Treating Acne Vulgaris: Systemic, Local and Combination Therapy

Laura J Savage; Alison M Layton

Disclosures

Expert Rev Clin Pharmacol. 2010;13(4):563-580. 

In This Article

Systemic Antibiotics

Antibiotics were the first effective treatment for acne. They are the most widely prescribed agents and are indicated for severe inflammatory acne, extensive truncal acne and moderate facial acne not responding to topical therapies. Response is variable; female patients with facial acne respond more favorably than male patients with marked seborrhea and truncal acne.[66] Acne does not represent a classical bacterial infection and antibiotics act largely through exerting effects that are independent of their antibacterial actions, mainly through anti-inflammatory mechanisms.[67–71] They reduce numbers of P. acnes, Staphylococcus epidermis and proinflammatory mediators (e.g., TNF-α, IL-1 and IL-6) in the microcomedo, and modulate the host response to these stimuli.[69–71]

Systemic antibiotics should be prescribed in an adequate dosage and the frequency and duration only continued for as long as they are deemed to be working. Patients with acne are often treated with multiple antibiotics and as a consequence, their flora is exposed to a significant selective pressure for resistance development.[72,73] Rotational antibiotics should therefore be avoided, and if combining topical and systemic antibiotics, the same chemical type should be used to avoid the emergence of resistant strains of P. acnes to different classes of antibiotics.[14] Resistance may manifest as a reduced response, no response or relapse.[58,60,74] A significant proportion of acne patients are colonized with resistant P. acnes before treatment is initiated, primarily owing to person-to-person contact with friends and family. Ross et al. demonstrated the prevalence of resistant P. acnes in household contacts of patients to be as high as 86%.[75]

The increasing emergence of P. acnes resistance to erythromycin and the correlation of erythromycin-resistant P. acnes and reduced response to erythromycin therapy[59] has resulted in the recommendation that erythromycin should be restricted to specific clinical situations only.[76] It is the antibiotic of choice for pregnant and breast feeding women, at a maximum dose of 1 g/day. Absorption of erythromycin is inhibited by carbohydrate in the stomach and, therefore, it is recommended that it is taken 30 min prior to eating.

Based on efficacy and safety data, and population levels of bacterial resistance, cyclines are recommended as the first-line antibiotic of choice.[46,66,77] Oxytetracycline (1 g/day) is frequently associated with poor compliance as it must be taken 30 min before food and not with milk to ensure adequate absorption. Second-generation cyclines are less likely to be affected by food and can be taken once daily, which may aid adherence, and of these, lymecycline (300–600 mg/day) and doxycycline (100–200 mg/day) should be used in preference to minocycline owing to its inferior side effect profile.[76] Cyclines are contraindicated in children less than 8–12 years of age (age varies according to national licences) as they can discolour dentition. In pregnancy, they can result in the inhibition of fetal skeletal growth and should be avoided.[78]

Trimethoprim (200–300 mg/day) has a similar efficacy to tetracycline,[79] but does not have a licence for acne and is reserved as a third-line antibiotic for cases where there is proven resistance to other agents.[80–82] It may also be used in young patients in whom tetracyclines are contraindicated. As it is used as a treatment for potentially serious cutaneous and systemic infections, such as those caused by methicillin-resistant Staphylococcus aureus it is advisable to limit its use to selected cases only.[82]

There are documented cases of acne improving with other classes of antibiotics, including oral azithromycin, cephalosporins and fluoroquinolones.[83,84] However, like trimethoprim, they are commonly used to treat a variety of systemic infections and as such, their use should be restricted and discouraged in acne. Clindamycin is highly lipophilic and very effective in acne, but adverse effects such as diarrhea (seen in 5–20% cases) and pseudomembranous colitis due to overgrowth of Clostridium difficle have limited its favor among prescribers.[85]

The question of duration of antibiotics in acne treatment has not been adequately researched and any published recommendations are not supported by strong scientific evidence. A total of 3 weeks is the reported minimum period before any obvious improvement is likely to be noted,[86] and a minimum of 3 months, extending to 6 months with topical therapy, is required to achieve maximum benefit.[76,87] Ozolins et al. compared five antibiotic regimens for mild-to-moderate facial acne and suggested that maximum improvement was actually reached before 3 months, at 6 weeks for both oral antibiotics and topical BPO.[32,74]

If a patient relapses after discontinuation, the same antibiotic should be restarted where possible. Topical BPO can be used for 7 days between courses to try to eliminate resistant organisms at the site of administration,[13,76] although no agent is able to fully eradicate resistant P. acnes. Oral isotretinoin has also been demonstrated to lower the carriage of resistant P. acnes on the skin, although this is no more effective and is slower to act than BPO.[88] Using regimens with increased treatment efficacy may lead to reduced exposure to antibiotics and, in turn, less resistance.

A number of publications have proposed how antibiotics should best be administered in order to achieve maximal therapeutic response, while avoiding resistance. The most comprehensive recommendations published by the Global Alliance to Improve Outcomes in Acne[14] are listed in Box 1.

Female patients should also be warned about the potential decreased efficacy of oral contraceptive and advised to take supplementary birth control precautions if oral antibiotics are to be incorporated into a regimen containing the contraceptive pill. However, with the exception of rifampicin-containing drugs, scientific evidence to support the notion that commonly prescribed antibiotics reduce blood concentrations and/or the effectiveness of oral contraceptives is lacking.[89]

A summary of oral antibiotic prescribing in acne vulgaris and potential adverse effects can be found in Table 2.[90]

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