Medication Summary
The following information primarily pertains to the treatment of Cutibacterium (formerly Propionibacterium) acne vulgaris.
Antibiotics used to treat anaerobic infections usually suffice for other types of Cutibacterium (formerly Propionibacterium) infections. These include the penicillins, carbapenems, and clindamycin. In addition, vancomycin and teicoplanin (investigational) have been used. Some of these antibiotics are discussed after the treatment of acne vulgaris. Daptomycin has been used for the treatment of Cutibacterium (formerly Propionibacterium) osteomyelitis. [41]
A first-in-class topical selective androgen receptor inhibitor, clascoterone 1% topical cream, was approved by the FDA in August 2020. Clascoterone cream targets androgen receptors in the skin to reduce cutaneous 5-alpha dihydrotestosterone. Favorable results, safety, and tolerability were reported from two phase 3 double-blind, vehicle-controlled, randomized, 12-week, trials that included a total of 1440 subjects. [42]
Topical Products
Class Summary
Acne products are used for the treatment of mild to moderate acne vulgaris. These agents may have antibacterial and comedolytic properties. In severe cases, the agents may be used as an adjunct in therapeutic regimens.
Erythromycin and benzoyl peroxide (Benzamycin)
This combination agent contains erythromycin, which is a macrolide antibiotic, and benzoyl peroxide. Benzoyl peroxide, in addition to being an antibacterial agent, is a keratolytic and desquamative agent. With benzoyl peroxide, free-radical oxygen is released upon administration, oxidizing bacterial proteins in sebaceous follicles and decreasing the number of anaerobic, bacterial, and irritating free fatty acids. This combination has keratolytic and comedolytic effects. Erythromycin is indicated for infections caused by susceptible strains of microorganisms. The combination drug may be applied topically twice daily.
Clindamycin and tretinoin (Ziana, Veltin)
This combination agent contains the topical antibiotic clindamycin 1.2% and tretinoin 0.025%. Clindamycin reduces Cutibacterium acnes (formerly Propionibacterium acnes) levels and is anti-inflammatory. Tretinoin normalizes differentiation of keratinocytes and is anti-inflammatory. Apply daily to affected areas.
Clindamycin and benzoyl peroxide (Acanya, Duac, BenzaClin)
This combination agent contains the topical antibiotic clindamycin and benzoyl peroxide. Clindamycin reduces C acnes (formerly P acnes) levels and is anti-inflammatory. Benzoyl peroxide is an antibacterial, comedolytic, and anti-inflammatory agent. Benzoyl peroxide reduces the risk of development of bacterial resistance to clindamycin. Acanya gel contains 2.5% benzoyl peroxide and Duac CS and BenzaClin contain 5% benzoyl peroxide. Apply Acanya and Duac CS once daily. BenzaClin is applied twice daily.
Azelaic acid (Azelex, Finacea)
Azelaic acid has been shown to help reduce inflammation and may aid in the treatment of postinflammatory hyperpigmentation. Apply azelaic acid twice daily. Improvement may be seen within 4 weeks.
Benzoyl peroxide (BenzEFoam, PanOxyl, Neutrogena Clear Pore, Benzac AC Wash)
Benzoyl peroxide is an oxidizing agent that possesses antibacterial properties and is comedolytic. The antibacterial activity results from the release of active or free-radical oxygen that can oxidize bacterial proteins. Benzoyl peroxide is oxidized into benzoic acid with contact to the skin. It is available over the counter and by prescription.
Retinoid-like Agents
Class Summary
These agents stimulate cellular retinoid receptors and help normalize keratinocyte differentiation and are comedolytic. In addition, they have anti-inflammatory properties. Oral isotretinoin also reduces sebum production in the skin. Retinoids are classified into 3 generations. The first comprises topical tretinoin and systemic isotretinoin. Acitretin is a second-generation retinoid used to treat psoriasis. The third-generation retinoids include topical adapalene tazarotene.
Topical tretinoin (Retin-A Micro, Atralin, Avita, Tretin-X, Renova)
Topical tretinoin inhibits microcomedo formation. It decreases cohesiveness of keratinocytes in sebaceous follicles, which allows for easy removal. It has anti-inflammatory properties. Topical tretinoin is available as a cream or gel.
