized to receive either clarithromycin extended-release 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days. Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: day 3; visit 3: days 8-12; visit 4: days 13-20; and visit 5: days 40-50). At the test-of-cure visit (visit 3 for clarithromycin ER and visit 4 for penicillin V) in per-protocol patients, clarithromycin ER was comparable to penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively). Clinical cure was achieved in > or = 94% of patients in each group. The most commonly reported adverse events (< or = 3% in either treatment group) were stomach-ache, diarrhea, dyspepsia and nausea.

Clarithromycin is superior to penicillin in eradicating group A beta-hemolytic streptococcus (GABHS).

The safety and efficacy of clarithromycin and penicillin V were compared in a randomized, investigator-blind study16. Children 6 months to 12 years of age received 5 days of clarithromycin suspension (n = 268) or 10 days of penicillin V suspension (n = 260). Children were evaluated for signs and symptoms of pharyngitis, and throat swabs for culture were obtained prior to therapy, at the end of therapy, and at follow-up. Clarithromycin and penicillin V produced comparable rates of clinical success (cure and improvement) at the posttreatment (97% and 94%) and follow-up (81% and 82%) evaluations. The GABHS eradication rate, however, was significantly higher with clarithromycin (94% vs 78%).

Penicillin vs. Cefuroxime axetil (Ceftin)

Lyme disease (erythema migrans)

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

The clinical study4 compared the efficacy and adverse effects of cefuroxime axetil or phenoxymethyl penicillin in the treatment of children with erythema migrans. Forty-six patients received cefuroxime axetil (group C) and 44, phenoxymethyl penicillin (group P). The clinical course during the post-treatment period revealed no significant differences between the two groups: the duration of erythema migrans (7.1 +/- 7.5 days in group C, 10.6 +/- 19.3 days in group P) and the appearance of minor manifestations of Lyme borreliosis (8.8% in group C, 9.1% in group P) were comparable; no major manifestations were recorded. Twelve months after antibiotic therapy all patients were free of symptoms. The patients treated with cefuroxime axetil had more adverse effects than did those treated with phenoxymethyl penicillin (26.1% versus 6.8%). "Herxheimer's reaction" at the beginning of treatment was identified more often in group C than in group P.

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.

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 tonsillopharyngitis.

Comparative, randomized, investigator-blind, multicentre trial5 studied the efficacy of cefuroxime axetil compared with penicillin V for recurrent tonsillopharyngitis (group A beta-haemolytic streptococci). A total of 236 children (aged 3-12 years) with culture-proven tonsillitis received either cefuroxime axetil suspension or penicillin V syrup. Cefuroxime axetil gave a significantly higher bacteriological eradication rate and improvement in symptoms than penicillin V. At day 2-5 after treatment the eradication rates were 99/114 (87%) for cefuroxime axetil vs 61/109 (56%) for penicillin V. The clinical cure (resolution of signs and symptoms) rates were 98/114 (86%) and 73/109 (67%) respectively. Up to 21-28 days post-treatment, 9/114 (8%) cefuroxime axetil patients and 37/109 (34%) penicillin V patients were treatment failures or had recurrence or reinfection of streptococcal tonsillopharyngitis. More than 90% of the patients who experienced bacteriological treatment failure at either the first or second follow-up had the same serotype isolated pre- and post-treatment. During the study period, 21/114 (18%) patients in the cefuroxime axetil group and 50/109 (46%) patients in the penicillin V group received additional antibiotics. No serious adverse events were noted and the mild adverse events were equally distributed among study groups: 15% for cefuroxime axetil and 14% for penicillin V.

Penicillin vs. Cefaclor (Ceclor)

Streptococcal pharyngitis

Cefaclor is more effective than penicillin V in staphylococcal infections in children.

Prospective randomized study11 compared the effectiveness of penicillin V and Cefaclor, each given for ten consecutive days. Cefaclor was given to 56 patients and penicillin V to 61 (children mean age 5.7 years). Reevaluation with a repeat bacteriologic study was performed in all patients at the end of the treatment period, or earlier in the event of new clinical manifestations, and towards D40. Among patients given penicillin V, bacteriologic failure rate at completion of therapy was 19.6%, clinical failure rate on D10 was 8%, and recurrence rate on D40 was 16.5%. Cefaclor exhibited greater bacteriologic and clinical effectiveness, with 3.4% bacteriologic failures on D10, 1.7% clinical failures on D10, 8.9% clinical recurrences between D10 and D40, and an overall 10.6% rate of failure or recurrence.

