This supplement has been commissioned and funded by Galderma and developed in partnership with Guidelines in Practice. Galderma suggested the topic and author, and carried out full medical approval on all materials to ensure compliance with regulations. The sponsorship fee included an honorarium for the author. The views and opinions of the author are not necessarily those of Galderma, or of Guidelines in Practice, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher.

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Managing common skin conditions without antibiotics

Dr George Moncrieff, past Chair of the Dermatology Council for England

Introduction

In 2015, the World Health Organization stated that antimicrobial resistance (AMR) is a crisis that requires an urgent global response.1 Antibiotics are essential preventive and curative treatments for infectious diseases, and AMR resulting from their misuse puts patients undergoing complex treatments such as surgery or chemotherapy at risk.1 Without immediate action to reduce the inappropriate prescribing of antibiotics, infectious diseases will become more difficult to treat, and deaths from resistant infections may increase from 700,000 to more than 10 million every year by 2050.2

Guidance on antimicrobial stewardship in the UK

The UK Government pledged to address the threat of AMR,3 and issued guidance aimed at reducing AMR by changing prescribing practice. NICE Guideline (NG) 15 was published in 2015 and covers the effective use of antimicrobial agents by all healthcare organisations to delay the emergence of AMR and ensure that antibiotics remain an effective treatment for infectious diseases.4 Subsequently in 2017, NICE published NG63, which aims to raise awareness of the appropriate use of antimicrobial agents, and the dangers associated with their overuse and misuse.5 Both NICE guidelines also make recommendations on changing people’s behaviour to reduce the development of AMR and the spread of resistant microbes.4,5

In 2019, Public Health England (PHE) updated its 2017 guidance on the management and treatment of common infections aimed at minimising the emergence of AMR in the community.6 The PHE guidance on antimicrobial prescribing recommends that antibiotics should only be prescribed when there is likely to be a clear clinical benefit, with self-care advice and non-antibiotic preparations provided instead when appropriate. If antibiotic treatment is unavoidable, PHE guidance recommends using the shortest effective course, and limiting the widespread use of topical antibiotics, especially where systemic preparations are available.6 Although the use of topical antibiotics may reduce the level of side-effects associated with  systemic antibiotic treatment, they are still associated with increased AMR when used to treat conditions such as skin infections or acne.7 Some good practice points on the use of topical antibiotics can be found in Box 1.6–9

Box 1: Good practice points on the use of topical antibiotics in dermatology6–9

  • The use of topical antibiotics to treat skin conditions is associated with an increase in antimicrobial resistance7
  • The antibiotics used to treat skin infections are often the same as those needed to treat more serious infections, despite effective alternative options being available6
  • Clinicians should think carefully before prescribing antibiotics for skin conditions, using effective antibiotic-sparing alternatives in preference6
  • Mild bacterial infections of the skin can often be managed with an antiseptic, e.g. benzalkonium chloride or chlorhexidine dihydrochloride8
  • If there is evidence of a severe infection or topical treatments are difficult to administer, a systemic antibiotic may be needed6
  • Patients must be carefully reviewed 3–4 months after starting any antibiotic treatment, which should be discontinued if there is no improvement9

Recently, the UK Government published its 2019–2024 national action plan to tackle antimicrobial resistance within and beyond the UK.10 The key aims of the plan are to reduce the burden of infection and optimise the use of antibiotics. Specific targets include a 10% reduction in the number of people with specific drug-resistant infections by 2025, and a 15% reduction in antimicrobial use in humans by 2024. The plan also promotes the introduction of new diagnostics, therapeutics, vaccines, and interventions.10 No new classes of antibiotic have been introduced since the 1980s,10 and investment in the research and development of new antibiotics is inadequate;2 this initiative is intended to counteract the contribution of these problems to the growing threat of AMR.10

Antibiotic use for skin conditions

Although antimicrobial prescribing is relevant to multiple specialties, dermatology is an area in which antibiotic use must be reduced to slow the emergence of AMR. Around 24% of people in the UK present to their GP with a skin complaint every year.11 In the UK in 2018, around 3.7 million prescriptions for anti-infective preparations were dispensed for skin conditions. Approximately 1.8 million prescriptions were issued for medications used to treat acne alone. Of the 1.6 million topical preparations prescribed for acne, 1 million contained an antibiotic.12 The  antimicrobial agents used for skin infections are often the same as those needed to treat serious infections, despite more effective alternative options being available for many dermatology patients. In addition, courses of antibiotics are commonly prescribed for months or even years for conditions such as acne and rosacea, often without any follow-up.9 Thus, the importance of antimicrobial stewardship in dermatology is considerable.

