Comparison of oral cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections

DIAGN MICROBIOLINFECT DIS 1993;16:123-129

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CLINICAL STUDIES

Comparison of Oral Cefpodoxime Proxetil and Cefaclor in the Treatment of Skin and Soft Tissue Infections Dennis L. Stevens, Francis Pien, and Margaret Drehobl

This multicenter, randomized, double-blind study was designed to compare the safety and efficacy of cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections. Patients were aged >~12 years with acute (<~7 days duration), single-site skin or skin-structure infections. The 7to lO-day treatment regimens were cefpodoxime proxetil (400 mg cefpodoxime) orally with food twice a day with cefaclormatched placebo (orally, fasting, three times a day); or cefaclor (Ceclor; 500 mg anhydrous equivalent) orally, fasting, three times a day, with cefpodoxime-matched placebo (orally with food twice a day). Clinical progress and cultures were evaluated upon admission to the study; on study days 7-10 and 15-18; and 2-3 weeks after treatment. Cefpodoxime had lower minimum inhibitory concentrations against the majority of

Staphylococcus species than did cefaclor. Both treatments were highly effective (99% pathogen eradication and 86% cure rate). These high eradication rates were not unexpected in this study of minor infections in which patients with resistant pathogens were excluded. Cefaclor had a higher failure rate [2 (4%) of 57], than did cefpodoxime 12 (1%) of 139; p not significant]. Most patients in both groups completed treatment as planned: 185 (74%) of 249 cefpodoxime-treated patients and 91 (75%) of 122 cefaclor-treated patients. Both treatments were well tolerated and considered safe and effective in the treatment of skin and skin structure infections. However, the twice-a-day dosing regimen for cefpodoxime proxetil compared with the three-times-a-day regimen for cefaclor may result in better patient compliance.

INTRODUCTION

past 20 years, a variety of antibiotics including dicloxacillin, erythromycin, clindamycin, a n d oral cephalosporins, such as cefaclor and cephalexin, have been used effectively in the treatment of skin infections. Recently, however, a n u m b e r of n e w cephalosporins produced by modification of the cephalosporin nucleus at positions 3 or 4 have become available for clinical use (Wise, 1990). These n e w cephalosporins, absorbed as either the parent comp o u n d or from a pro-drug formulation, tend to have longer half-lives and better tissue penetration than do earlier cephalosporins (Wise, 1990). Cefpodoxime proxetil is a new, oral pro-drug of cefpodoxime with a broad spectrum of activity (Wise, 1990; Holt et al., 1990; Fass a n d Helsel, 1988; Jones and Barry, 1987 and 1988). The ester linkage of cefpodoxime proxetil is h y d r o l y z e d in the gastrointestinal mucosa, allowing absorption of the active parent molecule, cefpodoxime. In vitro, cefpodoxime is active against such skin pathogens as St. pyogenes, S.

Skin and skin-structure infections (such as infected w o u n d s and burns, furuncles, carbuncles, folliculitis, cellulitis, abscesses, and pyoderma) are commonly caused by Streptococcus (St.) pyogenes or Staphylococcus (S.) aureus. In addition, in patients with underlying disease, Escherichia coU, Proteus mirabilis, and m a n y other pathogens m a y play a role. For the From the VA Medical Center (D.L.S.), Boise, Idaho; Departments of Medicine (F.P.), Straub Clinic, and the John A. Burns School of Medicine (F.P.), University of Hawaii, Honolulu, Hawaii; and Scripps Clinic and Research Foundation (M.D.), San Diego, California, USA. Address reprint requests to Dr. D.L. Stevens, Chief, Infectious Disease, VA Medical Center, 500 W. Fort Street, Boise, ID 83702, USA. Received 22 July 1992; revised and accepted 30 October 1992. © 1993 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/93/$6.00

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epidermidis, and S. aureus (including peniciUinase- and non-penicillinase-producing strains) (Wise, 1990; Holt et al., 1990; Fass and Helsel, 1988; Jones and Barry 1987 and 1988). In addition, cefpodoxime has a marked resistance to inactivation by most ~-lactamases (Jones and Barry, 1987). Cefpodoxime proxetil has been shown to have excellent tissue penetration and pharmacokinetics (for example, 2.1- to 2.8-h half-life) (Borin et al., 1990; O'Neill et al., 1990). It was found to be effective in the treatment of skin and soft tissue infections in a large, multicenter clinical trial in Japan (Yura et al., 1988). This multicenter, randomized, double-blind phaseIII study was designed to compare the safety and efficacy of cefpodoxime proxetil (400 mg cefpodoxime, b.i.d.) and cefaclor (500 mg, t.i.d.) in the treatment of skin and soft tissue infections.

