The purpose of this study was to compare the bacteriologic and clinical efficacy of oral cephalexin twice vs. three times daily vs. cefadroxil once daily as therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. A prospective open-label, observational cohort study was conducted over 18 months (January 2000-June 2001). Children enrolled had an acute onset of symptoms and signs of a tonsillopharyngeal illness and a laboratory-documented GABHS infection. Follow-up examination and laboratory testing occurred 21 ± 4 days following enrollment. Two hundred seventy-one patients were enrolled (intent to treat group): 63 received cephalexin twice daily, 124 received cephalexin three times daily, and 84 received cefadroxil once daily. Fifty-three children did not return for the follow-up visit, leaving 218 patients in the per-protocol group: 54 cephalexin twice daily treated, 94 cephalexin 3-times daily treated, and 70 cefadroxil once-daily treated. In the per-protocol group, bacteriologic cure for those treated with cephalexin twice daily was 87%, for cephalexin 3 times daily, it was 81% and for cefadroxil once daily it was 81% (p=0.61). The clinical cure rate for cephalexin twice-daily treatment was 91%; for three-times daily, it was 86%; and for cefadroxil once daily, it was 84% (p=0.56). Because treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences. Younger age of patient was significantly associated with bacteriologic (p=0.04) and clinical (p=0.01) failure independent of treatment group but in the adjusted logistic model no differences were found among the 3 treatment regimens. Cephalexin dosed twice daily or three times daily and cefadroxil dosed once daily appear equivalent in bacteriologic and clinical cure of GABHS tonsillopharyngitis.
Get full access to this article
View all access options for this article.
References
1.
1. Pickering LK, Peter G, Baker CJ, Gerber MA, Mac Donald NE, Orenstein WA, Patriarca P, Committee on Infectious Diseases. 2000 Red Book: Report of the Committee on Infectious Diseases, 25th ed.Elk Grove Village, IL: American Academy of Pediatrics, 2002.
2.
2. Kelkar PS, Li JT-C.Cephalosporin allergy. N Engl J Med. 2001;345:804-809.
3.
3. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol. 1995;74:167-170.
4.
4. Pichichero ME, Pichichero DM. Diagnosis of penicillin, amoxicillin, and cephalosporin allergy: reliability of examination assessed by skin testing and oral challenge. J Pediatr. 1998;132:137-143.
5.
5. Norrby SR. Side effects of cephalosporins. Drugs. 1987; 34(Suppl 2):105-120.
6.
6. Lin RY. A perspective on penicillin allergy. Arch Intern Med. 1992;152:930-937.
7.
7. Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S, Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics. 1995;96:758-764.
8.
8. Tarpay MM, Chartrand M, Cox A.The extended microbiology of group A streptococcal pharyngitis observations during a double-blind controlled study of cephalexin twice versus four-times daily. Infection. 1984;12:181-184.
9.
9. Barbhaiya RH, Shukla UA, Gleason CR, et al. Phase I study of multipledose cefprozil and comparison with cefaclor. Antimicrob Agents Chemother1990;34:1198-1203.
10.
10. Mc Carty JM, Renteria A, Doyle CA, Durham SJ, Hamilton H, Wilber RB, for the Cefprozil Multicenter Study Group. Cefprozil vs. cefaclor in the treatment of pharyngitis and tonsillitis. Infect Med. 1992;9(Suppl C):33-43.
11.
11. Randolph M.Clinical comparison of once-daily cefadroxil and thrice-daily cefaclor in the treatment of streptococcal pharyngitis. Chemotherapy. 1988;34:512-518.
12.
12. Christenson JC, Swenson E, Gooch WM III, Herrod JN. Comparative efficacy and safety of cefprozil (BMY-28100) and cefaclor in the treatment of acute group A beta-hemolytic streptococcal pharyngitis. Antimicrob Agents Chemother1991;35:1127-1130.
13.
13. Mc Carty JM. Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis. Eur J Clin Microbiol Infect Dis. 1994;13:846-850.
14.
14. Stillerman M, Isenberg HD. Streptococcal pharyngitis therapy: comparison of cyclacillin, cephalexin, and potassium penicillin V. Antimicrob Agents Chemother1970;10:270-276.
15.
15. Disney FA, Breese BB, Green JL, Talpey WB, Tobin JR. Cephalexin and penicillin therapy of childhood betahemolytic streptococcal infections. Postgrad Med j. 1971;47(Suppl):47-51.
