EFFICACY OF SINGLE DOSE AZITHROMYCIN ON PEDIATRIC STREPTOCOCCAL TONSILLOPHARYNGITIS.
PROCEEDING
The 3rd International Conference on
Pharmacy And Advanced Pharmaceutical Sciences
June 18
19, 2013 Yogyakarta, Indonesia
Book 2:
Clinical Pharmacy
Editors:
Abdul Rohman
Zullies Ikawati
Tri Murti Andayani
Riris Istighfari Jenie
Marlyn Dian Laksitorini
EFFICACY OF SINGLE DOSE AZITHROMYCIN ON PEDIATRIC
STREPTOCOCCAL TONSILLOPHARYNGITIS
Rasmaya Niruri1*, Rini Noviyani1, A.A. Agustia Sinta Dewi1,
FS.Suherman2, I Putu Tri Yasa3
1
Dept. of Pharmacy, Faculty of Math and Science,Udayana University,
Jimbaran, Bali.
2
3
Siloam Hospital, Kuta, Badung, Bali.
Pediatric Depatment, Sanjiwani Hospital, Gianyar, Bali.
*Corresponding author: Rasmaya Niruri
Email : rasmaya@yahoo.com
Abstract
Azithromycin,
which
is
indicated
for
streptococcal
tonsillopharyngitis, can be given in single dose regimen, but the dose size
is not established for pediatric tonsillopharyngitis. Therefore the drug dose
for otitis media is used, which is 30,0 mg/kg weight. The aim of this study
is to provide data of efficacy azithromycin 30,0 mg/kg weight in
tonsillopharyngitis pediatric patients.
Methods: This prospective-observational study on Children (2-12
years old) with tonsillopharyngitis who were showing positive test result
on Rapid Step Test (RST), was conducted in Clinic T, Gianyar, Bali from
March
November 2012. Patients pharynx and tonsils on day 1 and day
4 were monitored to determine the efficacy of single dose azithromycin.
Adverse effects of azithromycin were monitored in three consecutive days.
Results: Eighteen from 124 children with tonsillopharyngitis were fit
to sample-criteria. In first visit (day 1), all 18 patients took single dose
azithromycin (on the range of 29,6-30,0 mg/kg weight). On day 4, all
patients showed no swell and inflammation on the pharynx and tonsils.
Two of 18 patients suffered from nausea.
Conclusion: Single dose azithromycin (29,6-30,0 mg/kg weight)
was effective on 18 streptococcal tonsillopharyngitis pediatric patients and
it had minimal adverse effect.
Keywords: azithromicin, single dose, pediatric, tonsillopharingitis
INTRODUCTION
Upper respiratory tract infection (URTI) is the most common
infection in inpatient facilities in Indonesia. One of common URTI is
tonsillopharingitis (Kementerian Kesehatan Republik Indonesia, 2009).
Bacterial tonsillopharingitis is the most frequently caused by Group A betahemolitic Steptococci (GAS) (Pichichero,M.E., 1995). It was reported by
Topan A (2008) that azithromycin was the fourth largest antibiotic used for
URTI in Denpasar. However, in our preliminary study in early 2012, no
pediatric patients with steptococal tonsillopharingitis were found in
Denpasar. Different finding was in Clinic T, Gianyar, where this study was
conducted.
Azithromycin is indicated for streptococcal tonsillopharyngitis. This
antibiotic can be given in single dose regimen. However the dose is not
established for pediatric with tonsillopharyngitis, so the drug dose for otitis
media is used, which is 30,0 mg/kg weight (Charles, F.L., 2005). To
provide data of the efficacy azithromycin 30,0 mg/kg weight in
tonsillopharyngitis, this study was conducted by monitoring the condition of
pharynx and tonsils.
MATERIAL AND METHODS
This prospective-observational study was approved by Medical
School Udayana Univerisity - Sanglah Hospital ethics committee and
conducted in Clinic T, Gianyar, Bali from March
November 2012.
Inclusion criteria were age of 2-12 years, suffering from tonsillopharyngitis
(:swelling and inflammation of the pharynx and the tonsils), showing
positive test result on Rapid Step Test (RST), receiving only azithromycin
as antibiotic during the treatment, and not taking other antibiotics at least 7
days in advance. Patients who had allergy to azithromycin were excluded.