MATERIALS AND METHODS Patients Patients (aged />12 years and weighing >40.9 kg) with the signs and symptoms of acute (47 days duration), single-site skin or skin-structure infection (wound infection, folliculitis, cellulitis, ulcers, carbuncles, furuncles, abscesses, small burns, or infected dermatitis) were enrolled in the study. Patients were excluded from the study if they had hypersensitivity to cephalosporins, cephamycins, or penicillin; had used oral antimicrobial therapy or topical therapy (except antituberculous therapy or unsuccessful self-treatment with over-the-counter preparations for 42 days) within 5 days of entry; had neutropenia [white blood count (WBC) <2000/mm3], renal impairment (creatinine >2.5 mg/dl), or hepatic dysfunction (SGPT or ALT >200 IU/1, or bilirubin >3 mg/dl); had immunologic disease or neoplasm that occurred in the same body area or compromised general health; had severe vascular insufficiency to the infected site; had diabetic foot ulcer; septic arthritis, or osteomyelitis; or were currently enrolled in any other investigational procedure or had been previously enrolled in any cefpodoxime study. Female patients who were pregnant or breast feeding, or not practicing an acceptable contraceptive method, were also excluded. Patients whose admission cultures were negative, yielded a single organism that was not considered to be a pathogen, or contained any pathogens resistant to either study drug were not included in the study. However, patients with polymicrobial infections in which one pathogen was resistant, and, in the opinion of the investigator, was only colonizing the infected area, could be retained in the study. Patients were required to have taken at least 80% of the study medication without missing two

D.L. Stevens et al.

(cefpodoxime) or three (cefaclor) consecutive doses in order to be evaluated for efficacy. In addition, patients had to have a pathogen (isolated at admission from the infected site) that was susceptible to both cefpodoxime and cefaclor and have had repeat evaluation 0-6 days after therapy in order to be clinically evaluable.

Study Design In this multicenter, double-blind clinical trial, patients were randomized (2:1) to receive either (a) cefpodoxime proxetil (400 mg cefpodoxime, orally with food) twice a day with cefaclor-matched placebo (orally, fasting) three times a day; or (b) cefaclor (Ceclor, 500 mg anhydrous equivalent, orally, fasting) three times a day with cefpodoxime-matched placebo (orally, with food) twice a day. Treatment was to last 14 days; however, therapy could be discontinued after 7 days if a complete clinical cure was observed. At admission (visit 1) medical history was obtained; a physical examination (including vital signs), routine clinical laboratory tests (hematology, serum chemistry, and urinalysis), Coombs' test, and pregnancy test (if applicable) were performed; Gram stains and aerobic cultures were made of drainage from the infected site, and the material was evaluated for the presence of bacteria and white blood cells; and the severity of signs and symptoms was rated (mild--superficial layers of skin in a small area; moderate--superficial layers and limited involvement of deeper layers in a large area with some functional impairment; and severe--very large areas of involvement with deep penetration, systemic symptoms, and functional impairment). Clinical progress, Gram's stain and cultures, and clinical laboratory tests were evaluated at visit 2 (study days 7-10) and visit 3 (study days 15-18, end of treatment). At visit 4 (2-3 weeks after treatment), the patient's clinical condition was assessed; vital signs were obtained; and, if infection persisted or drainage was present, Gram stain and culture were performed. The microbiologic response was defined as follows: cure--each initial pathogen eradicated at endof-therapy visit; partial cure--some but not all pathogens eradicated; or failure--no initial pathogens eradicated. The clinical response was categorized as follows: cure---complete resolution of signs and symptoms of infection; or improvement--substantial improvement in signs and symptoms of infection; or Failure---condition unchanged or worse.

