A Comparison

of Cefpodoxime
Proxetil
and Cefaclor in the Treatment of Acute
Exacerbation
of COPD in Adults*
Phillips,

Harry

In

Charlesj

Van Hook,

M.D.,

F.C.C.P;

M.D.; and Wesley Mark Todd, M.D.

multicenter,

this

with

M.D.;

Butler,

Thomas

observer-blinded

study,

301

patients

Clinical

before

treatment,

COPD
proxetil

and

end oftherapy
follow-up

(4

treatment

during

isolates

philus

therapy

(study

(3 to 7 days posttreatment),
weeks
posttreatment).
The
were

Hae,nophilus

3 to 5),

at the

and at long-term
most common
preinfluenzae,

and Streptococcus

parainfluenzae,

days

Haemo-

pneumoniae.

116 of 128, 91 percent;

cefaclor,
59 of 64, 92
or end-of-therapy
clinical response
(cure
+ improved;
cefpodoxime,
99 of 100, 99 percent;
cefaclor,
45 of
49, 92 percent)
rates
for evaluable
patients.
Both drug
treatments
were
well-tolerated,
with a similar incidence
of
drug-related
adverse
events
(cefpodoxime
11 percent,
cefaclor 12 percent).
Cefpodoxime
(bid)
was as safe
and
effective
as cefaclor (tid) in the treatment
of acute exacerbation of COPD.
The less frequent
dosing
regimen
of
cefpodoxime
may improve
patient compliance
compared
to
those antibiotics
that require three
or four daily doses.
(Chest 1993; 104:1387-92)
doxime,

symptoms
of acute bacterial
exacerbation
of
were randomized
(2:1) to receive
either cefpodoxime
(200 mg, bid) or cefaclor
(250
mg, tid) for 10 days.
and
microbiologic
evaluations
were performed

signs

Sig-

nificantly

percent)

(p <0.001)
more
bacterial
isolates
were
susceptible
in vitro to cefpodoxime
(233 of 256, 91 percent)
than to cefaclor (215 of 255, 84 percent).
There were no
statistically
significant
differences
between
the two drug
regimens
in eradication
of the
initial
pathogen
(cefpo-

gastrointestinal

hronic
term
emphysema,

obstructive
pulmonary
disease
is a general
for respiratory
disorders,
including
asthma,
and chronic
bronchitis,
that decrease
air

flow. Acute
bacterial
infections
of the respiratory
tree
in patients
with
COPD
are common
and
associated
with significant
morbidity
and mortality,
often due to
respiratory
Since
from
from

ai,2
pathogenic

may

not

be

isolated

is often
isolation

based
on likely
of any specific

Therapeutic

agents

for acute

niae and 13-lactamase

positive
and
Haemophilus
influenzae,
Moraxella

exacerbation

its

*Frnm Columbiana
Clinic of Family Medicine,
Columbiana,
Ala;
the Department
of Medicine,
University
of Colorado,
Denver;
Texas Tech University
Health
Science
Center,
Lubbock
and the
Upjohn
Company,
Kalamazoo,
Mich.
Manuscript
received
December
31, 1992; revision accepted
March
200

Mildred

free
inhibitory

Street,

P0

Box

35051

1006,

pathogens.hut3

agent

treatment

dose

in the

gas-

was

following
the
of

results

mini-

common

of preliminary

proxetil
is a promfor respiratory
infec-

designed

to

the

compare

cefpodoxime
proxetil
in
bacterial
exacerbation
of COPD

efficacy

the
to

of

of acute

of cefaclor,

The

study

pml)
exceed

(MIC)

