efficacious and preferred by patients relative to desonide ointment.24 In a randomized controlled trial of 44 subjects with atopic dermatitis (ages 12 and older), subjects were treated with either desonide ointment or hydrogel twice daily for 4 weeks. The two formulations provided similar improvements in eczema signs and symptoms, but desonide hydrogel was rated by patients as significantly better than desonide ointment (P less than 0.05) in both absorption (at week 4) and (lack of) greasiness (at week 2). Other studies have demonstrated that desonide hydrogel can provide rapid alleviation of pruritus within 1 week and, importantly, does not suppress the HPA axis in pediatric patients.22, 23 Secondary Bacterial Infections Secondary bacterial infections are common complications of AD. Frequently caused by Staphylococcus aureus and Streptococcus pyogenes, such infections present with weeping, crusted, or pustulated lesions. Up to 80 to 100% of AD patients are colonized by S. aureus, compared to 5-30% of the general population.25, 26 Importantly, the density of S. aureus bacteria on the skin has been correlated with the clinical severity of AD.27 Several factors predispose AD patients to secondary bacterial infections. Due to mutations in filaggrin, patients with AD suffer from an inherent epidermal barrier dysfunction.28 The atopic immune response, including the overexpression of interleukin (IL)-4 and IL-13, may lead to further inhibition of filaggrin gene expression.29 In addition, the altered expression and secretion of antimicrobial peptides, which normally serve as endogenous antibiotics, contributes to innate susceptibility.30, 31 Topical antibiotics are integral to the treatment of bacterial infections in AD. Mupirocin 2% ointment is widely used, although concern exists over rising rates of resistance among S. aureus strains.32, 33 Methicillin-resistant Staphylococcus aureus (MRSA) represents a particularly troubling issue in the AD population, where rates of colonization are substantially higher than in the general population.34 Those with moderate-to-severe AD are especially at risk for MRSA colonization, which has in turn been linked to MRSA skin and soft tissue infections.35, 36 Retapamulin is a semisynthetic member of the pleuromutilin family of antimicrobials. Pleuromutilins were initially discovered in 1950s, with the first compounds—tiamulin and valnemulin—being approved for veterinary use. Pleuromutilin agents block protein synthesis in bacteria by binding to domain V of 23S rRNA and interfering with substrate binding.37 This mechanism of action is distinct from other antimicrobials, thereby reducing the likelihood of cross-resistance.38 The growing rates of anti-microbial resistance in bacteria, most notably MRSA, represent an important clinical consideration in selecting treatments. Retapamulin may provide an alternative not preferred treatment option for MRSA, especially where concern exists over mupirocin-resistance. In a study from six US dermatology centers, the susceptibility of S. aureus strains to different antimicrobials was tested.39 Among 218 isolates of S. aureus, 10.6% were mupirocin-resistant compared to only 0.5% that were retapamulin-resistant. Similar results were seen in a large analysis of 403 MRSA isolates, which found that 9% of strains were mupirocin-resistant versus only 0.25% that were retapamulin-resistant.40
Treatment regimens continue to evolve as clinicians and scientists gain greater insight into the pathophysiology of AD. Early intervention with emollients and topical steroids remain principle components to therapy, and the arrival of topical calcineurin inhibitors and phosphodiesterase-4 inhibitors has now provided an even wider range of options. Continued pediatric research into biologic agents, such as interleukin-4 and -13 inhibitors, as well as Janus kinase inhibitors, are likely to yield safe and effective systemic therapies in the near future. Importantly, the comorbidities of AD, such as infection, allergy, and psychosocial impairment, are increasingly being recognized and addressed in a multidisciplinary approach.In patients with poor control of AD, secondary bacterial infections are common complications, and the appropriate selection of antibiotic therapy can be challenging when faced with bacterial resistance. Although mupirocin remains a preferred first-line agent, growing concerns over MRSA resistance make retapamulin a treatment alternative in such pathogenic environments.
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- Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-32.
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Leon H. Kircik MD email@example.com