The patients pharynx and tonsils were monitored twice, which were in the
first visit (on day 1) and after three days of the treatment with single dose
azithromycin (on day 4: around 72 hours after the patients taking
azithromycin).
Azithromycin was effective when the pharynx and the
tonsils were not swollen and inflamed. Daily monitoring were conducted in
monitoring adverse effects through asking the patients directly (on day 1
and 4) and indirectly by using telephone communication (on day 2 dan 3 :
around 24 and 48 hours after receiving azithromycin syrup).
RESULT AND DISCUSSION
From 124 tonsillopharyngitis patients during this study between
March-October 2012, only 18 patients were fit to inclusion and exclusion
criteria. It was difficult to get patients with steptococcal tonsillopharyngitis.
It might be due to low prevalence in Indonesia. It was reported that a
prevalence of 6.1 % in Jakarta (Gitawati, R., Isnawati, A., 2009), 10,2% in
Yogyakarta (Jurianti, A., 2008), and 7,9% in Denpasar (Malino,I.Y., 2008),
but there was no data available in Gianyar.
Patients Characteristic
The majority (17 of 18) of tonsillopharyngitis patients was on 2-6
years old (Table 1). It might be because of the difference serum
concentration of Immunoglobulin A (IgA) in infant and children in different
ages. IgA is a major host defense to microorganism in URTI (MacKinnon
L.T, 1993). IgA development in infant and children may play important role
against the infection. At the age of 1 year, IgA serum concentration is 20%
of normal adult value.
It attains adult value by age of 4-6 years
(Weemaes, C., 2003).
Table 1. Patients characteristic (N=18)
Patients characteristic
N
Age (years old)
2
6
3
2
4
5
5
3
6
1
7
-
8
-
9
-
10
1
11
-
12
-
Weight (kg)
11,0-15,0 9
15,1-20,0 4
20,1-25,0 3
25,0-30,0 2
Efficacy of Single Dose Azithromycin
Since no data available of dose size for single dose azithromycin,
on pediatric tonsillopharingitis, therefore the drug dose in otitis media was
used, which was 30,0 mg/kg weight, maximum: 1500 mg (Charles F.L,
2005). Patients took azithromycin syrup (200mg/5ml) on the first visits
(after diagnosing with tonsillopharingitis and showing positive result on
RST). Oral syringe was used as an administration device to quantify the
desired dose of azithromycin syrup, because it provides the most accurate
measurement (Koda-Kimble, M.A, et.all., 2009). Patients received
azithromycin syrup in the dose range of 29,6
2) due to limitation number
30,0 mg/kg weight (Table
scale on the syringe, which showed desired
results (:the pharynx and the tonsils were not swollen and inflamed) in all
18 patients after three days of azithomicyn therapy.
There were 2 patients received azithromycin 29,8 mg/kg weight and
2 children got 29,6 mg/kg weight, which were less than literature dose
(30,0 mg/kg weight). However the patient showed a good response
because it might be still on therapeutic dose range in eradicating GAS.
Azithromycin is time-dependent killing antibiotic with prolong persistent
effects. Pharmacokinetic and pharmacodynamics
parameter, 24-hours
AUC (Area Under Curve) / MIC (Minimum inhibitory concentration),
performs persistent effects of azithromycin in bacteria killing. It was
reported that azithromicyn in 24-hours AUC/MIC ratio of 25 35 showed
success in the treatment of pneumococcal infection, which was caused by
S.pneumoniae (Craig, W.A, 2012). However the data for GAS in pediatric
streptococcal tonsillopharingitis is not established. Therefore, further study
to know effective 24-hours AUC/MIC ratio of azithromycin in steptococcal
tonsillopharingitis need to be conducted in order to determine the
appropriate dose.
Tabel 2. Azithomicin Dose Size in Single Dose Administration and
Patients Response
Id.