that cefpodoxime
the treatment

for
This

and

(0.16

equivalent

another

oral

cephalosporin

as effective
treatment
for patients
upper respiratory
tract

with

accepted

both

lower

and

16

METHODS
Patient

Population

Males
years

with

and

nonpregnant,

a body

weight

non-breast-feeding
40

kg were

eligible

women
for this

aged
study

18
if they

presented
with signs and symptoms
indicative
ofacute
exacerbation
of COPD,
including
cough,
fever (>37.7#{176}C, oral), or increased
sputum production/purulent
sputum
and absence
of pulmonary
infiltrate
on chest
radiograph.
Both hospitalized
patients
and
outpatients
were
eligible
for this study.
Patients
were
excluded
if
they suffered from a severe respiratory
tract infection that required
parenteral
antibiotic
treatment;
had hypersensitivity
to cephalosporims or a history of anaphylaxis
or severe reaction to penicillin;
had
received
antimicrobial
therapy within the previous 5 days, unless
resistance
to the previous
treatment
was documented
by microbiologic susceptibility
testing; were neutropenic
(WBC <2,000
mm);
CHEST

Downloaded From: http://journal.publications.chestnet.org/ on 04/02/2015

hydrolysis

concentration

indicate

safety

and sputum

acid

negative
strains
of
catarrhaks,
and

Cefpodoxime
proxetils
methoxymethyl
esterified
carboxyl
function
facilitate

Phillips,

mg/kg),

(0.63

tions.745

that

Haemophilus
parainfluenzae.6
Cefpodoxime
proxetil
is an orally
administered
prodrug
ofcefpodoxime,
an extended-spectrum
ceph-

24.
Reprint
requests:
Dr.
Columbiana,
Alabama

is resistant

ising

and

to the active drug, cefpodoxime.7

is active
against
pathogens
associated
with exacerbation
ofCOPD
and
to hydrolysis
by 3-lactamases.7#{176} Levels
of
demonstrated
in plasma
(2.2 pg/ml),
lung

cefpodoxime

studies

concentration

absorption

respiratory

pathogens
causative

inhibitory

mucosa
cefpodoxime

commonly

mum

of COPD
must, therefore,
be effective
against
a wide
range of pathogens
including
Streptococcus
pneumo-

alosporin.75
radical
and

trointestinal
In vitro,

a 200-mg

agent(s).3
Pathogens
commonly
associated
with acute
exacerbation
of COPD
have demonstrated
increasing
resistance
to traditional
therapies
for respiratory
infections.

minimum

tissue

organisms

up to 50 percent
of purulent
sputum
samples
patients
with
acute
exacerbation
of COPD,

antibiotic
therapy
rather
than
the

MIC

I 104 I 5 I NOVEMBER,

1993

1387

had moderate
to severe renal impairment
(serum creatinine
>2.5
mg/dl) or hepatic
dysfunction
(SGOT
>200
lUlL
or total bilirubin
>3.0
mg/dl);
suffered
from significant
immunologic/neoplastic
disease

or severe

that

might

any

other

vascular

potential,
patients,

or had

study;

not practicing
consent

drug;

been

their

prior

disorder

were

enrolled

enrolled

or in women

an acceptable

or if incompetent,

written informed
procedures.

a gastrointestinal

of study

protocol

proxetil

were

had

absorption

investigational

in a cefpodoxime
All

insufficiency;

affected

have

with

child-bearing

contraceptive

guardians,

method.

provided

to the initiation

in

previously

ofany

signed

study-specific

Design

Study

Patients
were randomly
assigned
(2:1) to receive
either
cefpodoxime proxetil (tablet; equivalent
of 200 mg cefpodoxime
bid) or
cefaclor
(capsule;
Ceclor,
Eli Lilly;
250 mg tid) for 10 days.
At
admission
(study
day 0), written
consent
and medical
history
were
obtained
and the following
evaluations
performed:
physical
examination
with vital signs,
clinical
laboratory
tests
(blood
chemistry,
platelets/differential,
pregnancy

