PHARMACOLOGY AND THERAPEUTICS

ERYTHROMYCIN VERSUS CEEADROXIL IN THE TREATMENT OF SKIN INFECTIONS NEIL S. HESKEL, M.D,,* NANCY C, SIEPMAN, PH.D., PHILIP J. PICHOTTA, B.S., ELIZABETH M. GREEN, B.S., AND RALPH W. STOLL, M.D.

Abstract

We excluded patients for the following reasons: those who had any chronic underlying skin infection or concurrent infection that might interfere with the efficacy evaluation of the acute infection; were pregnant or lactating; were being treated for burns or with either study drug for acne; were receiving any topical or systemic antibiotic or corticosteroid for the skin infection or had received a systemic antibiotic within 3 days of the start of the study; were suspected of having bacteremia; had a history of sensitivity to p-lactam or macrolide antibiotics; had been treated with an investigational drug within 4 weeks or with a long-acting injectable antibiotic within 6 weeks of entering the study; had a clinically significant impairment of hepatic function or any condition that would interfere with gastrointestinal absorption. All patients signed an informed consent before proceeding with the study. Each patient had a complete medical history and physical examination at the initial visit, including blood pressure, heart rate, body temperature, height, weight, clinical signs and symptoms, and a description of the infection site. Laboratory tests included hematology and coagulation determinations, serum chemistry, and urinalysis. Patients were assigned t'andomly to either the erythromycin or cefadtoxil groups, with equal number of patients randomized to each of the two drugs at each study site. The infection site was cultured within 48 hrs before study drug administration, except where the diagnosis was cellulitis (no culture was required in these cases). Each study site used local laboratories to identify the pathogen(s) and to determine susceptibility to both erythromycin and cefadroxil, using either disc zone size or MIC (mean inhibitory concentration) assays. The baseline pathogen(s) had to be sensitive to both erythromycin and cefadroxil, Penicillinase production was determined for Staphytococcus aureus isolates. Patients were allowed to enroll before culture results were known. Patients returned for a brief physical examination and assessment of clinical improvement after 3 to 5 days of therapy, and again at the end of treatment. Drug compliance, concomitant medications, and adverse events were recorded at the interim and final visits. If any patient left the study early, the investigator made every effort to obtain end-of-study data, including a physical examination, review of signs and symptoms, and repeat cultures and laboratory tests. Patients were withdrawn automatically from the study if there was no improvement in the infection after at least 3 days of therapy, if discontinuation was in the best interest of the patient (e.g., because of an adverse event), or at the patient's request. At the final visit, the culture of the infection site was repeated (if culturable material was available), and response to therapy was determined. The response was defined as a

Erythromycin is often overlooked for the treatment of skin and skin structure infections. We evaluated the efficacy and safety of erythromycin particles in tablets and of cefadroxil in 164 patients with skin infections; both treatments were given as 500 mg twice daily. One hundred percent of erythromycin and 96% of cefadroxil patients were clinically cured or improved, and 98% of susceptible pathogens were eradicated in both groups. Only three erythromycin patients and one cefadroxil patient left the study early because of GIrelated adverse events. Erythromycin, therefore, was as effective and safe as cefadroxil in the treatment of mild-tomoderate skin infections,

Staphylococcus aureus and group A streptococci cause the majority of acute pyogenic skin infections seen by the practitioner, which result most often from minor trauma. ^"^ Tbese infections usually are treated empirically, without the time and expense associated with bacterial cultures. Tbe choice of an antibiotic depends on expected efficacy, safety, and side-effect profile, or even cost considerations.'*'^ Although erythromycin is an effective, inexpensive tberapy for skin and skin structure infection, it is often overlooked as first-line therapy. We compared tbe efficacy and safety of erythromycin particles in tablets and cefadroxil, botb given as 500 mg twice daily, in tbe treatment of skin and skin structure infections in this randomized, double-blind, multi-center study. Materials and Methods The study population included adolescents and adults with skin or skin structure infections, either outpatients or hospitalized patients, who weighed at least 45.4 kg (100 pounds) and were otherwise in good health. Patients were admitted to the study with any of the following diagnoses: impetigo, cellulitis (including erysipelas), folliculitis, furunculosis, carbunculosis, abscess, wound infection, or infected sebaceous cyst. From the * Doctors' Clinic, Vero Beach, Elorida, and the Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois. Supported by a grant from Abbott Laboratories, Abbott Park, Illinois. Address for correspondence: Neil S. Heskel, M.D., 17 E Silver Palm Ave,, Melbourne, FL 32901. u , , V 131

International Journal of Dermatology Vol. 3t, No. 2, February 1992

clinical cure if the pretreatment signs and symptoms associated with the infection resolved within 72 hours after completion or discontinuation of treatment. If the pretreatment signs and symptoms associated with the infection improved but did not resolve within 72 hours after completion or discontinuation of treatment, then the response to therapy was defined as improved.