Adapalene (Differin)
Adapalene inhibits microcomedo formation. It decreases cohesiveness of keratinocytes in sebaceous follicles, which allows for easy removal. It has anti-inflammatory properties. Adapalene is available as a cream, lotion, or gel.
Tazarotene (Tazorac, Fabior, Avage)
Tazarotene inhibits microcomedo formation. It decreases cohesiveness of keratinocytes in sebaceous follicles, which allows for easy removal. It has anti-inflammatory and immunological properties. Tazarotene is available as a cream or gel.
Trifarotene (Aklief)
Trifarotene is an agonist of retinoic acid receptors (RARs), with particular activity at the gamma subtype of RAR. The stimulation of the RAR results in modulation of target genes that are associated with various processes, including cell differentiation and mediation of inflammation. The exact process by which trifarotene ameliorates acne is unknown. It is indicated for acne vulgaris for patients aged 9 years and older. Trifarotene is available as cream.
Isotretinoin (Claravis, Amnesteem, Absorica, Zenatane)
Isotretinoin is an oral retinoid indicated for recalcitrant, nodulocystic acne. It addresses all four pathogenic factors involved in the development of acne: follicular hyperkeratinization, inflammation, sebum production, and Cutibacterium acnes (formerly Propionibacterium acnes) growth. Treatment is weight-based, usually dosed initially 0.5 mg/kg and increased to 1 mg/kg in 2 divided doses for 15-20 weeks. Once-daily dosing is not recommended. The dose may be adjusted to administer up to 2 mg/kg/day. The patients must be registered into the government-regulated iPledge program in order to receive the medication.
Antibiotics
Class Summary
Oral antibiotics are useful in inflammatory acne, and improvement is usually seen after several weeks of use. Antibiotic monotherapy is discouraged due to risk of development of resistant bacteria.
Females should be warned about the development of Candida albicans vaginitis. A rare complication of long-term oral antibiotic use is the development of gram-negative folliculitis. Tetracycline class antibiotics can cause sun sensitivity. Doxycycline is associated with GERD, and should be taken at least 30 minutes prior to sleep. Minocycline is rarely associated with a lupuslike syndrome, minocycline-induced hyperpigmentation, and pseudotumor cerebri.
Topical antibiotics are used in almost all acne patients. Monotherapy should be avoided to reduce risk of antibiotic resistance. Concurrent use of benzoyl peroxide eliminates the risk of development of resistance. Topical antibiotics are available as monotherapy or in fixed-dose combination products along with benzoyl peroxide or retinoids. Topical antibiotics used include clindamycin and erythromycin, though resistance to erythromycin favors the use of clindamycin. Additionally, dapsone and minocycline are approved in topical dosage forms to treat acne vulgaris.
Tetracycline
Tetracycline inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunit(s). Tetracycline has anti-inflammatory activity. Tetracycline may be administered at 250-500 mg PO bid.
Minocycline (Solodyn, Minocin)
Minocycline treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species. The brand name Solodyn is an extended-release formulation indicated for acne and is prescribed as a weight-based 1-mg/kg dose per day. The minocycline dose should be lowered in patients with renal impairment.
Doxycycline (Doryx, Adoxa, Doxy 100, Vibramycin)
Doxycycline treats infections caused by susceptible gram-negative and gram-positive organisms. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Doxycycline may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. The brand name 150-mg Doryx is enteric coated, to reduce adverse gastrointestinal effects.
Sarecycline (Seysara)
Sarecycline is a tetracycline-derived antibiotic specifically created for dermatologic purposes. It possesses a narrow spectrum of activity compared with conventional tetracyclines. It is indicated for treatment of inflammatory lesions of non-nodular moderate-to-severe acne in adults and children aged 9 years or older.
Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)
Trimethoprim/sulfamethoxazole is an antibiotic with activity against many gram-positive and gram-negative organisms. It inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It is available as 80 mg trimethoprim and 400 mg sulfamethoxazole or as 160 mg trimethoprim and 800 mg sulfamethoxazole (double strength).
Clindamycin (Cleocin)
Clindamycin is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Clindamycin is commonly used topically, but it can be given orally. Oral monotherapy administration should be avoided to reduce the risk of antibiotic resistance. It may administered at 75-300 mg/day in divided doses.
