YAJOT-01823; No of Pages 4

American Journal of Otolaryngology–Head and Neck

Medicine and Surgery xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

American Journal of Otolaryngology–Head and Neck

Medicine and Surgery
jour nal homepage: www.elsevier. com/ locate/ amj oto

Management of recurrent tonsillitis in

children☆,☆☆,★
Diaa El Din El Hennawi a, Ahmed Geneid b, Salah Zaher c,
Mohamed Rifaat Ahmed a,⁎
a
Department of Otorhinolaryngology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
b
Department of Ear, Nose and Throat Disorders and Phoniatrics-Head and Neck Surgery, Helsinki, Finland
c
Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt

a r t i c l e in fo abstract

Article history: Objective: To compare azithromycin (AZT) and benzathine penicillin (BP) in the treatment of recurrent tonsillitis
Received 16 January 2017 in children.
Available online xxxx Methods: The study comprised of 350 children with recurrent streptococcal tonsillitis, 284 of whom completed
the study and 162 children received conventional surgical treatment. The rest of the children, 122, were divided
Keywords: randomly into two equal main groups. Group A children received a single intramuscular BP (600,000 IU for
Chronic tonsillitis children ≤ 27 kg and 1,200,000 IU for ≥27 kg) every two weeks for six months. Group B children received single
Benzathine penicillin
oral AZT (250 mg for children ≤ 25 kg and 500 mg for ≥25 kg) once weekly for six months.
Azithromycin
Results: Both groups showed marked significant reduction in recurrent tonsillitis that is comparable to results of
tonsillectomy. There were no statistical differences between group A and B regarding the recurrence of infections
and drug safety after six-month follow-up. Group B showed better compliance.
Conclusion: AZT proved to be good alternative to BP in the management of recurrent tonsillitis with results similar
to those obtained after tonsillectomy.
© 2017 Elsevier Inc. All rights reserved.

non-surgical treatment. The children who had surgery had three epi-
1. Introduction
sodes of sore throat on average compared to 3.6 episodes experienced
by the other children. One of the three episodes is the episode of pain
In the present state of medical literature, tonsils are considered as as-
caused by surgery. It seems that children with the more severe and
sets to the immunological system and they are removed or partially ex-
cised only when there is a medical necessity caused by their size, ☆ Conflicts of interests: None.

recurrent bacterial infections or tumor [1]. Recurrent tonsillitis has ☆☆ Financial and material support: None.

been defined as four or more confirmed infection episodes per year ★ Level of evidence: 3b.
⁎ Corresponding author.
with streptococci A-infection diagnosed in one of them [2]. Prevalence
E-mail addresses: ahmed.geneid@hus.fi (A. Geneid), Pedotomanager@entnet.org (S.
is from 11.0 to 12.3% with marked family burden and risk of man serious Zaher), m_rifaat@yahoo.com (M.R. Ahmed).
complication especially in developing countries [3]. Recurrent tonsillitis
is usually treated by either tonsillectomy or conservative medical treat-
ment when tonsillectomy criteria are not fulfilled or there is a contrain-
dication for tonsillectomy [4]. A review by Burton et al. in 2014 found
that children with recurrent acute tonsillitis have a small benefit from
adeno-/tonsillectomy [5]. The procedure will avoid only 0.6 episodes
of any type of sore throat in the first year after surgery compared to

Please cite this article as: El Hennawi DED, et al, Management of recurrent tonsillitis in children, American Journal of Otolaryngology–Head and
Neck Medicine and Surgery (2017), http://dx.doi.org/10.1016/j.amjoto.2017.03.001
 treat- ment measures than tonsillectomy is tempting especially
frequent tonsillitis are the ones who benefit from surgery in comparison
when the child has recurrent tonsillitis that falls little short of the
to the less severely affected children [5].
criteria for tonsillectomy [9].
Sirimanna et al. reported the usefulness of long-acting penicillin
The aim of the present study was to compare the efficacy of AZT and
in significant reduction of recurrent tonsillitis [6]. However, long
benzathine penicillin (BP)—both administered for six months in the
acting penicillin has multiple drawbacks such as hypersensitivity
management of recurrent tonsillitis—to conventional tonsillectomy.
reactions, anaphylaxis and severe local pain [7].
Azithromycin (AZT) is an Azalide, a subclass of macrolide
antibiotic which is widely distributed throughout the body, achieving 2. Materials and Thethods
higher con- centrations in tonsillar tissues with adequate therapeutic
levels during medication with minimal side effects [8]. 2.1. Design, setting and participants
Recurrent tonsillitis always present on a continuum rather than
a dichotic representation. Children seem to suffer from different A randomized controlled clinical trial study created in the otolaryn-
grades of recurrent tonsillitis. The possibility of having other gology department - Suez Canal University Hospital – Ismailia – Egypt

http://dx.doi.org/10.1016/j.amjoto.2017.03.001
0196-0709/© 2017 Elsevier Inc. All rights reserved.

