Background Skin colonization by antibiotic‐resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy.

Objective To assess the efficacy of oral isotretinoin in the control of antibiotic‐resistant propionibacteria.

Methods Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic‐resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne‐prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic‐resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics.

Results After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline‐resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic‐resistant strains from any site. Post‐treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post‐treatment at the two centres were similar but not identical.

Conclusions Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic‐resistant propionibacteria. However, viable populations of resistant isolates persisted post‐treatment at multiple sites. Novel methods are required to eradicate antibiotic‐resistant propionibacteria completely, especially from the nasal reservoir.