Age
Weight
(y.o)
(kg)
Dose
On Patient
mg
ml
Patient
Response
Literature
mg/
mg
ml
mg/
kg
kg
weight
weight
A
2
11,0
330
8,25
30,0
330
8,25
30,0
Good
B
4
16,5
490 12,25
29,8
495 12,37
30,0
Good
C
4
16,0
480 12,00
30,0
480 12,00
30,0
Good
D
4
13,0
390
9,75
30,0
390
9,75
30,0
Good
E
10
28,5
850 21,25
29,8
855 21,37
30,0
Good
F
2
12,0
360
9,00
30,0
360
9,00
30,0
Good
G
6
26,0
780 19,50
30,0
780 19,50
30,0
Good
H
5
24,0
720 18,00
30,0
720 18,00
30,0
Good
I
3
13,0
390
9,75
30,0
390
9,75
30,0
Good
J
5
23,0
690 17,25
30,0
690 17,25
30,0
Good
K
4
19,0
570 14,25
30,0
570 14,25
30,0
Good
L
2
11,8
350
8,75
29,6
354
8,85
30,0
Good
M
4
17,0
510 12,75
30,0
510 12,75
30,0
Good
N
5
25,0
750 18,75
30,0
750 18,75
30,0
Good
O
2
12,0
360
9,00
30,0
360
9,00
30,0
Good
P
2
13,0
390
9,75
30,0
390
9,75
30,0
Good
Q
3
13,5
400 10,00
29,6
400 10,00
30,0
Good
R
2
12,0
360
30,0
360
30,0
Good
9,00
9,00
Adverse effects
Commonly adverse effects of single dose azithromicin are
gastrointestinal complaints (17,2%) and diarrhea (11-12%) (Amrol, D.,
2007). On this study, only 2 patients suffered from nausea during this
monitoring time period. Gastrointestinal problems can be minimized by
taking azithromycin on an empty stomach (One hour before or 2 hours
after a meal) (Amrol , D., 2007)
CONCLUSION
Single dose azithromycin (29,6-30,0 mg/kg weight) was effective to
cure 18 streptococcal tonsillopharyngitis pediatric patients and it had
minimal adverse effect.
ACKNOWLEDGMENT
dr. Imanuel Y. Malino and Dr. dr. A.A. Oka Lely. Sp.A. for sharing the
knowledge and information.
REFERENCES
Amrol, D. 2007. Single-Dose Azithromycin Microsphere Formulation: A
Novel Delivery System For Antibiotics. Int J Nanomedicine. March:
2(1): 9 12.
Charles, F.L. 2005. Charles F.L, 2005. Drug Information Handbook, 11th
Edition. Lexi Company
Craig W.A. 2012. Does the Does matter. CID oxford journal. CID 2001:33
(Suppl 3).
Gitawati R, Isnawati A. 2009. Pola sensitivitas kuman dari isolat hasil usap
tenggorok penderita tonsilofaringitis akut terhadap beberapa
antimikroba betalaktam di Puskesmas Jakarta Pusat. Cermin
Dunia Kedokteran. 144:20-3.
Jurianti A. 2008. Faringitis Grup-A
-Hemolitik Streptokokus pada anak-
anak: klinis dan kultur usap tenggorok. Thesis. Universitas Gajah
Mada .Yogyakarta.
Kementerian Kesehatan Republik Indonesia. 2009. Profil Kesehatan
Indonesia Tahun 2009. Departemen Kesehatam RI. Jakarta.
Koda-Kimble, M.A, et.all. 2009. Applied Therapeutics: The Clinical Use Of
Drugs, 9th Edition. P.93.p.3, P.96.p7
Mackinnon, L.T., et.all. 1993. Decreased salivary immunoglobulin A
secretion rate after intense interval exercise in elite kayakers. Eur
J Appl Physiol Occup Physiol. ;67(2):180-4.
Malino, I.Y., et.all. 2008. Diagnostic Test of McIsaac Criteria on Group-A
-Hemolitik Steptococcus Acute Pharingitis. Thesis. Universitas
Gajah Mada. Yogyakarta. Indonesia.
Pichichero,M.E., 1995. Group A Streptococcal Tonsillopharyngitis: CostEffective Diagnosis and Treatment. Annals of Emergency
Medicine Volume 25, Issue 3, March, Pages 390 403.
Topan, A. 2008. Profil Penggunaan dan Gambaran Biaya Antibiotika pada
Terapi ISPA. Skripsi. Universitas Udayana. Denpasar. Indonesia
Weemaes, C., et all., 2003. Development of Immunoglobulin A in Infacy
and Childhood. Scandinavian Journal of Immunology, Blackwell
Publishing Ltd., 58: 642-648.
