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CHEST I 104 I 5 I NOVEMBER, 1993 1387
A Comparison of Cefpodoxime Proxetiland Cefaclor in the Treatment of AcuteExacerbation of COPD in Adults*Harry Phillips, M.D.; Charlesj Van Hook, M.D., F.C.C.P;
Thomas Butler, M.D.; and Wesley Mark Todd, M.D.
In this multicenter, observer-blinded study, 301 patients
with signs and symptoms of acute bacterial exacerbation ofCOPD were randomized (2:1) to receive either cefpodoximeproxetil (200 mg, bid) or cefaclor (250 mg, tid) for 10 days.
Clinical and microbiologic evaluations were performed
before treatment, during therapy (study days 3 to 5), at the
end oftherapy (3 to 7 days posttreatment), and at long-termfollow-up (4 weeks posttreatment). The most common pre-treatment isolates were Hae,nophilus influenzae, Haemo-
philus parainfluenzae, and Streptococcus pneumoniae. Sig-
nificantly (p <0.001) more bacterial isolates weresusceptible in vitro to cefpodoxime (233 of 256, 91 percent)
than to cefaclor (215 of 255, 84 percent). There were nostatistically significant differences between the two drug
regimens in eradication of the initial pathogen (cefpo-
doxime, 116 of 128, 91 percent; cefaclor, 59 of 64, 92percent) or end-of-therapy clinical response (cure + im-proved; cefpodoxime, 99 of 100, 99 percent; cefaclor, 45 of49, 92 percent) rates for evaluable patients. Both drugtreatments were well-tolerated, with a similar incidence ofdrug-related adverse events (cefpodoxime 11 percent, cef-aclor 12 percent). Cefpodoxime (bid) was as safe andeffective as cefaclor (tid) in the treatment of acute exacer-bation of COPD. The less frequent dosing regimen ofcefpodoxime may improve patient compliance compared to
those antibiotics that require three or four daily doses.
(Chest 1993; 104:1387-92)
I MIC = minimum inhibitory concentration
C hronic obstructive pulmonary disease is a general
term for respiratory disorders, including asthma,
emphysema, 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 ai�,2
Since pathogenic organisms may not be isolated
from up to 50 percent of purulent sputum samples
from patients with acute exacerbation of COPD,
antibiotic therapy is often based on likely pathogens
rather than the isolation of any specific causative
agent(s).3 Pathogens commonly associated with acute
exacerbation of COPD have demonstrated increasing
resistance to traditional therapies for respiratory in-
fections.�’� Therapeutic agents for acute exacerbation
of COPD must, therefore, be effective against a wide
range of pathogens including Streptococcus pneumo-
niae and 13-lactamase positive and negative strains ofHaemophilus influenzae, Moraxella catarrhaks, and
Haemophilus parainfluenzae.6
Cefpodoxime proxetil is an orally administered
prodrug ofcefpodoxime, an extended-spectrum ceph-
alosporin.7’5 Cefpodoxime proxetil’s methoxymethyl
radical and esterified carboxyl function facilitate 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 theUpjohn Company, Kalamazoo, Mich.
Manuscript received December 31, 1992; revision accepted March24.Reprint requests: Dr. Phillips, 200 Mildred Street, P0 Box 1006,Columbiana, Alabama 35051
gastrointestinal absorption and hydrolysis in the gas-
trointestinal mucosa to the active drug, cefpodoxime.7
In vitro, cefpodoxime is active against pathogens
commonly associated with exacerbation ofCOPD and
is resistant to hydrolysis by �3-lactamases.7’#{176} Levels of
cefpodoxime demonstrated in plasma (2.2 p�g/ml), lung
tissue (0.63 mg/kg), and sputum (0.16 p��ml) following
a 200-mg free acid equivalent dose exceed the mini-
mum inhibitory concentration (MIC)� of common
respiratory pathogens.hut3 The results of preliminary
studies indicate that cefpodoxime proxetil is a prom-
ising agent for the treatment for respiratory infec-
tions.7”4”5 This study was designed to compare the
safety and efficacy of cefpodoxime proxetil in the
treatment of acute bacterial exacerbation of COPD to
that of cefaclor, another oral cephalosporin accepted
as effective treatment for patients with both lower and
upper respiratory tract 16
Patient Population
METHODS
Males and nonpregnant, non-breast-feeding women aged � 18years with a body weight �40 kg were eligible for this study if they
presented with signs and symptoms indicative ofacute exacerbationof COPD, including cough, fever (>37.7#{176}C, oral), or increasedsputum production/purulent sputum and absence of pulmonaryinfiltrate 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 requiredparenteral antibiotic treatment; had hypersensitivity to cephalospo-
rims or a history of anaphylaxis or severe reaction to penicillin; hadreceived antimicrobial therapy within the previous 5 days, unlessresistance to the previous treatment was documented by microbio-logic susceptibility testing; were neutropenic (WBC <2,000 mm�);
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1388 Cefpodoxime Proxetil vs Cefaclor in COPD (Phillips et a!)
