Children with atopic dermatitis (AD) are prone to recurrent cutaneous and occasional systemic infections caused by Staphylococcus aureus. Antibiotic therapy represents an important component of the overall management of AD, especially during exacerbations of disease. Erythromycin is still widely used as a first-line antibiotic for this indication. We studied 115 consecutive children (mean age: 2.7 yr, range: 0.2–15) with moderate to severe AD (mean SCORAD: 43.2, range: 16–77) presenting to our outpatient department. Staphylococcus aureus was isolated from 100 of 115 (87%). Antimicrobial susceptibility testing revealed resistance against erythromycin in 18 and against roxithromycin in 19%, respectively. Six percentage of the strains were resistant or only intermediately susceptible to fusidic acid, 13% to amoxicillin and 1% to clindamycin. All strains isolated were susceptible to oxacillin, amoxicillin/clavulanic acid, cefadroxil and cefuroxim. The high rate of primary resistance to macrolides should be born in mind when starting antibiotic therapy in children with AD. Since Gram-positive cocci represent the only relevant microbial agents in AD, first generation cephalosporins such as cefadroxil, whose antimicrobial spectrum is basically restricted to Gram-positive bacteria, would appear to be the ideal first-line antibiotics for the treatment of bacterial superinfections.