Indian Journal of Pediatrics, Volume 71June, 2004 517

Special Article
Correspondence and Reprint requests : Dr. A.K. Moharana, V-7,
Naveen Shahdara, Delhi-110032. Fax : 91-11-26429471
Acute lower respiratory tract infections in children are a
worldwide public health problem with an estimated 4
million potentially preventable deaths every year.
1
Until
recently, penicillin and related drugs were the treatment
of choice for empiric therapy of pediatric lower
respiratory tract infections. However, concerns over the
emergence of penicillin and macrolide resistant strains of
Streptococcus pneumoniae, and beta-lactamase-producing
strains of Haemophilus influenzae and Moraxella catarrhalis
have led physicians to turn increasingly towards
alternatives, such as third generation cephalosporins.
2
Third generation cephalosporins retain sufficient activity
to warrant use in selected pneumococcal infections, even
those caused by completely penicillin-resistant strains.
Cefpodoxime proxetil is an orally administered
prodrug which is absorbed and de-esterified by the
intestinal mucosa to release the third generation
cephalosporin, cefpodoxime. Cefpodoxime is highly
active against both Haemophilus influenzae and Moraxella
catarrhalis including -lactamase producing strains, with a
minimum inhibitory concentration for 90% of tested
strains (MIC
90
) 1mg/L. It has also excellent coverage
against Streptococcal spp, especially S. pneumoniae (both
penicillin sensitive and resistant strains).
3
Cefpodoxime
has a similar potency to that of cefixime against gram ve
rods, but with greater activity against gram +ve cocci; also
the spectrum of activity is greater than that of cefuroxime,
Comparative Evaluation of Cefpodoxime Versus Cefixime
in Children with Lower Respiratory Tract Infections
Jayati Sengupta, A.K. Mondal
1
, Piyush Jain
2
, P.D. Garg
3
, N.C. Mathur
4
and A.K. Moharana
5
Amri Hospitals, Kolkata,
1
District Hospital, Howrah, Kolkata,
2
Genesis Clinic, Delhi,
3
Holy Child Hospital, Delhi,
4
Aditya Hospital, Hyderabad and
5
Ranbaxy Laboratories Ltd, Delhi.
cefaclor (2
nd
generation cephems) and cephalexin (1
st
generation cephem) against these microorganisms.
Moreover, cefpodoxime is more active against H.
influenzae including -lactamase producing strains than
amoxicillin/clavulanic acid.
3
Cefpodoxime is stable towards the most commonly
found plasmid mediated -lactamases and its broad
spectrum of anti-bacterial activity encompassing both
gram negative and gram positive bacteria renders it a
possible option for empirical use in a wide range of com-
munity acquired infections in both adult and pediatric
patients. The extended plasma half life of cefpodoxime
(1.9 to 3.7 h) permits twice daily administration.
4
In
children aged 2 months to 18 years, the recommended
dose of 10 mg/kg/day of cefpodoxime suspension for 10
days for the treatment of respiratory and urinary tract
infections and as well as those of the skin and soft tissues
has demonstrated a good bacteriological and clinical
efficacy. Cefpodoxime is well tolerated by pediatric
patients, with mild gastro-intestinal disturbances that are
consistent with those reported for other oral
cephalosporins.
5
Cefixime is another oral third generation
cephalosporin, used in Respiratory Tract Infections in
pediatric population. However, cefixime has poor efficacy
against staphylococcus, and streptococci. Therefore, it
should be avoided if staphylococci or pneumococci can
not be ruled out.
6
The present study was designed to
assess the clinical cure and bacteriological eradication
rates and tolerability of cefpodoxime suspension and to
Abstract. Objective: The emergence of penicillin and macrolide resistant strains, responsible for Acute Lower Respiratory
Tract Infections in children has offered third generation cephalosporins the platform to perform. The aim of the present study
was to evaluate two third generation oral cephalosporins for their empirical use in community acquired lower respiratory tract
infections in pediatric patients. An assessment of the clinical cure and bacteriological eradication rates and an overall tolerability
was made. Methods : It was a prospective, open, comparative, multicentric study. 776 children (Mean age 10 years) with LRTIs
were included and randomly allotted to two groups respectively. A total of 396 children were given cefpodoxime susp 5 mg/
kg b.i.d. and 380 patients on cefixime 4 mg/kg b.i.d. for 10-14 days. Results : At the end of therapy, the clinical success with
cefpodoxime was 97% as against 86.8% with cefixime. Bacterial eradication was 93.4% with cefpodoxime and 82.9% with
cefixime. Conclusion : Cefpodoxime has been found to be a well-tolerated and superior alternative to cefixime synergistically
documenting the extended spectrum of activity. [Indian J Pediatr 2004; 71 (6) : 517-521]
E-mail : ashok.moharana@ranbaxy.com
Key words : Cefpodoxime; Cefixime; LRTIs
Jayati Sengupta et al
518 Indian Journal of Pediatrics, Volume 71June, 2004
compare it with another cefixime in children with Lower
Respiratory Tract Infections (LRTIs) like, Acute
Exacerbations of Chronic Bronchitis (AECB) and
Community Acquired Pneumonia (CAP).