had moderate to severe renal impairment (serum creatinine >2.5mg/dl) or hepatic dysfunction (SGOT >200 lUlL or total bilirubin
>3.0 mg/dl); suffered from significant immunologic/neoplastic dis-
ease or severe vascular insufficiency; had a gastrointestinal disorder
that might have affected absorption of study drug; were enrolled in
any other investigational protocol or had been enrolled previously
in a cefpodoxime proxetil study; or in women with child-bearing
potential, were not practicing an acceptable contraceptive method.
All patients, or if incompetent, their guardians, provided signed
written informed consent prior to the initiation ofany study-specific
procedures.
Study Design
Patients were randomly assigned (2:1) to receive either cefpo-
doxime 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 exami-
nation with vital signs, clinical laboratory tests (blood chemistry,platelets/differential, urinalysis with microscopic examination),
pregnancy test if applicable, chest radiograph (posteroanterior,
lateral), respiratory tract culture (and/or blood culture)/Gram stain,
susceptibility testing ofisolated pathogens, and evaluation of clinical
signs and symptoms. Evaluations of vital signs, clinical laboratory
parameters, clinical status, and clinical signs and symptoms wererepeated 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-therapyvisit. Respiratory tract culture (and/or blood culture) with Gram
stain and susceptibility testing of isolated pathogens were optional
during therapy but were repeated at the end-of-therapy visit, as
well as at long-term follow-up if recurrent symptoms were present.
Microbiologic Cultures and Susceptibility Testing
Specimens were obtained for aerobic culture, Gram stain, andsusceptibility testing. Acceptable specimens included expectorated
sputum with <10 squamous 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 defined’7 as follows: cefpodoxime (10�g/disk)-susceptible �21 mm, moderately susceptible 18 to 20
mm, resistant �17 mm; cefaclor (30 p�g/disk)-susceplible �18 mm
(H influenzae �24 mm), moderately susceptible 15 to 17 mm (H
influenzae 19 to 23 mm), resistant �14 mm (H influenzae �18 mm).
Pathogens were also sent to a central microbiology laboratory atThomas Jefferson University(Philadelphia)for MIC determinations.
When disk zone inhibition information was not available, MIC datawere used to determine evaluabiity based on criteria recommended
by NCCLS’7 (cefaclor: susceptible �8 p.g/ml, moderately suscep-
tible 16 p.g/mI, resistant �32 �g/ml) and those proposed by Jones
and Barry” (cefpodoxime: susceptible �2 p.g/ml, moderately sus-
ceptible 4 �Lg/ml, resistant �8 p�g/ml). Only those patients with
pretreatment pathogen(s) determined to be susceptible or moder-
ately susceptible to their assigned study drug were retained in the
study.
