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Abstract. Acute Otitis Media (AOM) is the most frequent respiratory tract infection of infancy and childhood that is treated
with antimicrobial agents. The most common causative pathogens include Streptococcus pneumoniae, Hemophilus influenzae
and Moxarella catarrhalis, and therefore antibacterial management should target against these isolates. Cefaclor, a congener
of cephalexin monohydrate, is a semisynthetic cephalosporin antibiotic. It is an orally active cephalosporin which has
demonstrated activity against a wide range of organisms in vitro. Present study is designed as a multicentric prospective trial
to study and compare the efficacy and safety of cefaclor versus amoxicillin+clav in children with acute otitis media. One hundred
and sixty seven patients were evaluated for efficacy endpoints in the cefaclor arm comprised of 104 males and 63 females with
a mean age of 5.742.80 years and 185 patients in the amoxy-clav group comprised of 118 males and 67 females with a mean
age of 4.932.92 years. Both cefaclor and amoxy-clav caused a significant improvement in all the signs and symptoms after
a 10-day treatment period. However, between-the-group comparisons showed that the reduction in most of the symptoms was
significantly more in cefaclor arm as compared to amoxicillin-clav arm. The clinical success (clinical cure + improvement) at
the end of therapy was significantly more in cefaclor arm: 98% with cefaclor versus 85% with amoxicillin+clav, p<0.05 (Table
3). Failure cases were prescribed other antibiotics according to the culture sensitivity reports, as rescue medication. Bacterial
eradication rates were largely consistent with clinical responses. Bacteriological eradication was seen in 95% of patients in
cefaclor group and 78% of patients in amoxicillin+clav group. In conclusion, cefaclor is a well tolerated and effective antibacterial
option for acute otitis media in children and it is superior to the combination of amoxicillin+clav in efficacy and tolerability in acute
AOM. Moreover, its expanded spectrum of activity, ability to achieve adequate concentrations in tissues, suitability for twicedaily dosing, and proven tolerability suggest that it is a good alternative to agents traditionally used in acute otitis media.
[Indian J Pediatr 2005; 72 (3) : 233-238] E-mail: ashok.moharana@ranbaxy.com
Mukesh Aggarwal et al
Salmonella spp. and Haemophilus influenzae are more
susceptible to clinically achievable concentrations of
cefaclor than cephalexin. Cefaclor has been demonstrated
to be effective against beta-lactamase-producing H.
influenzae resistant to ampicillin. Efficacy of cefaclor has
been demonstrated in urinary tract, upper and lower
respiratory tract, and skin and soft tissue infections in
adults and children as well as in pediatric otitis media.
Adverse reactions, mostly gastrointestinal, are generally
mild and occur in few patients. 6 Combination of
amoxycillin and clavulanate (a beta-lactamase inhibitor)
have been used in various respiratory tract infections
including Otitis media.
On this background present study is designed as a
multicentric prospective trial to study and compare the
efficacy and safety of cefaclor versus amoxicillin+clav in
children with acute otitis media.
MATERIALS AND METHODS
Study Design
Under a prospective, open, comparative and multicentric
study patients were treated as out-door patients or
hospitalized during the treatment period and this was at
the discretion of the investigator. All participating
patients or their legal guardians provided consent prior to
enrollment. And the Institutional Review Board or
Independent Ethics Committee of each site approved the
study protocol.
Patients
In the study only the patients aged 6 months to 12 years
with clinical symptoms and tympanic membrane signs of
AOM, otoscopic evidence of acute inflammation
(dullness, cloudiness, erythema or bulging, perforation)
plus tympanometric-confirmed middle ear effusion in at
least 1 ear were enrolled. Both fresh and recurrent cases
(without complications like mastoiditis) were included.
Eligible patients were not on any other antibiotic therapy
when enrolled in the study.