16.
16. Stillerman M, Isenberg HD, Moody M.Streptococcal pharyngitis therapy. Comparison of cephalexin, phenoxymethyl penicillin, and ampicillin. Am J Dis Child. 1972;123:457-461.
17.
17. Gau DW, Horn RF, Solomon RM, Johnson P, Leigh DA. Streptococcal tonsillitis in general practice. A comparison of cephalexin and penicillin therapy. Practitioner1972;208:276-281.
18.
18. Rabinovitch M, Mac Kenzie R, Brazeau M, Marks MI. Treatment of streptococcal pharyngitis. I. Clinical evaluation. Can Med Assoc J1973;108:1271-1274.
19.
19. Matsen JM, Torstenson O, Siegel SE, Bacaner H.Use of available dosage forms of cephalexin in clinical comparison with phenoxymethyl penicillin and benzathine penicillin in the treatment of streptococcal pharyngitis in children. Antimicrob Agents Chemother1974;6:501-506.
20.
20. Disney FA, Dillon H, Blumer JL, et al. Cephalexin and penicillin in the treatment of group A beta-hemolytic streptococcal throat infections. Am J Dis Child. 1992;146:1324-1327.
21.
21. Ginsburg CM, Mc Cracken GH Jr, Crow SD, Steinberg JB, Cope F.A controlled comparative study of penicillin V and cefadroxil therapy of group A streptococcal tonsillopharyngitis. J Int Med Res. 1980;8(Suppl):82-86.
22.
22. Ginsburg CM, Mc Cracken GH Jr, Steinberg JB, et al. Treatment of Group A streptococcal pharyngitis in children. Restults of a prospective, randomizecl study of four antimicrobial agents. Clin Pediatr (Phila). 1982;21:83-88.
23.
23. Henness DM. A clinical experience with cefadroxil in upper respiratory tract infection. J Antimilcrob Chemother1982;10(Suppl B):125-135.
24.
24. Pichichero ME, Disney FA, Aronovitz GH, Talpey WB, Green JL, Francis AB. Randomized, single-blind evaluation of cefadroxil and phenoxymethylpenicillin in the treatment of streptococcal pharvngitis. Antimicrob Agents Chemother1987;31:903-906.
25.
25. Stromberg A, Schwan A, Cars O.Five versus ten days treatment of group A streptococcal pharyngotonsillitis: a randomized controlled clinical trial wvith phenoxymethylpenicillin and cefadroxil. Scand J Infect Dis. 1988;20:37-46.
26.
26. Holm SE, Roos K, Stromberg A.A randomized study of treatment of streptococcal pharyngotonsillitis with cefadroxil or phenoxymethylpenicillin (penicillin V). Pediatr Infect Disj. 1991;10(10 Suppl):S68-S71.
27.
27. Milatovic D.Evaluation of cefadroxil, penicillin and erythromycin in the treatment of streptococcal tonsillopharynigitis. Pediatr Infect Dis J. 1991;10(10 Suppl):S61-S63.
28.
28. O'Gradv F, Lambert HP, Finch RG, Greenwood D.Antibiotic and Chemotherapy: Anti-infective Agents and Their Use in Therapy, 7th ed.New York: Churchill Livingstone, 1997:217-219;256-267.
29.
29. Craig WA, Andes D.Pharmacokinetics and pharmacodynamics of antibiotics in otitis media. Pediatr Infect Dis J. 1996;15(3):255-259.
30.
30. Holm S, Henning C, Grahn E, Lomberg H, Stalev H.Is penicillin the appropriate treatment for recurrent tonsillopharyngitis? Results from a comparative randomized blind study of cefuroxime axetil and phenoxymethylpenicillin in children. The Swedish study group. Scand J Infect Dis. 1995;27:221-228.
31.
31. Roos K, Larsson P.Loracarbef versus phenoxymethylpenicillin in the treatment of recurrent streptococcal pharyngotonsillitis. Scand J Infect Dis. 1997;29:141-145.
33. Gerber MA, Randolph MF, De Meo K, Feder HM Jr, Kaplan EL. Failure of once-daily penicillin V therapy for streptococcal pharyngitis. Am J Dis Child. 1989;143:153-155.
34.
34. Disney FA, Hanfling MJHausinger SA. Loracarbef (LY163892) vs. penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis. Pediatr Infect Dis J. 1992;11(8 Suppl):S20-S26.