infections, were clinical failures, compared witb none in tbe erytbromycin group; tbis difference was not statistically significant (P=0.496). The clinical success of treatment was not related to factors sucb as investigator, sex, age, race, weigbt, or treatment duration. Twenty-one different pathogens were isolated from pretreatment cultures, for a total of 107 isolates (several patients had more than one pathogen identified). S. aureus, the most prevalent orgatiism, was isolated frotn 53 patients. Approximately 7 5 % of tbe isolated pathogens were susceptible to botb erytbromycin and cefadroxil. Two stapbylococci isolates were resistant to erytbromycin and none to cefadroxil. (Of 61 stapbylococci isolates from all patients, evaluable and nonevaluable, only four were resistant to erytbromycin and one to cefadroxil.) Only one patient in eacb group failed to bave eradication of a prestudy organism, for a bacteriologic cure rate of 98% in botb groups. Almost ail patients bacteriologic responses were consistent witb clinical outcomes. Of tbe 42 patients excluded from tbe efficacy evaluation because eitber no pathogen or no susceptible patbogen was isolated before treattnent, 28 patients lacked an isolated patbogen and 14 had no susceptible pathogens at baseline. Of the erythrotnycin-treated patients in tbe latter category (n=ll), tbere were six cases of resistance to S. epidermidis; two cases of resistance to eacb of four patbogens, E. aerogenes, P, aeruginosa, S. simulans,and stapbylococci coagulase-tiegative; and single cases of resistance to each of tbe following patbogens, S. aureus, C. freundii, and P-bemolytic streptococci. Of cefadroxil-treated patients who were excluded for the same reason (n=3), there were two cases of resistance of each £. aerogenes and P. aeruginosa. Interestingly, nine of tbe erythromycin-treated patients and two of the cefadroxil-treated patients experienced total eradication, although tbe response of tbe remaining patients was indeterminable due to a lack of information following treatment. Forty-three percent (35/82) and 30% (25/82) of tbe patients in tbe erytbromycin and cefadroxil groups, respectively, reported at least one adverse event, for a total of 106 reports. Tbis difference was not statistically significant (P=0.144). Tbe most common adverse events in botb groups were gastrointestinal complaints, reported by 35% (29/82) of the erythromycin-treated patients and 13% (11/82) of tbe cefadroxil-treated patients. Most of these complaints were mild to moderate in severity and included nausea, diarrhea, and abdominal pain. Three adverse events in each group (nausea, abdominal pain, and dyspepsia for eryrhromycin; headache, asthenia, and vomiting for cefadroxil) were classified as severe. Five patients in the erythromycin group (6%) and three in the cefadroxil group (4%) left the study early because of adverse events, tbree (4%) and one (1%) in each group, respectively, because of gastrointestinal complaints.

RESULTS

One hundred and sixty-four patients enrolled in tbe study, with 82 in each treatment group. A total of 59 patients were excluded from the efficacy evaluation before the study blind was broken, for the following reasons: either no pathogen or no susceptible pathogen was isolated before treatment (42 patients); pretreatment susceptibility results were not available (5 patients); less than minimum drug therapy (3 days) was taken (4 patients); there was no post-treatment culture (4 patients); less than 70% of tbe prescribed medication was taken (2 patients); inappropriate concomitant medications were taken (1 patient); or there was no post-treatment clinical assessment (1 patient). As a result, 105 patients had evaluable data at tbe end of the study, witb 51 in the erythromycin group and 54 in the cefadroxil group. The following discussion, with tbe exception of tbe safety evaluation, and where noted, is based on tbese 105 patients. Drug therapy lasted more commonly for 8 to 14 days (32 patients in tbe erythromycin group and 35 in the cefadroxil group). Twenty-four patients took their medication for longer than 14 days, eitber because of missed doses or because the first dose was taken in the afternoon of the first day atid the last dose on the 15th day. Thirteen patients received more than 3 but less tban 8 days of tberapy, but were still considered evaluable. Altbough it would have been optimal to treat all patients for the same period we believe that tbis duration of therapy does not affect tbe validity of tbe study. There were no statistically or clinically significant differences between treatment groups or between evaluable and nonevaluable patients with respect to demographic characteristics. The most common, diagnoses were cellulitis (26 patients), infected sebaceous cyst (15 patients), folliculitis (14 patients), abscess (13 patients), and impetigo (12 patients). The clinical evaluation included 49 erythromycintreated patients and 54 cefadroxil-treated patients (two patients in the erythromycin group were clinically unevaluable). Eighty percent (39/49) of the erythromycin group and 70% (38/54) of tbe cefadroxil group were clinically cured after the last dose. An additional 10 erythromycin patients and 14 cefadroxil patients were classified as improved, for overall clinical success rates (cured or improved) of 100% and 96% for the erythromycin and cefadroxil groups, respectively. Two patients in the cefadroxil group, both with wound 132

Treatment of Skin tnfections Heskel et al.

