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Doi:10.1016/j.ijporl.2009.02.004

International Journal of Pediatric Otorhinolaryngology 73 (2009) 757–759 International Journal of Pediatric Otorhinolaryngology j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / i j p o r l Rate of eradication of group A beta-hemolytic streptococci in children withpharyngo-tonsillitis by amoxicillin and cefdinir Department of Pediatrics, Georgetown University, Schools of Medicine, 4431 Albemarle st NW, Washington, DC 20016, USA Background: Cephalosporins were found to be more effective than penicillins in the eradication of group A b-hemolytic streptococcal (GABHS) from tonsillar tissues. This study investigated the effect of amoxicillin and cefdinir therapies on the rate of eradication of GABHS from the tonsils of children with Patients and methods: Of 50 children suffering from PT 25 were treated with amoxicillin (40 mg/(kg d) or250 mg every 8 h) and 25 with cefdinir (14 mg/(kg d) or 600 mg once a day) for 10 days. Pharyngo- tonsillar cultures were obtained from all children before treatment and on the 1st, 2nd, 3rd, 4th, 7th, and Results: GABHS was eradicated more rapidly from children treated with cefdinir as compared to those receiving amoxicillin. A smaller number of patients with GABHS were found in those treated withcefdinir as compared to amoxicillin throughout the treatment period. Eradication of GABHS from 68% (8of 25 patients) was noted in those treated with cefdinir after 2 days and those treated with amoxicillinafter 4 days. The differences between the number of patients who had a bacteriological cure betweenthose receiving cefdinir to those getting amoxicillin was statistical significant at day 4 (32% vs. 8%). At theend of therapy GABHS was recovered from 5 (20%) and 2 (8%) of the patients. The group that receivedcefdinir, had a more rapid reduction in fever on the first after initiation of therapy as compared to thosereceiving amoxicillin. The fever reduction in those receiving cefdinir occurred a day earlier than in thosegetting amoxicillin.
Conclusions: Fever was reduced and GABHS was eradicated more rapidly from children treated withcefdinir as compared to amoxicillin.
ß 2009 Elsevier Ireland Ltd. All rights reserved.
penicillins in eradicating these organisms from recurrentlyinflamed tonsils in children Shorter course of 5 days of The failure of penicillins including amoxicillin to eradicate cephalosporins including cefdinir were also found superior to group A b-hemolytic streptococci (GABHS) from inflamed tonsils is penicillins in the eradication of GABHS from tonsillar tissues of great concern Various theories have been offered to explain However, the rate of eradication of GABHS from the tonsils by these this phenomenon. One is that b-lactamase-producing bacteria agents as compared to penicillins has not been explored.
(BLPB) protects GABHS by inactivating penicillins In previous This study investigated the effect of amoxicillin and cefdinir studies, BLPB were recovered from over 75% of the cores of tonsils therapies on the rate of eradication of GABHS from the tonsils and of patients who had tonsillectomy for recurrent infection .
reduction of fever in children with acute pharyngo-tonsillitis (PT).
Another explanation is that the preservation of the a-hemolyticstreptococci (AHS) that are part of the normal oral flora is an important contributor to the eradication of GABHS Some ofthese bacteria have been shown in vitro to compete and, thus, interfere with the growth of GABHS .
Antimicrobials including cephalosporins that are active against The population studied was middle class, residing in suburban GABHS as well as BLPB were found to be more effective than locations in the vicinity of Washington, DC. Included in the studywere patients seen consecutively for acute GABHS PT in an acutecare clinic. GABHS was isolated from the pharyngo-tonsillar area * Corresponding author. Tel.: +1 202 363 4253; fax: +1 202 244 6809.
from all patients. Acute PT was defined as acute onset of sore throat plus at least one of the following: anterior cervical 0165-5876/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved.
doi: I. Brook, A.E. Gober / International Journal of Pediatric Otorhinolaryngology 73 (2009) 757–759 adenitis; temperature >38.3 8C (101 8F); pharyngeal or tonsillar exudate or pharyngeal injection. The Institutional Review Board Number of patients (%) treated with either amoxicllin or cefdinir where group Astreptococcus was recovered.
granted the study approval. Past medical history, includingtherapies with antimicrobial therapy and day-care attendance was obtained by using a questionnaire and by checking medical records. Included were the first 25 children who completed treatment with either amoxicillin or cefdinir and were followed up as described below. Excluded were those who received antimicrobial therapy or suffered from GABHS PT in the previous 3 months. Patients were requested not to take any antipyretic or any other medication during the treatment period. Parents were asked to take the patient oral temperature every 8 h duringwaking hours.
