Bacteriological resistance in acne: A call to action

Acne is common in adolescence but is also increasingly seen in adulthood, with about 40% of adults being affected. Topical and systemic oral antibiotics have been used for more than 40 years in the treatment of acne lesions. In the 1970s, evidence of resistance to topical erythromycin and clindamycin was reported and, since then, antibiotic resistance in acne has been increasing worldwide. Antibiotic exposure can be significant in acne treatment because the patient population is large and there is a tendency for prolonged treatment regimens to be prescribed. The overuse of antibiotics is now considered a major public health problem. Action is therefore required to encourage judicial and appropriate use of antibiotics in acne management in line with available evidence-based guidelines. Alternatives to topical antibiotics for the treatment of acne should be considered. Topical antibiotics should no longer be used as monotherapy in acne treatment and use in combination regimens should be limited to a maximum of four weeks. Evidence from studies suggests that, as for topical antibiotics, oral antibiotics should not be used as monotherapy, but instead should be combined with a topical retinoid or benzoyl peroxide for a maximum of four months. Correct and appropriate use of antibiotics in the treatment of acne will help to preserve their utility in the face of increasing antibiotic resistance but greater awareness of the issues is required among prescribing physicians.     

South‐East Asia study alliance guidelines on the management of acne vulgaris in South‐East Asian patients

The management of acne in South‐East Asia is unique, as Asian skin and local variables require a clinical approach unlike that utilized in other parts of the world. There are different treatment guidelines per country in the region, and a group of leading dermatologists from these countries convened to review these guidelines, discuss current practices and recent advances, and formulate consensus guidelines to harmonize the management of acne vulgaris in the region. Emphasis has been placed on formulating recommendations to impede the development of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne Consensus Conference system for grading acne severity. The group recommends that patients may be treated with topical medications including retinoids, benzoyl peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a combination of retinoids and BPO with or without antibiotics for mild acne; topical retinoid with topical BPO and a oral antibiotic for moderate acne; and oral isotretinoin if the patient fails first‐line treatment (a 6‐ or 8‐week trial of combined oral antibiotics and topical retinoids with BPO) for severe acne. Maintenance acne treatment using topical retinoids with or without BPO is recommended. To prevent the development of antibiotic resistance, topical antibiotics should not be used as monotherapy or used simultaneously with oral antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection, is likewise recommended. Patient education and good communication is recommended to improve adherence, and advice should be given about the characteristics of the skin care products patients should use.     

The use of oral antibiotics in treating acne vulgaris: a new approach

Although acne is not an infectious disease, oral antibiotics have remained a mainstay of treatment over the last 40 years. The anti‐inflammatory properties of oral antibiotics, particularly the tetracyclines, are efficacious in treating inflammatory acne lesions. Common prescribing practices in Dermatology exert significant selection pressure on bacteria, contributing to the development of antibiotic resistance. Antibiotic use for acne not only promotes resistance in Propionibacterium acnes, but also affects other host bacteria with pathogenic potential. This review will summarize the commonly used treatments for acne vulgaris, and how they should be combined as rational treatment. The indications for using oral antibiotics in acne will be highlighted. Strategies described in the literature to conserve the utility of oral antibiotics will be summarized. These include limiting the duration of antibiotic therapy, concomitant use of a topical non‐antibiotic agent, use of subantimicrobial dose doxycycline, and the introduction of topical dapsone.     

New and emerging treatments in dermatology: acne

ABSTRACT:  Topical retinoids, benzoyl peroxide, azelaic acid, and topical and oral antibiotics remain the milestone of treatment for mild to moderate acne vulgaris. Oral isotretinoin is useful for the treatment of severe nodular acne, treatment-resistant acne, and acne with a risk of physical or psychological scarring. Hormonal treatment in female acne is useful in resistant or late-onset acne. With increasing concerns regarding teratogenicity of isotretinoin and increasing antibiotic resistance, there is a clear need for therapeutic alternatives to these long-used treatments. Research in the pathogenesis of acne has allowed for new therapies and future perspectives regarding acne to evolve. They include low-dose long-term isotretinoin regimens, insulin-sensitizing agents, 5α-reductase type 1 inhibitors, topical photodynamic therapy, new combination formulations, dietary interventions, and antiinflammatory agents such as lipoxygenase inhibitors.     

