Topical antibacterial therapy for acne vulgaris

Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial treatments indicated for mild-to-moderate acne vulgaris. Topical antibiotics act both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous follicle and as anti-inflammatory agents. Benzoyl peroxide is a powerful antimicrobial agent that rapidly destroys both bacterial organisms and yeasts. Topical clindamycin and erythromycin have been proven to be effective against inflammatory acne vulgaris in concentrations of 1-4% with or without the addition of zinc. However, none of the antibacterials tested was more effective than benzoyl peroxide, which also has the advantage of not being associated with antimicrobial resistance.Topical antibacterial therapy should be discontinued once improvement is observed. If no improvement is observed within 6-8 weeks, the agent should be discontinued and a therapeutic switch considered. The primary limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous irritation or dryness.Antibacterial therapy can be used in combination with other agents. Combining topical antibiotics and topical retinoids may enhance the efficacy, since the retinoid will improve the penetration of the antibiotic. Combining a topical antibiotic with benzoyl peroxide may increase the bactericidal effect of the antibiotic and reduce the potential for bacterial resistance. Topical and oral antibacterials should not be used in combination for the treatment of acne vulgaris, since this association may increase the risk of bacterial resistance.     

Topical clindamycin in the management of acne vulgaris

A small cadre of antimicrobials are commonly used and regarded as effective and safe, as systemic and topical treatments of acne vulgaris. These include oral tetracycline, doxycycline, minocycline and topical clindamycin and erythromycin. Topical antimicrobials work via both antimicrobial and non-antimicrobial mechanisms: the former due to suppression of the growth of propionibacterial species (especially Propionibacterium acnes and P. granulosum). Clindamycin appears to be superior in efficacy compared with erythromycin and tetracycline. However, the emergence and spread of resistance among propionibacteria to both erythromycin and clindamycin calls into question their long-term viability as topical anti-acne therapies. Only through judicious use of combination topical therapies (e.g., topical retinoid, benzoyl peroxide or azelaic acid plus clindamycin or erythromycin) and the practice of effective infection control (i.e., handwashing between seeing patients in the clinic) can both clindamycin's and erythromycin's widespread utility be preserved in this disorder.     

Topical clindamycin in the management of acne vulgaris

A small cadre of antimicrobials are commonly used and regarded as effective and safe, as systemic and topical treatments of acne vulgaris. These include oral tetracycline, doxycycline, minocycline and topical clindamycin and erythromycin. Topical antimicrobials work via both antimicrobial and non-antimicrobial mechanisms: the former due to suppression of the growth of propionibacterial species (especially Propionibacterium acnes and P. granulosum). Clindamycin appears to be superior in efficacy compared with erythromycin and tetracycline. However, the emergence and spread of resistance among propionibacteria to both erythromycin and clindamycin calls into question their long-term viability as topical anti-acne therapies. Only through judicious use of combination topical therapies (e.g., topical retinoid, benzoyl peroxide or azelaic acid plus clindamycin or erythromycin) and the practice of effective infection control (i.e., handwashing between seeing patients in the clinic) can both clindamycin's and erythromycin's widespread utility be preserved in this disorder.     

Evaluating FMX-101 as a promising therapeutic for the treatment of acne

ABSTRACT

Introduction

Oral minocycline is a mainstay of therapy for moderate-to-severe acne; however, systemic side effects which include hepatotoxicity, lupus-like syndrome, drug hypersensitivity syndrome, autoimmune hepatitis, polyarteritis nodosa, gastrointestinal side effects and skin hyperpigmentation are of concern. Topical antibiotics commonly used in acne, such as erythromycin and clindamycin, present high P. acnes resistance rates which has opened the market for new topical antibiotics. FMX-101 is a novel topical minocycline foam that has shown promising results in phase I, II and III trials for the treatment of moderate-to-severe acne with a better safety profile than oral minocycline.     