Table 2Presence of fever in children treated with cefdinir or amoxicillin.
Amoxicillin (40 mg/(kg d) or 250 mg every 8 h for 10 days) was routinely used in all patients. However, cefdinir (14 mg/kg or 600 mg once a day for 10 days) was administered to those who had a history of a non-type I penicillin allergy. Patients were treated presumptively based on clinical diagnosis.
Compliance was measured by a check-off dosage card and inspection of the unused medicine. Patients who failed to take more than two dosages were excluded from evaluation. Patients were requested to return their medicine supply and check-off cards after the end of treatment. Five patients who failed to comply with the antimicrobial therapy were excluded from the analysis.
The distribution of the patients’ age, and gender was similar in thetwo groups.
Adverse effects were noted in 7 patients: diarrhea (>3 watery stools in 24 h) in 3 patients each on amoxicillin and cefdinir, andvomiting in 1 patient on amoxicillin.
Pharyngo-tonsillar cultures were obtained from all children with a sterile cotton swab before treatment and on the 1st, 2nd, 3rd, 4th, 7th, and 12th days. The swab was placed in a transportsystem for aerobic bacteria (Culturette1; Marion Scientific Corp., This study compared the efficacy of bacterial eradication and Rockford, IL) and inoculated on sheep blood (5%) within 24 h of reduction of fever by two modes of therapy of tonsillitis due to collection. The plates were incubated at 37 8C under 5% carbon GABHS, one using amoxicillin, and the other an extended dioxide, and examined at 24 and 48 h. GABHS was identified by spectrum cephalosporin (cefdinir). Of the two, cefdinir was more determining bacitracin sensitivity, and serologic grouping by rapidly effective in eradicating GABHS and ultimately led to Phadebact1 coagglutination (Pharmacia Diagnostics Inc., Piscat- higher eradication of GABHS, confirming previous studies that away, NJ). Statistical analysis was done by the chi-square test with illustrated the superior eradication of GABHS by cephalosporins over penicillins The maximal eradication of GABHS bycefdinir (92%) was attained at the 4th day of therapy, as compared to 80% by amoxicillin attained only at day 10. Thismay explain the superiority of shorter 5-day course of A total of 50 children (27 males and 23 females) were evaluated.
cephalosporins over 10 days of penicillins . The faster The median age of the children was 7 years and 8 months (range, efficacy of cefdinir may be due to its activity against BLPB 4.5–16 years). No difference was noted in the age and gender recovered from patients (i.e., Staphylococcus aureus, Haemophilus between the two groups of patients. GABHS was eradicated more influenzae and Moraxella catarrhalis) and its relative lower rapidly from children treated with cefdinir as compared to those activity against AHS (some of which possess interfering receiving amoxicillin. A smaller number of patients with GABHS capability against GABHS). Furthermore, the fever reduction in were found in those treated with cefdinir as compared to those receiving cefdinir occurred a day earlier than in those amoxicillin throughout the treatment period. Eradication of GABHS from 68% (8 of 25) patients was noted in those treated One explanation for the failure of penicillins to eradicate with cefdinir after 2 days and those treated with amoxicillin after 4 GABHS tonsillitis is that repeated administration of these agents days. The differences between the number of patients who had a may select BLPB that can protect not only themselves from bacteriological cure between those receiving cefdinir to those penicillins but also penicillin-susceptible pathogens The getting amoxicillin was statistical significant at day 4 (32% vs. 8%) recovery of aerobic and anaerobic BLPB in more than three- (p < .05) ). At the end of therapy GABHS was recovered fourths of the patients with recurrent GABHS tonsillitis , the from 5 (20%) and 2 (8%) of the patients.
ability to measure b-lactamase activity in the core of the tonsils The group that received cefdinir, had a more rapid reduction in , and the response of patient with recurrent GABHS PT to fever on the first day after initiation of therapy as compared to antimicrobial agents effective against BLPB support this those receiving amoxicillin. The fever reduction in those receiving cefdinir occurred a day earlier than in those getting amoxicillin An additional untoward effect of penicillins therapy is the potential eradication, in the absence of BLPB, of AHS that possess I. Brook, A.E. Gober / International Journal of Pediatric Otorhinolaryngology 73 (2009) 757–759 inhibiting activity of GABHS These AHS may have a are warranted to evaluate the long-term efficacy of these agents on beneficial role by competing with GABHS, and preventing BLPB and AHS in the treatment of acute and recurrent GABHS PT.
