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Antimicrobial Agents and Chemotherapy, November 2005, p. 4787-4788, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4787-4788.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Efficacy of Penicillin versus Cefdinir in Eradication of Group A Streptococci and Tonsillar Flora

Itzhak Brook1* and Perry A. Foote2

Department of Pediatrics, Georgetown University School of Medicine, Washington, D.C.,1 Department of Otorhinolaryngology, University of Florida, Alachua General Hospital, Gainesville, Florida2

Received 4 May 2005/ Returned for modification 1 July 2005/ Accepted 21 August 2005


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ABSTRACT
 
Core tonsillar cultures were obtained from 40 children with recurrent tonsillitis treated with either penicillin or cefdinir. Group A beta-hemolytic streptococci were isolated from 11 penicillin- and 3 cefdinir-treated (P < 0.001) patients. ß-Lactamase producers were recovered from 17 penicillin- and 3 cefdinir-treated (P < 0.01) patients. Inhibiting alpha-hemolytic streptococci were isolated less often from penicillin-treated patients than from cefdinir-treated patients.


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TEXT
 
Penicillin failure to eradicate group A beta-hemolytic streptococci (GABHS) from inflamed tonsils is of great concern (8). One explanation of this phenomenon is that ß-lactamase-producing bacteria (BLPB) protect GABHS by inactivating penicillin (1). Another explanation is that the preservation of alpha-hemolytic streptococci (AHS) that possess interfering capabilities against GABHS contribute to the eradication of this organism (13).

Several classes of antimicrobials that are active against GABHS and BLPB are more effective than penicillin in eradicating GABHS from recurrently inflamed tonsils (1, 5, 7). A possible explanation for the improved efficacy of cephalosporins over penicillin is the activity of cephalosporins against BLPB and their relative inactivity against AHS.

This study investigated the effects of penicillin and cefdinir therapies on the core tonsillar aerobic bacterial flora of children with recurrent tonsillitis.

Patients consecutively scheduled for elective tonsillectomies because of recurrent GABHS tonsillitis were included. Criteria for inclusion were a history of recurrent GABHS pharyngotonsillitis (at least six episodes within the preceding 2 years, with at least four by GABHS) and an age of >4 years. Excluded were subjects who received antimicrobials or had any infection during the previous month. The study was performed between June 1998 and June 2002 and was approved by the Institutional Review Board. Each subject had general physical and otolaryngological examinations, a complete blood cell count, and urinalysis.

Following a tonsillectomy, one tonsil was cauterized with a heated scalpel, and an incision was made through the area. The tonsillar core was swabbed with a sterile, cotton-tipped applicator that was placed onto an anaerobic transport medium (Port-A-Cul; BBL, Cockeysville, Md.) and inoculated within 24 h onto sheep's blood (5%), chocolate, and MacConkey agar plates (all media from BBL, Becton Dickinson Co., Cockeysville, Md.). The plates were incubated aerobically at 37°C (MacConkey) and under 5% CO2 and were examined at 24 and 48 h (11). ß-Lactamase activity was determined on five colonies of each morphological feature of all isolates by using a Cefinaz disk (BBL, Cockeysville, Md.).

Inhibitory activities of five separate colonies of AHS from each patient were tested against one strain of a recent clinical isolate of GABHS. Minidrops of log-phase broth cultures of the isolates were transferred with a Steers steel pin replicator to vitamin K1-enriched Brucella blood agar plates and allowed to dry for 15 min. A log-phase broth culture of the target strain was applied adjacent to each of the isolated strains, and the plates were incubated in 5% CO2 at 37°C for 48 h. Bacterial interference was defined as any reproducible inhibition of growth.

Penicillin V (17 mg/kg of body weight, or 250 mg every 8 h) was routinely prescribed prior to surgery. Cefdinir (14 mg/kg, or 600 mg once a day) was administered to those with a history of a non-type I penicillin allergy. Included were the first 20 patients who received penicillin and the first 20 who got cefdinir that met the inclusion criteria. Patients were instructed to take the medication prior to surgery for 10 days. Compliance was checked by inspection of the unused medication. Statistical significance was calculated by Fisher's exact test (two-sided), unadjusted.

Forty patients (24 males) participated in this study. Their mean age was 7 years, 4 months (range, 4 to 12 years). The distributions of the patients' ages, genders, urinalyses, white blood counts, and previous antimicrobial therapies were similar for the two groups.