Statistical Analyses
All 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
to the first dose of study drug, bacterial pathogen(s) isolated atadmission from respiratory tract or blood culture that was suscep-
tible or moderately susceptible to the assigned study drug, taken
at least 80 percent of the assigned medication without missing twoconsecutive doses of cefpodoxime or three consecutive doses ofcefaclor, treatment with study drug for at least 7 consecutive days(responders) or �3 days (nonresponders), evaluated 2 to 8 days aftercompletion oftherapy (interim and long-term follow-up evaluationswere 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-of-therapy microbiologic response, and microbiologic outcome for eachpathogen. Clinical outcome was defined as clinical cure (completedisappearance 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 totherapy at study completion or time of withdrawal), or recurrence(requirement for antimicrobials between end-of-therapy and long-term follow-up visit). Patients who received another antimicrobialagent due to inadequate response by end oftherapy were consideredto be failures. Clinical outcomes were determined indepen-
dently of microbiologic outcomes. Microbiologic response was
defined as microbiologic cure (all evaluable pathogens eradicated,or no culturable material, or nonpurulent sputum), microbiologicpartial cure (eradication ofat least one, but not all, initial pathogens
cases ofpolymicrobial infections), or microbiologic failure (initial
pathogen[s] not eradicated). Microbiologic outcome for each path-ogen was defined as eradication (culture negative or unobtainabledue to improvement/cure), recurrence (eradication at end of therapywith recurrence of same pathogen at long-term follow-up), orsuperinfection (isolation of new pathogen[s] from initial site ofinfection during or immediately after therapy).
Safety parameters that were monitored included changes in vitalsigns, results of clinical laboratory assays, and adverse events.Adverse events were classified by the investigators as to seriousness,
severity (mild, moderate, or severe), and relationship to study drug
(drug-related: reasonable possibility that the event was caused bythe study drug).
All statistical tests were two-sided with p levels <0.05 consideredto indicate statistical significance. All variables were analyzed usingthe 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 varia-bles. The method of weighted least squares was used to computetest statistics for evaluability rate, race, sex, end-of-therapy micro-biologic and clinical cure rates, and end-of-therapy microbiologic
eradication rates. Ordered responses were computed using a mean
score response function,’9 while responses that could not be orderedwere computed using a logit model.” A Fisher’s exact test for 2 x 2tables was computed for medical history frequencies and pretreat-
ment physical examination abnormalities. Fisher’s exact tests werealso used to analyze adverse event data. A x2 analysis was computedfor severity ofinitial infection and in vitro susceptibility categories.
Primary efficacy parameters were analyzed using ANOVA and
confidence limit intervals. When normal ranges for clinical labora-
tory parameters were not supplied by each investigator’s laboratory,
normal ranges were taken from Haistead and Halstead.”
Patient Population
RESULTS
A total of 301 patients, 194 administered cefpo-
doxime proxetil and 107 administered cefaclor, were
enrolled in the study and included in the safety
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CHEST I 104 I 5 I NOVEMBER, 1993 1389
Table 1-Demographic Characteristics (Mean± SkindardDeviation) and Initial Infection Severity
for Efficacy EValUab1#{128}Ibtients
CefpodoximeProxetil Cefaclor p Value
Age, yr 54.2± 17.3 51.9± 16.5 Not significant
Weight, kg 78.9± 18.1 81.0± 19.9 Not significantHeight,cm 168.2±10.4 172.6±11.1 0.022
Sex(%) 0.030Male 46 (46) 32 (65)
Female 54 (54) 17 (35)
Race (%) Not significant
White 85 (85) 43 (88)
Black 7 (7) 3 (6)
Hispanic 8 (8) 2 (4)
Other 0 1 (2)Infection severity (%) Not significant
Mild 34 (34) 13 (27)
Moderate 64 (64) 34 (69)
Severe 2 (2) 2 (4)
analyses. Among patients evaluable for safety there
were no significant differences between the two drug
groups in demographics, infection severity, medical
history, or physical examination abnormalities noted
at admission. Approximately one half of the patientsin both drug groups completed treatment as planned
(cefpodoxime 111 of 194, 57 percent; cefaclor 56 of
107, 52 percent). The most common reason for pre-
mature study discontinuation was ineligibility after
the start of study medication (cefpodoxime 65 of 194,
34 percent; cefaclor 39 of 107, 36 percent), generally
as a result of a negative pretreatment culture.No significant difference in the number of patients
evaluable for efficacy analyses between cefpodoxime
(100 of 194, 52 percent) and cefaclor (49 of 107, 46
percent) treatment groups was observed. The two
most common reasons for nonevaluabiity were nega-
live pretreatment cultures (cefpodoxime 66 of 194, 34
percent; cefaclor 39 of 107, 36 percent), and resistant
pathogens (cefpodoxime 15 of 194, 8 percent; cefaclor
13 of 107, 12 percent). Evaluable patients in the two
treatment groups were similar in age, weight, race,
and infection severity (Table 1). Ninety-seven percent
of cefpodoxime and 92 percent of cefaclor-evaluablepatients received therapy for 10 or 11 days.