Topically administered clindamycin in the treatment of acne vulgaris and other dermatologic disorders

Clindamycin is a macrolide antibiotic that has been used orally and topically in the treatment of acne vulgaris. Unfortunately, oral administration is associated with pseudomembranous colitis in up to 10% of patients; consequently, it is no longer a generally accepted form of acne therapy. Topical application is an effective, safer alternative. Topical formulations may be extemporaneously prepared or purchased as a pre-mixed hydroalcoholic solution. Adverse effects associated with topical preparations are few and mostly minor. Topical clindamycin is also used in the treatment of erythrasma, rosacea, periorificial facial dermatitis, and folliculitis.     

Acne vulgaris: a review of antibiotic therapy

Antibiotic therapy has been integral to the management of inflammatory acne vulgaris for many years. Systemic antibiotics work via antibacterial, anti-inflammatory and immunomodulatory modes of action, and have been found to be useful in managing moderate-to-severe acne. Commonly prescribed antibiotics include tetracyclines, erythromycin and trimethoprim, with or without sulfamethoxazole. In selecting the appropriate antibiotic for patients needing to receive topical or systemic antibiotic therapy, the clinician should take into account the severity of the acne, cost-effectiveness, the safety profile of the drug and the potential for development of resistance. The widespread and long-term use of antibiotics over the years has unfortunately led to the emergence of resistant bacteria. The global increase in the antibiotic resistance of Propionibacterium acnes may be a significant contributing factor in treatment failures. It is therefore essential that clinicians prescribing antibiotics for the treatment of acne adopt strategies to minimise further development of bacterial resistance. This includes addressing compliance issues, using combination therapies, avoiding prolonged antibiotic treatment, and avoiding concomitant topical and oral antibiotics with chemically dissimilar antibiotics.     

Emerging drugs for acne

Acne vulgaris is a common skin disorder that affects most individuals at some point in their lives. It may result in significant morbidity, including cutaneous scarring and psychological impairment. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, and systemic isotretinoin. There are growing concerns of rising antibiotic resistance, significant side effects of isotretinoin therapy, and lack of safe and effective treatment for pregnant females. Recent advances in the pathogenesis of acne have led to a greater understanding of the underlying inflammatory mechanisms and the role the Propionibacterium acnes and biofilms. This has led to the development of new therapeutic targets. This article reviews emerging treatments of acne, including topical picolinic acid, topical antibiotic dapsone, systemic zinc salts, oral antibiotic lymecycline, new formulations of and synergistic combinations of benzoyl peroxide, photodynamic therapy with topical photosensitizers and potential acne vaccines.     

A new treatment for acne vulgaris combining benzoyl peroxide with clindamycin

Topical acne therapies are widely used for the treatment of mild to moderately severe acne vulgaris. However, many available treatments have limitations associated with their use, including lengthy time to response, cosmetic acceptability, and photosensitivity. Combinations of topical antibiotics and comedolytics are especially useful, but some formulations have stability challenges. A new combination formulation that contains 1% clindamycin and 5% benzoyl peroxide (BenzaClin Topical Gel) is currently available. In clinical trials, clinical improvement occurred at the first two follow-up visits and continued throughout treatment. In addition, combination therapy with clindamycin/benzoyl peroxide gel rapidly reduces Propionibacteria acnes counts and suppresses the emergence of clindamycin-resistant P. acnes. This formulation is stable at room temperature for up to 2 months after compounding. The aqueous gel vehicle is less drying, and there is no photosensitivity associated with its use. This study compares the combination treatment of 1% clindamycin and 5% benzoyl peroxide topical gel with other therapeutic options for mild to moderately severe acne vulgaris.     