The 3rd International Conference on
Pharmacy And Advanced Pharmaceutical Sciences
June 18
19, 2013 Yogyakarta, Indonesia
Book 2:
Clinical Pharmacy
Editors:
Abdul Rohman
Zullies Ikawati
Tri Murti Andayani
Riris Istighfari Jenie
Marlyn Dian Laksitorini
EFFICACY OF SINGLE DOSE AZITHROMYCIN ON PEDIATRIC
STREPTOCOCCAL TONSILLOPHARYNGITIS
Rasmaya Niruri1*, Rini Noviyani1, A.A. Agustia Sinta Dewi1,
FS.Suherman2, I Putu Tri Yasa3
1
Dept. of Pharmacy, Faculty of Math and Science,Udayana University,
Jimbaran, Bali.
2
3
Siloam Hospital, Kuta, Badung, Bali.
Pediatric Depatment, Sanjiwani Hospital, Gianyar, Bali.
*Corresponding author: Rasmaya Niruri
Email : rasmaya@yahoo.com
Abstract
Azithromycin,
which
is
indicated
for
streptococcal
tonsillopharyngitis, can be given in single dose regimen, but the dose size
is not established for pediatric tonsillopharyngitis. Therefore the drug dose
for otitis media is used, which is 30,0 mg/kg weight. The aim of this study
is to provide data of efficacy azithromycin 30,0 mg/kg weight in
tonsillopharyngitis pediatric patients.
Methods: This prospective-observational study on Children (2-12
years old) with tonsillopharyngitis who were showing positive test result
on Rapid Step Test (RST), was conducted in Clinic T, Gianyar, Bali from
March
November 2012. Patients pharynx and tonsils on day 1 and day
4 were monitored to determine the efficacy of single dose azithromycin.
Adverse effects of azithromycin were monitored in three consecutive days.
Results: Eighteen from 124 children with tonsillopharyngitis were fit
to sample-criteria. In first visit (day 1), all 18 patients took single dose
azithromycin (on the range of 29,6-30,0 mg/kg weight). On day 4, all
patients showed no swell and inflammation on the pharynx and tonsils.
Two of 18 patients suffered from nausea.
Conclusion: Single dose azithromycin (29,6-30,0 mg/kg weight)
was effective on 18 streptococcal tonsillopharyngitis pediatric patients and
it had minimal adverse effect.
Keywords: azithromicin, single dose, pediatric, tonsillopharingitis
INTRODUCTION
Upper respiratory tract infection (URTI) is the most common
infection in inpatient facilities in Indonesia. One of common URTI is
tonsillopharingitis (Kementerian Kesehatan Republik Indonesia, 2009).
Bacterial tonsillopharingitis is the most frequently caused by Group A betahemolitic Steptococci (GAS) (Pichichero,M.E., 1995). It was reported by
Topan A (2008) that azithromycin was the fourth largest antibiotic used for
URTI in Denpasar. However, in our preliminary study in early 2012, no
pediatric patients with steptococal tonsillopharingitis were found in
Denpasar. Different finding was in Clinic T, Gianyar, where this study was
conducted.
Azithromycin is indicated for streptococcal tonsillopharyngitis. This
antibiotic can be given in single dose regimen. However the dose is not
established for pediatric with tonsillopharyngitis, so the drug dose for otitis
media is used, which is 30,0 mg/kg weight (Charles, F.L., 2005). To
provide data of the efficacy azithromycin 30,0 mg/kg weight in
tonsillopharyngitis, this study was conducted by monitoring the condition of
pharynx and tonsils.
MATERIAL AND METHODS
This prospective-observational study was approved by Medical
School Udayana Univerisity - Sanglah Hospital ethics committee and
conducted in Clinic T, Gianyar, Bali from March
November 2012.
Inclusion criteria were age of 2-12 years, suffering from tonsillopharyngitis
(:swelling and inflammation of the pharynx and the tonsils), showing
positive test result on Rapid Step Test (RST), receiving only azithromycin
as antibiotic during the treatment, and not taking other antibiotics at least 7
days in advance. Patients who had allergy to azithromycin were excluded.
