retapamulin and Dermatitis

New antibacterial agents with activity against pathogenic strains resistant to established antibiotics are needed to treat patients with secondarily infected dermatitis (SID).. We sought to determine the clinical safety and efficacy of topical retapamulin ointment 1% versus oral cephalexin for the treatment of SID.. Patients with SID were randomly assigned to retapamulin ointment 1% (twice daily [bid]) for 5 days, or oral cephalexin (500 mg bid) for 10 days. The primary efficacy end point was clinical response at follow-up. Secondary outcomes included microbiologic response at follow-up, safety, and compliance.. Retapamulin was as effective as cephalexin (clinical success rates at follow-up: 85.9% and 89.7%, respectively). Microbiologic success rates at follow-up were 87.2% for retapamulin and 91.8% for cephalexin. Retapamulin was well tolerated and the topical formulation was preferred over the oral drug.. An imbalance existed in the number of patients with the clinical outcome "unable to determine" (15 retapamulin, 2 cephalexin), mainly because of their failure to attend the study visit. If those who failed to attend visits (who did not withdraw as a result of drug-related events) are removed from the analysis, the clinical success rates are 89.9% for retapamulin and 89.7% for cephalexin.. Retapamulin ointment 1% (bid) for 5 days was as effective as oral cephalexin (bid) for 10 days in treatment of patients with SID, and was well tolerated.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Cephalexin; Child; Child, Preschool; Dermatitis; Dermatitis, Atopic; Diterpenes; Double-Blind Method; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Methicillin Resistance; Middle Aged; Ointments; Skin Diseases, Infectious; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Community-Acquired Infections; Dermatitis; Dermoscopy; Disease Models, Animal; Diterpenes; Drug Monitoring; Green Fluorescent Proteins; Interleukin-1alpha; Interleukin-1beta; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Mupirocin; Staphylococcal Skin Infections