Temporal shifts of the microbiome associated with antibiotic treatment of purpuric drug eruptions related to epidermal growth factor receptor inhibitors.

Abstract

Epidermal growth factor receptor (EGFR) inhibitors are selective and effective treatments for cancers with relevant mutations. Purpuric drug eruptions are an uncommon but clinically significant dermatological side effect related to EGFR inhibitor use that are associated with positive bacterial cultures and responsive to antibiotic treatment. However, the longitudinal temporal shifts in the skin microbiome that occur before and after antibiotic treatment of purpuric drug eruptions remain largely unknown. To characterize temporal changes in the skin and mucosal microbiomes before and after antibiotic treatment of EGFR inhibitor-related purpuric drug eruptions. Twelve patients who experienced EGFR inhibitor-related purpuric drug eruptions were recruited from a dermato-oncology clinic in Taiwan from May 2017 to April 2018. Swabs were obtained from skin lesions and the nasal mucosa before and after antibiotic treatment of purpuric drug eruptions. After the amplification and sequencing of bacterial 16S rRNA genes, the diversity and compositions of microbiomes sampled at different time points were compared. The alpha diversity (represented by the Shannon index) of the skin microbiome increased significantly in the recovered phase of purpuric drug eruptions compared with that of the active phase. By contrast, the nasal microbiome showed no significant change in alpha diversity. The relative abundance of Staphylococcus significantly decreased in samples from skin of the recovered phase, which was confirmed by analysis of compositions of microbiomes (ANCOM) and the ALDEx2 analysis packages in R. The cutaneous microbiome of purpuric drug eruptions showed a significant increase in alpha diversity and a decrease in the relative abundance of Staphylococcus following antibiotic treatment. These findings may help guide antimicrobial therapy of this EGFR inhibitor-related condition.