Microbiologic Results
Two hundred fifty-nine pathogens were isolated
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
exacerbation of chronic bronchitis.
In vitro susceptibility test results were reported for
256 isolates against cefpodoxime and 255 isolates
against cefaclor. In vitro susceptibility results are
based primarily on MIC criteria and secondarily on
disk zone size. Significantly more (p<O.OO1) pretreat-
ment isolates were susceptible and moderately sus-
ceptible to cefpodoxime than to cefaclor (233 of 256,
91 percent vs 215 of 255, 84 percent, respectively).
Twenty-three pretreatment isolates (9 percent) were
resistant to cefpodoxime, whereas 40 isolates (16
percent), including 6 strains of H influenzae, were
resistant to cefaclor. Results for selected individual
pathogens are listed in Table 2. The MIC1OO of cefpo-
doxime was lower than that of cefaclor against Spneumoniae, H influenzae (f3-lactamase positive or
negative), and H parainfluenzae (�3-lactamase negative)
isolates.
End-of-therapy eradication rates for pathogens in
evaluable patients were similar between cefpodoxime
proxetil (116 of 128, 91 percent) and cefaclor (59 of
64, 92 percent). Eradication rates for the most com-
monly identified pathogens are listed in Table 3.
There were no significant differences in end-of-
therapy microbiologic outcomes of the two treatment
groups. After microbiologic evaluation, 90 of 100 (90percent) cef1�odoxime-treated patients were consid-
ered cured, 7 of 100 (7 percent) partially cured, and 3
of 100 (3 percent) failed; the values for cefaclor-treated
Table 2-In Vitro Susceptibility (Minimum inhibitory Concentration) Reaultsfor Selected Pretreatment Ththogens
No. (%) 0 f Isolates
Cefpodoxime Cefaclor
Moderately Moderately
Susceptible Susceptible Resistant Susceptible Susceptible Resistant
H influenzae 10 (100) . . . . . . 5 (50) 3 (30) 2 (20)
�-lactamase positive
H influenzae 37 (100) . . . . . . 31 (84) 5 (13) 1 (3)
�-lactamase negative
S pneumoniae 25 (100) . . . . . . 25 (100) . . . ...
M catarrhahs 8 (100) . . . . . . 8 (100) . . . ...
f3-lactamase positiveH parainfluenzae 29 (100) . . . . . . 26 (90) 3 (10) ...
�3-lactamase negative
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1390 Cefpodoxime Proxetil vs Cefaclor in COPD (Phillips et a!)
Table 3-Ththogen Eradication Rates in Evoiuable Thtients
(Number ofEradica�ed Pathogens/Number ofPatients With
Assessable I�sthogen Response)for Most Commonlyidentified l�h,�g�ij*
Cefpodoxime,No. (%)
Cefaclor,No. (%)
H influenzae �v3 (100) �3/3 (100)�-Iactamase positive 6/6 (100) 111 (100)
�-lactamase negative 21123 (91) &‘9 (89)
H parainfluenzae &6 (100) 2/2 (100)
�-lactamase positive 2/2 (100) 2/2 (100)
f3-lactamase negative 11112 (92) 10/11 (91)
S pneumoniae 12114 (86) 9/12 (75)
Mcatarrhalis �3 (100) 0
�3-lactamase positive &7 (86) 0fI-lactamase negative 3/3 (100) 1/1 (100)
�These pathogens represent 62 percent (79 of 128) ofthe pathogens
isolated before treatment from valuable cefpodoxime-treated pa-
tients and 64 percent (41 of64) of those isolated before treatment
from evaluable cefaclor-treated patients.
patients were 44 of49 (90 percent), 2 of49 (4 percent),
and 3 of49 (6 percent), respectively. Evaluable patients
presenting with a single pathogen had a higher micro-
biologic cure rate than those with multiple pathogens
in both treatment groups.