Treatment of common skin conditions

PHE provides recommendations on the treatment of acne and eczema, which are summarised in Box 2.6 NICE covers the treatment of acne, eczema, and rosacea in three informative clinical knowledge summaries published in 2018, 2017, and 2018, respectively.8,13,14 The treatment of acne, eczema, and rosacea are also covered by guidelines issued by the Primary Care Dermatology Society (PCDS), last reviewed in 2019.15–17 Some treatment options recommended by the PCDS guidance are not yet covered by the NICE clinical knowledge summaries. This remainder of this article provides the most up-to-date recommendations on best practice in the treatment of these common skin conditions.

Box 2: PHE good practice points for acne and eczema6

Acne vulgaris

  • Mild (open and closed comedones) or moderate (inflammatory lesions):
    • first line: self-care (wash with mild soap; do not scrub; avoid make-up)
    • second line:
      • topical retinoid, applied thinly once daily for 6–8 weeks
      • benzoyl peroxide, 5% cream once daily for 6–8 weeks
    • third line: add antibiotic—systemic where possible
      • oral tetracycline, 500 mg twice daily for 6–12 weeks
      • oral doxycycline, 100 mg once daily for 6–12 weeks
      • topical clindamycin, 1% cream, applied thinly twice daily for 12 weeks
  • If treatment failure occurs or acne is severe (nodules and cysts):
    • add oral antibiotic (for 3 months maximum) and refer:
      • oral tetracycline, 500 mg twice daily for 6–12 weeks
      • oral doxycycline, 100 mg once daily for 6–12 weeks

Eczema

  • No visible signs of infection:
    • antibiotic use (alone or with steroids) encourages resistance and does not improve healing
  • With visible signs of infection:
    • use oral flucloxacillin or clarithromycin or topical treatment (reserved for very localised lesions to reduce risk of bacteria becoming resistant)
      • oral flucloxacillin, 250–500 mg 4 times a day for 7 days
      • oral clarithromycin, 250–500 mg twice daily for 7 days
      • topical fusidic acid, applied thinly three times daily for 5 days
      • MRSA: topical mupirocin, 2% ointment three times daily 5 days

MRSA=methicillin-resistant Staphylococcus aureus

Best practice in acne

Acne is characterised by lesions that can be non-inflammatory and/or inflammatory, and is caused by blockage and inflammation of the pilosebaceous unit (the hair follicle, hair shaft, and sebaceous gland).13 Most doctors rely on systemic or topical antibiotics, or a combination of the two, to manage acne.9 However, multiple factors should be addressed before considering any antibiotic treatment, and effective non‑antibiotic treatment options should be considered before antibiotics.

Considerations before introducing acne treatments

The relationship between diet and acne is unclear.13 However, foods with a high glycaemic index, especially those that stimulate insulin-like growth factor-1, such as chocolate and cocoa powder, may have a relationship with acne.13,18–20 Certain dairy products and their milk proteins have also been linked with severity of acne.20 Conversely, a diet rich in fish20 may help with the symptoms of acne, and coconut oil is rich in lauric acid, which has been shown to have antimicrobial activity against Propionibacterium acnes.21

PHE recommends that people with acne should avoid using make-up.6 It is understandable that a person with severe acne may feel the need to cover up their spots, but they should be encouraged to use non-comedogenic make-up.13

The first- and second-generation combined contraceptive pills contain androgenic progesterones, such as levonorgestrel and norethisterone, which can aggravate acne.22 Pills containing desogestrel and norgestimate are unlikely to exacerbate acne, whereas those containing drospirenone or cyproterone acetate will actually treat acne.23

Some drugs, including lithium, oral steroids, and anabolic steroids, may aggravate acne.24 Patients often deny using anabolic steroids, but it is worth considering because acne is unlikely to improve if a patient continues to use anabolic steroids.

Acne can be related to underlying conditions, such as polycystic ovarian syndrome (PCOS) and non‑classical congenital adrenal hyperplasia (NCCAH), which should be considered and managed appropriately. PCOS is extremely common and, depending on the criteria used for diagnosis, affects up to 20% of women.25 NCCAH affects about 1% of the population, and presents with hirsutism and resistant recurrent acne.26 An early morning 17-hydroxy progesterone blood level can easily diagnose NCCAH,26 which is important if it is the underlying cause of acne, because it will only resolve once this hormone deficiency is addressed. It is also important because they may have a compromised hormone response to extreme stress (e.g. a life-threatening infection or illness).