Guidelines for the management of acne vulgaris in adolescents

This article reviews the treatment of acne in adolescents. The choice of therapy should be principally based on the type of lesion and the severity of the acne, but psychosocial disability relating to the disease and the presence of scarring may also influence the approach to treatment.Mild acne generally requires topical treatment only. Benzoyl peroxide, azelaic acid, and antibacterials are generally used for inflammatory lesions. Topical retinoids are particularly effective for noninflamed lesions, and combination therapies are useful for mixed lesions. Moderately severe acne generally requires oral antibacterials. Tetracyclines/oxytetracycline and erythromycin are usually the first-line antibacterials. Second-generation tetracyclines, such as lymecycline, doxycycline, and minocycline, show improved absorption. Minocycline has the advantage of being rarely associated with Propionibacterium acnes antibacterial resistance, but can occasionally lead to potentially serious adverse effects. Trimethoprim is a useful third-line antibacterial therapy for patients resistant to other antibacterial therapies. Benzoyl peroxide should generally be used in combination with oral antibacterials as this has been shown to reduce the development of antibacterial resistance. For severe nodular acne, isotretinoin is the treatment of choice. In addition, over recent years dermatologists have increasingly used this drug to treat patients with moderate acne which has not responded to other systemic therapies, particularly when associated with scarring or significant psychological disability. However, this use is outside the current license of the drug. Isotretinoin is associated with a number of serious adverse effects and careful monitoring of patients during therapy is required.Physical therapies for the treatment of acne nodules and macrocomedones are also important adjuncts to drug therapies.     

Medical treatment of rosacea with emphasis on topical therapies

Due to the development and release of newer topical formulations, the diagnosis and treatment of rosacea has received renewed attention over the past 3-5 years both in the literature and at medical symposia. Rosacea is a very common facial dermatosis. In the US, rosacea is estimated to affect > 14 million people, predominantly adults with approximately 60% of cases diagnosed before the age of 50. A frustrating aspect of the disease is its inherent chronicity punctuated with periods of exacerbation and relative remission. A variety of subtypes have been identified which correlate with clinical presentation. Although the pathogenesis of rosacea is poorly understood, multiple topical agents are available. The efficacy of topical therapy for rosacea relates primarily to reduction in inflammatory lesions (papules, pustules), decreased intensity of erythema, a reduction in the number and intensity of flares and amelioration of symptoms, which may include stinging, pruritus and burning. The list of main topical agents utilised for the treatment of rosacea include metronidazole, sulfacetamide-sulfur, azelaic acid and topical antibiotics (clindamycin, erythromycin). Depending on the severity at initial presentation, topical therapy may be combined with systemic antibiotic therapy (e.g., oral tetracycline derivative). Newer therapeutic choices primarily involve improved vehicle formulations, which demonstrate favourable skin tolerability and cosmetic elegance.     

Managing rosacea: a review of the use of metronidazole alone and in combination with oral antibiotics

BACKGROUND: Rosacea is an extremely common chronic dermatosis affecting an estimated 14 million Americans. Rosacea is most commonly managed with topical metronidazole, sometimes in combination with oral antibiotics. PURPOSE: To review published studies about topical metronidazole therapy for rosacea, both as a monotherapy and in conjunction with oral antibiotics. METHODS: Medline searches were conducted for clinical trials using metronidazole, tetracycline, and doxycycline for rosacea. RESULTS: Topical metronidazole has been well studied as a rosacea therapy. Twice-daily dosing of metronidazole 1.0% cream is as effective as 250 mg tetracycline twice daily. Metronidazole 1.0% gel used once daily is as effective as azelaic acid 15% gel dosed twice daily. When dosed at subantimicrobial levels, doxycycline 20 mg taken twice daily is effective in decreasing inflammatory lesions and erythema associated with rosacea. Metronidazole 0.75% lotion is more effective when used in combination with doxycycline 20 mg dosed twice daily. DISCUSSION: Metronidazole in 0.75% strength lotion, cream, and gel and 1.0% metronidazole cream and gel are all efficacious in treating rosacea. Combination treatment with oral antibiotics at both antimicrobial and subantimicrobial doses is an efficacious means of treating rosacea. Maintenance treatment with topical metronidazole decreases relapses and allows for longer intervals between flares.     

Adverse events related to topical drug treatments for acne vulgaris

ABSTRACT

Introduction: Acne vulgaris is a widespread skin disease. Topical therapy is a standard treatment for mild to moderate acne. Given the complex pathophysiology of acne, various agents with complementary action are nowadays frequently combined to increase the efficacy of therapy.

Area covered: This review focus on safety profile of topical agents used for the treatment of acne vulgaris, including topical retinoids, benzyl peroxide, azelaic acid, topical antibiotic, and combined agents. Data from clinical trials but also metanalyses, systematic reviews, and other secondary analyses are presented.