Women commonly seek care for rosacea: dermatologists frequently provide the care

Rosacea is a common dermatosis affecting the central portion of the face. The purpose of this study is to describe the demographics of patients and the treatments prescribed. Data on rosacea visits from 1990 to 1997 were obtained from the National Ambulatory Medical Care Survey There were 1.1 million outpatient visits for rosacea annually in the United States. Most rosacea patients were Caucasian (96%). Most visits were by women (69%), and the mean age (SD) of patients was 50 +/- 17 years. Visits to dermatologists accounted for 78% of visits. Common comorbid diagnoses included actinic keratoses, acne and cysts, and seborrheic and contact dermatitis. Topical metronidazole was the most commonly prescribed treatment; tetracycline was the most commonly prescribed systemic therapy. Combination treatment with an oral and a topical agent was commonly used. Because rosacea appears most often in fair-skinned women, these patients may benefit from the textural features and safety profiles of certain topical metronidazole preparations newly available and from oral antibiotics (eg, tetracycline). People with rosacea should be aware of the experience that dermatologists have in treating this disorder.     

Rosacea and its management: an overview

BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the population. The prevalence of rosacea is highest among fair-skinned individuals, particularly those of Celtic and northern European descent. Since a cure for rosacea does not yet exist, management and treatment regimens are designed to suppress the inflammatory lesions, erythema, and to a lesser extent, the telangiectasia involved with rosacea. OBJECTIVES: This review outlines the treatment options that are available to patients with rosacea. METHODS: Published literature involving the treatment or management of rosacea was examined and summarized. RESULTS: Patients who find that they blush and flush frequently, or have a family history of rosacea are advised to avoid the physiological and environmental stimuli that can cause increased facial redness. Topical agents such as metronidazole, azelaic acid cream or sulfur preparations are effective in managing rosacea. Patients who have progressed to erythematotelangiectatic and papulopustular rosacea may benefit from the use of an oral antibiotic, such as tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the rosacea flare-up under control. Treatment with a topical agent, such as metronidazole, may help maintain remission. Patients with ocular involvement may benefit from a long-term course of an antibiotic and the use of metronidazole gel. A surgical alternative, laser therapy, is recommended for the treatment of telangiectasias and rhinophyma. Patients with distraught feelings due to their rosacea may consider cosmetic camouflage to cover the signs of rosacea. CONCLUSIONS: With the wide variety of oral and topical agents available for the effective management of rosacea, patients no longer need to feel self-conscious because of their disorder.     

Treatment of rosacea

A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole.     

Recent Advances in Acne Pathogenesis: Implications for Therapy

Acne pathogenesis is a multifactorial process that occurs at the level of the pilosebaceous unit. While acne was previously perceived as an infectious disease, recent data have clarified it as an inflammatory process in which Propionibacterium acnes and innate immunity play critical roles in propagating abnormal hyperkeratinization and inflammation. Alterations in sebum composition, and increased sensitivity to androgens, also play roles in the inflammatory process. A stepwise approach to acne management utilizes topical agents for mild to moderate acne (topical retinoid as mainstay ± topical antibiotics) and escalation to oral agents for more resistant cases (oral antibiotics or hormonal agents in conjunction with a topical retinoid or oral isotretinoin alone for severe acne). Concerns over antibiotic resistance and the safety issues associated with isotretinoin have prompted further research into alternative medications and devices for the treatment of acne. Radiofrequency, laser, and light treatments have demonstrated modest improvement for inflammatory acne (with blue-light photodynamic therapy being the only US FDA-approved treatment). However, limitations in study design and patient follow-up render these modalities as adjuncts rather than standalone options. This review will update readers on the latest advancements in our understanding of acne pathogenesis and treatment, with emphasis on emerging treatment options that can help improve patient outcomes.     

Medikamentöse Therapie der Akne

Acne is treated according to the clinical picture and the pathophysiologically relevant mechanisms, such as seborrhea, follicular hyperkeratosis, P. acnes colonisation,and inflammation. In mild forms of acne, topical therapy is most appropriate. Comedonal acne can be treated with topical retinoids; papulopustular acne with a combination of retinoids and topical antimicrobial substances (benzoyl peroxide, antibiotics, or azelaic acid). Moderate forms or those with extrafacial involvement can be treated with oral antibiotics combined with topical retinoids or benzoyl peroxide. Acne conglobata and other severe manifestations are treated with oral isotretinoin. Women are also treated with oral contraceptives containing anti-androgenic progestins. If inflammation is prominent, initial short term treatment with oral glucocorticoids is helpful. Second-line agents include oral zinc or dapsone. Following successful treatment, topical retinoids are suitable for maintenance therapy.     

