Journal of Antimicrobial Chemotherapy (2000) 45, Topic T1, 2330

JAC

Comparison of short-course (5 day) cefuroxime axetil with a standard

10 day oral penicillin V regimen in the treatment of tonsillopharyngitis
Dieter Adama*, Horst Scholzb and Manfred Helmerkingc
a

Department of Antimicrobial Therapy, Dr v. Haunersches Childrens Hospital, University of Munich,

Munich; bInstitute for Infectiology, Microbiology and Hygienics, Municipal Hospital Buch, Berlin;
c
Algora Clinical Research, Munich, Germany
Oral penicillin V given three times daily in doses of 50,000100,000 IU daily has been the
standard treatment for tonsillopharyngitis for the last few decades. These regimens, initially
recommended by the American Heart Association, were extrapolated from iv dosing with longacting forms of penicillin which had been shown to prevent post-streptococcal sequelae. More
recently, several antibiotics, including cefuroxime axetil, have been shown to be at least as
effective as penicillin G in eradicating group A -haemolytic streptococci (GABHS) but their
influence on post-streptococcal sequelae has never been assessed in a large-scale trial. The
German Society for Pediatric Infectious Diseases (DGPI) undertook a large study of cultureproven tonsillopharyngitis involving several agents and included a 1 year follow-up to establish the effect on sequelae. In one arm of this study, cefuroxime 250 mg bid was compared with
50,000 IU penicillin V given in three divided doses. Cefuroxime axetil was more effective than
oral penicillin V in eradicating GABHS at the assessment 24 days post-treatment (441/490
(90%) patients versus 1196/1422 (84%) patients; P
0.001). Clinically, the two agents were
equivalent in efficacy, and carriage rates were similar (11.1% and 13.8%, respectively) in
patients receiving cefuroxime axetil and penicillin V, 78 weeks post-treatment. One case of
glomerular nephritis occurred in a patient given penicillin V. There were no post-streptococcal
sequelae confirmed for patients treated with cefuroxime axetil. The findings confirm the previously reported efficacy of short-course (45 day) treatments with cefuroxime axetil and indicate
that short-course treatment is comparable to the standard oral penicillin V regimen in preventing post-streptococcal sequelae.

initial data on prevention of rheumatic heart disease came

principally from studies in adults in the US armed forces
which were considered not necessarily comparable to the
civilian condition. In 1981 Schwarz et al. re-evaluated duration of treatment in a study which compared patients with
proven GABHS infection treated for 7 or 10 days with
penicillin V in tid regimens.6 They concluded that the 10
day regimen was more effective than a 7 day regimen in
eradicating GABHS but also concluded that persistence
of S. pyogenes even after adequate therapy may be
common (Figure 1). In this study, compliance was carefully assessed by diary cards, return of unused medication
and urinary assay as a marker of penicillin dosage. Penicillinuria was present in 6681% of patients throughout the
study. Six years later, Gerber et al.7 revisited the question of

Introduction
The efficacy of penicillin in the treatment of group A
streptococcal disease was first documented early in the
1940s. It was noted by the pioneer workers that streptococci returned if penicillin treatment was terminated early.
Goerner et al. also showed in 1947 that the carrier state
could be eliminated from most patients if penicillin was
given for 10 days.1
In the early 1950s, Wannamaker, Denny and others provided proof of the preventative effect of long-acting injections of penicillin against rheumatic fever following group
A -haemolytic streptococci (GABHS) infection.24 By
1953 the American Heart Association recommended treatment of GABHS with oral penicillin for 10 days.5 The

*Infectious Diseases Unit, Kinderklinik der Universitt, Lindwurmstrasse 4, 80337 Mnchen, Germany.
Tel: 49-89-5160-3122; Fax: 49-89-5160-5388.