Fifteen evaluable patients (10 of 100 evaluable
cefpodoxime patients [10 percent], 5 of 49 evaluable
cefaclor patients [10 percent]) had bacterial persist-
ence at the end-of-therapy evaluation. Pathogens iso-
lated from these patients at the end of therapy were
still susceptible to both study drugs, except for a
Citrobacter diversus isolate (resistant to both drugs by
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 eval-
uated as clinically cured or improved at the end of
therapy.
Maintenance oferadication from the end of therapy
to long-term follow-up in evaluable patients was not
significantly different between drug groups (cefpo-
doxime 96 of 96, 100 percent; cefaclor 47 of 50, 94
percent). Recurring pathogens in the cefaclor group
were Streptococcus morbillorum, S pneumoniae, and
f3-lactamase negative H influenzae. Twelve cefpo-
doxime-treated patients (12 percent) and 13 cefaclor-
treated patients (27 percent) were diagnosed with
superinfections at the interim or end-of-therapy visit.
Clinical Results
Most patient’s cough, intensity of dyspnea, and
sputum production and/or purulence decreased during
the course of the study regardless of therapy. At the
end of therapy, there were no sigificant differences in
positive clinical response (cure + improved) rate (cef-
podoxime 99 of 100, 99 percent; cefaclor 45 of 49, 92
percent) or in distribution of clinical outcomes be-
tween the two drug treatments. For the cefpodoxime-
treated group, 65 of 100 patients (65 percent were
evaluated as having had a clinical cure; 34 (34 percent)
as showing clinical improvement; and 1 patient (1percent) was considered a clinical failure. For the
cefaclor-treated group, 28 of 49 (57 percent) patientswere considered cured; 17 (35 percent) improved; and
4 (8 percent) failed. The sole clinical failure in thecefpodoxime group involved Escherichia coli; clinical
failures in the cefaclor group involved S pneumoniae,
S morbillorum, H influenzae (f3-lactamase negative),
H parainfluenzae (�3-lactamase negative), and Serratia
liquefaciens.
Recurrence at long-term follow-up was similar be-
tween the two drug groups, with 18 percent (16 of 90)
of cefpodoxime-treated patients and 14 percent (6 of
43) of cefaclor-treated patients experiencing a recur-
rence of symptoms.
Safety F�vfile
There were no significant differences observed in
the number of patients experiencing a drug-related
adverse event (cefpodoxime 22 of 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. Gastrointesti-
nal complaints were the most commonly reported
drug-related adverse events for both drug groups.
There were no significant differences observed be-
tween treatment groups in the number of patients
reporting drug-related gastrointestinal events (cefpo-
doxime 17 of 194, 9 percent; cefaclor 8 of 107, 8percent), diarrhea (cefpodoxime 10 of 194, 5 percent;
cefaclor 3 of 107, 3 percent), or nausea (cefpodoxime
5 of 194, 3 percent; cefaclor 3 of 107, 3 percent).
The majority of drug-related events were mild or
moderate for both treatment groups. One cefpodoxime
patient reported severe diarrhea and stomach cramps.
Four patients (3 cefpodoxime, 1 cefaclor) discontinued
the study due to drug-related adverse events (cefpo-
doxime: nausea/vomiting, headache, abdominal
cramps/diarrhea; cefaclor: nausea/heartburn/perioral
numbness).
Changes consistent with resolution ofinfection were
observed in vital signs and clinical laboratory param-
eters. Seven patients (five cefpodoxime, two cefaclor)
experienced potentially clinically significant changes
in laboratory values (increased SGOT, WBC, platelets)
that appeared during the course of the study; the
relationship ofthese abnormal values to study therapy
is not known.