Please cite this article as: El Hennawi DED, et al, Management of recurrent tonsillitis in children, American Journal of Otolaryngology–Head and
Neck Medicine and Surgery (2017), http://dx.doi.org/10.1016/j.amjoto.2017.03.001
2 D.E.D. El Hennawi et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery xxx (2017) xxx–xxx

and Alexandria University Children Hospital – Egypt from March 2005 2) ASOT and ESR levels were taken before the start of the study and
to May 2012. The study protocol was approved by the local faculty six months after it. 3) Symptoms' severity was assessed using the vi-
ethics committee and written informed consent was obtained from all sual analog scale for symptoms severity as described above. 4) The
patients relevant. safety of drugs were assessed by the detection of adverse effects,
which were classified as minor and accepted adverse effects (GIT
2.2. Patient eligibility and enrolment upset, dizziness) or major, necessitating the exclusion of the child
from the study (anaphylaxis, jaundice, a prolonged QT interval).
A total of 350 children with recurrent tonsillitis were included in the 5) Satisfaction assessment was made by asking direct questions to
study. Recurrent tonsillitis was defined as four or more episodes of ton- the patients, their parents, and the medical staff. Patients' satisfac-
sillitis per year (for children of either gender) with two of the episodes tion was classified as a) the patient is comfortable and accepts the
confirmed to be group A streptococcal infection. The enrolled children regimen; b) the patient is not comfortable but accepts and continues
were aged from five to 12. The 350 children enrolled fulfilled the inclu- the regimen; c) the patient is not comfortable and does not accept
sion criteria and did not have any significant co-morbidities. Significant the regimen and discontinues it (whereupon they were excluded
morbidities included rheumatic heart disease, rheumatic fever, marked from the study).
anesthetic risk, sensitivity to AZT or BP, the intake of drugs that might
interfere with AZT or BP, hepatic impairment, or long QT syndrome (a 2.5. Statistical analysis
prolonged QT interval of N 45 ms in ECG).
Data collected were processed using SPSS version 18 (SPSS Inc.,
2.3. Study plan Chicago, IL, USA). Quantitative data were expressed as means ± SD
while qualitative data were expressed as numbers and percentages.
Children were divided randomly and equally into two groups. The Student's t-test was used to compare the significance of difference
Randomization was performed prior to study commencement as fol- for the quantitative variables that followed a normal distribution.
lows: Opaque envelopes were numbered sequentially from 1 to 350.
A computer-generated table of random numbers was used for group 2.6. Ethical considerations
assignment; if the last digit of the random number was from 0 to 4,
assignment was to group 1 (received conventional tonsillectomy), The study protocol was approved by the faculty's ethical committee
and if the last digit was from 5 to 9, assignment was to group 2 (re- and written informed consent was obtained from the parents of the
ceived BP or AZT). Group 2 was randomized again in similar manner children enrolled in the study after an explanation of the study's design,
in group A and group B. The assignments were then placed into the and the benefits and risks associated with the treatment regimen.
opaque envelopes and the envelopes sealed. As eligible participants
