1387

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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