Antibiotics, a double-edged sword when managing skin disease

Long regarded mainly as a source of infection, the human skin microbiota is nowadays commonly accepted as an important driver of health and wellbeing.¹ By promoting immune responses and defense, it plays a key role in tissue repair and barrier functions by inhibiting colonization or infection by opportunistic pathogens.²

To each skin site, its own microbiota

The skin microbiota harbors millions of bacteria, as well as fungi and viruses in lower relative abundances. Corynebacterium, Cutibacterium (formerly known as Propionibacterium), Staphylococcus, Micrococcus, Actinomyces, Streptococcus and Prevotella are the most common genera of bacteria encountered on the human skin.³ However, the relative abundance of bacterial taxa greatly depends on the local microenvironment of the particular piece of skin being considered, and especially on its physiological characteristics, i.e., whether it is sebaceous, moist or dry. Hence lipophilic Cutibacterium species dominate sebaceous sites while Staphylococcus and Corynebacterium species are particularly abundant in moist areas.⁴

From physiology to pathology, the ambivalent role of C. acnes

The aerotolerant anaerobe C. acnes is one of the most abundant bacterial species in the skin microbiota. It has been implicated in acne, a chronic inflammatory disorder of the skin with complex pathogenesis.⁵ In contrast with previous thinking, recent studies indicate that C. acnes hyperproliferation is not the only factor implicated in the development of acne.⁶ In fact, a loss of balance between the different C. acnes strains, together with a dysbiosis of the skin microbiota will trigger acne.⁶ Moreover, interactions between S. epidermidis and C. acnes are of critical importance in the regulation of skin homeostasis: S. epidermidis inhibits C. acnes growth and skin inflammation. In turn, C. acnes, by secreting propionic acid which participates, among other things, in maintaining the pilosebaceous follicle acidic pH, inhibits the development of S. epidermidis. Malassezia, the most abundant skin fungus is also thought to play a role in refractory acne by recruiting immune cells, though its involvement needs to be further explored.⁶

Acne treatment, an important source of antibiotic resistance

Despite being used routinely to treat acne, topical and oral antibiotics have proved to be problematic in several ways. A first concern expressed by experts is the disruption to the skin microbiota, although precise data on the subject remain scarce. In this vein, a recent longitudinal study compared the cheek microbiota of 20 acne patients before and after six weeks of oral doxycycline therapy. Interestingly, antibiotic exposure was associated with an increase in bacterial diversity; according to the authors, this could be due to a diminished colonization by C. acnes, which would liberate space to allow the growth of other bacteria.⁷

However, the most significant concern over the use of antibiotics for acne treatment relates to bacterial resistance. First observed in the 1970s, it has been a major worry in dermatology since the 1980s.⁸ C. acnes resistance is by far the most documented: the latest data point to resistance rates reaching over 50% for erythromycin in some countries, 82-100% for azithromycin and 90% for clindamycin. As for tetracyclines, although still largely effective against the majority of C. acnes strains, their resistance rates are rising, ranging from 2% to 30% in different geographic regions.⁹ And antibiotic resistance is not limited to C. acnes: while topical antibiotics used by acne patients (especially as monotherapy) have been shown to increase the emergence of resistant skin bacteria such as S. epidermidis, oral antibiotics have been associated with the increased emergence of antibiotic-resistant oropharyngeal S. pyogenes.^8,10 In addition, increased rates of upper respiratory tract infection and pharyngitis have been reported as being associated with the antibiotic treatment of acne.^11,12

A call for a limited use of antibiotics in acne

The potential consequences of antibiotic resistance triggered by acne treatment are numerous: failure of the acne treatment itself (see clinical case), infection by opportunistic pathogens (locally or systemically), and the dissemination of resistance among the population.⁸ Despite this, the levels of antibiotic prescriptions for acne remain high and for longer durations than recommended in the guidelines.¹³ Against this background of mounting concerns, experts are calling for a more limited use of antibiotics in the treatment of acne.¹³ In particular, a strategy has been proposed in this regard by the Global Alliance to Improve Outcomes in Acne (see box below).