23
2000 The British Society for Antimicrobial Chemotherapy

D. Adam et al.
duration of therapy for penicillin V using 5 and 10 day
treatments. They confirmed the need for 10 days of treatment and that 5 days of therapy was less effective.
By 1994, a broader range of antibiotics was being used
for treatment of tonsillopharyngitis and shorter therapeutic courses (45 days of treatment) were being compared
with the standard tid 10 day regimen for penicillin V. In
most of these studies, GABHS eradication rates were
80% but no information on prevention of rheumatic
fever was available. In six of the studies in which 45 days
of treatment with an oral cephalosporin (967 patients)
was compared with 10 days of treatment with penicillin V
(1022 patients) the shorter treatments were equivalent
or superior in bacteriological eradication and clinical
response.813 In contrast, in the two studies where 5 or 7
days of penicillin V treatment was compared with 10 day
penicillin V treatment, the shorter courses resulted in
significantly greater bacteriological failure rates.6,7 These
findings support the current recommendations for a full
10 day course of oral penicillin V therapy.
When the current study was planned in 1995 it was felt
that the incidence of post-streptococcal sequelae was still
decreasing but there was general concern that shorter
treatment courses might lead to an increased incidence of
post-streptococcal sequelae such as rheumatic fever or
glomerulonephritis. This concern was heightened by
clusters of rheumatic fever which occurred in the USA and
elsewhere in the late 1980s.1416 The German Society for
Pediatric Infectious Diseases was also aware that no studies
since the 1950s had attempted to monitor the incidence of
post-streptococcal sequelae, including sequelae following
the reference treatment10 day therapy tid with oral penicillin V.
Accordingly, the German Society for Pediatric Infectious Diseases undertook a study to address the question of
eradication rates of GABHS using a number of antibiotics
which had potential for use in 5 day therapy regimens.
Each antibiotic was compared with the standard tid 10 day
penicillin V treatment. The number of patients recruited
to the full study was sufficient to detect a difference in
incidence of post-streptococcal sequelae in the 5 day and
10 day treatments.17 The study was designed to include
a 1 year follow-up period to capture any late sequelae
6 months or 1 year after the GABHS infection. Specific
data are presented here for one arm of the study in which
cefuroxime axetil 250 mg bid was compared with the reference regimen, penicillin V 50,000 IU per day given in three
divided doses.

in Germany between December 1995 and May 1998.

Microbiological investigations were done by two central
laboratories. The Institute for Medical Microbiology,
Friedrich Schiller University Hospital, Jena, was responsible for all serotyping of GABHS. The study protocol
was approved by the Local Ethics Committee, and signed
patient consent was obtained in accordance with the
Declaration of Helsinki and with national guidelines.
Patients eligible for inclusion were aged 118 years, with
an established diagnosis of group A streptococcal tonsillopharyngitis. Evidence of acute bacterial infection was
characterized by fever 38C (oral or rectal) and at least
one of the following symptoms: exudate of the pharynx or
tonsils; erythema and swelling of the pharynx or tonsils;
sore throat, especially on swallowing; and a positive rapid
screening test for GABHS confirmed by throat culture.
Further inclusion criteria were patient/parent (or legal
guardian) information and informed consent.

Exclusion criteria
Patients were excluded from the study if they met any of
the following criteria: missing informed consent; known
allergy to study antibiotics ( -lactams, e.g. penicillins,
cephalosporins, carbacephems or macrolides); antimicrobial therapy within 48 h immediately before study entry or
in the preceding 2 weeks for long-acting antibacterials;
patients previously included in the study (e.g. patients with
recurrent disease during follow-up in this study); intercurrent infections or additional disorders likely to interfere
with the clinical course of the disease in this study; pregnancy or lactation; evidence of significant hepatic and/or
renal impairment; malabsorption disorders or other gastrointestinal disease that could affect absorption of the oral
study drug; rheumatic diseases or glomerulonephritis in
the medical history of the patient or persons living in the
same household; haematological disease, immunological
or neoplastic disease or immunosuppressive therapy. If the
screening test was not confirmed by the bacteriological
culture in the reference laboratory, the patient was also
excluded.