The study excluded the patients with appearance and
history more suggestive of chronic otitis media with
effusion, ventilation tube, perforated tympanic
membrane, and chronic suppurative otitis media; serious
chronic disease (for example, cystic fibrosis, valvular heart
disease); previous complications (septic complications,
hearing impairment); children with complicated AOM
(eg. mastoiditis), facial abnormalities, that would
confound evaluation of the therapeutic response; known
severe renal disease; patients hypersensitive/contraindicated to study drug.
Study procedure
Either cefaclor 20 mg/kg 40-mg/kg per day in 3
divided doses for 10 days (cefaclor arm) or Amoxycillin
+ clavulanate 45mg/kg every 12hrly or 40mg/kg every
8hrly for 10 days (amoxycillin arm) was administered to
234
Cefaclor Group
Amoxy+ Clav Group
167
185
Male
Female
Male
Female
104
63
118
67
5.742.80
4.93 2.92
Mukesh Aggarwal et al
TABLE 2. Comparison of Change in Symptom Scores in the Two Groups
Cefaclor Group
% Change
p-value*
% Change
p-value*
-97.87%
-93.33%
-88.28%
-92.77%
-85.6%
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
-74.61%a
-77.77%b
-66.14% a
-80.68% b
-67.97%a
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
-93.33%
-90.98%
-92.94%
p<0.001
p<0.001
p<0.001
-75.84%a
-78.33% b
-83.78%c
p<0.001
p<0.001
p<0.001
Systemic Infection
Presence of Cough, Vomiting & Diarrhea
Fever
-85.39%
-90%
p<0.001
p<0.001
-73.4% b
-76.54%a
p<0.001
p<0.001
Symptoms
Earache/Otalgia
Irritability
Lethargy
Infection
Exudation
Cefaclor group
3
1
1
1
20*
9*
9*
3
Amoxy+Clav. Group
96.6%
2.4%
1%
80%
5%
15%
95%
5%
0%
78%
16%
6%
Diarrhea
Nausea
Vomiting
Bloating
-40.00%
% Change
Fever
Erythema
Bulging (Otoscopy)
Exudation
Infection
Irritability
Earache / Otalgia
-20.00%
Lethargy
0.00%
-60.00%
Cefaclor
Amoxy+Clav
-80.00%
-100.00%
-120.00%
Symptoms
50%
50%
40%
% physicians
35%
33%
30%
25%
20%
18%
20%
11%
10%
6%
2%
0%
0%
Excellent
Very good
Good
Fair
Poor
Grading of efficacy
50.00%
39.90%
37.70%
33.80%
32.30%
34.60%
29.20%
31.50%
25.00%
23.80%
21.50%
25.00%
16.50%
20.20%
19.80%
11.80%
10.20%
13.50%
11.90%
3.80%
5.80%
0.80%
0.80%
0.00%
Excellent
Ass essment Of Overall
Tolerability
Cefaclor Group
Good
Poor
Amoxy+Clav Group
0.00%
Excellent
Assessment Of Overall
Tolerability
Very Good
Cefaclor Group
Good
Fair
Poor
Amoxy+Clav Group
237
Mukesh Aggarwal et al
catarrhalis. Cefaclor eradicated pathogens in 95% of the
patients compared to 78% in amoxy-clav group. The
clinical effectiveness of cefaclor may be related to its
excellent in vitro activity against a wide range of
organisms. Its spectrum of activity is wider than that of
cephalexin.
Cefaclor was better tolerated by our study population
compared to amoxicillin+clav. The side effects observed
in both groups were of mild intensity and no patient
withdrew from the study due to adverse events.
CONCLUSION
For acute otitis media in children, cefaclor is a well
tolerated and effective antibacterial option. It is superior
to the combination of amoxicillin+clav in efficacy and
tolerability in acute AOM. Moreover, its expanded
spectrum of activity, ability to achieve adequate
concentrations in tissues, suitability for twice-daily
dosing, and proven tolerability suggest that it is a good
alternative to agents traditionally used in acute otitis
media.
238
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