The Journal of Dermatology Vol.

32: 788792, 2005

Topical Antibiotic Treatment of Impetigo with Tetracycline

Shuichi Kuniyuki, Kazuhito Nakano, Naoki Maekawa and Shinsuke Suzuki
Abstract Forty-nine children aged 0.213 years with bullous and eroded lesions, from which Staphylococcus aureus was isolated, were diagnosed with impetigo and entered into a randomized, open-labeled trial of topical oxytetracycline hydrochloride (tetracycline) compared with a combination of topical tetracycline and oral antibiotics. After one week of topical tetracycline treatment, 22 of the 28 patients were clinically cured, and the remaining six patients had improved. In the other treatment group, 14 patients of 21 were clinically cured and 7 patients improved by the combination of topical tetracycline and oral antibiotics. There were no significant differences between the two groups. Therefore, the present study suggests that topical tetracycline treatment is effective for the treatment of impetigo. Key words: impetigo; MRSA; treatment; tetracycline

Introduction Impetigo is the most common skin infection in children; it is caused mainly by Staphylococcus aureus. In recent years, there have been increasing numbers of reports of MRSA strains and gentamycin-resistant S. aureus strains (15). Therefore, the appropriate use of antibiotics appears to be important for the treatment of patients with impetigo. Topical antibiotic treatment with mupirocin or fusidic acid has been shown to yield results equal to or even better than oral treatment (69). Some authors have recommended that mupirocin should be reserved for nasal carriage of Staphylococcus aureus in specific groups of patients (10, 11). In contrast, a number of groups have reReceived January 14, 2005; accepted for publication May 12, 2005. Department of Dermatology, Osaka City General Hospital, Osaka, Japan. Reprint requests to: Shuichi Kuniyuki, M.D., Department of Dermatology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori, Miyakojima-ku, Osaka 534-0021, Japan.

ported that fusidic acid resistance is on the increase (12). Some authors have reported that both bactroban ointment and chlortetracycline cream are safe and effective forms of treating minor skin infections (13, 14). Because minocycline has been reported to be highly effective against MRSA (1517), we supposed that topical tetracycline might show a good clinical effect in the treatment of impetigo. We also supposed that topical tetracycline would have as good an effect as the combination of topical tetracycline and oral antibiotics. Therefore, we compared the effectiveness of topical tetracycline and the combination of topical tetracycline and oral antibiotics in the present study. Patients and Methods
Participants Forty-nine patients participated in a bacteriologically controlled, randomized, open-label, parallel group comparison of topical 3% oxytetracycline-hydrochloride (tetracycline) ointment versus a combination of topical tetracycline and oral antibiotics for the treatment of impetigo. Patients aged 0.213 years of either sex who had bullous or eroded lesions from which

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Table 1.

Demographic summary of evaluable patients The combination of topical tetracycline and an oral antibiotic Topical tetracycline alone 28 4.1 112 16/12 15 13

No. of patients Mean age, y Age range, y Sex M/F Pathogen isolated methicillin-sensitive Staphylococcus aureus methicillin-resistant Staphylococcus aureus

21 4.4 0.213 11/10 11 10

Table 2.

Final clinical evaluations Cured Improved 7 3 0 4 6 Failure 0 0 0 0 0 Total 21 6 5 10 28

The combination of topical tetracycline and an oral antibiotic cefdinir fosfomycin minocycline Topical tetracycline

14 3 5 6 22

Staphylococcus aureus had been cultured, were admitted to the study. Specimens for culture were obtained by swabbing the lesions. When present, the crust was lifted, and the exposed lesional tissue was cultured. We excluded patients who were immunocompromised, patients with extensive lesions, infections of deeper skin structures, or temperatures >38.5C, and patients who had used topical or systemic antibiotics in the previous 48 hours. Outcomes The patients were randomized and received either topical tetracycline, to be applied three times daily, or a combination of topical tetracycline and oral antibiotics (sefdinir, minomycin, or fosfomycin). The standard doses of sefdinir, minocycline, and fosfomycin administered to the children were 9 mg/kg/day, 4 mg/kg/day, and 40 mg/kg/day, respectively. Study data were obtained at two time points: the baseline/screening examination; and the follow-up examination on Day 7. The second observation period was after seven days of therapy.

Patients were evaluated clinically. Evaluation of clinical efficacy Each patients clinical response to the treatment was evaluated subjectively and categorized into one of the following groups: cured: all of the lesions had resolved; improved: the lesions were significantly improved but incompletely resolved; failure: there was no apparent response to therapy. Statistical analysis The Mann-Whitney U-test was used to compare each treatment group.