colonization and subsequent infection with GABHS. However,since these organisms are generally as susceptible to penicillins as is GABHS, they can also be eradicated by penicillin therapy . In [1] A.S. Gastanaduy, E.L. Kaplan, B.B. Huwe, C. McKay, L.W. Wannamaker, Failure of contrast, AHS are usually more resistant to cephalosporins .
penicillin to eradicate group A streptococci during an outbreak of pharyngitis, This difference in susceptibility and the resistance of cephalospor- ins to b-lactamase produced by S. aureus and other aerobic bacteria [2] I. Brook, The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection, Rev. Infect. Dis. 6 (1984) 601–607.
may explain their improved activity as compared with penicillin in [3] I. Brook, A.E. Gober, Role of bacterial interference and b-lactamase-producing the treatment of acute GABHS PT . The presence of AHS that bacteria in the failure of penicillin to eradicate group A streptococcal pharyngo- inhibits the growth of GABHS has been described by Crowe et al.
tonsillitis, Arch. Otolaryngol. Head Neck Surg. 121 (1995) 1405–1409.
[4] P.A. Foote Jr., I. Brook, Penicillin and clindamycin therapy in recurrent tonsillitis: . They observed increased bacteriocin production by AHS after effect of microbial flora, Arch. Otolaryngol. Head Neck Surg. 115 (1989) 856–859.
GABHS colonization. This led to the hypothesis that bacteriocin [5] J.R. Casey, M.E. Pichichero, Meta-analysis of cephalosporin versus penicillin production may result from selective pressure exerted by GABHS, treatment of group A streptococcal tonsillopharyngitis in children, Pediatrics113 (2004) 866–882.
and also that these substances might inhibit colonization of the [6] I. Brook, Antibacterial therapy for acute group A streptococcal pharyngotonsillitis: upper respiratory tract and aid in eradication of GABHS. Roos et al.
short-course versus traditional 10-day oral regimens, Paediatr. Drugs 4 (2002) and Brook and Gober showed that the production of [7] M.E. Pichichero, W.M. Gooch 3rd., Comparison of cefdinir and penicillin V in the -lactamase by the oropharyngeal flora and the lack of tonsillar treatment of pediatric streptococcal tonsillopharyngitis, Pediatr. Infect. Dis. J. 19 colonization by inhibiting AHS was associated with the failure of penicillin to cure GABHS tonsillitis.
[8] I. Brook, J.D. Gillmore, Evaluation of bacterial interference and beta-lactamase The occurrence of these phenomena was also shown in vivo production in the management of experimental infection with group A beta-hemolytic streptococci, Antimicrob. Agents Chemother. 37 (1993) 1452–1455.
using a subcutaneous abscess animal model In mice infected [9] I. Brook, P.A. Foote, Efficacy of penicillin versus cefdinir in eradication of group with GABHS and an interfering AHS (Streptococcus salivarius), A streptococci and tonsillar flora, Antimicrob. Agents Chemother. 49 (2005) penicillin eliminated both organisms. Penicillin did not, however, [10] I. Brook, P. Yocum, Quantitative measurement of beta-lactamase in tonsils of reduce the number of GABHS or the AHS in the presence of a BLPB children with recurrent tonsillitis, Acta Otolaryngol. (Stockh.) 98 (1984) 556–559.
(S. aureus). In contrast, a second generation cephalosporin [11] E. Grahn, S.E. Holm, K. Roos, et al., Interference of alpha-hemolytic streptococci eliminated GABHS and S. aureus, but not the cephalosporin- isolated from tonsillar surface, on beta-hemolytic streptococci, Streptococcuspyogenes: a methodological study, Zentralbl. Microbiol. 254 (1983) 459–468.
resistant AHS. S. aureus protected GABHS from penicillin but not [12] C.C. Crowe, E. Sanders, S. Longley, Bacterial interference. II. The role of the normal from the cephalosporin. Furthermore, cephalosporin therapy throat flora in prevention of colonization by group A streptococcus, J. Infect. Dis.
eradicated GABHS while preserving the AHS.
[13] K. Roos, E. Grahn, S.E. Holm, Evaluation of beta-lactamase activity and microbial This study highlights the rapid eradication of GABHS by interference in treatment failures of acute streptococci tonsillitis, Scand. J. Infect.
cephalosporins as compared with amoxicillin. Further studies

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