were entered into the trial, these envelopes were opened in sequen- 3. Results
tial order to give each patient his or her random group assignment.
The envelopes were opened by the ORL specialist after patient con- 3.1. ASOT and ESR levels
sent and just prior to the treatment method; Group A received med-
ical treatment with BP and group B received AZT. Subgroup A The tonsillectomy group had a mean ESR level of 70.3 ± 13.1 ml/h
children received single intramuscular. during the last episode of tonsillitis before tonsillectomy. Six months
BP (600,000 IU for children ≤ 27 kg and 1,200,000 IU for children after the operation this level dropped to 8.7 ± 1.9 ml/h (P = 0.005).
≥ 27 kg) every two weeks for six months [10)]. Subgroup B children re- The mean ASOT for the tonsillectomy group was 436 IU/ml before sur-
ceived single oral AZT (250 mg for children ≤ 25 kg and 500 mg for gery and declined to 115 IU/ml after six months with statistically signif-
children ≥ 25 kg) once weekly for six months [11]. Children in the AZT icant improvement (P = 0.006).
subgroup were subjected to ECG, calculation of the QT interval and The mean ASOT before treatment in group A was 476 IU/ml and
liver enzymes before starting the treatment. 491 IU/ml in group B. After six-months follow-up a statistically signifi-
Out of the 350 children, only 284 managed to complete the study. cant reduction in the ASOT in both groups occurred as group A became
The children had a mean age of 7.4 ± 1.6 years. 126 IU/ml while group B became 141 IU/ml (Table 1). There was no sta-
350 children randomly divided into tonsillectomy and medical treat- tistically significant difference between the two groups.
ment group with 175 in each. Drop out of 13 children in the tonsillecto- The mean ESR level also showed a statistically significant reduction
my group and 53 children in the conservative medical treatment one. in its values from before treatment to the end of the six-months
Tonsillectomy group was 162 children. Conservative medical treatment follow-up (Table 1). However, there was no statistically significant dif-
group was 122 children. 61 children in group A that received BP while ference between group A and group B in terms of the improvement
61 children in group B received AZT. More patients dropped out of the
conservative medical treatment group. It is postulated that this may Table 1
be due to some of them seeking conventional tonsillectomy in the pri- The mean degree of the ASOT in both groups after treatment.
vate health care sector or due to poor compliance with the conservative Group Before treatment After treatment
medical treatment.
Mean SD Mean SD
ASOT A 476 18 126⁎ 14
2.4. Objective and outcome measurement assessment
B 491 16 141⁎ 13
ESR A 68.7 9.7 9.4⁎ 3.2
Data collected included complete medical histories with an empha- B 71.2 12.3 10.2⁎ 2.8
sis on recurrent tonsillitis. Symptoms' severity was assessed using a vi- Dysphagia A 8.1 1.5 5.3 1.8
sual analog scale for symptoms' severity (with 0 indicating no B 8.7 1.1 4.9 1.4
Fever A 9.3 1.1 4.3 0.9
symptoms and 10 indicating the most severe symptoms). In addition,
B 8.9 2.3 4.1 1.2
a complete ENT and general physical examination were carried out be- Arthralgia A 7.2 0.9 3.9 1.8
fore the start of the study. CBC, ASOT, and ESR data were collected from B 7.9 1.4 3.6 0.9
all children at the beginning of the study and after six months. Body ache A 8.7 1.4 3.7 1.1
The outcomes were assessed through the following measures: B 8.1 0.8 3.2 1.7