Treatment and examination

Patients were screened and baseline physical examination
and assessment of clinical symptoms and screening test for
GABHS (confirmed by throat culture) were performed.
Dose administration began on the same day. Patients were
randomized to receive either a 5 day treatment with cefuroxime axetil 250 mg bid or 20 mg/kg/day (maximum
500 mg) or a 10 day treatment with penicillin V 50,000
IU/kg bodyweight daily in three doses.
Safety and efficacy were evaluated on days 79 (24 days
after the end of treatment in the 5 day treatment groups),

Materials and methods

Study design and inclusion criteria
This phase IV, randomized, open-label, comparative,
multicentre study was performed at 137 paediatric centres
24

Short-course cefuroxime in tonsillopharyngitis

days 1214 (79 days after treatment in the 5 day group and
24 days after the end of treatment in the 10 day treatment
group) and days 1719 (79 days after the end of treatment
in the 10 day treatment group)

improvement, reduction in the severity and/or number

of signs and symptoms; failure, marginal resolution, persistence or worsening of symptoms, discontinuation of
therapy owing to poor efficacy. For final clinical outcome
the categories responder (cure and improvement) and
non-responder (failure) were used.

Follow-up
Patients were examined 78 weeks after the end of treatment (follow-up) for culture and post-streptococcal sequelae, after 6 months for streptococcal sequelae and again
after 12 months for streptococcal sequelae.

Microbiological assessment
Microbiological response was assessed 24 days after the
end of treatment and at follow-up after 78 weeks. Bacteriological response was defined as follows: eradication,
absence of GABHS in the culture 24 days post-treatment;
persistence, presence of GABHS in the post-treatment
evaluation; relapse, GABHS eliminated during therapy
but present at a later visit.
Asymptomatic carriers of group A streptococci were
identified 78 weeks post-treatment and the frequency of
clinical relapse and new infections was determined from
GABHS serotyping.

Efficacy assessment
The primary efficacy outcomes in this study were clinical
and microbiological response at the end of treatment (final
assessment 79 days post-treatment). Further evaluation
criteria were: the incidence of rheumatic fever and
glomerulonephritis with late follow-up after 6 and 12
months; identification of asymptomatic A-streptococcal
carriers 78 weeks after the end of treatment; the frequency
of clinical relapse and new infections defined after GABHS
serotyping; and the frequency of adverse events.

Rheumatic fever and glomerulonephritis

A diagnosis of rheumatic fever was recorded if at least
two of the primary symptoms (carditis, polyarthritis,
chorea, erythema marginatum and subcutaneous nodules)
or one primary and two secondary symptoms (fever,
arthralgia, increased erythrocyte sedimentation rate (ESR)
and C reactive protein, leucocytosis, PR elongation in the
ECG) were present. The signs and symptoms for
glomerulonephritis were pain in the kidney region, oedema,
hypertension, central nervous system symptoms, haematuria, proteinuria and the paediatricians assessment if
glomerulonephritis was confirmed based on additional
diagnostics.

Evaluation of symptoms
Patients were monitored by the investigator at the end-oftreatment and follow-up visits. A patient was considered a
treatment failure for subsequent visits if concomitant
antimicrobials were given. Assessments included clinical
efficacy (cure, improvement, failure) and microbiological
data (eradication, persistence or relapse). A physical
examination was done at the pretreatment visit and clinical
symptoms were recorded before treatment and after the
end of treatment (24 days and 79 days post-treatment).

Bacteriological testing

Patient population, sample size and statistical

methods

Tonsil swabs were taken from each patient before randomization for rapid screening for GABHS confirmed by
throat culture, swabs were also taken 24 days post-treatment and at follow-up 78 weeks post-treatment. Swabs
were sent by mail, in agar storage and transport medium,
to the two central laboratories. Susceptibility testing
(agar disc diffusion) was performed according to NCCLS
methodology.18

The principal analytical objectives were to assess equivalence of the 5 day treatment groups with the 10 day
penicillin V group with respect to the primary efficacy endpoints. The sample size was calculated to establish equivalence in efficacy for tonsillopharyngitis treatment between
the 5 day treatment groups and the 10 day penicillin V
group. Sample sizes were calculated as follows (based on a
2
test): in the 5 day therapy group, 600 patients were
randomized of whom 530 were evaluable. This assumes
13% of patients would be unevaluable. In the 10 day
therapy group 1800 patients were randomized of whom
1590 were evaluable.