urinalysis

test

with

if applicable,

microscopic

chest

examination),

radiograph

(posteroanterior,

to the first dose

drug, bacterial
pathogen(s)
isolated at
tract or blood culture
that was susceptible or moderately
susceptible
to the assigned
study drug, taken
at least 80 percent of the assigned medication
without missing two
consecutive
doses of cefpodoxime
or three consecutive
doses of
cefaclor,
treatment
with study drug for at least 7 consecutive
days
(responders)
or 3 days (nonresponders),
evaluated 2 to 8 days after
completion
oftherapy
(interim and long-term
follow-up evaluations
were not required),
and not used nonstudy
systemic antimicrobials
between
study admission
and end-of-therapy
evaluation
(except
failures).
Primary
efficacy parameters
included
clinical outcome,
end-oftherapy microbiologic
response,
and microbiologic
outcome for each
pathogen.
Clinical outcome was defined as clinical cure (complete
disappearance
or return
to baseline
of signs and symptoms),
clinical
improvement
(significant
improvement
but not complete
resolution
of signs
and symptoms),
clinical
failure (liftie or no response
to
therapy at study completion
or time of withdrawal),
or recurrence
(requirement
for antimicrobials
between
end-of-therapy
and longterm follow-up
visit). Patients
who received
another antimicrobial
agent due to inadequate
response by end oftherapy
were considered
admission

of study

respiratory

lateral), respiratory
tract culture
(and/or
blood culture)/Gram
stain,
susceptibility
testing ofisolated
pathogens,
and evaluation
of clinical

to

signs

defined as microbiologic
cure (all evaluable
pathogens
eradicated,
or no culturable
material,
or nonpurulent
sputum), microbiologic
partial
cure (eradication
ofat least one, but not all, initial pathogens

and

symptoms.

Evaluations

of vital

signs,

clinical

well

therapy

but

were

as at long-term

repeated

follow-up

at the

laboratory

end-of-therapy

if recurrent

symptoms

visit,
were

as

of

cases

Specimens
susceptibility

were obtained
for aerobic culture,
Gram stain, and
testing. Acceptable
specimens
included
expectorated

sputum

<10

with

Susceptibility

squamous

Testing

endothelial

cells

and

>25

WBCs

per

high power field, transtracheal

aspirate,
protected
brush endoscopic
brushings,
or blood culture isolates.
Isolated
organisms
were tested for susceptibility
to study
drugs
according
to the procedures
ofthe
National
Committee
for Clinical
Laboratory
Standards
(NCCLS).7
Susceptibilities
on the basis of
zone diameter
inhibition
were defined7
as follows: cefpodoxime
(10
g/disk)-susceptible
21
mm, moderately
susceptible
18 to 20
mm,
(H

resistant

17

influenzae

influenzae
Thomas

by

were

used

zone

and

14

mm

information
susceptible

resistant

(cefpodoxime:

4 Lg/ml,

pretreatment

resistant

pathogen(s)

susceptible

to their

32

susceptible

pg/ml).

determined

determinations.

assigned

study

suscep-

proposed

by Jones

drug

moderately

those

patients

susceptible
were

suswith

or moderretained

during

in the

were

Microbiologic

or immediately

determined

indepenresponse

or microbiologic

was

failure

(initial

after

therapy).

Adverse

events

were monitored
included changes in vital
of clinical
laboratory
assays, and adverse
events.
were classified
by the investigators
as to seriousness,

severity

(mild,

moderate,

results

that

(drug-related:
reasonable
the study drug).

or severe),

and

possibility

that the event

relationship

to study

drug

was caused

by

All statistical
tests were two-sided
with p levels
<0.05
considered
to indicate statistical significance.
All variables
were analyzed using
the model:
result
mean
(overall
treatment
mean) + treatment
(effect of study drug) + error (random error symmetric about zero).
Analysis
of variance
(ANOVA)
was used
to analyze
age,
height,
weight, pretreatment
vital signs, and continuous
laboratory
variables. The method
of weighted
least squares
was used
to compute
test statistics
for evaluability
rate, race, sex, end-of-therapy
microbiologic

and

score

clinical
rates.

response

tables

was

cure

rates,

Ordered

function,9

were computed
data

MIC

recommended

p.g/ml,
Only

at

outcomes
outcomes.

infections),

parameters

eradication

moderately

those

to be

(H

mm).