Pharmacological treatments

Topical retinoids normalise follicular keratinisation, promoting the drainage and inhibiting the formation of comedones.13 The European Dermatology Forum recommends topical retinoids for comedonal and mild-to-moderate papulopustular acne,27 whereas NICE recommends them as the first-line treatment for all patients with acne.13,28 Most topical retinoids (excluding adapalene) can cause some photosensitivity and should therefore be applied once daily at night. Topical retinoids take up to 8 weeks to work, and may irritate the skin at first,13,28 so they should be introduced gradually over a few weeks to allow tolerance to develop. Adapalene is less irritating than isotretinoin or tretinoin.29

Benzoyl peroxide is a mild comedolytic and potent antibacterial agent that reduces the local population of P. acnes and the production of irritant fatty acids in the sebaceous glands.13,30 It is effective for both comedones and inflammatory lesions.13,30 A maximum concentration of 2.5% benzoyl peroxide is sufficient; there is no benefit of using a higher concentration, such as 5%.31 NICE recommends benzoyl peroxide first-line for mild acne.13 Like topical retinoids, benzoyl peroxide is slightly irritant, with a mild burning sensation on first application, reddening and peeling within a few days, and increased peeling during the first weeks of treatment, which subsides in a day or two if treatment is temporarily discontinued.30 It is usual to start with a lower strength and increase the concentration gradually, and scaling and redness often subside with treatment continued at a reduced frequency of application.28 Patients should be warned to avoid the eyes, mouth, nose, and mucous membranes, and that it may bleach or discolour hair and fabrics.30

Azelaic acid has antimicrobial action and a direct influence on follicular hyperkeratosis, inhibiting the proliferation of keratinocytes, normalising the disturbed terminal epidermal differentiation processes in acne, and reducing colonisation density of P. acnes and prevalence of free fatty acids in skin surface lipids.28,32 It may be useful if topical retinoids and benzoyl peroxide are poorly tolerated;14,28 it can be especially helpful for mild acne where there is some post-inflammatory hyperpigmentation (as is often seen in darker skin types) because it has a weak depigmenting effect.33

Nicotinamide has some anti-inflammatory properties, and has beneficial effects on inflammatory acne,28,34 with evidence indicating that it is as effective as topical clindamycin.35

Oral isotretinoin is an extremely effective treatment for acne, specifically in patients with scarring or persistent acne that does not respond adequately to standard treatment.13,36 The exact mechanism of action of isotretinoin is unclear, but it improves the clinical picture of severe acne through suppression of sebaceous gland activity, reduction in the size of sebaceous glands, and a dermal anti‑inflammatory effect. Most patients on isotretinoin experience marked dryness of their skin and lips; other mucosal surfaces, such as eyes, may also be affected. Oral isotretinoin is teratogenic, and is therefore contraindicated in women of childbearing potential, who are required to use double contraception and adhere to the Pregnancy Prevention Programme for up to 1 month after treatment. Isotretinoin may have an adverse effect on mood: depression, anxiety, and suicidal ideation have been reported in patients using isotretinoin.36 However, severe acne is itself associated with low mood and suicidal ideation.13,37

In 2003, a European Directive on oral isotretinoin stated that it should only be used in severe, nodular, and conglobate acne that is not responding to appropriate antibiotics and topical therapy,38 with the inference that isotretinoin should not be used as first‑line therapy for severe acne. However, the European Dermatology Forum believes that oral isotretinoin should be considered as the first-choice treatment for severe acne because of its clinical efficacy and ability to prevent scarring and improve patients’ quality of life.27 The summary of product characteristics for isotretinoin states that it can be prescribed by or under the supervision of physicians with expertise in the use of systemic retinoids for the treatment of severe acne and a full understanding of the risks of isotretinoin therapy and monitoring requirements;36 however, NICE and PCDS guidance recommends referral to a consultant dermatologist for prescription of isotretinoin.13