Susceptibility Testing Susceptibility was defined on the basis of zone diameter of inhibition using 10 ~g cefpodoxime (417

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Cefpodoxime versus Cefaclor for Skin Infection

mm resistant, 18-20 m m moderately susceptible, and /21 mm susceptible) and 30 ~g cefaclor (~14 m m resistant, 15-17 mm moderately susceptible, and ~18 mm susceptible) disks. In addition, MIC criteria for susceptibility were based on the recommendations of Jones and Barry (1988) (cefpodoxime ~8 ~g/ml resistant, 4 ~g/ml moderately susceptible, and ~2 ~g/ml susceptible) and the National Committee for Clinical Laboratory Standards (NCCLS) (cefaclor MIC ~32 ~g/ml resistant and ~2 ~g/ml susceptible) (NCCLS, 1990a and b). MIC testing was performed by a central reference laboratory at Thomas Jefferson University, Philadelphia.

Statistical Methods The targets for patient enrollment for this study were calculated based on a test, described by Blackwelder (1982) and Makuch and Simon (1978), of the null hypothesis that the probability of success with cefaclor was at least a given (that is, "clinically significant") amount better than that with cefpodoxime. We assumed that the true probability of success with cefaclor was 0.9, with the targeted enrollment of 120 evaluable cefpodoxime and 60 evaluable cefaclor patients. Therefore, we note that the probability of correctly concluding that the success rate for cefpodoxime was not more than 15% and less than that for cefaclor was 0.94. Primary efficacy measures included end-of-therapy microbiologic and clinical cure rates and pathogen eradication rates. Statistical analysis of efficacy and safety results from all patients (that is, intentionto-treat analysis) was performed and revealed no significant differences between the two treatment groups. Efficacy results reported herein reflect analyses of evaluable patients only. All statistical tests were two-sided with a significance level of P ~ 0.05. Continuous variables (including age, weight, height, pretreatment signs and symptoms, vital signs, and clinical laboratory assays) were analyzed using analysis of variance (ANOVA). In addition, paired t-tests were used to test changes within treatment groups from baseline to follow-up. Parameters with significant t-tests were analyzed using the following basic analysis model to evaluate differences between treatments: result = mean (overall mean) + treatment (effect of study drug) + error (random error term, symmetric about zero). Categorical variables (including evaluability proportion, race, sex, cure rates, and eradication rates) were analyzed using weighted least squares and/or response functions (Grizzle et al., 1969) and/or logit model (Feinberg, 1980). A Fisher's exact test for 2 x 2 tables was computed for infection history, medical history frequencies, and pretreatment physical exam abnormalities. In addition, Fisher's exact test was used in the analysis of

adverse event incidence. The two groups were compared as to distribution of pretreatment in vitro disk susceptibility categories (chi-square test), and pathogen eradication versus recurrence rates and clinical cure versus recurrence rates at long-term follow-up (Fisher's exact test).

RESULTS Patients All 371 patients enrolled in the study (249 cefpodoxime and 122 cefaclor) were evaluable for safety. The majority of patients in each treatment group completed therapy as planned [185 (74%) of 249, cefpodoxime; 91 (75%) of 122, cefaclor]. Approximately half of the patients in each treatment group were evaluable for efficacy [139 (56%) of 249, cefpodoxime; 57 (47%) of 122, cefaclor]. The primary reasons for nonevaluability in both groups were resistant pathogens (15%), negative pretreatment cultures (10%), and patients lost to follow-up (5%). Severity of pretreatment infection for evaluable patients was as follows: severe--16 (12%) cefpodoxime and 7 (12%) cefaclor; moderate---89 (64%) cefpodoxime and 34 (60%) cefaclor; and mild--34 (25%) cefpodoxime and 16 (28%) cefaclor. Duration of treatment for evaluable patients was as follows: cefpodoxime--7-8 days, 54%; 9-13 days, 9%; 14-15 days, 37%; and 16 days, 1%; and cefaclor--7-8 days, 44%; 9-13 days, 7%; 14-15 days, 46%; and 16-17 days, 4%. During the treatment phase of the study, patients assigned to cefpodoxime received 400-12,400 mg of medication (mean of all patients, 7200 + 3300 rag; and mean of evaluable patients, 8000 ___ 2700 rag), whereas those assigned to cefaclor received 50024,000 mg (mean of all patients, 13,900 + 6100 mg; and mean of evaluable patients, 16,300 + 5300 rag). The demographic characteristics, diagnosis, and infection history of patients evaluable for efficacy are summarized in Table 1. The two treatment groups were well matched. No statistically significant differences (except for weight and previous infection; see Table 1) or clinically significant differences were noted between treatment groups.