Results Patients A total of forty-nine patients were enrolled in this study, which was conducted in Osaka, Japan, between January 2002 and December 2003. Twenty-eight patients received topical tetracycline and 21 patients received a combination of topical tetracycline and an oral antibiotic (6 patients with

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cefdinir, 5 patients with fosfomycin and 10 patients with minocycline). The mean age of the topical tetracycline group was 4.1 years with a range of 112 years. The mean age of the combination of topical tetracycline and oral antibiotic group was 4.4 years with a range of 2 months to 13 years. Each treatment group showed comparable demographic characteristics, and there were no clinically significant differences between the groups at the baseline. The groups were also comparable with respect to baseline characteristics (Table 1). Bacteriological evaluation There were 49 pretreatment pathogens isolated from the evaluable patients in the two treatment groups; all forty-nine cases were Staphylococcus aureus. Antibiotic susceptibilities Methicillin-resistant S. aureus comprised about half of the isolates (twenty-three of the 49 S. aureus: 47%). In contrast, only one of the 49 isolates (2%) was resistant to minocycline. Clinical evaluation The final clinical evaluations are shown in Table 2. Successful responses (cured) were seen in 22 (79%) of 28 patients in the topical tetracycline group. In the combination of topical tetracycline and oral antibiotic group, successful responses were seen in 14 (67%) of 21 patients. A beneficial response (cured, improved) was seen in 28 (100%) of 28 patients in the topical treatment group and in 21 (100%) of 21 patients in the topical with oral treatment group. There were no significant differences between the two treatment groups with regard to patient global evaluation (Table 2). Discussion There were no significant differences between the two treatment groups with respect to patient details. Both groups improved clinically with no significant differences. Therefore, these outcomes suggest that top-

ical tetracycline treatment is effective in the treatment of impetigo, although oral antibiotic treatment has long been the first choice for the treatment of this disease (1). In recent years, however, the resistance of staphylococci to oral antibiotics has increased dramatically (2, 6, 7, 18, 19). George and Rubin (20) recommended the use of a topical antibiotic for a period of seven days in a systemically well patient with limited disease. In general, children comply better with topically administered treatment than with oral treatment (21), and fewer systemic side effects occur (2). Fusidic acid is recommended as the topical antibiotic of first choice in the Dutch College of General Practitioners guidelines for the treatment of impetigo (10). However, some authors discourage the topical use of fusidic acid because of its value in systemic treatment (3, 22). In contrast, topical mupirocin has been shown to yield results equal to or even better than those of oral treatment (6, 7, 21, 23), although other authors have recommended that mupirocin be reserved for treatment of nasal carriage of S. aureus (10, 11). Low percentages of gentamicin-sensitive strains among S. aureus isolates have also been reported by other groups: 45% (Sase et al.) (15), 24% (Miida, et al.) (16) and 30% (Iijima, et al.) (17). Thus, it appears that the effect of gentamicin on S. aureus is limited. Since gentamicin has been used generally in Japan for many years, it is commonly accepted that the use of antibiotics promotes bacterial substitution and leads to the appearance of drug-resistant bacterial strains (24). It is likely that the frequent use of topical gentamicin has induced the appearance of bacterial strains resistant to gentamicin (24, 25). However, topical tetracycline offers a safe and equally rapid solution for eliminating skin pathogens without the risk of any systemic side effects in specific groups of patients (13, 14). Chlortetracycline is a topical antibiotic which is often used to treat skin

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infections (13, 14). It has a broad spectrum of activity and is active against gram-positive cocci and gram-negative bacteria. Some authors have reported that both bactroban ointment and chlortetracycline cream are safe and effective forms of treatment for minor skin infections (13, 26). We therefore compared the effectiveness of topical tetracycline and the combination of topical tetracycline and oral antibiotics in the treatment of children with impetigo in the present study. There were no significant differences between the two treatment groups with respect to patient characteristics, treatment duration, severity, or type of infection. Both groups improved clinically with no significant difference in results. In conclusion, these findings suggested that mild and moderate impetigo can be sufficiently treated with topical tetracycline treatment (21, 23). References
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23) Bass JW, Chan DS, Creamer KM, et al: Comparison of oral cephalexin, topical mupirocin, and topical bacitracin for treatment of impetigo, Pediatr Inf Dis J, 16: 708709, 1997. 24) Akiyama H, Abe Y, Shimoe K, et al: Changes of susceptibilities of Staphylococcus aureus during topical application on experimental staphylococcal skin infection in mice, Jpn J Dermatol, 103;