Clinical assessment
Clinical response for the primary efficacy analysis 24 days
after the end of treatment (final assessment 79 days posttreatment) was assessed using the following criteria: cure,
complete resolution of signs and symptoms that established
the acute infection according to the inclusion criteria;

Bacteriological efficacy. Comparing 10 days of penicillin V

(1590 patients) with cefuroxime axetil (530), an elimination
25

D. Adam et al.

Figure 1. Patients included in the study.

rate after therapy of 88%4.4% would be equivalent

( 2.5% one-sided; , 20%);

Results
This prospective, randomized, multicentre study was
conducted by the German Society for Pediatric Infectious
Diseases during the period from December 1995 to May
1998. One hundred and thirty-seven centres, located
throughout Germany, took part in the study. Children and
adolescents aged 118 years with acute tonsillopharyngitis,
a positive culture for GABHS and no history of rheumatic
fever or glomerulonephritis in their household were
recruited to the study on the basis of a positive rapid
GABHS test which was subsequently confirmed by culture
(Table).

Clinical efficacy. Comparing 10 days of treatment penicillin

V (1590 patients) and cefuroxime axetil (530) cure/
improvement at end of treatment of 94%3.4% would be
equivalent ( 2.5% one-sided; , 20%).

Safety
All patients who received at least one dose of the study
medication were included in the safety analysis. Any adverse
event during the study was recorded and the relationship to
therapy and severity was assessed by the investigator. An
adverse event was classified as serious if it was fatal or life
threatening, permanently disabling, required or prolonged
hospitalization or was a congenital anomaly, cancer or
overdose. A treatment-related adverse event was one
which was judged by the investigator to be possibly or probably related to a study drug, or if the study drug relationship was indicated as unknown. The severity was rated as
mild, moderate or severe.

Incidence of rheumatic fever and glomerulonephritis

In the sector of the study that compared cefuroxime axetil
250 mg bid with the standard oral penicillin V regimen,
there were no cases of glomerular nephritis in the cefuroxime arm of the study and only one case at the 67 week visit
in a patient who had received penicillin V. This patient had
26

Short-course cefuroxime in tonsillopharyngitis

Table. Demographic data of evaluable patients

moderately severe infection with a further 15% of infections described as severe. Erythema of the pharynx or
tonsils and oral or rectal temperature 38C was noted for
99% of all patients included in the study. Exudate of
pharynx or tonsils was reported in about two-thirds of
cases. Approximately 17% of patients reported contact
with others with similar symptoms; 6% mentioned contact
with relatives, while 35% of patients reported infections in
contacts at school or kindergarten.

Cefuroxime axetil Penicillin V

(5 day)
(10 day)
Number evaluable
Age, years (%)
2
25
611
11
not reported
mean (range)
Males/females, %
Mean weight, kg (range)

501

1474

1 (0.2)
237 (47.3)
242 (48.3)
21 (4.2)
0
6.2 (116)
49.8/50.2
24.3 (1069.3)

11 (0.7)
725 (49.2)
691 (46.9)
46 (3.1)
1
6.0 (117)
49.3/50.7
24.3 (9.280)

Eradication of GABHS
GABHS was eradicated at the first follow-up visit 24 days
after the end of treatment in 90.0% (441/490) patients
receiving cefuroxime axetil and 84.1% (1196/1422) patients
given penicillin V. This difference was statistically significant, indicating superiority of the cefuroxime axetil treatment (P 0.001 using a two-sided 2 test. The one-sided
equivalence test as per protocol, which was not designed to
show superiority, showed bacteriological equivalence of
the two regimens (Figure 2).
All of the isolates collected during the study were fully
susceptible to penicillin and to cefuroxime. The incidence
of macrolide resistance was approximately 4.6% with a
further 6.8% showing intermediate susceptibility to this
antibiotic class. There was some regional variation in
susceptibility to macrolides in the range 75.694.2%.