Charles Parish, M,D., Philadelphia, Pennsylvania; Gary E. Ruoff, M.D., Kalamazoo, Michigan; and John A. Strobis, M.D., Boca Raton, Elorida.

CONCLUSIONS

In this study, we evaluated tbe use of erythromycin particles in tablets and of cefadroxil, eacb given as 500 mg twice daily, in the treatment of skin and skin structure infections. We found no differences between treatments by eitber measure of efficacy: clinical success rate or bacteriologic response. Previous reports established tbe efficacy of twice daily erythromycin therapy in pharyngitis,*"" but minimal published information is available on this regimen in the treatment of skin

REFERENCES

1. 2. 3.

Dillon'^ compared the use of erytbromycin and clindamycin, botb drugs given twice daily in tbe treatment of streptococcal, stapbylococcal, and mixed streptococcal-stapbylococcal skin infections. After 10 days of tberapy, bacteriologic cure rates were 82% and 83% for clindamycin and erythromycin, respectively. Bleeker'-* evaluated tbe efficacy of two forms of erytbromycin, both given as 500 mg twice daily, in 20 patients with papulopusttilar acne, with improvement measured as reduction in the number of papules and pustules. Both erythromycin base and stearate formulations were effective in reducing tbe number of lesions in tbese patients. Our study bas confirmed tbe efficacy of twice daily dosing of erytbromycin base (as erytbromycin particles in tablets) in a variety of skin infections, witb clinical success and bacteriologic eradication rates of 100% and 98%, respectively.

4.

5. 6.

7.

8. 9.

10. DRUG NAMES

11.

erytbromycin: PCE, E-Mycin, Robimycin cefadroxil: Duricef Acknowledgments: The following investigators participated in the study: Reid Binder, M.D., Oceanside, California; Rohert G, Hassett, D.O., Arlington, Texas; Wilbert C. Jordan, M.D., Compton, California; M. Rashid A. Khairi, M.D,, Indianapolis, Indiana, Gabriel Mayer, M.D., Orlando, Florida; Roland S, Medansky, M.D,, Chicago, Illinois; Lawrence

12. 13.

Causey WA. Staphylococcal and streptococcal infections of the skin. Prim Care 1979; 6:127-139. Feldman P, Lunfield Y. Antibiotic choice for pyodermas (letter), J Am Acad Dermatol 1987; 17:859-860. Green HG. Cephalosporin therapy of soft tissue infections: An overview. J Int Med Res 1980; 8(suppl. 1) :53-57. Derrick CW, Reilly K. The role of cephalexin in the treatment of skin and soft tissue infections. Postgrad Med J 1983; 59(suppl. 5):43-46. Feingold DS, Wagner RF. Antibacterial therapy. J Am Acad Dermatol 1986; 14:535-548. Shapera RM, Hable KA, Matsen JM. Erythromycin therapy twice daily for streptococcal pharyngitis. JAMA 1973; 266:531-535. Jackson D, Thomas HB. The clinical and bacteriological assessment of a twice daily formulation of erythromycin stearate: A general practice study. J Int Med Res 1975; 3:77-85. Derrick CW, Dillon HC, Erythromycin therapy for streptococcal pharyngitis. Am J Dis Child 1976; 130:175-178, Ginsburg CM, McCracken GH, Steinberg JB, et al. Management of Group A streptococcal pharyngitis: A randomized controlled study of twice-daily erythromycin ethylsuccinate versus erythrornycin estolate. Ped InfDis 1982; 1:384-387. Ginsburg CM, McCracken GH, Crow SD, et al, Erythromycin therapy for Group A streptococcal pharyngitis. Am J Dis Child 1984; 138:536-539. Hovi T, Svahn T, Valtonen V. Twice-a-day regitrten of erythromycin base is effective in the treatment of acute streptococcal tonsillitis, Scand J Infect Dis 1987; 19: 661-666. Dillon HC. Topic and systemic therapy for pyodermas. Int J Dermatol 1980; 19:443-451. Bleeker J. Tolerance and efficacy of erythromycin stearate tablets versus enteric-coated erythromycin base capsules in the treattrtent of patients with acne vulgaris. J Int Med Res 1983;11:38-41.

Butterflies are a very common choice for tattoos in women. From the World of Tattoos collection, Honolulu, HI. Submitted by Norman Goldstein, M.D., Honolulu, HI.

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Erythromycin versus cefadroxil in the treatment of skin infections.

Erythromycin is often overlooked for the treatment of skin and skin structure infections. We evaluated the efficacy and safety of erythromycin particl...
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