MIC

not available,

p.g/ml,
and

18

laboratory

on criteria

g/ml)

mm

microbiology
was

(cefaclor:

18
15 to 17 mm

(H influenzae

University(Philadelphia)for
inhibition

based

Barry

ately

resistant

evaluabiity

16 p.g/mI,

ceptible

susceptible

to determine

NCCLS7

tible

(30 pg/disk)-susceplible

moderately

also sent to a central

Jefferson
disk

were

cefaclor

mm),

19 to 23 mm),

Pathogens
When

mm;

24

ofpolymicrobial

infection

signs,
Cultures

Clinical

microbiologic

pathogen[s]
not eradicated).
Microbiologic
outcome
for each pathogen was defined as eradication
(culture negative or unobtainable
due to improvement/cure),
recurrence
(eradication
at end of therapy
with recurrence
of same pathogen
at long-term
follow-up),
or
superinfection
(isolation
of new pathogen[s]
from initial site of
Safety

present.

Microbiologic

and

failures.

dently

parameters,
clinical status, and clinical signs and symptoms
were
repeated
during therapy
(study
days 3 to 5), at the end of therapy
(days 3 to 7 posttreatment),
and at long-term
follow-up
(4 weeks
after completion
of therapy).
Any
laboratory
finding
that was
abnormal
at long-term
follow-up
was monitored
until
resolved.
Physical
examinations
were repeated
only at the end-of-therapy
visit.
Respiratory
tract culture
(and/or
blood
culture)
with Gram
stain and susceptibility
testing
of isolated
pathogens
were optional
during

be

from

while

infection

Primary
efficacy
confidence
limit

intervals.

tory

were

normal

ranges

microbiologic
using

responses

for medical

ofinitial

parameters

end-of-therapy
were

using a logit model.

computed

ment physical examination

also used to analyze adverse
for severity

and

responses

parameters

that

history

and

data.
in

a mean

could not be ordered

A Fishers exact test for 2 x 2

abnormalities.
event

computed

frequencies

and

pretreat-

Fishers exact tests were

A x2 analysis was computed

vitro

susceptibility

categories.

were analyzed
using
ANOVA
and
When normal
ranges
for clinical
labora-

not supplied

by each

were taken from Haistead

investigators

laboratory,

and Halstead.

study.

RESULTS
Statistical
All

Analyses

patients

administered

study

medication

were

considered

evaluable
for safety analyses. To be considered
evaluable
for efficacy
analyses,
patients were required
to have had the following:
no major
deviations
from inclusion/exclusion
criteria,
radiographic
absence
ofpulmonary
infiltrate,
a pretreatment
culture taken 3 days prior

1388

Downloaded From: http://journal.publications.chestnet.org/ on 04/02/2015

Patient

Population

A total of 301 patients,

194 administered
doxime
proxetil
and 107 administered
cefaclor,
enrolled
in the study
and
included
in the
Cefpodoxime

Proxetil

vs Cefaclor

in COPD

cefpowere
safety

(Phillips

et a!)

Table

Characteristics
(Mean
and Initial Infection
Severity
for Efficacy
EValUab1#{128}Ibtients

Skindard

1-Demographic

treatment

Deviation)

groups

and infection

of cefpodoxime
patients

Cefpodoxime
Proxetil

Cefaclor

yr

54.2

Weight, kg
Height,cm
Sex(%)

17.3

51.9

78.9 18.1
168.210.4

16.5

Not

81.0 19.9
172.611.1

46

(46)

32

(65)

Female

54

(54)

17

(35)

White

85

(85)

43

(88)

Black

(7)

(6)

Hispanic

(8)

(4)

(2)

Not significant

Other

0
severity

Moderate
Severe

analyses.