The patients pharynx and tonsils were monitored twice, which were in the
first visit (on day 1) and after three days of the treatment with single dose
azithromycin (on day 4: around 72 hours after the patients taking
azithromycin).
Azithromycin was effective when the pharynx and the
tonsils were not swollen and inflamed. Daily monitoring were conducted in
monitoring adverse effects through asking the patients directly (on day 1
and 4) and indirectly by using telephone communication (on day 2 dan 3 :
around 24 and 48 hours after receiving azithromycin syrup).
RESULT AND DISCUSSION
From 124 tonsillopharyngitis patients during this study between
March-October 2012, only 18 patients were fit to inclusion and exclusion
criteria. It was difficult to get patients with steptococcal tonsillopharyngitis.
It might be due to low prevalence in Indonesia. It was reported that a
prevalence of 6.1 % in Jakarta (Gitawati, R., Isnawati, A., 2009), 10,2% in
Yogyakarta (Jurianti, A., 2008), and 7,9% in Denpasar (Malino,I.Y., 2008),
but there was no data available in Gianyar.
Patients Characteristic
The majority (17 of 18) of tonsillopharyngitis patients was on 2-6
years old (Table 1). It might be because of the difference serum
concentration of Immunoglobulin A (IgA) in infant and children in different
ages. IgA is a major host defense to microorganism in URTI (MacKinnon
L.T, 1993). IgA development in infant and children may play important role
against the infection. At the age of 1 year, IgA serum concentration is 20%
of normal adult value.
It attains adult value by age of 4-6 years
(Weemaes, C., 2003).
Table 1. Patients characteristic (N=18)
Patients characteristic
N
Age (years old)
2
6
3
2
4
5
5
3
6
1
7
-
8
-
9
-
10
1
11
-
12
-
Weight (kg)
11,0-15,0 9
15,1-20,0 4
20,1-25,0 3
25,0-30,0 2
Efficacy of Single Dose Azithromycin
Since no data available of dose size for single dose azithromycin,
on pediatric tonsillopharingitis, therefore the drug dose in otitis media was
used, which was 30,0 mg/kg weight, maximum: 1500 mg (Charles F.L,
2005). Patients took azithromycin syrup (200mg/5ml) on the first visits
(after diagnosing with tonsillopharingitis and showing positive result on
RST). Oral syringe was used as an administration device to quantify the
desired dose of azithromycin syrup, because it provides the most accurate
measurement (Koda-Kimble, M.A, et.all., 2009). Patients received
azithromycin syrup in the dose range of 29,6
2) due to limitation number
30,0 mg/kg weight (Table
scale on the syringe, which showed desired
results (:the pharynx and the tonsils were not swollen and inflamed) in all
18 patients after three days of azithomicyn therapy.
There were 2 patients received azithromycin 29,8 mg/kg weight and
2 children got 29,6 mg/kg weight, which were less than literature dose
(30,0 mg/kg weight). However the patient showed a good response
because it might be still on therapeutic dose range in eradicating GAS.
Azithromycin is time-dependent killing antibiotic with prolong persistent
effects. Pharmacokinetic and pharmacodynamics
parameter, 24-hours
AUC (Area Under Curve) / MIC (Minimum inhibitory concentration),
performs persistent effects of azithromycin in bacteria killing. It was
reported that azithromicyn in 24-hours AUC/MIC ratio of 25 35 showed
success in the treatment of pneumococcal infection, which was caused by
S.pneumoniae (Craig, W.A, 2012). However the data for GAS in pediatric
streptococcal tonsillopharingitis is not established. Therefore, further study
to know effective 24-hours AUC/MIC ratio of azithromycin in steptococcal
tonsillopharingitis need to be conducted in order to determine the
appropriate dose.
Tabel 2. Azithomicin Dose Size in Single Dose Administration and
Patients Response
Id.
