Occurrence of Group A β-Hemolytic
Streptococcal Pharyngitis in the Four Months After Treatment of an Index
Episode With Amoxicillin Once-daily or Twice-daily or With Cephalexin
Carlos E.
Armengol, MD, J. Owen Hendley, MD
Nov 21, 2012
Pediatr Infect Dis J. 2012;31(11):1124-1127. © 2012
Lippincott Williams & Wilkins
Abstract and Introduction
Abstract
Background:
Prospective studies using bacterial eradication as the endpoint have
demonstrated that once-daily amoxicillin is as effective as twice-daily
amoxicillin for treatment of Group A [beta]-hemolytic streptococcal (GABHS)
pharyngitis.
Objective: The aim of this study was to determine, in a retrospective
study, whether treatment of symptomatic GABHS pharyngitis with once-daily
amoxicillin was as effective in preventing clinical recurrences as twice-daily
amoxicillin or cephalexin in pediatric office practice, using patient-initiated
return visits for streptococcal pharyngitis as a pragmatic, clinical endpoint.
Methods: The charts of consecutive patients 2 years of age and older
with laboratory-proven GABHS pharyngitis for a period of 2 years were reviewed
to identify index cases of streptococcal pharyngitis and subsequent episodes.
Age, weight, antibiotic treatment and time from index to subsequent episodes of
GABHS pharyngitis were recorded.
Results: In 1402 index episodes, patients received amoxicillin
once-daily (231), amoxicillin twice-daily (846) or cephalexin (325). The risk
of symptomatic streptococcal pharyngitis in the 4 months after treatment of the
index episode was not statistically different among the 3 treatment groups:
amoxicillin once-daily (15.1%), amoxicillin twice-daily (19.6%) and cephalexin
(19.1%). There was a trend toward reduction in the risk of recurrences in the 6
weeks after completion of antibiotics in the cephalexin (9%) group compared
with the combined amoxicillin (13%) groups.
Conclusions: Amoxicillin once-daily or twice-daily was equally effective
in terms of frequency of recurrence of symptomatic GABHS pharyngitis.
Introduction
Group A [beta]-hemolytic streptococcal (GABHS) pharyngitis
is treated to prevent rheumatic fever and to ameliorate symptoms. A 10-day
course of amoxicillin is commonly prescribed in pediatric practice, usually as
a twice-daily or thrice-daily dosing regimen. Once-daily dosing of amoxicillin
has been endorsed by the American Academy of Pediatrics [1] and the
American Heart Association [2] because studies [3–7] have demonstrated the efficacy of once-daily dosing for
bacteriologic eradication in patients with GABHS pharyngitis. Four [3–6] of 5 studies
demonstrated eradication in more than 80% of patients at the first visit after
completion of therapy (); 2 [3,5] of the 5 provided data on clinical cure at a scheduled
follow-up visit after treatment.
Table 1. Summary of Randomized Controlled Trials of Once-daily
Amoxicillin
Study | Ages | Amoxicillin | Number | Comparison | Number | Return | Percent | Acquisition | Clinical |
Shvartzman et al 3 | 3 | 50 | 75 | Penicillin | 82 | 1–2, | 100 | n/a | No |
Feder et al 4 | 3–18 | 750 | 84 | Penicillin | 77 | 1, | 89 | n/a* | Not |
Clegg et al 5 | 3–18 | 1000 | 326 | Amoxicillin | 326 | 14–21 | 80 | 15 | 90.8 |
Lennon et al 6 | 5–12 | 1500 | 177 | Penicillin | 176 | 3–6, | 87.3 | 5 | Not |
Pichichero et al 7 | 6 | 775 | 290 | Penicillin | 289 | 3–5, | 65.3 | n/a | 86 |
*Data on serotype acquisitions were presented in total for
all follow-up periods.
†7-day course.
‡Serotyping was not done at the first visit after treatment
completion.
BID indicates twice-daily; TID, thrice-daily; QID, 4 times daily.