MATERIALS AND METHODS
Study Design
It was a prospective, open, comparative multicentric
study. In addition, the Institutional Review Board or
Independent Ethics Committee of each site approved the
study protocol and the legal guardians of all participating
patients provided written informed consent prior to
enrollment.
Patients
Children (6 months to 12 years) of either sex with
diagnosis of Lower Respiratory Tract Infections (LRTIs),
which included patients with Community Acquired
Pneumonia, and Acute Exacerbations of Chronic
Bronchitis were included in the study.
The Lower Respiratory Tract Infection was
characterized by increased cough, sputum production
and dyspnoea. Sputum had to be purulent or had to
show a change in the character of sputum from the steady
state level (i.e., patient status before current episode of
Lower Respiratory Tract Infections). Fever could be
present. Patients with a history of hypersensitivity to
cefpodoxime, cefixime or any other member of
cephalosporin class of antimicrobial agents were excluded
from the study.
Study Procedure
Patients fulfilling the inclusion criteria received either
cefpodoxime suspension 5 mg/kg b.i.d or cefixime 4 mg/
kg b.i.d for 10-14 days without regard to meals. Patients
were evaluated on 1
st
day through the end of therapy (on
10
th
day).
Patients requiring antacids containing aluminium and
magnesium salts were administered 8 hours before or
after cefpodoxime or cefixime administration. If the
symptoms were not controlled or worsened, additional
medications could be given depending at the discretion of
the investigator and this rescue medication was recorded
in the Case Record Form.
Patients were considered to be compliant with the
study medication if at least 80% of study medications
were taken according to the prescribed regimen.
Otherwise patient was considered to be non-compliant.
Evaluation Visits
The physician examined the patient and recorded for
adherence to therapy, any adverse drug reactions and the
clinical response on the following days:
Visit 0: Day 0, study admission visit ; Visit 1: Day 5-7,
midtherapy visit ; Visit 2: Day 10-14, end of therapy.
Symptoms of LRTI and fever were assessed at each visit.
Patients were also monitored for any complications.
Efficacy Assessment
The main outcome measures were:
1. Bacteriological and clinical response of signs and
symptoms of respiratory tract infections determined at
end of therapy determined. 2. No. of cases in which
change of antibiotics was needed. 3. Physician Global
evaluation of patient condition (using a 5-point scale) ;
1=Excellent, 2=Very Good, 3 = Good, 4= Fair, 5 =Poor
Clinical Outcome was defined as follows:
Clinical cure (Defined as complete resolution of signs
and symptoms); Improved (If clinical signs & symptoms
diminished but did not completely resolve); Failure (if the
signs and symptoms worsened, persisted or reappeared).
Safety Assessment
Patients were closely monitored for clinical adverse
events. The severity of clinically adverse events was
categorized by the investigators as mild, moderate, or
severe. The investigators also classified the relationship of
adverse events to the study drugs as either certainly,
probably, or possibly drug related; not drug related; or
with an unknown relationship to the study drug. Global
assessment of overall tolerability was also recorded on a
5-point scale (1=excellent, 2 =very good, 3=good, 4=fair,
5=poor).
Statistical Analysis
Age is presented as mean SD. Symptom assessment was
done with actual patient numbers. Rest of the data is
presented as percentages. Comparison of signs and
symptoms of disease before and after therapy was done
by paired t-test. The limit of significance was set at p
value < 0.05.
RESULTS
Patient Characteristics
396 patients included in the cefpodoxime arm of the
study comprised 242 males and 154 females with a mean
age of 10.402.85 years and 380 patients in the cefixime
arm comprised 221 males and 159 females (Table 1). All
children had one or more pretreatment symptoms of
respiratory tract infection; the most frequent were cough,
increased, thickened, foul odour sputum, dyspnoea, and
crepitations or wheeze on auscultation. Many children
also had signs of systemic infection: fever, chills and chest
pain.