1) Medical history and clinical evaluation by the end of the trial. ⁎ P = 0.005, n = 61 for group A and B.

Please cite this article as: El Hennawi DED, et al, Management of recurrent tonsillitis in children, American Journal of Otolaryngology–Head and
Neck Medicine and Surgery (2017), http://dx.doi.org/10.1016/j.amjoto.2017.03.001
 D.E.D. El Hennawi et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery xxx (2017) xxx–xxx
degree of the ESR. Flow chart of the study, pre- and post-treatment as-
sessments are shown in Fig. 1.
3.2. Severity of symptoms
The means of the score for the intensity of the symptoms of tonsilli-
tis before treatment among group A and group B are summarized in
Table 1. No statistically significant differences were found between
the groups.
Six months after starting the treatment, the means of the scores for
the intensity of the symptoms of tonsillitis in group A group B were cal-
culated. There was a marked statistically significant improvement in
both groups from before treatment to the end of the six-months
follow-up (P = 0.03). However, there was no statically significant dif-
ference between the two groups (Table 1).
In terms of the adverse effects encountered in the AZT group, three
patients had minor adverse reactions e.g. nausea, vomiting, and abdom-
inal cramps with diarrhea. ECG was carried out for all the patients as a
baseline and all showed a normal sinus rhythm. In regular ECG follow-
ups, 50 patients (82%) of the AZT group showed QT prolongation and
11 patients (18%) showed shortening. The mean of QT rose significantly
from 41.6 + 1.7 ms before treatment to 43.8 + 2.9 ms (P = 0.007) after.
There was no statistically significant difference between genders re-
garding changes in QT interval. Also, liver enzymes did not show a sig-
nificant rise from before treatment to after treatment, nor was there a
difference between group A and group B. No serious adverse reactions
were reported in either group. No patients developed rheumatic activity
during the study and follow-up period.
Being comfortable with the treatment was assessed in both groups
on a single parameter dichotic scale of comfortable vs. uncomfortable.
Group A had a lower level of 36 (59.1%) comfortable patients, versus
25 who reported discomfort (40.9%). However, the uncomfortable
group continued the treatment till the end of the year. Satisfaction
among group B patients was significantly higher among 58 patients
(95.61%). Only three reported to be uncomfortable (4.9%) but they
Fig. 1. Pre- and post-treatment assessments of the children in different groups.
Please cite this article as: El Hennawi DED, et al, Management of recurrent tonsillitis in children, American Journal of Otolaryngology–Head and
Neck Medicine and Surgery (2017), http://dx.doi.org/10.1016/j.amjoto.2017.03.001
3
also continued the treatment. It is evident that the AZT patients were
more comfortable with the drug than the BP patients, with a statically
significant difference between both groups regarding satisfaction.
N 90% of both groups were taking the drug regularly. There was no
statically significant difference between the groups regarding
compliance.
4. Discussion
Recurrent tonsillitis is considered to be one of the common reasons
for primary care visits to physicians. Recurrent tonsillitis among chil-
dren has a considerable impact on the quality of life, not only due to
the effects on children but also the burden on the parents when their
child is suffering. Tonsillectomy remains a common procedure, especial-
ly in western countries [12]. However, a number of immunological stud-
ies on the effects of tonsillectomy point to the importance of a
conservative attitude from an immunological point of view towards
adenotonsillectomy [13].
The aim of this study has been to look into alternatives to tonsillec-
tomy, especially when the tonsillectomy criteria are not fully fulfilled,
resources are not available or the parents opt for medical treatment.
The two alternatives were BP and AZT.
Although intramuscular BP is still the drug of choice for the treat-
ment and prevention of recurrent acute rheumatic fever, there are
international data reporting an incidence rate of allergic reactions
of about 3.2% with 0.2% reporting an anaphylaxic reaction due to
monthly BP injections. Unfortunately, there were three deaths docu-
mented in Zimbabwe resulting from BP produced by three different
manufacturers [14].
Previous studies have shown that in comparison to oral penicillin,
intramuscular penicillin has been more effective with rheumatic fever
recurrence and streptococcal throat infections [15].
Azithromycin which is Azalide antibiotic, has better compliance and
is much easier to take than intramuscular BP.
4 D.E.D. El Hennawi et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery xxx (2017) xxx–xxx
The present study showed that there is no significant difference be-
tween the group A and B in regard to recurrent tonsillitis after six-
months follow-up. The ASOT and ESR levels were also reduced to nor-
mal and there was no statistically significant difference between the
groups.
AZT has been proven to be very effective in treating group A strepto-
coccal tonsillopharyngitis when it presents in the acute form [16].
The main concern for using AZT in long treatment has been its pos-
sible association with increased cardiovascular risk and may lead to
cardiovascular-related death in high-risk patients. A meta-analysis of
randomized controlled trials by Almalki and Guo, reported AZT safety
in patients studied in 12 trials included in the meta-analysis from
1990 to 2013 [17]. Nevertheless, its safety and effectiveness is compara-
ble to Penicillin V [18].
Long-term prophylaxis against streptococcal infections using AZT
was attempted by Snider et al. in the prophylaxis of children with
PANDAS (pediatric autoimmune neuropsychiatric disorders associated
with streptococcal infections). A 12-month trial administration of AZT
and penicillin was done and showed effectiveness in decreasing strepto-
coccal infections [19].
The results of this study show the efficacy of AZT in preventing re-
current tonsillitis and reducing ASOT and ESR levels to a range compa-
rable to those of BP and tonsillectomy. The children were more
comfortable with an AZT regimen rather than a BP regimen. Minor ad-
verse reactions were reported with AZT.
The message of this study is that treatment options other than ton-
sillectomy exist for treating recurrent tonsillitis. AZT, which is one of
the treatments, proved to be safe and effective in our study. Further
studies should look into the possibility of having shorter regimens of
AZT when treating recurrent tonsillitis.
5. Conclusion
The treatment of recurrent tonsillitis is equally effective by treat-
ment with AZT or BP in comparison to tonsillectomy. AZT was as effec-
tive as BP and tonsillectomy against recurrent tonsillitis after six months
of treatment.
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