Oral antibiotics: an option in acne but consider the risks

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SummaryPractice pointsPathophysiology of acneInitial acne assessment and adviceWhich oral antibiotics are effective?Minocycline is a second line oral antibioticTetracyclines associated with inflammatory bowel disease (IBD)Antibiotic resistanceFollow-up regularly with patientsFor more informationReferences

Summary

Acne is the most common skin disease of adolescence and few teenagers escape the experience.1 The severity of acne varies considerably and in some individuals it persists well beyond the teenage years.2

Most patients with acne have a mild-to-moderate condition and the social, emotional and physical impact of acne can be managed by their GP.3,4 People with mild-to-moderate acne who have not responded to over-the-counter products or treatment with topical retinoids alone may benefit from adding topical antibiotics and/or benzoyl peroxide to topical retinoids.3-5 Oral antibiotics can be combined with benzoyl peroxide or a topical retinoid (and/or use the combined oral contraceptive pill for women) for those with moderate-to-severe acne.3,4

Teenagers are more likely to adhere to oral antibiotics than topical treatments which take a long time to apply.6 However reserve oral antibiotics for moderate-to-severe acne because of their greater potential for serious side effects,7-10 compared with topical treatments alone.

Plan regular follow-ups to encourage adherence and to ensure efficacy and safety of treatment. Recent studies have found an association with tetracycline antibiotics and autoimmune disease; this highlights the need to frequently assess response and whether continuing treatment is indicated.11-13

Practice points

  • Health professionals can help manage the social, emotional and physical impact of acne by addressing patient concerns, providing reassurance and practical advice.
  • Counsel patients to avoid squeezing acne lesions, use a mild skin-cleansing regimen, eat a healthy diet and avoid overexposure to the sun.4
  • Individualise treatment according to the type, severity and extent of the condition:3
    • For mild-to-moderate acne in those who have not responded to over-the-counter products or topical retinoids alone, add topical antibiotics and/or benzoyl peroxide to topical retinoids.3-5
    • For moderate-to-severe acne, options include indicated oral antibiotics combined with benzoyl peroxide or a topical retinoid (and/or use a combined oral contraceptive for women).3,4
    • For severe acne with nodules and cysts and for people at risk of scarring or experiencing severe psychological distress, refer to a dermatologist.3,4
  • To minimise the risk of antibiotic resistance and adverse effects, limit oral antibiotic courses to 3–6 months.3
  • After acne has cleared, maintenance therapy for 3–12 months or longer with a topical retinoid is a good option to prevent recurrence.3,14
  • Prepare patients with a realistic treatment plan, and inform them about potential adverse effects to aid adherence.3
  • Regular follow-up is important to assist with adherence and to ensure efficacy and safety of treatment. For patients with moderate-to-severe acne ± nodules ± cysts who have not responded to a course of oral antibiotics, consider adding antiandrogen therapy in females and/or refer to a dermatologist for oral isotretinoin treatment.
  • Timely and effective treatment of acne minimises the risk of long-term scarring and psychological distress.3

Pathophysiology of acne

Acne usually begins just before or during puberty when the output of sebum by hair follicles on the face and upper trunk increases substantially.15 Acne lesions can be classified as non-inflammatory (open and closed comedones), inflammatory (pustules, red papules, nodules and cysts), resolving macules or long-term scars.4

The role of Propionibacterium acnes in the pathogenesis of acne has never been formally proven, and there is some doubt that it has a causal role.16 The triglycerides present in sebum act as an energy source for P. acnes, which colonises both healthy and diseased follicles.16 P. acnes is part of the normal skin flora and is present in nearly all adults. While it is certainly present in acne-affected skin it is currently unclear whether it is causal.