Among

(34)

13

Results

(64)

34

(69)

(2)

(4)

evaluable

Approximately
groups
completed

one

for

mature

study
discontinuation
of study medication

the

start

34

percent;

as a result

cefaclor

safety

percent)

treatment

most common
live pretreatment
percent;
pathogens
13 of 107,
Table

ineligibility

groups

was

39 of 107,

(cefpodoxime
12 percent).
2-In

Vitro

number

In

vitro

on

Twenty-three

to

percent),

including
to cefaclor.
are listed

observed.

The

46

and

resistant

(Minimum

inhibitory

6 strains
Results
in Table

lower
than
H influenzae

negative),

H parainfluenzae

and

(233 of 256,
respectively).

(9 percent)

40

were

isolates

(16

of H influenzae,
were
for selected
individual
2. The MIC1OO of cefpo-

that

of

cefaclor

against

(f3-lactamase

positive

(3-lactamase

or

negative)

eradication

64, 92 percent).
monly
identified
There

Eradication

for

rates

pathogens

were

no

microbiologic

groups.
percent)

After microbiologic
cef1odoxime-treated

for

are listed

significant

therapy

ered

rates

patients
were similar
between
(116 of 128, 91 percent)
and

pathogens

of the

evaluation,
patients

of

the most comin Table 3.

differences

outcomes

in

cefpodoxime
cefaclor
(59

in
two

end-of-

treatment

90 of 100 (90
were
consid-

7 of 100 (7 percent)
partially
cured,
and 3
failed; the values
for cefaclor-treated

cured,

100 (3 percent)

of

Concentration)

Reaultsfor

(%) 0 f

Selected

Ththogens

Pretreatment

Isolates

Moderately
Resistant

Susceptible

Susceptible

Resistant

(50)

3 (30)

2 (20)

31

(84)

5 (13)

25

(100)

37 (100)

25

.
.

(3)

negative

S pneumoniae

(100)

8 (100)

.
.

.
.

8 (100)

.
.

...

...

positive

H parainfluenzae

3-lactamase

on

positive

M catarrhahs

f3-lactamase

are

secondarily

Cefaclor

Moderately
Susceptible

10 (100)

H influenzae

-lactamase

reported
for
255
isolates

isolates.

two

were nega66 of 194, 34

isolates

Cefpodoxime

-lactamase

isolated

results

and

whereas

doxime
was
pneumoniae,

No.

H influenzae

were
and

criteria

cefpodoxime,

End-of-therapy

15 of 194, 8 percent;
cefaclor
Evaluable
patients
in the two

Susceptible

were

susceptibility

MIC

pretreatment

resistant

evaluable
proxetil

of patients

cefpodoxime
(49 of 107,

36 percent),

Susceptibility

pathogens

ceptible
to cefpodoxime
than to cefaclor
91 percent
vs 215 of 255,
84 percent,

generally

reasons
for nonevaluabiity
cultures
(cefpodoxime

cefaclor

after

culture.

between
cefaclor

cefaclor.

pathogens

65 of 194,

36 percent),

in the

difference

fifty-nine

primarily

resistant

cefaclor
56 of
reason
for pre-

pretreatment

evaluable
for efficacy
analyses
(100 of 194, 52 percent)
and

there

two drug
medical
noted

(cefpodoxime

39 of 107,

of a negative

significant

No

was

hundred

based

half of the patients

treatment
as planned

(cefpodoxime
111 of 194, 57 percent;
107, 52 percent).
The most common

Two

disk zone size. Significantly

more (p<O.OO1)
pretreatment
isolates
were
susceptible
and moderately
sus-

were no significant
differences
between
the
groups
in demographics,
infection
severity,
history,
or physical
examination
abnormalities
at admission.
in both
drug

significant

(27)

64

patients

of cefaclor-evaluable

from all patients,

with the most common
isolates
being
H influenzae,
H parainfluenzae,
and S pneumoniae.
The types of pathogens
isolated
were similar
to those
observed
in other studies
involving
patients
with acute

against
Not

34

race,
percent

for 10 or 11 days.