TABLE 1. Demographic Profile and Baseline Characteristics of
Patients Enrolled
Characteristic Cefpodoxime Group Cefixime Group
Total no. of patients 396 380
Male 242 221
Female 154 159
Age (years)* 10.402.85 10.852.86
*Values are mean SD.
Comparative Evaluation of Cefpodoxime Versus Cefixime
Indian Journal of Pediatrics, Volume 71June, 2004 519
Efficacy Parameter Assessment
Both cefpodoxime and cefixime caused a significant
improvement in all the signs and symptoms after a 10-14
day treatment period. However, between-the-group
comparisons showed that the reduction in these
symptoms was better with cefpodoxime arm compared to
cefixime group. The percentage decrease in signs and
symptoms at the end of therapy in the two treatment
groups is shown in Fig 1.
The clinical success (clinical cure + improvement) at
the end of therapy was significantly better with
cefpodoxime group: 97% with cefpodoxime versus 86.8%
with cefixime (Table 2). Bacteriological eradication
(eradication + presumed eradication) was seen in 93.4% of
patients in cefpodoxime group and 82.9% of patients in
cefixime group. In 7% of patients, clinical symptoms
worsened, and they were shifted to cefpodoxime arm in
their second visit, where they showed excellent response.
Global Assessment
94% physicians rated treatment with cefpodoxime as
excellent to good versus 81% with cefixime (Table 3). The
same pattern of response was observed in the patients
assessment as well, with 92% patients/patients guardians
rating the treatment as excellent to good in cefpodoxime
group versus 80% in the cefixime group (Table 4).
Adverse Effect Profile
Gastrointestinal side effects were the only adverse events
reported, most of which were mild and self-limiting in
nature in the cefpodoxime group. Therefore, none of the
patients withdrew from the therapy. However, loose
motion was more commonly reported (13%) in the
Fig. 1. Comparative evaluation of symptom resolution
TABLE 2. Comparative Clinical and Bacteriological Outcomes
Clinical Cefpodoxime Cefixime
outcome Group Group
Cure 61.3% 43%
Improvement 35.7% 43.8%
Clinical Success 97.0% 86.8%
(Cure + Improvement)
Failure 3.0 % 13.2%
Bacteriological outcome
Eradication 93.4% 82.9%
(+presumed eradication)
Failure 6.6% 17.1%
TABLE 3. Physicians Global Assessment on Clinical Efficacy.
Cefpodoxime Cefixime
Excellent 50% 36%
Very good 33% 20%
Good 11% 25%
Fair 6% 8%
Poor 0% 1%
TABLE 4. Patients Global Assessment on Clinical Efficacy
Cefpodoxime Cefixime
Excellent 48% 32%
Very good 31% 24%
Good 13% 24%
Fair 7% 8%
Poor 1% 2%
-120.00%
-100.00%
-80.00%
-60.00%
-40.00%
-20.00%
0.00%
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Cefixime
Jayati Sengupta et al
520 Indian Journal of Pediatrics, Volume 71June, 2004
cefixime arm, compared to 3.4% in the cefpodoxime arm.
Overall tolerability of study medications was assessed
by physicians at the end of the study. 95% rated the
tolerability of cefpodoxime as excellent to good versus
79% of cefixime. Similarly, 92% of the patients rated
tolerability of cefpodoxime as excellent to good versus
78% in cefixime group (Figs. 2 and 3)
DISCUSSION
Acute respiratory infections include acute exacerbations
of chronic bronchitis (AECB), pneumonia, bronchitis,
bronchiolitis, sinusitis, of which lower respiratory tract
infections account for high morbidity and mortality.
7
The
overall impact of LRTIs in developing countries is 12
times greater than in developed countries.
8
In India, acute
respiratory infections (ARIs) are responsible for 1 million
deaths and it has a reported occurrence of 3-7 attacks of
ARIs/child/year, of which 10-15% are due to lower
respiratory tract infections.
9
Choice of antibiotics in
various respiratory ailments was a simple matter until
few years ago, as gram positive organisms (mainly
S.pneumoniae) were predominantly implicated in LRTIs.
However, with increasing recognition of gram negative
organisms and compromised efficacy of penicillins and
macrolides with emergence of resistant bacterial species,
choice of an antibiotic has become more complicated.
9
Cefpodoxime proxetil is an oral third generation
cephalosporin with a broad spectrum of antibacterial
activity. The drug has in vitro activity against many
common gram positive and gram negative pathogens
associated with common pediatric infections, making the
drug a useful option for empirical therapy.