Because of their efficacy in reducing the number of inflammatory lesions, NICE recommends the use of antibiotics if no improvement is seen with non-antibiotic agents.13,28 However, NICE states that antibiotics should only be considered after non-antibiotic options have failed, and should be prescribed for a maximum of 3 months to limit AMR development. Topical monotherapy with antibiotics is not recommended by NICE because of the risk of antibiotic resistance, and topical antibiotics should only be prescribed in combination with benzoyl peroxide.13 Likewise, PHE discourages the use of topical antibiotics, especially when systemic formulations of the same antibiotic are available.6 The European Dermatology Forum concurs that topical monotherapy with antibiotics is generally not recommended for comedonal acne, mild‑to‑moderate papulopustular acne, or severe papulopustular/moderate nodular acne because of serious concerns regarding the risk of developing AMR.27 Systemic antibiotics should be considered if acne fails to respond to topical preparations, but antibiotic selection should take into account side-effects, contraindications, and levels of resistance in P. acnes. Similarly to topical antibiotics, systemic antibiotics should be prescribed in combination with a topical retinoid or benzoyl peroxide.13 Concomitant use of topical and systemic antibiotics should be avoided because of the increased risk of AMR development.13,28

Occasionally, especially with widespread acne involving less accessible areas such as the back, a systemic antibiotic can be justified, but the patient must be carefully reviewed 3–4 months after starting treatment, and treatment should be discontinued if there is no improvement.9 A follow-up consultation should be conducted to determine whether the acne is fully controlled, and if so, the patient should switch to maintenance therapy with a topical retinoid.13 Data from the Clinical Practice Research Datalink showed that around two-thirds of patients who had a new acne consultation had no acne follow-up consultations in the subsequent year, with 51.3% of patients prescribed an antibiotic at their initial consultation—24.9% receiving a systemic antibiotic, 23.6% receiving a topical antibiotic, and 2.8% receiving both a systemic and a topical antibiotic.9 This is contrary to NICE guidance, which states that follow-up should be arranged 8–12 weeks after each treatment step.13

Best practice in rosacea

Acne rosacea is a chronic, inflammatory skin condition that can affect the cheeks, nose, eyes, chin, and forehead, and is characterised by recurrent episodes of facial flushing, persistent erythema, telangiectasia, papules, pustules, and/or associated eye symptoms.14 The exact cause is unknown, but people with papulopustular rosacea have a higher density of Demodex mites, which usually exist harmlessly on the skin, and may be a contributing factor.

Non-pharmacological options

Before starting pharmacological treatment, it is important to recommend the avoidance of triggers. Common aggravating triggers for rosacea are summarised in Box 3.14,17 Because the skin is often a little dry, patients should be advised to protect the skin barrier with emollients, which may reduce stinging and burning of the skin. In addition, patients should be advised to apply high-factor sunblock, which will offer protection against sunlight. Camouflage make-up can also be useful to mask persistent erythema.14,17

Box 3: Common aggravating triggers for rosacea14,17

  • Certain drinks and foods, such as alcohol, hot drinks, caffeine, cheese, and spicy foods
  • Extremes of temperature, heat, sunlight, and humid conditions
  • Drugs that cause vasodilation, such as calcium channel blockers
  • Topical corticosteroids
  • Emotional stress
  • Strenuous exercise

Pharmacological treatments

NICE recommends avoiding the use of long-term antibiotics given growing concerns about AMR.14 Indeed, although inflammatory rosacea does respond to antibiotics such as topical metronidazole and systemic tetracyclines and erythromycin, these drugs are crucial for treating more serious infections, and their action in rosacea is unlikely be related to their antimicrobial activity but rather to their anti-inflammatory properties.39 Low-dose (sub-antimicrobial) doxycycline is an option, however, and there is some evidence that this does not interfere with the normal microbiome.14,40

Erythema can be distressing for patients with rosacea, and topical brimonidine gel, which reduces erythema by cutaneous vasoconstriction, is the most effective treatment for flushing and fixed erythema.14,40 The MOSAIC study showed that when topical brimonidine is used in combination with topical ivermectin, it is virtually always tolerated.41 Patients may experience itching and burning with the use of brimonidine gel,14 although this usually settles with continued use.42 However, telangiectasias can be rendered more visible by brimonidine, because the background erythema blanches whereas the telangiectasias are insensitive.14,42

The efficacy of oral ivermectin for helminth and mite infestations is established, but in recent years topical ivermectin has become available for rosacea. This non‑antibiotic cream, applied once daily, offers effective control of inflammatory rosacea, usually in just a few weeks, and has an acceptable tolerability profile. The exact mechanism of action of ivermectin in rosacea is unknown, but its anti‑inflammatory and anti-parasitic activities are thought to target the aetiological factors of the disease.43

The PCDS guideline on rosacea also includes brimonidine gel, beta blockers, and carvedilol as non-antibiotic treatment options for rosacea,17 and a recent study showed that the use of brimonidine gel in the morning and ivermectin cream in the evening is highly effective and well tolerated.41 With these two topical treatments, it is now possible to manage most patients with rosacea with almost total control of their disease, and the need for an antibiotic is very rare.