apparently responded satisfactorily both clinically and

bacteriologically in the period immediately post-treatment
for tonsillopharyngitis. There were no cases of rheumatic
fever in either treatment arm. One patient treated with
cefuroxime axetil had a recurrence of an infection that had
been treated with antibiotics 5 months before the study
began, involving a post-infection vasculitis. This was
judged not to be rheumatic fever. Again, this patient had
responded both bacteriologically and clinically in the 29
day period following treatment for tonsillopharyngitis. The
risk of glomerulonephritis or rheumatic fever is a negligible
factor in antimicrobial strategies against acute GABHS
tonsillopharyngitis.

Recurrence of tonsillopharyngitis
A high proportion of patients recruited in both arms of the
study had a previous history of tonsillopharyngitis: 37.9%
(190/501) patients treated with cefuroxime axetil and
39.2% (578/1474) patients given penicillin V. During the
1 year follow-up period, 21% (105/501) of patients given
cefuroxime axetil and 24.4% (360/1474) of the penicillintreated patients had one or more occurrences of tonsillopharyngitis. Two patients in each arm of the study had four
or more episodes of tonsillopharyngitis but almost 80%

Cefuroxime 250 mg bid for 5 days versus penicillin V

for 10 days
In this report, the clinical and bacteriological results of one
section of the study are reported in detail. This was the
comparison between cefuroxime axetil given 250 mg bid
for 5 days compared with 50,000 IU/day penicillin V tid for
10 days. Details of the patients recruited and follow-up
through the study are shown in Figure 1. Inevitably in such
a long study, some patients were lost to follow-up but
overall almost 70% remained in the study throughout.
Of the 2364 patients recruited to the two arms of the
study on the basis of a positive rapid GABHS test, 2100
(88.8%) were confirmed as culture-positive. Culture of
GABHS was used as the inclusion criterion for evaluable
patients in the study, because the primary objective was to
assess the incidence of late sequelae following cultureproven GABHS infection.

Figure 2. Eradication of GABHS 24 days after the end of treatment with cefuroxime axetil 250 mg bid (CAE) or oral penicillin
V 50,000 IU/day in three divided doses (Pen V). Stippling
indicates negative culture and hatching indicates positive culture.

Patient demographics
Approximately 70% of all patients in the cefuroxime axetil
and penicillin V arms of the study were judged to have
27

D. Adam et al.
had only one further tonsillopharyngitis infection in the
12 months after treatment. Of those who reported a recurrence, 43.8% (46/105) of patients in the cefuroxime axetil
group and 48.6% (175/360) of patients given penicillin V
had a history of recurrent tonsillopharyngitis on recruitment to the study.

Clinical efficacy
Cefuroxime axetil bid for 5 days was comparable to penicillin V tid for 10 days in clinical efficacy assessed 24 days
after the end of treatment (Figure 4). The two treatments
were statistically equivalent using the one-sided equivalence test as per protocol. In a two-sided test, cefuroxime
axetil was shown to be superior to penicillin V clinically
(P 0.001). This finding was similar to results obtained by
Gehanno & Chiche19 and Aujard et al.20 in studies comparing 4 day cefuroxime axetil regimens with standard 10
day penicillin V treatment. In these studies, eradication
rates for GABHS were similar to those obtained in the
current study. Symptom alleviation was significantly
more rapid following cefuroxime axetil treatment for the
following symptoms: reduction in fever, sore throat and
dysphagia.19

Asymptomatic carriage
Seven to eight weeks after the end of treatment, patients
were re-examined and culture or rapid testing was used to
detect persisting GABHS, possibly indicating asymptomatic carriage of Streptococcus pyogenes. Figure 3 shows
the results for 1750 patients who were available for followup. No significant difference was seen in the carriage rates
for the two regimens, 11.1% for patients receiving cefuroxime axetil versus 13.8% for penicillin. The findings confirm
those from many other studies which show asymptomatic
carriage rates of 638% after treatment.19