10
Findings from this multicenter study indicate that
cefpodoxime is an effective antimicrobial agent for LRTI
in chidren and its efficacy is comparable to that of
cefixime. There was a marked improvement in all the
signs and symptoms associated with LRTIs over 10-14
days of the study. Clinical success was obtained in 97%
patients in cefpodoxime group versus 86.8% in cefixime
Fig 3. Global tolerability assessment by patients
Fig. 2. Global tolerability assessment by physicians
30%
39%
23%
7%
1%
11%
35%
32%
14%
8%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Excellent Very good Good Fair Poor
Grading of tolerability
%

p
a
t
i
e
n
t
s
Cepodoxime
Cefixime
32%
43%
20%
4%
1%
14%
33%
32%
13%
8%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Excellent Very good Good Fair Poor
Grading of tolerability
%

p
h
y
s
i
c
i
a
n
s
Cepodoxime
Cefixime
Comparative Evaluation of Cefpodoxime Versus Cefixime
Indian Journal of Pediatrics, Volume 71June, 2004 521
group and bacteriological eradication was achieved in
93.8% patients on cefpodoxime versus 82.9% of patients
on cefixime.
The results of this study are in line with those of earlier
multicentre, randomized, comparative clinical trials
carried out to assess the efficacy of cefprozil in the
treatment of common pediatric infections. In randomized
controlled trials conducted in children with acute otitis
media, oral cefpodoxime proxetil 8 to 10 mg/kg/day for
5 to 10 days was at least as effective or better as standard
regimens of amoxicillin/clavulanic acid, cefixime,
cefuroxime axetil or cefaclor as assessed by either clinical
or bacteriological criteria. The clinical and bacteriological
efficacy of 5 day treatment with cefpodoxime was
clinically and bacteriologically similar to 10 day course of
penicillin V in the treatment of children with pharyngitis
and/or tonsillitis. In randomized controlled clinical trials
in children with LRTIs, clinical and bacteriological
efficacy rates achieved with cefpodoxime proxetil treat-
ment were similar to those produced by cefuroxime axetil
and amoxicillin/clavulanic acid. Cefpodoxime proxetil
also demonstrated clinical efficacy in pediatric patients
with skin and soft tissue infections.
11
Schito GC et al
12
, in their multicentric survey, from
three European countries tried to monitor the activity of
widely used oral antibiotics against common respiratory
pathogens. Studies were conducted in Italy, Spain, and
Austria to monitor resistance patterns among respiratory
Streptococcus pneumoniae, H influenzae, M catarrhalis, Strep
pyogenes, Staph aureus and K pneumoniae to cefaclor,
cefuroxime, cefixime, cefpodoxime and macrolides.
Cefpodoxime was more potent than cefaclor and cefixime,
against pneumococci, especially strains with decreased
sensitivity to penicillin, and more active than cefaclor and
cefuroxime against gram ve respiratory pathogens.
Pneumococci and staphylococci displayed a very high
level of in vitro macrolide resistance. The investigators
suggested that cefpodoxime represents an appropriate
choice in the treatment of community acquired
respiratory tract infections in European countries.
Liu P and co-workers
13
reported significantly higher
cefpodoxime concentration in interstitial tissues, like
lungs tissues, in their comparative evaluation of
cefpodoxime versus cefixime. Their findings indicate that,
taking into account pharmakokinetic/dynamic
considerations, cefpodoxime is likely to be more
efficacious than cefixime, due to its greater tissue
penetration. Our study findings support this hypothesis,
by showing significantly better clinical and bacteriological
outcome with cefpodoxime compared to cefixime.
The twice-daily regimen of cefpodoxime also was
acceptable to most patients as with cefixime, and
compliance to these medications was also good. It has
been seen that patient compliance is inversely related to
the frequency of dosing and directly related to the efficacy
of the drug.
14
Most of the other standard antimicobials
used have a thrice or four times daily regimen.
Cefpodoxime was better tolerated than cefixime by our
study population. The side effects observed with
cefpodoxime were of mild intensity and no patient
withdrew from the study due to adverse events. The
gastrointestinal adverse events seen in the present study
correlate with those reported in earlier studies. Higher
gastro-intestinal side effects associated with cefixime, like
loose motion was due to alteration of the normal flora in
the gut.
CONCLUSION
Cefpodoxime proxetil is a well tolerated and superior
alternative to the earlier oral third generation cefixime for
LRTIs in children. Moreover, its expanded spectrum of
activity , and better tolerability as compared to cefixime
proves the fact that it should be accepted as a first-line
anti-microbial in pediatric LRTIs.
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