Stemming the tide of antimicrobial resistance: implications for management of acne vulgaris

EFFECTIVE NON-ANTIBIOTIC ALTERNATIVES

The aetiology of acne is complex. Though P. acnes is strongly implicated in pathogenesis, acne is not an infection and effective antimicrobials do not eliminate P. acnes from the skin. A primary defect in sebum production triggers hyperproliferation of follicular keratinocytes resulting in inflammation via multiple pathways.⁸ The relative importance of antibacterial versus anti-inflammatory actions of antibiotics in the management of acne remains unclear.

Benzoyl peroxide (available over-the-counter in many countries, including the UK) is an effective non-antibiotic antimicrobial agent that can be used alone or in addition to antibiotics. It acts as a bactericidal agent that is equally effective against antibiotic resistant and susceptible strains of P. acnes and can also reduce the development of resistance within the resident skin microflora. It has limited impact at controlling selective pressure from oral antibiotics at body sites other than the area of application.

Topical retinoids, such as adapalene (Differin^®), isotretinoin (Isotrex^®) and tretinoin, act on abnormal keratinisation and also have anti-inflammatory properties. They are a potential skin irritant, which can lead to early abandonment of treatment unless appropriate advice to mitigate this is given.¹

Box 1 provides a summary of treatment guidelines and Box 2 contains resources providing information for patients, including advice on mitigating local reactions to topical agents.

For some women, combined oral contraceptives (particularly 3rd generation) or co-cyprindiol (Dianette^®) can be effective alternatives to antibiotics, particularly when combined with topical treatments.⁹ However, co-cyprindiol should be discontinued three to four menstrual cycles after the acne has resolved.¹⁰

HOW TO AVOID ANTIBIOTIC RESISTANCE

The UK guideline suggests that either benzoyl peroxide or a topical retinoid, such as adapalene (Differin), should be used first line.¹⁰ For moderate acne that is localised, a fixed dose combination topical product is recommended when benzoyl peroxide or topical retinoid monotherapy is ineffective. Oral antibiotics with topical benzoyl peroxide are recommended if the acne is more widespread or risk factors (for example, scarring) are present.

Three recently published evidence-based guidelines from the US, Canada, and Europe agree with UK guideline in recommending that neither topical nor oral antibiotics should be used as monotherapy.^11–13 Though the use of fixed-dose combination of benzoyl peroxide/adapalene (Epiduo^®) has increased in recent years, combination clindamycin/benzoyl peroxide (Duac^®), and erythromycin (Zineryt^®) remain by far the most commonly prescribed topical preparations for acne in England and Wales.¹⁴ Rates of resistance to erythromycin and clindamycin in P. acnes isolates from countries that use topical antibiotics for acne extensively vary from 45% to 91%, strongly implicating topical use in the emergence of resistance.³

There have been few head-to-head comparisons of topical therapies including fixed dose combinations versus oral antibiotics so their comparative efficacies, especially in moderate acne, are not certainly known. Until such information becomes available, it would seem preferable to avoid oral antibiotics, except when justified by severity, distribution of lesions, scarring or other risk factors. Expert consensus and current guidelines recommend keeping courses of antibiotics relatively short, with a maximum duration of 3–4 months. While the acne may not be cleared after this time in all patients, most should be sufficiently improved to switch to a topical non-antibiotic maintenance regimen that will continue to reduce the number of lesions and prevent recurrence.

Consideration of earlier referral to secondary care can be considered in preference to extending treatment duration with antibiotics or trying various different ones. Oral isotretinoin may avoid the need for multiple courses of antibiotics and, despite recent concerns expressed in the media about rising rates of prescribing, reviews have not shown an increase in depression following initiation of isotretinoin.¹ However, prescriptions for oral isotretinoin are still administered under the supervision of a consultant dermatologist due to potentially serious adverse effects that include the very high risk of teratogenicity.