exacerbation
of chronic
bronchitis.
In vitro susceptibility
test results
256 isolates
against
cefpodoxime

(%)

Mild

92 percent

therapy

weight,

significant

Not significant
0.022
0.030

(%)

Infection

in age,

1). Ninety-seven

p Value

Male
Race

similar
(Table

and

received

Microbiologic
Age,

were

severity

29

(100)

26

3 (10)

(90)

...

negative

CHEST

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104

I 5 I NOVEMBER,

1993

1389

Table 3-Ththogen
Eradication
Rates
(Number
ofEradicaed
Pathogens/Number
Assessable

in Evoiuable

Thtients

ofPatients

Isthogen
Response)for
identified
lh,gij*

With

Commonly

Most

evaluated

Cefpodoxime,
No. (%)
H influenzae
-Iactamase
-lactamase

percent)
or in distribution
of clinical
outcomes
between
the two drug treatments.
For the cefpodoximetreated
group,
65 of 100 patients
(65 percent
were
as having

had a clinical

clinical

improvement;

as showing

Cefaclor,
No. (%)

percent)

was

(100)

3/3

(100)

cefaclor-treated

group,

28 of 49 (57 percent)

(100)

111

(100)

were

cured;

17 (35 percent)

negative

21123

(91)

&9

(89)

considered

4 (8 percent)
cefpodoxime

(100)

2/2

(100)

2/2

(100)

negative

11112

(92)

2/2
10/11

(100)
(91)

12114

(86)

9/12

(75)

(100)

H parainfluenzae

3-lactamase

positive

&7

(86)

fI-lactamase

negative

3/3

(100)

1/1

liquefaciens.
Recurrence

(79 of 128) ofthe

pathogens

pathogens

represent

62 percent

isolated before treatment

from valuable
tients and 64 percent
(41 of64)
of those
evaluable

cefaclor-treated

were

44 of49

cefpodoxime-treated
isolated

(90 percent),

biologic
cure rate than those
in both treatment
groups.
Fifteen
evaluable
patients

2 of49

patients

from

these

with
(10

patients

both

evaluable

of therapy

were

study

drugs,
except
for a
(resistant
to both drugs by

isolate

disk zone), an Acinetobacter

anitratus
isolate
(resistant
to cefpodoxime
by both
disk zone
and
MIC),
and an
Enterobacter
cloacae
isolate
(resistant
to cefaclor
by
MIC but not disk zone).
These
resistant
pathogens
were

isolated

from

cefpodoxime-treated

patients

uated
as clinically
cured
or improved
therapy.
Maintenance
oferadication
from the
to long-term
significantly

follow-up
different

96 of 96,

100 percent;

cefaclor

pathogens
morbillorum,

in the

f3-lactamase

patients
(12 percent)
(27 percent)
were

superinfections

at the

the

interim

end

patients
production

course

of the

cough,

not
(cefpo-

was

47 of 50,
cefaclor
Twelve

94

group
and
cefpo-

and 13 cefaclordiagnosed
with

or end-of-therapy

and/or
study

intensity
purulence
regardless

of

negative),

at long-term

follow-up

Serratia

and

was

similar

be-

groups,
with
18 percent
(16 of 90)
patients
and
14 percent
(6 of
patients
experiencing
a recur-

visit.

dyspnea,

decreased
of therapy.

were

no significant

differences

observed

in

a drug-related
194, 11 percent;

cefaclor
13 of 107, 12 percent)
or in the number
of
drug-related
adverse
events
(cefpodoxime
32, cefaclor
15) between
the two treatment
groups.
Gastrointestinal complaints
drug-related

were
adverse

There

were

tween

treatment
groups
in the number
of patients
drug-related
gastrointestinal
events
(cefpo-

reporting

no

the most
commonly
reported
events
for both
drug
groups.