GABHS were isolated from 11 (55%) of the penicillin-treated group and 3 (15%) of the cefdinir-treated group (P = 0.019). (Table 1) Thirty-three BLPB (Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis) were recovered from 17 (85%) of those treated with penicillin, and four BLPB were found in 3 (15%) of those treated with cefdinir.


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  		TABLE 1. Aerobic organisms isolated from the cores of excised tonsils from 40 children

Patients treated with penicillin had a significantly lower number of AHS (including those with inhibiting capability) and gamma-hemolytic streptococci compared to those treated with cefdinir (6 versus 15, total number of AHS [P = 0.01], and 2 versus 10, AHS with inhibiting capability [P = 0.014], respectively) (Table 1).

This study compared two modes of therapy for recurrent tonsillitis due to GABHS, one using penicillin and the other an expanded-spectrum cephalosporin (cefdinir). Cefdinir was more effective in eradicating GABHS, reducing the number of BLPB, and preserving AHS that are capable of inhibiting GABHS. The superiority of cefdinir may be due to its activity against the aerobic BLPB (Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis) recovered from the patients and its relative lack of activity against AHS (including interfering ones) (10).

One explanation for the failure of penicillin to eradicate GABHS tonsillitis is that repeated administration of penicillin may select BLPB that can protect GABHS from penicillin (1). The recovery of aerobic and anaerobic BLPB in over three-quarters of patients with recurrent GABHS tonsillitis (1, 7, 13), the ability to measure ß-lactamase activity in the tonsillar core (2), and the response of patients with recurrent GABHS tonsillitis to antimicrobials effective against BLPB (1, 5, 7, 13) support this explanation.

An additional untoward effect of penicillin therapy is the potential eradication, in the absence of BLPB, of AHS that possess inhibiting activity of GABHS (6, 9, 13). In contract, AHS are usually more resistant to cephalosporins (6, 10). This difference in susceptibility and the resistance of cephalosporins to ß-lactamase may explain the improved activity of cephalosporins compared with that of penicillin in the treatment of acute GABHS tonsillitis (5). These phenomena were demonstrated with a subcutaneous-abscess mouse model (3).

The presence of AHS that inhibit growth of GABHS through bacteriocin production was described by Crowe et al. (6), who postulated that these substances might inhibit colonization and aid in eradication of GABHS. Roos et al. (13) and Brook and Gober (4) showed that the presence of BLPB and the lack of tonsillar colonization by inhibiting AHS were associated with the failure of penicillin to cure GABHS tonsillitis. A series of three studies from Göteborg, Sweden (14-16), demonstrated the utility of inoculation of the nasopharynx with interfering AHS in the prevention of recurrent GABHS pharyngotonsillitis.

This study offers an explanation for the observed superiority of cefdinir as well as other cephalosporins over penicillin in the eradication of GABHS tonsillitis (5, 12). Further studies are warranted to evaluate the efficacy of these agents on BLPB and AHS in the treatment of acute and recurrent tonsillitis.


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ACKNOWLEDGMENTS
 
The study had no financial support from any pharmaceutical company.


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FOOTNOTES
 
* Corresponding author. Mailing address: 4431 Albemarle St. NW, Washington, DC 20016. Fax: (202) 244-6809. Phone: (301) 295-2698. E-mail: ib6{at}georgetown.edu. Back