Penicillin vs. Cefadroxil

Streptococcal pharyngitis

Cefadroxil and penicillin V are similarly effective in the treatment of streptococcal pharyngitis in children.

The efficacy of cefadroxil, an orally administered broad spectrum cephalosporin, was compared with that of penicillin V in several studies comprising more than 550 children with group A beta-haemolytic streptococcal (GABHS) pharyngitis9. Both agents alleviated clinical signs and symptoms and eradicated GABHS from the upper respiratory tract within 18 to 24 hours of the initiation of therapy. Approximately 8% of the patients treated with either cefadroxil or penicillin V had strains of GABHS isolated from 1 of their follow-up throat cultures which were considered bacteriological treatment failures. Compliance was greater than 90% with all of the regimens used, but was significantly better with cefadroxil given once daily than with penicillin V given 3 times daily. There were no serious adverse reactions.

Penicillin vs. Ciprofloxacin (Cipro)

Otitis, Sinusitis

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

Eighty adults suffering from otitis media, sinusitis (maxillaris or frontalis) or peritonsillitis were treated with 500 mg ciprofloxacin 2 times daily (n = 40) or with 2 g penicillin V 3 times daily (n = 40)15. The patients were randomly allocated. Three groups of patients resulted, clinically and bacteriologically evaluable, or only clinically evaluable because the isolated strains were resistant to ciprofloxacin or penicillin V or because no strains were isolated. 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. Clindamycin

Orofacial infections

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

The efficacy of clindamycin and phenoxymethylpenicillin in the treatment of orofacial infections was compared in a randomised study3: 30 patients received clindamycin 150 mg every 6 h for seven days, and 30 received phenoxymethylpenicillin (penicillin V) 1 g every 12 h for seven days. All patients but one in each group responded satisfactorily to treatment. Although the clindamycin group had a shorter duration of pain, swelling and fever, the differences between the groups were not statistically significant. Of the 60 microbiological specimens 23 yielded only anaerobic bacteria, 34 both anaerobic and aerobic bacteria, two aerobic bacteria only and one no growth. In the penicillin group one case of severe diarrhoea occurred, and six patients in the clindamycin group had moderate to severe gastrointestinal discomfort, including one case of Clostridium difficile associated diarrhoea. This difference was however not statistically significant. The results support the continued use of penicillin for treatment of orofacial infections, with clindamycin serving as an effective alternative.

Further reading

References
  • 1. 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
  • 2. Dykhuizen RS, Golder D, Reid TM, Gould IM. Phenoxymethyl penicillin versus co-amoxiclav in the treatment of acute streptococcal pharyngitis, and the role of beta-lactamase activity in saliva. J Antimicrob Chemother. 1996 Jan;37(1):133-8. 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. Adam D, Scholz H, Helmerking M. Comparison of short-course (5 day) cefuroxime axetil with a standard 10 day oral penicillin V regimen in the treatment of tonsillopharyngitis. J Antimicrob Chemother. 2000 Feb;45 Suppl:23-30. PubMed
  • 9. Gerber MA. A comparison of cefadroxil and penicillin V in the treatment of streptococcal pharyngitis in children. 1986;32 Suppl 3:29-32. PubMed
  • 10. 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
  • 11. Cohen R, de La Rocque F, Boucherat M, Lecompte MD, Bouhanna A, Wollner A, Ponet D, Elbez A, Richoux F, Brami A, et al. Cefaclor versus penicillin V in staphylococcal infections in children. Ann Pediatr (Paris). 1991 Apr;38(4):289-95. PubMed
  • 12. Thomsen J, Sederberg-Olsen J, Balle V, Hartzen S. Children with secretory otitis media: amoxicillin-clavulanate is superior to penicillin V in a double-blind randomized study. Arch Otolaryngol Head Neck Surg. 1997 Jul;123(7):695-9. PubMed
  • 13. Brook I. Treatment of patients with acute recurrent tonsillitis due to group A beta-haemolytic streptococci: a prospective randomized study comparing penicillin and amoxycillin/clavulanate potassium. J Antimicrob Chemother. 1989 Aug;24(2):227-33. 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
  • 15. 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
  • 16. 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

Published: March 31, 2008
Last updated: July 24, 2013

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