Initial acne assessment and advice

Before prescribing treatment for acne consider general issues and aggravating factors such as medicines which can worsen acne (e.g. corticosteroids, anticonvulsants), occupational exposures such as industrial oils and underlying hormonal issues such as polycystic ovarian syndrome.3,4

For mild acne with superficial lesions, whiteheads, blackheads, papules and pustules recommend over-the-counter cleansers and topical products containing ingredients such as benzoyl peroxide, salicylic acid, glycolic acid, lactic acid, sulfur or resorcinol.3

Established scars caused by severe acne will not respond to topical or oral treatment.4 Patients with severe acne and those at risk of scarring or experiencing severe psychological distress will require referral to a dermatologist.3,4

Health professionals can help manage the social, emotional and physical impact of acne by addressing patient concerns, providing reassurance and practical advice such as:4

  • Do not squeeze acne lesions — picking or squeezing lesions can make acne worse and increase the risk of permanent scarring.
  • Use a mild skin-cleansing regimen — avoid vigorous scrubbing of affected skin, and using astringent or exfoliating agents.
  • Eat a healthy diet — while diet has not been directly implicated in causing acne, it is reasonable for an individual to avoid specific foods that are linked to flare-ups.
  • Avoid over-exposure to the sun — treated skin is prone to sunburn, sun protection should include use of noncomedogenic SPF 30+ broad-spectrum sunscreens.

Which oral antibiotics are effective?

Individualise acne treatment according to the severity and extent of the disease. Treat patients with mild to moderate acne, who have not responded to over-the-counter products or topical retinoids alone by adding topical antibiotics and/or benzoyl peroxide to topical retinoids, rather than oral antibiotics.4 For patients with moderate papulopustular acne ± trunk involvement ± nodules, Australian guidelines recommend adding doxycycline 50–100 mg daily to benzoyl peroxide or topical retinoid or, for female patients, consider prescribing a combined oral contraceptive pill.4

Limit courses to 3–6 months to minimise antibiotic resistance and adverse effects. After acne has cleared, maintenance therapy for 3–12 months or longer with a topical retinoid is a good option to prevent recurrence.3,14

If tetracycline antibiotics are not tolerated or are contraindicated, e.g. in pregnancy, erythromycin 250–500 mg orally, twice daily is an alternative.4

Minocycline is a second line oral antibiotic

Guidelines recommend minocycline 50–100 mg orally daily if doxycycline is not tolerated, however it has a less favourable risk–benefit profile for treating acne compared with doxycycline.7 Like doxycycline, minocycline can cause gastrointestinal upset, benign intracranial hypertension and tooth discolouration.10 However, a recent meta-analysis showed no evidence that minocycline has a more prolonged effect or is more effective in acne resistant to other therapies7 and minocycline is associated with more severe adverse effects such as irreversible hyperpigmentation.7 Long-term treatment with minocycline can result in severe autoimmune liver damage9 and lupus erythematosus.8,17

Tetracyclines associated with inflammatory bowel disease (IBD)

A recent UK study of around 95,000 people found an association with tetracycline antibiotics and the development of inflammatory bowel disease (IBD).13 The absolute number of people with IBD was small, but the effect was significant.13 However, a subsequent study found no association between tetracycline antibiotic exposure and IBD, but rather suggested childhood antianaerobic antibiotic exposure is associated with IBD development.11

Although a causal link has not been established between tetracycline antibiotic use and the development of lBD, consider this potential risk when prescribing these medicines.13

Antibiotic resistance

Some risk factors for developing or acquiring antibiotic-resistant P. acnes include:

  • prolonged antibiotic therapy
  • multiple courses of antibiotics
  • poor adherence with treatment.14

It is no surprise that resistance among P. acnes, and other bacteria, is on the rise.18 Acne is not a classic bacterial infection and therefore, unlike other infections, resistance to an antibiotic does not translate directly to treatment failure. This is partly because antibiotics may exert effects not related to their antibacterial actions, such as anti-inflammatory actions.5 Antibiotic resistance in acne may manifest as a reduced response, no response or relapse.19,20 It can also impact the effect of antibiotics on other pathogenic organisms in the future.5

The Global Alliance to Improve Outcomes in Acne expert group note that resistance in P. acnes varies worldwide and can be somewhat hard to predict.5,21,22 In addition, susceptibility testing for P. acnes is not practical on a routine basis and does not necessarily influence therapeutic decisions.5 The group recommend taking steps that are known to limit the potential for antimicrobial resistance.5