Safety and tolerance

Both penicillin V and cefuroxime axetil were well tolerated: 1543 patients received penicillin V of whom eight
(0.5%) reported skin reactions and five (0.32%) had diarrhoea, while of the 525 patients included in the safety
evaluation for cefuroxime axetil, six (1.14%) reported diarrhoea and only two (0.38%) reported skin reactions. Four
patients in the penicillin group and five in the cefuroxime
axetil group reported nausea or vomiting. There were no
severe adverse events attributable to either agent.

Discussion
Figure 3. Asymptomatic carriage of GABHS 78 weeks after the
end of treatment with either cefuroxime axetil 250 mg bid (CAE)
or oral penicillin V 50,000 IU/day in three divided doses (Pen V).
Stippling indicates negative culture and hatching indicates
positive culture.

Cefuroxime axetil has been evaluated in a number of

studies in comparison with penicillin V in conventional 10
day regimens2123 and in several 45 day treatment studies
in both adults and children.19,20 Eradication rates in all
studies have been consistently high, similar to the 90%
eradication rate obtained in this study. A direct comparison of 5 day and 10 day treatment with cefuroxime axetil
also showed bacteriological and clinical equivalence
between the two regimens.23,24 It therefore appears that a
short-course treatment offers the same prospect of GABHS
eradication, prevention and clinical efficacy as 10 day penicillin treatment or longer courses of cefuroxime axetil.
The issue of GABHS carriage remains a confounding
factor in studies of tonsillopharyngitis. Clearly, whatever
treatment is used, there is a possibility of carriage which
may not always be detected if numbers of organisms are
very low or if S. pyogenes is able to survive intracellularly
which may be the case.25 Use of a 5 day course of cefuroxime axetil was at least equivalent to a 10 day course of
penicillin V clinically and possibly may be more effective in
terms of eradicating GABHS, particularly in recurrent
infection.26
The efficacy of -lactam antibiotics depends on main-

97.2*

Figure 4. The clinical efficacy 24 days post-treatment of 250 mg

bid cefuroxime axetil (CAE) compared with 50,000 IU/day oral
penicillin V in three divided doses (Pen V) in the treatment of
GABHS culture-proven tonsillopharyngitis. Stippling indicates
negative culture and hatching indicates positive culture.

28

Short-course cefuroxime in tonsillopharyngitis

tenance of serum concentrations of antibiotic in excess of
the MIC at the site of infection for periods of 2040% of the
dosage interval to achieve a bacteriostatic effect and for
longer to achieve a bactericidal effect.27 Penicillin V,
although exquisitely active against S. pyogenes (MIC 0.06
mg/L), is not absorbed particularly well and peak serum
levels reach only 1.0 mg/L after administration of 240 mg
penicillin V orally, 28 falling to below the detection limit in
8 h. Craig28 proposed that the important pharmacodynamic
criteria for penicillins are that serum concentrations need
to be above the MIC for 3040% of the dosage interval. Penicillin levels in tonsillar tissue may therefore be
borderline in terms of antibacterial cover, particularly if
-lactamase-producing commensal strains are also present.2932 Cefuroxime levels following cefuroxime axetil
250 mg dosage remain above the MIC (0.03 mg/L) for
100% of the dosing interval of 12 h.33
It is tempting when discussing tonsillopharyngitis to
focus solely on the S. pyogenespenicillin interaction but
penicillin interacts with the entire nasopharyngeal flora
and affects other components of that flora.31 The very
low levels of penicillin which are likely to be achieved in
tonsillar tissue may be sub-clinically active against other
important commensals or potential pathogens such as
Streptococcus pneumoniae. These low levels may have
played a role in development of penicillin resistance over
time in S. pneumoniae. There may be benefit in considering
use of a more diverse range of agents in tonsillopharyngitis
which clearly happens in practice. Use of shorter treatment
courses is likely to enhance compliance and reduce overall
antibiotic usage, both of which are likely to be beneficial.
From the study we have evidence that late complications
of tonsillopharyngitis remain very rare in Germany indicating negligible circulation of specific rheumatogenic strains.
A 5 day antibiotic treatment regimen with cefuroxime
axetil did not result in more post-streptococcal sequelae
when compared with standard penicillin V treatment.
Cefuroxime axetil 250 mg bid for 5 days was superior to
oral penicillin V in eradicating GABHS and in terms of
overall clinical efficacy. The results show that a 5 day treatment with cefuroxime axetil is effective in treatment of
culture-proven tonsillopharyngitis.