DISCUSSION
Chronic obstructive pulmonary disease is the fifth
most frequently reported cause ofdeath in the United
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CHEST I 104 I 5 I NOVEMBER, 1993 1391
States.� Bacterial exacerbation ofCOPD is associated
with declines in respiratory function and significant
morbidity and mortality; however, precise identifica-
tion of causative pathogens through sputum culture is
not possible in as many as 50 percent of the patients.3
For example, in the present study, 35 percent of the
patients had negative sputum cultures despite signs
and symptoms consistent with acute bacterial exacer-
bation of COPD. Traditionally, therefore, acute exac-
erbation of COPD would be treated by the prompt
initiation of broad-spectrum antibiotic therapy, with
such agents as ampicillin, amoxicillin/clavulanate, ci-
profloxacin, cefaclor, tetracycline, or trimethoprim/
sulfamethoxazole #{149}6Although recommended protocols
using traditional agents are usually effective,6 in recent
years, pathogens commonly associated with acute
exacerbation of COPD have increasingly become re-
sistant to many of these therapies.4’5 Continued devel-
opment ofnew antimicrobial agents and improvement
of currently available agents (eg, broad-spectrum
cephalosporins) are, therefore, essential in order to
minimize the effects of acute exacerbation of COPD
through adequate antimicrobial therapy.
Cefpodoxime proxetil, a new orally administered
prodrug of the extended-spectrum cephalosporin cef-
podoxime, has a broad spectrum of in vitro activity
against those pathogens commonly found in patients
with exacerbation ofCOPD. In the present study, the
MICIOO ofcefpodoxime was lower than that of cefaclor
against S pneumoniae, H influenzae (13-lactamase pos-
itive or negative), and H parainfluenzae isolates. In
addition, significantly more bacterial isolates were
susceptible in vitro to cefpodoxime than to cefaclor.
In the present study, cefpodoxime proxetil therapy
resulted in excellent eradication ofinfecting pathogens
(91 percent), including S pneumoniae, H influenzae,
M catarrhalie, and H parainfluenzae, as well as excel-
lent microbiologic cure rates (90 percent) and positive
clinical response rates (99 percent). In addition, cef-
podoxime proxetil administered twice a day was as
effective as treatment with cefaclor three times a day.
Dosage frequency is an important determinant of
drug comp1iance.� For example, in a study in which
pill containers recorded medication usage, compliance
rose from 59 percent on a tid regimen to 84 percent
on a bid regimen.� Cefpodoxime proxetil’s bid dosing
regimen may help to improve compliance over anti-
biotic regimens that require more frequent dosing.
Compliance may also be influenced by the incidence
and severity of side effects. In the present study,
cefpodoxime and cefaclor were equally well tolerated.
The most frequent side effects of either medication
were gastrointestinal complaints of the type and
frequency usually associated with oral antibiotics.
A potential limitation of any clinical trial is the
population size. To ensure that we obtained sufficienfly
large samples (cefpodoxime- and cefaclor-treated pa-
tients), we generated a series of power curves. We
used the assumptions that the true probability of
success with cefaclor is 0.9 and the number of
evaluable patients given cefpodoxime would be twice
the number given cefaclor. With the sample sizes
attained (100 evaluable cefpodoxime-treated patients
and 49 evaluable cefaclor-treated patients), we calcu-
lated that the probability of correctly concluding that
the rate of success for cefpodoxime proxetil is not
more than 15 percent less than for ceclor was 0.89.
In summary, cefpodoxime proxetil is a safe and
effective treatment for acute exacerbation of COPD.
In this study, cefpodoxime and cefaclor were equally
tolerated and demonstrated similar efficacy with re-
gard to pathogen eradication, as well as positive
clinical and microbiologic patient responses. More-
over, a significanfly greater number of pathogens
isolated before treatment were susceptible or moder-
ately susceptible in vitro to cefpodoxime than to
cefaclor.
ACKNOWLEDGMENT: The authors thank Jay P. Hansen for hishelp in coordinating study activities. The following investigatorsparticipated 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., Char-lotte, 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., RedwoodCity, Calif; John H. Rowlands, M.D., Tacoma, Wash; Judy A. Stone,M.D., Cumberland, Md; Carl P. Weidenbach, D.V.M., M.D.,Plainview, Tex; Chris Zuschke, M.D., Mobile, Ala.
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