35.
35. Block SL, Hedrick JA, Tyler RD. Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents. Pediatr Infect Dis j1992;11:919-925.
36.
36. Dajani AS, Kessler SL, Mendelson R, Uden DL, Todd WM. Cefpodoxime proxetil vs. penicillin V in pediatric streptococcal pharyngitis/tonsillitis. Pediatr Infect Dis j. 1993;12:275-279.
37.
37. Gooch WM 3rd, Mc Linn SE, Aronovitz GH, et al. Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcalpharyngitis. Antimicrob Agents Chemother. 1993;37:159-163.
38.
38. Mc Carty JM. Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis. Eur J Clin Microbiol Infect Dis. 1994;13:846-850.
39.
39. Pichichero ME, Mc Linn SE, Gooch WM 3rd, Rodriquez W, Goldfarb J, Reidenberg BE. Ceftibuten vs. penicillin V in group A beta-hemolytic streptococcal pharyngitis. Member of the Ceftibuten Pharyngitis International Study Group. Pediatr Infect Disj1995;14(7 Suppl):S102-S107.
40.
40. Nemeth MA, Mc Carty J, Gooch WM 3rd, Henry D, Keyserling CH, Tack KJ. Comparison of cefdinir and penicillin for the treatment of streptococcal pharyngitis. Clin Ther1999; 21:1525-1532.
41.
41. Assem E, Vickers M.Tests for penicillin allergy in man. II. The immunological cross-reaction between penicillins and cephalosporins. Immunology. 1964;27:255-269.
42.
42. Anderson JA. Cross-sensitivity to cephalosporins in patients allergic to penicillin. Pediatr Infiect Dis. 1986;5:557-561.
43.
43. Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med. 1987;107:204-215.
44.
44. Abraham E.The chemistry of new antibiotics. Am J Med. 1965;39:692-696.
45.
45. Flynn E.Biological and chemical studies of the cephalosporins. Antionicrob Agents Clemotherc1966;6:715-726.
46.
46. Newton GG, Hamilton-Miller JM. Cephaloridine: chemical and biochemical aspects. Postgrad Med J. 1967;43(Suppl):10-37.
47.
47. Grieco M.Cross-allergenicity of the penicillins and the cephalosporins. Arch Intern Med. 1967;119:141-145.
48.
48. Scholand JF, Tennebaum Jl, Cerilli GJ. Anaphylaxis to cephalothin in a patient allergic to penicillin. JAMA. 1968;206:130-132.
49.
49. Petz LD. Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis. 1978;137(Suppl):S74-S79.
50.
50. Mendelson LM, Ressler G, Rosen JP, Selcow JE. Rouitine elective penicillin allergy skin testing in children and adolescents; study of sensitization. J Allergy Clin Immunol. 1984;73 (1 pt 1):76-81.
52. Pichichero ME. Cephalosporins are superior to penicillin for treatment of streptococcal tonsillopharyngitis: is the difference worth it?Pediatr Infect Dis J1993;12:268-274.
53.
53. Pichichero ME, Green JL, Francis AB, et al. Recurrent group A streptococcal tonsillopharyngitis. Pediatr Infect Disj1998;17:809-815.
54.
54. Steele RW, Estrada B, Begue RE, Mirza A, Travillion DA, Thompson MP. A double-blind taste comparison of pediatric antibiotic suspensions. Clin Pediatr. 1997;36:193-199.
55.
55. Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med. 1990;150:1881-1884.
56.
56. Pichichero ME, Margolis PA. A comparison of cephalosporins and penicillins in the treatment of group A beta-hemolytic streptococcal pharyngitis: a meta-analysis supporting the concept of microbial copathogenicity. Pediatr Infect Dis J. 1991;10:275-281.
57.
57. Pichichero ME, Disney FA, Talpey WB, et al. Adverse and beneficial effects of immediate treatment of group A beta-hemolytic streptococcal pharyngitis in an emergency department. Pediatr Infect Dis J. 1986;5:655-655.
58.
58. El-Dahar NT, Nijazi SS, Rawashdeh NM, et al. Immediate vs. delayed treatment of group A beta-hemolytic streptococcal pharyngitis with penicillin V. Pediatr Infect Dis J. 1991;10:126-130.
59.
59. Gerber MA, Tanz RR, Kabat W, et al. Potential mechanisms for failure to eradicate group A streptococci from the pharynx. Pediatrics. 1999;104:911-917.