Microbiologic Susceptibility The most common pathogens isolated in pretreatment cultures included S. aureus (~-lactamase-positive, ~-lactamase-negative, and ~-lactamase status unknown), S. epidermidis, S. haemolyticus, S. hominis, S. warneri, S. pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. The susceptibility of these clinical isolates was as follows:

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TABLE 1 D e m o g r a p h i c Characteristics, Diagnosis, and Infection History of Patients Evaluable for Efficacy Analysis Parameter

Cefpodoxime

Cefaclor

Age, year (mean +_ SD)

42.2 + 17.7 (n = 139)

44.2 _+ 18.9 (n --- 57)

Weight, kg (mean _+ SD)~

81.7 _+ 20.2 (n = 138)

75.5 -+ 16.8 (n -- 57)

Height, cm (mean _+ SD)

172.4 _+ 10.9 (n = 138)

Race, no. (%) White Black Asian Hispanic Other

109 11 8 6 5

(78) (8) (6) (4) (4)

170.5 +_ 9.6 (n = 56) 44 6 2 3 2

(77) (11) (4) (5) (4)

Sex, no. (%) Male Female

93 (67) 46 (33)

30 (53) 27 (47)

Diagnosis, no. (%) Abscess Acute burn Carbuncle Cellulitis Folliculitis Furuncle Infected wound Paronychia Pyoderma Ulcer Other

48 (35) 1 (1) 3 (2) 24 (17) 3 (2) 10 (7) 22 (16) 9 (6) 5 (4) 1 (1) 13 (9)

20 (35) 0 1 (2) 10 (18) 2 (4) 5 (9) 12 (21) 5 (9) 0 1 (2) 1 (2)

Previous skin infection, b no. (%) No Yes

79 (57) 60 (43)

41 (72) 16 (28)

aCefpodoxirne patients were significantly (P = 0.04) heavier than cefaclor patients. bMore cefpodoxime than cefaclor patients (P = 0.054) had a previous skin infection.

susceptible--367 (89.1%) of 412, cefpodoxime; and 375 (90.8%) of 413, cefaclor; m o d e r a t e l y susceptib l e - 2 3 (5.6%) of 412, cefpodoxime; and 104 (2.5%) of 413, cefaclor; and resistant--22 (5.3%) of 412, cefpodoxime; and 28 (6.8%) of 413, cefaclor. Overall, the two t r e a t m e n t g r o u p s w e r e similar with respect to the in vitro susceptibility for p a t h o g e n s with reported m i n i m u m inhibitory concentration (MIC) and/or disk z o n e size. H o w e v e r , the MICs against the majority of the Staphylococcus species (13-1actamase-positive S. aureus, S. epidermidis, and S. warneri; Tables 2 a n d 3) and St. pyogenes (MIC10o 0.03 p,g/ml vs 0.50 t~g/ml) w e r e lower with cefpodoxime than with cefaclor.

TABLE 2

In vitro Susceptibility of P r e t r e a t m e n t Isolates of Selected Staphylococcus Species Cumulative No. (%) of Isolates Susceptible

MIC (l~g/ml)

Cefpodoxime

Cefaclor

0.50 1.00 2.00 4.00 8.00 16.00 32.00

Staphylococcus aureus 13 lactamase positive 1 (1) 1 (1) 86 (70) 33 (27) 111 (90) 83 (67) 122 (99) 109 (89) 123 (100) 120 (98) 123 (100) 122 (99) 123 (100) 123 (100)

0.50 1.00 2.00 4.00

3 19 22 23

Staphylococcus aureus [3 lactamase negative (13) 3 (13) (83) 15 (65) (96) 22 (96) (100) 23 (100)

0.25 0.50 1.00 2.00 4.00

11 43 57 57 58

Staphylococcus epidermidis (19) 1 (1) (74) 7 (12) (98) 41 (71) (98) 55 (95) (100) 58 (100)

0.50 1.00 2.00 4.00

2 5 5 5

Staphylococcus warneri (40) 0 (100) 0 (100) 3 (60) (100) 5 (100)