Table 1. Summary of Randomized Controlled Trials of Once-daily
Amoxicillin
Study | Ages | Amoxicillin | Number | Comparison | Number | Return | Percent | Acquisition | Clinical |
Shvartzman et al 3 | 3 | 50 | 75 | Penicillin | 82 | 1–2, | 100 | n/a | No |
Feder et al 4 | 3–18 | 750 | 84 | Penicillin | 77 | 1, | 89 | n/a* | Not |
Clegg et al 5 | 3–18 | 1000 | 326 | Amoxicillin | 326 | 14–21 | 80 | 15 | 90.8 |
Lennon et al 6 | 5–12 | 1500 | 177 | Penicillin | 176 | 3–6, | 87.3 | 5 | Not |
Pichichero et al 7 | 6 | 775 | 290 | Penicillin | 289 | 3–5, | 65.3 | n/a | 86 |
*Data on serotype acquisitions were presented in total for
all follow-up periods.
†7-day course.
‡Serotyping was not done at the first visit after treatment
completion.
BID indicates twice-daily; TID, thrice-daily; QID, 4 times daily.
Bacteriologic eradication of GABHS is not a pragmatic
endpoint from the perspective of the physician in office practice and the
child's parent. Follow-up throat cultures on each patient with GABHS
pharyngitis at a scheduled posttreatment office visit is not realistic.
Instead, effectiveness of treatment of "strep throat" is determined
by the frequency of recurrence of symptomatic pharyngitis necessitating a
return visit for diagnosis and treatment. Whether subsequent streptococcal
pharyngitis is from failure to eradicate the serotype causing the first episode
or from acquisition of a new serotype is of little practical interest to
parents. The frequency with which streptococcal pharyngitis is diagnosed in the
weeks after completion of once-daily therapy for an initial episode has not
been examined in clinical practice.
The current study was conducted in a private pediatric
office setting where antibiotic choice and dosing were at the discretion of the
treating pediatrician. The frequency of streptococcal pharyngitis in patients
treated for an index episode with once-daily amoxicillin, twice-daily
amoxicillin or cephalexin was compared during the 4-month period after
diagnosis of the index episode. The pragmatic endpoint of recurrence of
symptomatic streptococcal pharyngitis was the same for the 3 antibiotic
regimens.
Methods
Setting
A retrospective chart review was conducted using the patient
records at a private, general pediatric practice serving Charlottesville, VA,
and a 5-county area. The central office of this practice is open for scheduled
appointments 365 days per year until 10 P.M. each evening; 2 satellite offices
in this practice are closed in the evenings and on weekends. Satellite patients
are seen at the central office for urgent visits when the satellites are closed
or overbooked. The central and satellite offices use identical testing methods.
This study was approved by the University of Virginia Health Sciences Center
Institutional Review Board.
Collection of Specimens
Clinical scoring of patients was not done. Physicians in the
practice discourage testing asymptomatic patients, and patients are not seen
only for streptococcal testing. Instead, each patient is seen at a scheduled
office visit and evaluated by a physician before any testing. If the examining
physician judges the patient to have symptoms and signs consistent with
streptococcal pharyngitis, the physician personally collects the pharyngeal
specimen using 2 swabs, both of which are processed by a medical technologist
in the office's moderate complexity laboratory. A streptococcal rapid antigen
detection (RAD) test is done on 1 swab; when the RAD test is negative, the
second swab is inoculated on a sheep blood agar plate, which is incubated for
48 hours. [8] In our community, back-up throat cultures are done
routinely.
Identification of an Index Episode
Index episodes of GABHS pharyngitis in patients 2 years of
age and older were identified during August through May in 2 different year
spans: 2003 to 2004 and 2007 to 2008. Only the records of the central office
laboratory were reviewed to identify index patients; each patient's first
occurrence of a positive RAD test or back-up throat culture was designated the
index episode of streptococcal pharyngitis for that patient. Each patient's
chart was reviewed to record any subsequent streptococcal pharyngitis episodes
that were diagnosed at either the central or satellite offices in the ensuing 4
months. If a patient had episodes of streptococcal pharyngitis during both
study years, the patient was considered to have had 2 index episodes.
Definitions
Streptococcal pharyngitis was diagnosed in a child with
symptoms (eg, sore throat, fever, absence of cold symptoms) and a positive RAD
test or back-up throat culture. Episodes of symptomatic streptococcal
pharyngitis in the 4 months after treatment of the index episode were recorded.
Streptococcal strains were not serotyped.
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