Clindamycin topical (ClindaGel, Cleocin-T, ClindaMax)
Topical clindamycin is a lincosamide for treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is commonly used topically, but it can be given orally. Apply a thin film twice daily, except for the gel form, which is applied once daily.
Erythromycin topical (Akne-mycin, Erygel, Ery)
Topical erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is commonly prescribed for acne as a topical gel in combination with benzoyl peroxide. Its use is limited because of resistant Cutibacterium acnes (formerly Propionibacterium acnes) strains. Apply twice daily after washing the skin and drying it.
Daptomycin (Cubicin)
Daptomycin binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis, ultimately causing cell death. It is indicated for complicated skin and skin-structure infections caused by S aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S dysgalactiae, and E faecalis (vancomycin-susceptible strains only). Daptomycin has been used for the treatment of Cutibacterium (formerly Propionibacterium) osteomyelitis.
Dapsone topical (Aczone)
Dapsone is a sulfone antibiotic that also has anti-inflammatory properties that are largely thought to contribute to its efficacy for treating mild-to-moderate acne. It is well tolerated, with infrequent and mild adverse events mainly involving local administration site such as dryness, stinging, and erythema. It is available as 5% twice-daily and 7.5% once-daily formulations. The current American Academy of Dermatology guidelines preceded the FDA approval of the 7.5% formulation. Although no research has compared the efficacy of the 5% formulation with the 7.5% formulation, both have been separately shown to be efficacious and safe. The 7.5% formulation has the additional compliance factor of once-daily application.
Minocycline topical (Amzeeq)
The mechanism of action of minocycline foam in treating acne vulgaris is not known. It is indicated for topical treatment of acne vulgaris in adults and children aged 9 years or older.
Estrogens/Progestins
Class Summary
Hormonal therapies can be used in females with acne, especially those with premenstrual acne flares in whom other therapies have failed. Patients may also have signs of hyperandrogenism (eg, hirsutism, irregular menses, menstrual dysfunction). Serum androgen levels may or may not be elevated.
Available options include combination estrogen-progestin oral contraceptive pills, which suppress ovarian androgen production as well as androgen receptor blockers that block the effect of androgens peripherally at the sebaceous gland.
Ethinyl estradiol, drospirenone, and levomefolate (Beyaz)
Ethinyl estradiol, drospirenone, and levomefolate is a combination of estrogen and progestin that treats acne in adult women. It suppresses ovarian production of androgens.
Ethinyl estradiol and norethindrone (Estrostep Fe, Tilia Fe, Tri-Legest Fe, Femcon FE)
Ethinyl estradiol and norethindrone is a combination of estrogen and progestin that treats acne in adult women. It suppresses ovarian production of androgens.
Ethinyl estradiol and norgestimate (Ortho Tri-Cyclen, Tri-Estarylla, Tri-Previfem, Tri-Sprintec)
Ethinyl estradiol and norgestimate is a combination of estrogen and progestin treats acne in adult women. It suppresses ovarian production of androgens.
Ethinyl estradiol and drospirenone (Yaz, Zarah, Gianvi, Ocella, Yasmin)
Ethinyl estradiol and drospirenone is a combination of estrogen and progestin that treats acne in adult women. It suppresses ovarian production of androgens.
Aldosterone Antagonists, Selective
Class Summary
Aldosterone antagonists may reduce free testosterone levels and compete with androgens binding at the sebaceous gland.
Spironolactone (Aldactone)
Spironolactone is an aldosterone antagonist that competes with testosterone and dihydrotestosterone binding at the receptor in the sebaceous gland. It also reduces free testosterone levels as more blood is bound by an increased quantity of SHBG. To treat acne in women, 25-200 mg once daily may be administered.
Topical Androgen Receptor Inhibitors
Class Summary
These agents compete with androgens, specifically dihydrotestosterone, for binding to the androgen receptors within the sebaceous gland and hair follicles.
Clascoterone topical (Winlevi)
Clascoterone 1% topical cream is indicated for treatment of acne vulgaris in patients aged 12 years and older.
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Acne, grade I; multiple open comedones.
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Acne, grade II; closed comedones.
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Acne, grade III; papulopustules.
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Acne, grade IV; multiple open comedones, closed comedones, and papulopustules, plus cysts.
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Acne with reactive hyperpigmentation; before treatment.
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Acne with reactive hyperpigmentation; after treatment.