Expert opinion: In general, topical agents used for acne vulgaris have a favorable safety profile. The most commonly reported AEs were associated with local skin irritation, usually mild to moderate in intensity, intermittent, and rarely led to the cessation of therapy. Irritative potential seems to be highest for BPO and topical retinoids. Due to the possibility of development of Cutibacterium acnes resistance, topical antibiotics should not be used in monotherapy but as a part of combination therapy. In female adolescent and adults of childbearing potential, topical retinoids should be used with caution, because they are contraindicated in pregnant females (FDA Pregnancy category) C (adapalene, tretinoin) and X (tazarotene).     

Evidence-based review: fixed-combination therapy and topical retinoids in the treatment of acne

Topical fixed-combination products and topical retinoid monotherapy are established first-line treatments for mild-to-moderate acne vulgaris, yet adequate comparative data are lacking. The following evidence-based review addresses the question: "In patients with mild-to-moderate acne, are topical fixed-combination products or topical retinoids a more efficacious choice in reducing noninflammatory, inflammatory and total lesions after 12 weeks of treatment?" To identify relevant studies, a PubMed search was performed using "acne" and search terms for adapalene, tretinoin, tazarotene, benzoyl peroxide, clindamycin, or erythromycin. Forty-two studies from January 1991 to November 2009 were included. The studies were evaluated using the Strength of Recommendation Taxonomy, and all but seven received the highest level of evidence grade. To evaluate efficacy, a side-by-side comparison was made using reduction in acne lesion counts at week 12 for study groups treated with fixed-combination therapy or retinoid monotherapy. Twenty-nine studies containing relevant efficacy data for fixed-combination therapy and retinoid monotherapy are summarized here. Nine studies compared fixed-combination therapy with retinoid monotherapy; in eight of these studies, fixed-combination therapy was significantly more efficacious in reducing acne lesion counts. This evidence-based review analyzes clinical evidence to date for these therapies to provide guidance in determining appropriate treatment for patients with mild-to-moderate acne.     

Antibiotic susceptibility of coagulase-negative staphylococci isolated from goats' milk

The antibiotic susceptibility of 70 strains of coagulase-negative staphylococci (CNS) isolated during the 2001 lactating period from the milk of dairy goats, was evaluated. The antibiotics tested were benzylpenicillin, cloxacillin, amoxicillin, amoxicillin plus clavulanic acid, cephalonium and cefoperazone, erythromycin and tylmicosin, kanamycin and tetracycline. Minimum inhibitory concentration (MIC) measurements showed that all β-lactams (except cefoperazone) were effective against Staphylococcus epidermidis and Staphylococcus caprae, whereas the other antibiotics were either less effective or showed no activity. Other CNS species showed very variable sensitivity to the antibiotics; testing would be required before therapy for the clinical control of goat mammary infections.     

772株葡萄球菌中红霉素对克林霉素诱导耐药检测

目的:了解葡萄球菌对红霉素及克林霉素的耐药性,结合药敏试验结果,为临床合理选择抗生素提供可靠依据。方法:按照2004年版美国临床实验室标准化委员会(NCCLs)推荐的纸片扩散方法,测定并判读葡萄球菌对红霉素和克林霉素的耐药性,并以D-试验测定红霉素对克林霉素的诱导耐药表型。结果:红霉素和克林霉素同时耐药在耐甲氧西林葡萄球菌(MRSA)和甲氧西林敏感型葡萄球菌(MSSA)中分别占45.50%(192/422)和55.14%(193/350);对红霉素耐药而克林霉素敏感的MRSA和MSSA中,D-试验阳性(即对克林霉素具有诱导耐药性者)分别为69.72%和30.58%。D-试验阳性占所测葡萄球菌的24.48%,占对红霉素耐药而克林霉素敏感菌株的30.58%。结论:红霉素诱导克林霉素发生耐药应引起关注,开展药敏试验及D-试验,检测葡萄球菌中红霉素对克林霉素诱导性耐药,可指导临床医师合理选用大环内酯类、克林霉素类抗菌药物。     

Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris

Background: Owing to the use of topical and systemic antibiotics for acne vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is increasing worldwide. Topical benzoyl peroxide (BPO) is an alternative to antibiotics in the treatment of acne vulgaris. Objective: This review describes and evaluates recent clinical literature regarding the efficacy and tolerability of BPO. Methods: A PubMed literature search was conducted using the keywords benzoyl peroxide, acne, and combination therapy. Results: BPO is equally effective at concentrations of 2.5, 5.0 and 10%. However, a concentration-dependent irritant dermatitis can occur with higher concentrations. The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines. BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris.     

