Non-antibiotic Isotretinoin Treatment Differentially Controls Propionibacterium acnes on Skin of Acne Patients

Abstract

Emergence and potential transfer of antibiotic resistance in skin microorganisms is of current concern in medicine especially in dermatology contexts where long term treatment with antibiotics is common. Remarkably, non-antibiotic therapy in the form of isotretinoin – a non-antimicrobial retinoid is effective at reducing or eradicating the anaerobe Propionibacterium acnes which is causally involved in the complex pathogenesis of Acne vulgaris. This study measured the extent of colonization of P. acnes in patients with primary cystic or severe acne from three defined skin sites in ‘non-lesion’ areas before, during and after treatment with isotretinoin. Patients attending acne clinics were investigated using standardized skin sampling techniques and the recovery of anaerobic P. acnes from 56 patients comprising 24 females and 32 males (mean age 22 years, age range 15–46 years) who were given a standard course of isotretinoin (1 mg/kg/day) are reported. P. acnes cultured from the external cheek surface of patients following treatment showed a significant reduction (1–2 orders of magnitude) compared with their pre-treatment status. Interestingly, other distinct sites (nares and toe web) failed to show this reduction. In addition, high levels of antibiotic-resistant P. acnes were recorded in each patients’ skin microbiota before, during and after treatment. In this study, microbial composition of the skin appears substantially altered by isotretinoin treatment, which clearly has differential antimicrobial effects on each anatomically distinct site. Our study confirmed that orally administered isotretinoin shows good efficacy in the resolution of moderate to severe acne that correlates with reductions in the number of P. acnes on the skin, including resistant isolates potentially acquired from previous treatments with antibiotics. Our study suggests that the role of tetracycline’s and macrolides, which are currently first line treatments in dermatology, might be reserved for severe or life-threatening infections since current antibiotic stewardship guidelines from medical departments no longer prescribe these antibiotics for routine use.

Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne

“…A study of 56 patients with cystic or severe acne vulgaris treated with oral isotretinoin (1 mg/kg per day) reported that the colonization of the skin with P. acnes was modified; oral isotretinoin, though not an antibiotic, correlated with a reduction in the numbers of P. acnes , including isolates resistant to antibiotics, that were cultured from the cheeks, but there was no effect in P. acnes sampled from other anatomic sites 67 .…”

Skin microbiota: Friend or foe in pediatric skin health and skin disease

“…Whether or not the relative abundance of C acnes is greater in acne patients compared to healthy controls, or whether the levels correlate with disease severity, is unclear. Nonetheless, all studies to date support C acnes as a factor in acne pathogenesis . A small pilot study with 8 pre‐adolescent acne patients demonstrated that in addition to C acnes , both Streptococcus and Staphylococcus spp.…”

“…Few studies demonstrate the direct effects of acne treatments on the skin microbiome. In general, benzoyl peroxide, lymecycline, topical clindamycin, isotretinoin, and oral minocycline all decrease the bacterial load on the skin, including C acnes , and increase bacterial diversity on the skin by the end of treatment . These treatments are not specific to C acnes , but instead trigger global diversity changes within the skin microbiome community, changes that may persist well beyond the treatment end date.…”

“…Nonetheless, all studies to date support C acnes as a factor in acne pathogenesis. [67][68][69][70][71][72][73] A small pilot study with 8 preadolescent acne patients demonstrated that in addition to C acnes, both Streptococcus and Staphylococcus spp. are highly abundant compared to age-matched control subjects, suggesting these species may also contribute to acne pathogenesis in this age group.…”

“…In general, benzoyl peroxide, lymecycline, topical clindamycin, isotretinoin, and oral minocycline all decrease the bacterial load on the skin, including C acnes, and increase bacterial diversity on the skin by the end of treatment. 69,[71][72][73] These treatments are not specific to C acnes, but instead trigger global diversity changes within the skin microbiome community, changes that may persist well beyond the treatment end date. For example, isotretinoin leads to a shift in C acnes ribotypes, with an increase in the abundance of healthy strains on the skin for at least 5 months posttherapy.…”