significant

differences

17 of 194, 9 percent;
diarrhea
(cefpodoxime

doxime
percent),

cefaclor
3 of 107,
5 of 194, 3 percent;
The

majority

3 percent),

observed

cefaclor
8 of 107,
10 of 194, 5 percent;
or nausea

cefaclor

(cefpodoxime

3 of 107,

of drug-related

be-

3 percent).

events

were

mild

or

moderate
for both treatment
groups.
One cefpodoxime
patient
reported
severe
diarrhea
and stomach
cramps.

of therapy

and
during

Four patients
(3 cefpodoxime,
the study due to drug-related
doxime:

1 cefaclor)
adverse

nausea/vomiting,

cramps/diarrhea;

headache,

cefaclor:

discontinued
events
(cefpoabdominal

nausea/heartburn/perioral

numbness).
Changes

consistent

with

resolution

ofinfection

observed
in vital signs and clinical
laboratory
eters. Seven
patients
(five cefpodoxime,
two
experienced
in laboratory
that appeared
relationship
is not

were
paramcefaclor)

potentially
clinically
significant
changes
values (increased
SGOT, WBC,
platelets)
during
the course
of the study;
the
ofthese

abnormal

values

to study

therapy

known.

At the

end of therapy,
positive
clinical

podoxime

of

Results

Most
sputum

end

eval-

S pneumoniae,

H influenzae.

negative

doxime-treated
treated
patients

Clinical

at the

in evaluable
patients
between
drug
groups

percent).
Recurring
were
Streptococcus

doxime

S pneumoniae,
negative),

Fvfile

There

bacterial
persistPathogens
iso-

end

and

in the
clinical

(f3-lactamase

the number
of patients
experiencing
adverse
event
(cefpodoxime
22 of

5 of 49 evaluable

at the

patients

failure
coli;

involved

(3-lactamase

tween
the two drug
of cefpodoxime-treated
43) of cefaclor-treated
rence of symptoms.
Safety

pathogens

100

of

cefaclor
group
H influenzae

the

(4 percent),

multiple

[10 percent],

still susceptible
to
Citrobacter
diversus

treatment

Evaluable
patients
had a higher
micro-

cefaclor
patients
[10 percent])
had
ence at the end-of-therapy
evaluation.
lated

pa-

before

patients.

(6 percent),
respectively.
with a single pathogen

cefpodoxime

(100)

failures
in the
S morbillorum,

(1

For

improved;

failed.
The sole clinical
group involved
Escherichia

&6

and 3 of49
presenting

1 patient

failure.

6/6

positive

patients

a clinical

v3

-lactamase
f3-lactamase
S pneumoniae
Mcatarrhalis

from

34 (34 percent)

and

positive

H parainfluenzae

These

considered

cure;

there were no sigificant

differences
in
response
(cure + improved)
rate (cef99 of 100, 99 percent;
cefaclor
45 of 49, 92

1390

Downloaded From: http://journal.publications.chestnet.org/ on 04/02/2015

DISCUSSION

Chronic
obstructive
pulmonary
disease
is the fifth
most frequently
reported
cause ofdeath
in the United
Cefpodoxime

Proxetil

vs Cefaclor

in COPD (Phillips

et a!)

States.

Bacterial

exacerbation

with declines
morbidity
and

ofCOPD

is associated

in respiratory
function
and
mortality;
however,
precise

significant
identifica-

tion of causative
pathogens
through
sputum
culture
is
not possible
in as many as 50 percent
of the patients.3
For example,
patients

in the

had

negative

symptoms

and

present

study,

sputum

consistent

cultures

with

such

profloxacin,

exacerbation
sistant
opment

of COPD
ofnew

are,
effects

therefore,
of acute

has

a broad
pathogens

lower

than

cure

response

rates

rates

as well

(90 percent)

(99 percent).

proxetil

administered

as treatment

with

cefaclor

frequency

is an

important

Dosage

comp1iance.

on a bid
regimen

regimen.
may

regimens

Compliance

side

effects.

cefaclor

frequent

side

were

was

as

determinant

of

in which

To ensure

bid

dosing

over antidosing.