Newer Approaches to the Treatment of Acne Vulgaris

The multifactorial etiology of acne vulgaris makes it challenging to treat. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, azelaic acid, and systemic isotretinoin. Adjunctive and/or emerging approaches include topical dapsone, taurine bromamine, resveratrol, chemical peels, optical treatments, as well as complementary and alternative medications. The purpose of this paper is to discuss the therapies available for acne and their latest developments, including new treatment strategies (i.e. re-evaluation of the use of oral antibiotics and avoidance of topical antibiotic monotherapy, use of subantimicrobial antibiotic dosing, use of low-dose isotretinoin, optical treatments), new formulations (microsponges, liposomes, nanoemulsions, aerosol foams), new combinations (fixed-combination products of topical retinoids and topical antibiotics [essentially clindamycin] or benzoyl peroxide), new agents (topical dapsone, taurine bromamine, resveratrol) and their rationale and likely place in treatment. Acne vaccines, topical natural antimicrobial peptides, and lauric acid represent other promising therapies.     

Benzoyl Peroxide-Based Combination Therapies for Acne Vulgaris

Benzoyl peroxide, with its broad-spectrum antimicrobial activity, is among the most widely used topical agents in the treatment of inflammatory acne vulgaris. Benzoyl peroxide is marketed either alone or in combination with other topical antibiotics; namely, erythromycin and clindamycin. The combination products confer specific advantages over benzoyl peroxide alone, particularly in decreasing the in vivo follicular counts of Propionibacterium acnes, the anaerobic bacterium implicated in the pathogenesis of acne. In addition, the topical treatment of inflammatory acne has been complicated by the development of P acnes resistance to topical erythromycin and clindamycin. Combination products containing benzoyl peroxide and the topical antibiotics have been shown to both: (i) prevent the development of antibiotic resistance in acne patients; and (ii) confer significant clinical improvement to patients who have already developed antibiotic resistance.     

Acne therapy with topical benzoyl peroxide,antibiotics and azelaic acid

Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite the fact that only few randomized trials have been published, BPO is considered the standard in topical acne treatment. Anaerobic bacteria are reduced by oxidative mechanisms and the induction of resistant strains is reduced. Topical formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect is dose‐dependent, but the irritation increases with higher concentrations. Usually 5 % BPO is sufficient to control acne grade I‐II. Due to its strong oxidative potential, patients should be advised that BPO may bleach colored and dark clothing, bedding and even hair. BPO is safe for use in pregnant and lactating females because it is degraded to benzoic acid. It is a cost‐effective treatment for acne grade I–II. Patients with papulopustular acne grade I–II, particularly with marked inflammation, show satisfactory improvement with topical antibiotic treatment. The following compounds are available and effective: erythromycin, clindamycin and tetracycline (the latter being less frequently used). A review in 1990 suggested that topical tetracycline was ineffective in the treatment of acne. Along with eliminating Propionibacterium acnes, the main mechanism of topical antibiotics is their antiinflammatory effect. All three penetrate the epidermal barrier well and are similarly efficacious. Randomized trials have shown that in concentrations of 2–4 %, their effects are comparable to oral tetracycline and minocycline. Combination therapy with retinoids or benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and reduce comedones, while topical antibiotics primarily address inflammation. One side effect of topical antibacterial treatment is an increase in drug‐resistant resident skin flora with gram‐negative microorganisms prevailing, which can lead to gram‐negative folliculitis. All three antibiotics fluoresce under black light which may produce interesting effects in a discotheque. There are two reports of topical clindamycin causing pseudomembranous colitis after long‐term and widespread usage. Azelaic acid has a predominant antibacterial action, although it is not considered as an antibiotic in the classical sense. Furthermore, it possesses a modest comedolytic effect. Burning upon application is common. Since azelaic acid is naturally present, systemic side effects are not likely to occur, making it safe for acne treatment during pregnancy and lactation.     

A current review of topical benzoyl peroxide: new perspectives on formulation and utilization

Benzoyl peroxide (BPO) is the most widely used topical acne treatment, with significant antibacterial, antikeratolytic, and comedolytic activity. It has been shown to be extremely effective as monotherapy and in combination with antibiotics or retinoids for managing comedonal and inflammatory acne lesions. As numerous clinical studies have shown, the combination of BPO plus a topical antibiotic is not only more effective but also is often better tolerated than either agent alone. Unlike antibiotics, no bacterial resistance has been noted. Adding BPO to any long-term antibiotic regimen in acne is generally recommended to help reduce populations of drug-resistant variants. Although effective combinations of BPO and antibiotics or retinoids are used, BPO monotherapy can also be extremely effective in treating mild to moderate acne with no resistance issues.     