Intense pulsed light or pulsed dye laser therapies may offer permanent resolution of erythema and telangiectasia, and only a few treatment sessions are usually required.14,17

Best practice in eczema

The first event in the development of eczema is breakdown of the skin barrier, allowing the penetration of allergens and triggering a flare of eczema. Patients experience itching alongside inflamed, cracked, and often infected skin lesions,44 and scratching further damages the skin. Thus, prevention is the best treatment.

Non-pharmacological treatment

Protecting the skin barrier by complete emollient therapy and avoiding detergents is crucial.44 Creams should always be prescribed in a pump dispenser; if an ointment is supplied, the patient must be advised to extract it with a clean spoon or spatula to prevent infection, because an audit found that 53% of emollient containers were infected from dipping fingers directly into the emollient.45

Pharmacological treatments

Used appropriately, topical steroids are effective at controlling the inflammation of eczema,8 relieving the itch and thereby preventing further damage.46 However, they do compromise the immune response to infection, and skin infections can sometimes develop. Furthermore, they are only licensed for short courses as they will compromise the skin barrier.46

Topical immunomodulators such as tacrolimus and pimecrolimus are effective at treating eczema, and are a second‑line preventative option for skin prone to flares in moderate or severe eczema.8 They may also help to reverse corticosteroid-induced skin atrophy.47 NICE recommends that they are prescribed by a specialist.8

Eczema may flare because of bacterial infection, and the most common infective organism is Staphylococcus aureus.48 When recurrent infective flares are a problem, topical antiseptics such as benzalkonium and chlorhexidine are usually effective,8 although benzalkonium is a known irritant,49 and chlorhexidine can rarely cause allergic reactions.50 Topical antibiotics are frequently used, especially in combination with topical corticosteroids, but clinically infected eczema flares recover quickly with the use of mild-to-moderate steroids, with no benefit from the addition of topical or systemic antibiotics.48

Summary

The importance of antimicrobial stewardship in dermatology is considerable: patients are often prescribed long courses of antibiotics, contrary to the recommendations set out in guidelines, despite the fact that alternative treatments are available that both manage skin conditions more effectively and preserve antimicrobial agents. Non-antibiotic approaches should be adopted in all patients, such as the avoidance of triggers, management of underlying causes in the case of acne, and use of emollients for rosacea and eczema. A topical retinoid, alone or in combination with benzoyl peroxide, represents an effective non‑antibiotic option for the treatment of acne. Effective alternatives to topical and systemic antibiotics are now available for rosacea, and combined use of brimonidine gel and ivermectin offers an approach for most patients with this condition that obviates the need for antibiotics. Prevention is the best treatment for eczema, involving the avoidance of triggers and routine use of emollients; although infection often plays an important part in eczema flares, clinically infected eczema recovers quickly with the use of mild-to-moderate steroids without the addition of topical or systemic antibiotics.

Key points

  • Antimicrobial stewardship in dermatology is vital: patients are often prescribed long courses of antibiotics, despite the fact that effective, antibiotic‑sparing treatments are available
  • Non-antibiotic approaches should be adopted in all patients, such as the avoidance of triggers, management of underlying causes in acne, and use of emollients for rosacea and eczema
  • In acne, switching to a topical retinoid is effective; however, systemic isotretinoin can only be prescribed by a specialist in the UK at present
  • Effective alternatives to topical and systemic antibiotics are now available for rosacea, and combined use of brimonidine gel and ivermectin offers an antibiotic‑sparing approach for most patients
  • Prevention is the best treatment for eczema, involving the avoidance of triggers and routine use of emollients; although infection can trigger eczema flares, mild‑to‑moderate steroids provide rapid improvement without the need for topical or systemic antibiotics

Conflicts of interest

George Moncrieff has acted as a consultant or speaker for several companies, including Dermal Laboratories Ltd, Galderma UK Ltd, and Leo Laboratories Limited.

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EPI19-08-0185

Date of preparation: December 2019