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REFERENCES
 
    1
  1. Brook, I. 1984. The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection. Rev. Infect. Dis. 6:601-607.[Medline]
    2. 2
  2. Brook, I., and P. Yocum. 1984. Quantitative measurement of beta-lactamase in tonsils of children with recurrent tonsillitis. Acta Oto-Laryngol. 98:556-559.[Medline]
    3. 3
  3. Brook, I., and J. D. Gilmore. 1993. Evaluation of bacterial interference and beta-lactamase production in management of experimental infection with group A beta-hemolytic streptococci. Antimicrob. Agents Chemother. 37:1452-1455.[Abstract/Free Full Text]
    4. 4
  4. Brook, I., and A. E. Gober. 1995. Role of bacterial interference and beta-lactamase-producing bacteria in the failure of penicillin to eradicate group A streptococcal pharyngotonsillitis. Arch. Otolaryngol. Head Neck Surg. 121:1405-1409.[Abstract/Free Full Text]
    5. 5
  5. Casey, J. R., and M. E. Pichichero. 2004. Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children. Pediatrics 113:866-882.[Abstract/Free Full Text]
    6. 6
  6. Crowe, C. C., E. Sanders, and S. Longley. 1973. Bacterial interference. II. The role of the normal throat flora in prevention of colonization by group A streptococcus. J. Infect. Dis. 128:527-532.[Medline]
    7. 7
  7. Foote, P. A., Jr., and I. Brook. 1989. Penicillin and clindamycin therapy in recurrent tonsillitis. Effect of microbial flora. Arch. Otolaryngol Head Neck Surg. 115:856-859.
    8. 8
  8. Gastanaduy, A. S., E. L. Kaplan, B. B. Huwe, C. McKay, and L. W. Wannamaker. 1980. Failure of penicillin to eradicate group A streptococci during an outbreak of pharyngitis. Lancet ii:498-502.
    9. 9
  9. Grahn, E., S. E. Holm, C. Ekedahl, and K. Roos. 1983. Interference of alpha-hemolytic streptococci isolated from tonsillar surface on beta-hemolytic streptococci (Streptococcus pyogenes)—a methodological study. Zentbl. Bakteriol. Mikrobiol. Hyg. A 254:459-468.
    10. 10
  10. Jones, R. N., and A. L. Barry. 1988. BMY-28100, a new oral cephalosporin: antimicrobial activity against nearly 7,000 recent clinical isolates, comparative potency with other oral agents, and activity against beta-lactamase producing isolates. Diagn. Microbiol. Infect. Dis. 9:11-26.[CrossRef][Medline]
    11. 11
  11. Murray, P. R., E. J. Baron, J. H. Jorgensen, M. A. Pfaller, and R. H. Yolken. 2003. Manual of clinical microbiology, 8th ed. ASM Press, Washington, D.C.
    12. 12
  12. Pichichero, M. E., and W. M. Gooch III. 2000. Comparison of cefdinir and penicillin V in the treatment of pediatric streptococcal tonsillopharyngitis. Pediatr. Infect. Dis. J. 19(Suppl. 12):S171-S173.[Medline]
    13. 13
  13. Roos, K., E. Grahn, and S. E. Holm. 1986. Evaluation of beta-lactamase activity and microbial interference in treatment failures of acute streptococci tonsillitis. Scand. J. Infect. Dis. 18:313-319.[Medline]
    14. 14
  14. Roos, K., E. Grahn, S. E. Holm, H. Johansson, and L. Lind. 1993. Interfering alpha-streptococci as a protection against recurrent streptococcal tonsillitis in children. Int. J. Pediatr. Otorhinolaryngol. 25:141-148.[CrossRef][Medline]
    15. 15
  15. Roos, K., S. E. Holm, E. Grahn, and L. Lind. 1993. Alpha-streptococci as supplementary treatment of recurrent streptococcal tonsillitis: a randomized placebo-controlled study. Scand. J. Infect. Dis. 25:31-35.[Medline]
    16. 16
  16. Roos, K., S. E. Holm, E. Grahn-Hakansson, and L. Lagergren. 1996. Recolonization with selected alpha-streptococci for prophylaxis of recurrent streptococcal pharyngotonsillitis—a randomized placebo-controlled multicentre study. Scand. J. Infect. Dis. 28:459-462.[Medline]

Antimicrobial Agents and Chemotherapy, November 2005, p. 4787-4788, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4787-4788.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Casey, J. R., Kahn, R., Gmoser, D., Atlas, E., Urbani, K., Luber, S., Pellman, H., Pichichero, M. E. (2008). Frequency of Symptomatic Relapses of Group A {beta}-Hemolytic Streptococcal Tonsillopharyngitis in Children From 4 Pediatric Practices Following Penicillin, Amoxicillin, and Cephalosporin Antibiotic Treatment. CLIN PEDIATR 47: 549-554 [Abstract]  
  • Brook, I. (2007). Penicillin Failure in the Treatment of Acute and Relapsing Tonsillopharyngitis Is Associated With Copathogens and Alteration of Microbial Balance: A Role for Cephalosporins. CLIN PEDIATR 46: 17S-24S [Abstract]  
  • Casey, J. R. (2007). Selecting the Optimal Antibiotic in the Treatment of Group A {beta}-Hemolytic Streptococci Pharyngitis. CLIN PEDIATR 46: 25S-35S [Abstract]  
  • Brook, I., Gober, A. E. (2006). Recovery of interfering and {beta}-lactamase-producing bacteria from group A {beta}-haemolytic streptococci carriers and non-carriers.. J Med Microbiol 55: 1741-1744 [Abstract] [Full Text]  

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