Age
Weight
(y.o)
(kg)
Dose
On Patient
mg
ml
Patient
Response
Literature
mg/
mg
ml
mg/
kg
kg
weight
weight
A
2
11,0
330
8,25
30,0
330
8,25
30,0
Good
B
4
16,5
490 12,25
29,8
495 12,37
30,0
Good
C
4
16,0
480 12,00
30,0
480 12,00
30,0
Good
D
4
13,0
390
9,75
30,0
390
9,75
30,0
Good
E
10
28,5
850 21,25
29,8
855 21,37
30,0
Good
F
2
12,0
360
9,00
30,0
360
9,00
30,0
Good
G
6
26,0
780 19,50
30,0
780 19,50
30,0
Good
H
5
24,0
720 18,00
30,0
720 18,00
30,0
Good
I
3
13,0
390
9,75
30,0
390
9,75
30,0
Good
J
5
23,0
690 17,25
30,0
690 17,25
30,0
Good
K
4
19,0
570 14,25
30,0
570 14,25
30,0
Good
L
2
11,8
350
8,75
29,6
354
8,85
30,0
Good
M
4
17,0
510 12,75
30,0
510 12,75
30,0
Good
N
5
25,0
750 18,75
30,0
750 18,75
30,0
Good
O
2
12,0
360
9,00
30,0
360
9,00
30,0
Good
P
2
13,0
390
9,75
30,0
390
9,75
30,0
Good
Q
3
13,5
400 10,00
29,6
400 10,00
30,0
Good
R
2
12,0
360
30,0
360
30,0
Good
9,00
9,00
Adverse effects
Commonly adverse effects of single dose azithromicin are
gastrointestinal complaints (17,2%) and diarrhea (11-12%) (Amrol, D.,
2007). On this study, only 2 patients suffered from nausea during this
monitoring time period. Gastrointestinal problems can be minimized by
taking azithromycin on an empty stomach (One hour before or 2 hours
after a meal) (Amrol , D., 2007)
CONCLUSION
Single dose azithromycin (29,6-30,0 mg/kg weight) was effective to
cure 18 streptococcal tonsillopharyngitis pediatric patients and it had
minimal adverse effect.
ACKNOWLEDGMENT
dr. Imanuel Y. Malino and Dr. dr. A.A. Oka Lely. Sp.A. for sharing the
knowledge and information.
REFERENCES
Amrol, D. 2007. Single-Dose Azithromycin Microsphere Formulation: A
Novel Delivery System For Antibiotics. Int J Nanomedicine. March:
2(1): 9 12.
Charles, F.L. 2005. Charles F.L, 2005. Drug Information Handbook, 11th
Edition. Lexi Company
Craig W.A. 2012. Does the Does matter. CID oxford journal. CID 2001:33
(Suppl 3).
Gitawati R, Isnawati A. 2009. Pola sensitivitas kuman dari isolat hasil usap
tenggorok penderita tonsilofaringitis akut terhadap beberapa
antimikroba betalaktam di Puskesmas Jakarta Pusat. Cermin
Dunia Kedokteran. 144:20-3.
Jurianti A. 2008. Faringitis Grup-A
-Hemolitik Streptokokus pada anak-
anak: klinis dan kultur usap tenggorok. Thesis. Universitas Gajah
Mada .Yogyakarta.
Kementerian Kesehatan Republik Indonesia. 2009. Profil Kesehatan
Indonesia Tahun 2009. Departemen Kesehatam RI. Jakarta.
Koda-Kimble, M.A, et.all. 2009. Applied Therapeutics: The Clinical Use Of
Drugs, 9th Edition. P.93.p.3, P.96.p7
Mackinnon, L.T., et.all. 1993. Decreased salivary immunoglobulin A
secretion rate after intense interval exercise in elite kayakers. Eur
J Appl Physiol Occup Physiol. ;67(2):180-4.
Malino, I.Y., et.all. 2008. Diagnostic Test of McIsaac Criteria on Group-A
-Hemolitik Steptococcus Acute Pharingitis. Thesis. Universitas
Gajah Mada. Yogyakarta. Indonesia.
Pichichero,M.E., 1995. Group A Streptococcal Tonsillopharyngitis: CostEffective Diagnosis and Treatment. Annals of Emergency
Medicine Volume 25, Issue 3, March, Pages 390 403.
Topan, A. 2008. Profil Penggunaan dan Gambaran Biaya Antibiotika pada
Terapi ISPA. Skripsi. Universitas Udayana. Denpasar. Indonesia
Weemaes, C., et all., 2003. Development of Immunoglobulin A in Infacy
and Childhood. Scandinavian Journal of Immunology, Blackwell
Publishing Ltd., 58: 642-648.