In atopic dermatitis (AD), the stratum corneum of patients appears to have 
alterations that predispose them to colonization and invasion by various 
bacteria, most notably Staphylococcus aureus (S. aureus). This bacterial 
co-existence is accepted to be an important factor in AD disease activity. 
Exactly when to initiate antimicrobial treatment is controversial, but such 
intervention, when warranted, has repeatedly been demonstrated to improve the 
course of AD. However, the increase in antibiotic resistance presents a 
therapeutic challenge in the management of AD patients, which highlights the 
need for novel mechanism topical antibacterial agents. Retapamulin is a 
relatively new pleuromutilin antibiotic designed for topical use. In vitro 
studies have demonstrated its low potential for the development of antibacterial 
resistance and high degree of potency against Gram-positive bacteria found in 
skin infections, including many S. aureus strains that are resistant to 
methicillin, fusidic acid, and mupirocin. Clinical studies exploring the 
treatment of secondarily infected dermatitis reveal that the efficacy of topical 
retapamulin is comparable to a 10-day course of oral cephalexin or to topical 
fusidic acid. Retapamulin appears to be a much needed antimicrobial option for 
treating the AD population due to their common carriage of bacterial pathogens 
and frequency of infectious complications.