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Findings from a series of laboratory experiments provide proof of principle that topical antimicrobial treatments can have a long-lasting impact on the skin microbiome and indicate that further studies are warranted to understand the ramifications for cutaneous health and disease, say researchers from the University of Pennsylvania.
“It is well-documented that treatment with oral antimicrobial drugs leads to dramatic and persistent effects on resident bacterial communities in the gut with the potential for serious consequences, such as the development of Clostridium difficile infection. Interest in the effects of topical treatment with antimicrobial agents has centered mainly on bacterial resistance, while there has been a lack of research investigating effects on the stability of the skin microbiome,” said Adam J SanMiguel, Ph.D., lead author of the study published in a June issue of Antimicrobial Agents and Chemotherapy. The studies were conducted in the laboratory of Elizabeth Grice, Ph.D., of the University of Pennsylvania, and the study’s corresponding author.
Gram stain of staphylococcus on skin. Photo: Elizabeth A. Grice, Ph.D.The study shows that topical antibiotics and antiseptics disrupt the skin microbiome. During the recovery time, there is a small window of opportunity for colonization and the growth of opportunistic and pathogenic organisms. Although preliminary, the research shows that topical antimicrobial treatments have a potential for increasing the susceptibility to infection by altering the protective resident microorganism community, he said.
A first group of experiments investigated the effects of antibiotic and antiseptic treatment on the skin microbiome. Hairless mice were treated with topical mupirocin ointment, triple antibiotic ointment (bacitracin, neomycin, polymyxin B), alcohol, or povidone-iodine. The results showed an immediate shift in skin bacterial populations in response to the antibiotics, with the triple combination having a greater effect than the more narrow spectrum agent, mupirocin, and the changes persisted for several days post-treatment. In contrast, the antiseptic treatments were associated with more minor changes in skin bacterial populations, although levels of commensal Staphylococcus spp. were decreased.
“We were surprised by the relative effects of the antibiotics versus antiseptics because we hypothesized that the antiseptics would have a greater impact considering their broader mechanisms of action. Our initial experiments were done using 16S rRNA gene sequencing to evaluate the skin bacteria. To determine whether the findings were real or an artifact of our methodology, we also repeated these analyses with the use of culture-based methods, and found that these results recapitulated our original outcomes,” Dr. SanMiguel said.
To investigate the ramifications of disrupting the skin microbiome, further experiments evaluated how the treatments affected levels of Staphylococcus aureus on the skin. The results showed that elimination of resident Staphylococcus spp. with antimicrobial treatment could increase susceptibility to colonization with S. aureus, while animals precolonized with the resident Staphyloccci had reduced S. aureus colonization.
The findings of the research suggest ideas for various future studies to investigate the effects of topical antibiotics and antiseptics on the skin microbiota and strategies for maintaining cutaneous health and protecting against disease. Ramifications for patients with atopic dermatitis is an area of key interest, and Dr. SanMiguel noted that results of a recently published paper by Nakatsuji et al. [Sci Transl Med. 2017;22;9(378)] reporting that human skin commensal bacteria can reduce S. aureus colonization in patients with atopic dermatitis are complementary to his group’s findings.
“As a follow-up to this information, I expect that we will be seeing future studies investigating the role of commensal organisms and effects of antibiotic and antiseptic treatments on atopic dermatitis flares,” he told Dermatology Times.
The laboratory investigations also suggest further study is warranted to investigate the use of mupirocin for decolonizing S. aureus carriers.
“There is definitely an advantage to mupirocin prophylaxis to remove endogenous S. aureus from the nares and other body sites in certain individuals. However, the findings of our study indicate there may be a need to monitor treated people considering the possibility that mupirocin also eliminates protective resident bacteria and could thereby promote infection with other nosocomial and community-acquired pathogens,” Dr. SanMiguel said.
CITATION: Adam J. SanMiguel, Jacquelyn S. Meisel, Joseph Horwinski, Qi Zheng and Elizabeth A. Grice. "Topical antimicrobial treatments can elicit shifts to resident skin bacterial communities and reduce colonization by Staphylococcus aureus competitors," Antimicrobial Agents and Chemotherapy. June, 19 2017. DOI:10.1128/AAC.00774-17 (http://bit.ly/2vJsh3v)