Strategies to limit antibiotic resistance4,5

  • For mild-to-moderate acne in those who have not responded to over-the-counter products or topical retinoids alone add topical antibiotics and/or benzoyl peroxide to topical retinoids.
  • For moderate-to-severe acne use oral antibiotics + benzoyl peroxide treatment or topical retinoid.
  • Avoid using antibiotics (either oral or topical) as monotherapy.
  • Avoid using oral antibiotics with topical antibiotics particularly if using different antibiotics.
  • The ideal duration of oral antibiotic therapy is 3 months, however an interim review of response may be appropriate at 6–8 weeks.
  • Do not switch antibiotics without adequate justification; when possible, use the original antibiotic for subsequent courses if patients relapse.
  • Avoid use of antibiotics for maintenance therapy, use topical retinoids with benzoyl peroxide added for an antimicrobial effect if needed.
  • Use benzoyl peroxide concomitantly as a leave-on or as a wash. Using benzoyl peroxide for 5–7 days between antibiotic courses may reduce resistant organisms on the skin; however, benzoyl peroxide does not fully eliminate the potential for resistant organisms.

Note: Recommendations are based primarily on expert opinion because of a lack of studies and different designs and methodologies of existing studies.

Follow-up regularly with patients

Timely and effective treatment of acne minimises the risk of long-term scarring and psychological distress.3 Being a chronic condition, treatment regimens may need to be altered frequently to ensure efficacy and safety. Only use antibiotics (in combination therapy) for prolonged periods where clinical benefit is likely.14

For patients with moderate-to-severe acne ± nodules ± cysts who have not responded to a course of oral antibiotics consider adding anti-androgen therapy in females and/or refer to a dermatologist for oral isotretinoin treatment.3,4

Adherence to acne treatments can be problematic — teenagers in particular are notorious for being non-adherent.23 A large-scale multi-centre observational study investigated adherence with acne treatment and found poor adherence was independently correlated with young age (most strongly with <15 years but also in the 15–25 year age group).23

Topical treatments are most challenging — lack of time for application of treatment is a common reason for non-adherence.6 Any topical acne preparation (either over-the-counter or prescribed) can cause skin irritation.3 This problem can be overcome with practical advice e.g. use treatments on alternate days when beginning, avoid using facial cleansers and scrubs before application.3

Work out a realistic treatment plan for teenagers and inform them about potential adverse effects, otherwise their expectations will not be met and adherence will be poor.3,23 Emphasise that acne treatments may take several weeks to work.3

Importance of regular follow up

  • Adherence to treatment. A longer duration between doctor visits is associated with decreased adherence.6
  • Efficacy of treatment. Regimens may need to be altered according to a change in the disease severity.3
  • Preventing the spread of antibiotic resistant P. acnes. Regimens may need to be altered due to reduced response attributed to antibiotic resistance.5
  • Safety. Adverse effects from treatments can occur at any stage. Patients taking long-term or repeated courses may be more susceptible to adverse effects.7-9

For more information

References
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  3. See J. Drug treatment in acne. Aust Prescr 2012;35:180–2. [Full text]
  4. Therapeutic Guidelines Limited. eTG complete dermatology. Melbourne: 2010. [Online] (accessed 12 September 2013).
  5. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009;60:S1–50. [PubMed]
  6. Lott R, Taylor SL, O'Neill JL, et al. Medication adherence among acne patients: a review. J Cosmet Dermatol 2010;9:160–6. [PubMed]
  7. Garner SE, Eady A, Bennett C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2012;8:CD002086. [PubMed]
  8. Schlienger RG, Bircher AJ, Meier CR. Minocycline-induced lupus. A systematic review. Dermatology 2000;200:223–31. [PubMed]
  9. Lawrenson RA, Seaman HE, Sundstrom A, et al. Liver damage associated with minocycline use in acne: a systematic review of the published literature and pharmacovigilance data. Drug Saf 2000;23:333–49. [PubMed]
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