rheumatic fever (by treatment of the preceding streptococal infection

with various amounts of depot penicillin). American Journal of
Medicine 10, 67395.
4. Wannamaker, L. W., Denny, F. W., Perry, W. D., Rammelkamp,
C. H., Eckhardt, G. C., Houser, H. B. et al. (1953). The effect of penicillin prophylaxis on streptococcal disease rates and the carrier
state. New England Journal of Medicine 249, 17.
5. Breese, B. B., Bellows, M. T., Fischel, E. E., Kuttner, A., Maesell,
B. F., Rammelkamp, H. J. et al. (1953). Prevention of rheumatic
fever: statements of American Heart Association Council on rheumatic fever and congenital heart disease. Journal of the American
Medical Association 151, 1413.
6. Schwartz, R. H., Wientzen, R. L., Pedreira, F., Feroli, E. J., Mella,
G. W. & Guandolo, V. L. (1981). Penicillin V for group A streptococcal pharyngotonsillitisa randomized trial of seven vs ten days
therapy. Journal of the American Medical Association 246, 17905.
7. Gerber, M. A., Randolph, M. F., Chanatry, J., Wright, L. L., De
Meo, K. & Kaplan, E. L. (1987). Five vs ten days of penicillin V
therapy for streptococcal pharyngitis. American Journal of Diseases
of Childhood 141, 2247.
8. Peyramond, D., Tigaud, S., Bremard-Oury, C. & Scheimberg, A.
(1994). Multicenter comparative trial of cefixime and phenoxymethylpenicillin for group A -hemolytic streptococcal tonsillitis.
Current Therapeutic Research 55, Suppl. A, 1421.
9. Aujard, Y., Boucot, I., Brahimi, N., Chiche, D. & Bingen, E.
(1995). Comparative efficacy and safety of four-day cefuroxime
axetil and ten-day penicillin treatment of group A -hemolytic
streptococcal pharyngitis in children. Pediatric Infectious Disease
Journal 14, 295300.
10. Tack, K. J., Henry, D. C., Gooch, W. M., Brink, D. N., Keyserling, C. H. & the Cefdinir Pharyngitis Study Group. (1998). Five day
cefdinir treatment for streptococcal pharyngitis. Antimicrobial
Agents and Chemotherapy 43, 10735.
11. Pichichero, M. E., McLinn, S. E., Gooch, W. M., Rodriguez, W.,
Goldfarb, J., Reidenberg, B. E. & members of the Ceftibuten Pharyngitis International Study Group. (1993). Ceftibuten vs penicillin V in
group A -hemolytic streptococcal pharyngitis. Pediatric Infectious
Disease Journal 12, S6470.
12. Portier, H., Chavanet, P., Gouyon, J. B. & Guetat, F. (1990).
Five day treatment of pharyngotonsillitis with cefpodoxime proxetil.
Journal of Antimicrobial Chemotherapy 26, Suppl. E, 7985.
13. Adam, D., Scholz, H. & the Pharyngitis Study Group. (1996).
Five days of erythromycin estolate versus ten days of penicillin V in
the treatment of group A streptococcal tonsillopharyngitis in children.
European Journal of Clinical Microbiology and Infectious Diseases
15, 7127.

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