R e s p o n s e Rates At the e n d of therapy, 99% of the p a t h o g e n s in evaluable patients were eradicated in both the cefpodoxime (169 of 171) a n d the cefaclor (74 of 75) treatm e n t groups. A total of 137 (99%) of 139 patients treated with cefpodoxime and 56 (98%) of 57 patients treated with cefaclor had eradication of their infecting pathogen(s). The p a t h o g e n s f o u n d in the three patients w h o were not microbiologic cures were S. epidermidis a n d St. agalactiae (one cefpodoxime patient each), and S. aureus (one cefaclor patient). T r e a t m e n t with both s t u d y drugs resulted in an 86% clinical cure rate. The p a t h o g e n s that accounted for the four failures were t w o S. agalactiae, one S. canis, and one 13-1actamase-positive S. aureus for the cefpodoxime t r e a t m e n t group; a n d two [3-1actamasepositive S. aureus for the cefaclor t r e a t m e n t group. There were no significant differences b e t w e e n the two treatments in p a t h o g e n eradication, bacterio-

Cefpodoxime versus Cefaclor for Skin Infection

TABLE 3

Eradication Rates for Selected Staphylococcus Species

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TABLE 5

End-of-Therapy Clinical Response for Evaluable Patients

No. (%) of Patients Patient Group

Cefpodoxime

Cefaclor

No. (%) of Patients Evaluation

Cefpodoxime

Cefaclor

Evaluable patients a Nonevaluable patients

Staphylococcus aureus [3 lactamase positive 54/54 (100) 19/20 (95) 31/32 (97) 9/12 (75)

Cure Improvrnent Failure

Evaluable patients Nonevaluable patients

Staphylococcus aureus 13lactamase negative 11/11 (100) 5/5 (100) 2/2 (100) 4/5 (80)

Cure Improvement Failure

Patients with single pathogen 99 (88) 38 (84) 13 (12) 5 (11) 1 (1) 2 (4)

Evaluable patients a Nonevaluablepatients a

Staphylococcus epidermidis 27/28 (96) 19/19 (100) 9/10 (90) 5/5 (100)

Evaluable patients a Nonevaluable patients

Staphylococcus warneri 4/4 (100) 1/1 (100) 0 0

Cure Improvement Failure

Patients with multiple pathogens 21 (81) 11 (92) 4 (15) 1 (8) 1 (4) 0

Cure Improvement Failure

Patients with surgical intervention 50 (89) 21 (84) 6 (11) 4 (16) 0 0

Cure Improvement Failure

Patients without surgical intervention 70 (84) 28 (88) 11 (13) 2 (6) 2 (2) 2 (6)

qncludes patients in whom same genus and species pathogens showed different susceptibility profiles. logic cure, or clinical cure rates (Tables 4 and 5). However, the clinical failure rate for cefpodoxime (1%) was lower than that for cefaclor (4%) (Table 5). In addition, the response rate (cure + improvement) for patients with infected w o u n d s was higher for cefpodoxime patients [22 (100%) of 22] than for cefaclor patients [10 (83%) of 12]. TABLE 4

End-of-Therapy Bacteriologic Response for Evaluable Patients No. (%) of Patients

Evaluation

Cefpodoxime

Cefaclor

Cure Failure

All evaluable patients 137 (99) 56 (98) 2 (1) 1 (2)

Cure Failure

Patients with single pathogen 11 (98) 44 (98) 2 (2) 1 (2)

Cure Failure

Patients with multiple pathogens 26 (100) 12 (100) 0 0

Cure Failure

Patients with surgical intervention 55 (98) 24 (96) 1 (2) 1 (4)

Cure Failure

Patients without surgical intervention 82 (99) 32 (100) 1 (1) 0

All evaluable patients 120 (86) 49 (86) 17 (12) 6 (11) 2 (1) 2 (4)

There were no significant differences in eradication for cure rates a m o n g patients with single or multiple pathogens, or with or w i t h o u t surgical intervention; however, all the end-of-therapy clinical failures for evaluable patients occurred in patients w h o did not receive surgical intervention (Table 5). Safety No significant differences were observed between the two drug treatments in either overall adverse medical-event frequency or severity or drug-related adverse-event frequency or severity. Of the 249 cefpodoxime-treated patients, 47 (18.9%) reported 64 adverse events j u d g e d by the investigator to be drug related; 18 (14.8%) of the 122 cefaclor-treated patients reported 28 such events. Gastrointestinal disturbance was the most c o m m o n l y reported complaint in both treatment groups, affecting 38 (15.3%) of the cefpodoxime-treated patients and 11 (9.0%) of the cefaclor-treated patients. There were no statistically significant differences b e t w e e n treatment groups in the frequency or type of drug-related adverse events. The majority of adverse events for both drug groups were mild, with 14% of the events in

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both groups rated as severe. Fifteen cefpodoximetreated patients (6%) and four cefaclor-treated patients (3%) withdrew from the study due to adverse events, including both drug-related events (such as diarrhea, nausea, and headache), as well as nondrug-related events (such as increased urination at night and an auto accident). There were no significant differences between treatment groups in the percentage of patients who dropped out of the study. One patient in the cefpodoxime group died of a myocardial infarction judged not to be related to the study medication. No drug-related clinically significant or serious changes in vital signs or clinical laboratory parameters, except those associated with the resolution of infection, were noted. However, eight cefpodoxime and 11 cefaclor patients developed elevated SGPT values during the study, possibly related to alcohol abuse.