effects
complaints

clinical

and
a

would
be twice
sample
sizes

cefpodoxime-treated

patients

patients),

of correctly
cefpodoxime

microbiologic

significanfly

we

calcu-

concluding
proxetil

that
is not

before

treatment
in

of COPD.
were equally

efficacy
with rewell
as positive

patient
greater

susceptible

responses.

number

were
vitro

to

More-

of

pathogens

susceptible

or moder-

cefpodoxime

than

to

cefaclor.
ACKNOWLEDGMENT:
The authors
thank Jay P. Hansen
for his
help
in coordinating
study
activities.
The following
investigators
participated
in this study:
Roblee
R. Allen,
M.D. , Sacramento,
Cali1 Lary Amacker,
M.D.,
Memphis,
Tenn;
Michael
Bronze,
M.D.,
Memphis,
Tenn;
Robert D. Chiulli,
M.D.,
Clinton,
Mass;
Sanford
Chodosh,
M.D.,
Boston;
Gregory
V. Collins,
M.D.,
Charlotte,
NC;Jerrold
Flatt,
D.O.,
Des Moines,
Ia; Geoffrey
Grambau,
M.D., Kalamazoo,
Mich; Jon A. Green,
M.D.,
Martinez,
Ca1i1
JavierGuerra,
M.D. , El Paso, Tex; Barbara Hanna,
M.D.,
Anniston,
Ala; Scott A. Heatley,
M.D.,
Redwood
City, Calif
Joseph
Henkle,
M.D. , Springfield,
Ill; Michael
Hill,
M.D.,
New
Orleans,
La;
Zachary
Hutchens,
M.D.,
Centerville,
Tenn;
Richard
W Kearley,
M.D.,
Baton
Rouge,
La; Barry
Marniorstein,
M.D.,
Bellevue,
Wash;
Herbert
Moskow,
M.D.,
Denmark,
SC; John
A. Powell,
M.D. , Fort Rucker,
Ala; J. Joseph Prednergast,
M.D.,
Redwood
City,
Calif; John H. Rowlands,
M.D.,
Tacoma,
Wash; Judy A. Stone,

Md; Carl P. Weidenbach,

D.V.M.,
Zuschke,
M.D., Mobile, Ala.

present

study,

the

type

oral antibiotics.
clinical
trial

that we obtained

and

sample

from

the

1309-14
2 US Department

of chronic

general

of Health

and

report

Surgeon

of the

on Smoking
3 Lentino

and
JR.

management
biol

of lower

M.D.,

Public
Md,

The
lung

Health

tract

and

in a
317:

health

disease:

Service,

Office

1984

of sputum

respiratory

course

Resources.

obstructive

Nonvalue

RG.

Epidemiological

munity-acquired

Chemother

1990;
RB,

6 Chodosh
chitis:

culture

in

J Clin

infections.

the

Micro-

RF.

Am J Med

ofthe

suffering

cephalosporin.

Current

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1991;

proxetil:

dosage,

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26(suppl

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VL. In vitro

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91(suppl
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ofU-76,252

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Am J Med

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The

obstruction
J Med 1987;

1987; 25:758-62

4 Finch

oral

N Engi

Rockville,

DA.

MG.

airways

Human

General.

Health,

Lucks

Cline

population.

of smoking-chronic

Chemother

sufficienfly

GA,

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8 Fass RJ, Helsel

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JW, Traver

of different

tory pathogens.

well tolerated.
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B, Bloom

5 Facklam

equally

frequency
usually
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with
A potential
limitation
of any
size.

cef-

by the incidence
the

the

and demonstrated
similar
pathogen
eradication,
as

prognosis

a day.

in a study

In

of
of

treatment
for acute
exacerbation
study, cefpodoxime
and cefaclor

1 Burrows

times

proxetils
help to improve
compliance
that require
more frequent
of

that the true

probability
is 0.9
and
the
number

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Cefpodoxime

Proxetil vs

CefaC$Or