Optimizing topical combination therapy for the treatment of acne vulgaris

Given the multifactorial and complex contributors to acne development, combination therapy is standard of care. By addressing multiple pathogenic factors, combination therapy provides a quicker and more efficacious treatment outcome than monotherapy. Topical retinoids normalize follicular keratinocyte differentiation and are anti-inflammatory. Their use is limited by the potential for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects. Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed-dose combination products or two separate medications. BPO has the added benefit of being comedolytic and can minimize the risk for bacterial antibiotic resistance. Like topical retinoids, BPO may cause skin irritation, burning, erythema, and peeling. Managing cutaneous side effects when using multiple products that cause irritation can be a challenge. Careful product selection, dose titration, and patient-directed regimens can help to optimize outcomes. This review presents the latest data on two topical acne products that have demonstrated excellent efficacy and tolerability profiles. In addition, their in vitro profiles suggest the potential for combination use, affording greater dosing flexibility.     

Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders.

Azelaic acid is a naturally occurring saturated dicarboxylic acid which, on topical application (usually as a 20% cream), has been shown to be effective in the treatment of comedonal acne and inflammatory (papulopustular, nodular and nodulocystic) acne, as well as various cutaneous hyperpigmentary disorders characterised by hyperactive/abnormal melanocyte function, including melasma and, possibly, lentigo maligna. In addition, azelaic acid has an antiproliferative and cytotoxic effect on the human malignant melanocyte, and preliminary findings indicate that it may arrest the progression of cutaneous malignant melanoma. The mechanism of this selective cytotoxic action of azelaic acid is unclear, but may possibly be related to its inhibition of mitochondrial oxidoreductase activity and DNA synthesis. In controlled studies, topical azelaic acid demonstrated comparable anti-acne efficacy to topical tretinoin, benzoyl peroxide, erythromycin and oral tetracycline, while in patients with melasma azelaic acid proved at least as effective as topical hydroquinone. On topical application azelaic acid is well tolerated, with adverse effects apparently limited to a generally mild and transient local cutaneous irritation. Thus, topical azelaic acid, employed either as monotherapy or in combination with other treatments, is likely to prove of value in the management of acne and several hyperpigmentary disorders, most notably melasma.     

Study results of benzoyl peroxide 5%/clindamycin 1% topical gel, adapalene 0.1% gel, and use in combination for acne vulgaris

Combination therapy is the standard of care in the management of acne vulgaris. It is essential to treat as many aspects of acne pathogenesis as possible. Due to increasing insensitivity of Propionibacterium acnes to antibiotics, the concomitant use of other topical agents that exhibit other modes of antibacterial and anti-inflammatory activity is integral to the successful treatment of acne. The combination of topical benzoyl peroxide and clindamycin gel has been shown to be more effective than either agent alone. The addition of a topical retinoid may further enhance therapeutic results. This 12-week study evaluated the safety and efficacy of initial topical benzoyl peroxide 5%/clindamycin 1% gel as monotherapy and in combination with adapalene gel versus adapalene gel monotherapy in the management of acne.     

The modern age of acne therapy: a review of current treatment options

This review of current acne treatments begins with the crucial discovery in 1979 of isotretinoin treatment for nodulocystic acne. This drug s approval in 1982 revolutionized therapy, since it was the first oral acne-specific drug, and it provided prolonged remissions. In addition, it may prevent the emergence of resistant bacteria, a problem linked to the traditional use of antibiotics for acne. Patients who are not candidates for isotretinoin therapy may benefit from one of the other drugs or drug combinations reviewed, including the third-generation topical retinoids adapalene and tazarotene, retinoic acid reformulated in new vehicles, azelaic acid, and topical antibiotics. Proper selection and education of patients are essential, since serious consequences may result from poorly monitored use of antibiotics and retinoid.