D.L. Stevens et al.

or type of drug-related adverse events. (The P value for ~ error in this study was determined to be 0.11.) In contrast to cefaclor, in which the presence of food results in a 50% reduction in maximum serum concentration, cefpodoxime is better absorbed after food intake (Wise, 1990; Hughes et al., 1989 and 1990; Glynne et al., 1978). In addition, cefpodoxime has a better tissue penetration and a longer elimination half-life than did cefaclor and other traditional cephalosporins, allowing for dosing twice a day rather than three times a day (Wise, 1990; O'Neill et al., 1990; Yura et al., 1988). The twice-daily dosing regimen of cefpodoxime may result in better patient compliance. It has been shown that compliance improves dramatically as prescribed dose frequency decreases (Pullar et al., 1988; Eisen et al., 1990). For example, in one study that employed a pill container that recorded the time and date of medication removal, compliance increased from 59.0% on a t.i.d. regimen to 74.9% on a b.i.d, regimen (Eisen et al., 1990).

DISCUSSION Cefpodoxime proxetil is a new broad-spectrum oral cephalosporin (Wise, 1990; Fass and Helsel, 1988; Utsui et al., 1987). In the present study, cefpodoxime proxetil (400 mg cefpodoxime) b.i.d, was as safe and effective as cefaclor (500 mg) t.i.d, in the treatment of skin and skin structure infections. Each treatment resulted in a clinical cure rate of 86% and a pathogen eradication rate of 99%. The clinical failure rate for cefaclor was 4%; for cefpodoxime, 1% (P NS). Although the in vitro activity profiles of both agents were excellent, cefpodoxime showed lower MICs against the majority of Staphylococcus species and St. pyogenes isolates. This result is supported by previous reports of cefpodoxime's greater antimicrobial activity against such Staphylococcus species as S. aureus when compared with traditional oral antibiotics (that is, cefaclor or amoxicillin) (Chang et al., 1990; Wiedemann and Jansen, 1990; Yokota et al., 1988). Both cefpodoxime and cefaclor were well tolerated by patients enrolled in this study. The most commonly reported adverse events for both cefpodoxime and cefaclor involved gastrointestinal disturbances, primarily diarrhea and nausea, typical of oral antibiotic agents. There were no significant differences between the two groups in the frequency

CONCLUSION Cefpodoxime twice a day and cefaclor three times a day were equally safe and effective in the treatment of skin and skin structure infections. Because it must be taken only twice a day and can be taken without regard to food intake, cefpodoxime may result in better patient compliance than that found with cefaclor or other traditional cephalosporins that must be taken three times a day. This study was supported in part by the Upjohn Company, Kalamazoo, Michigan. The following investigators participated in this study: Maxwell Barus, MD, Leads, ME; Marvin J. Bittner, MD, Omaha, NE; Charles W. Chappuis, MD, New Orleans, LA; Scott D. Clark, MD, Longmont, CO; Steven Curry, MD, Phoenix, AZ; Margaret Drehobl, MD, San Diego, CA; R. Brooks Gainer II, MD, Morgantown, WV; Bernard F. Gipson, Jr., MD, Denver, CO; Benjamin A. Lipsky, MD, Seattle, WA; Frank Padberg, Jr., MD, East Orange, NJ; Francis D. Pien, MD, Honolulu, HI; Anthony Puopolo, MD, Milford, MA; Paul G. Sandall, MD, Albuquerque, NM; Malcolm Sperling, MD, Fountain Valley, CA; Dennis L. Stevens, MD, PhD, Boise, ID; Terry L. Swezey, MD, Vero Beach, FL; Syde Taheri, MD, Buffalo, NY; and John A. Weigelt, DVM, MD, Dallas, TX.

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Cefpodoxime v e r s u s Cefaclor for Skin Infection

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