Update on topical antibiotics in dermatology

Topical antibiotics are used for various purposes in dermatology. Some of the most common uses include treatment of acne, treatment and prevention of wound infection(s), impetigo or impetiginized dermatitis, and staphylococcal nasal carrier state. It is important for the dermatologist to be familiar with the spectrum of activity, the mechanism of action, and the variables that may interfere with the antibiotic of choice. The following discussion will review an update on topical antibiotic use in acne, wound care, impetigo, and in staphylococcal nasal carriers.     

Acne fulminans and erythema nodosum during isotretinoin therapy responding to dapsone

Acne vulgaris is very common, 85% of teenagers being affected at any one time. In most cases, the disease is mild and patients do not present to the dermatologist. Most are instead treated with over-the-counter products and conventional treatment such as peeling agents or topical and systemic antibiotics. Isotretinoin has revolutionized the treatment of severe acne unresponsive to oral antibiotics. Explosive and very severe acne such as pyoderma faciale, acne conglobata and acne fulminans are rare, the features that distinguish acne fulminans from the other conditions being systemic upset with fever, joint pain, malaise and leucocytosis,^1–3 while there have been two reports of the condition associated with erythema nodosum.^4,5 The recommended treatment for acne fulminans is a combination of oral steroids and systemic antibiotics, isotretinoin probably not being the treatment of choice.⁶ We now report a patient who developed acne fulminans and erythema nodosum within 3 weeks of starting isotretinoin and then responded to dapsone without oral steroids.     

Optimizing use of oral antibiotics in acne vulgaris

Oral antibiotics are commonly used to treat acne vulgaris, primarily in patients presenting with moderate to severe facial or truncal disease severity. These agents are most appropriately used in combination with a topical regimen containing benzoyl peroxide and a topical retinoid. The most common oral antibiotics for treating acne vulgaris are the tetracycline derivatives, although macrolide agents such as erythromycin have also been used extensively. Over the past 4 decades, as the sensitivity of Propionibacterium acnes to several oral and topical antibiotics has decreased, the efficacy of oral tetracycline and erythromycin has markedly diminished, leading to increased use of doxycycline, minocycline, and other agents, such as trimethoprim/sulfamethoxazole.     

Topical nadifloxacin 1% cream vs. topical erythromycin 4% gel in the treatment of mild to moderate acne

Topical antibiotics are the mainstay of therapy in mild to moderate inflammatory acne. Topical erythromycin is one of the most common prescribed topical antibiotics. Nadifloxacin, another topical antibiotic for acne, was recently introduced into the market in our country. In this study, we compared the efficacies and safety of topical nadifloxacin 1% cream and erythromycin 4% gel in acne. A total of 86 patients with mild to moderate facial acne were randomized into two treatment groups. The efficacies of the drugs were assessed by lesion counts. An acne severity index (ASI) was also calculated. In both groups, there was a significant reduction in lesion counts and ASI scores beginning from the first visit at week 4. This reduction continued throughout the 12-week study period. Both treatments were well tolerated. We conclude that when topically applied, both nadifloxacin 1% cream and erythromycin 4% gel are equally effective and safe treatments for mild to moderate facial acne.     

Therapeutic potential of azithromycin in rosacea

BACKGROUND: Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side-effects. Therefore, a need for an effective agent with few side-effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne. We planned a study to evaluate the efficacy and safety of azithromycin in rosacea. METHODS: An open-labeled study was performed in a population of 18 patients, with Plewig-Kligman stage 2 rosacea. Patients were given oral azithromycin for 12 weeks in decreasing doses. RESULTS: Fourteen subjects completed the trial. The treatment produced therapeutic benefits with regard to total scores as well as inflammatory lesion scores. At the end of 12 weeks, there was a 75% decrease in total scores (P < 0.001) and an 89% decrease in inflammatory lesion scores compared with basal values. Improvement continued during the 4 weeks after treatment. Adverse effects were minimal and well tolerated in most patients. CONCLUSION: Azithromycin is a promising agent in the treatment of rosacea with its few side-effects and good patient compliance.     

Analysis of common side effects of isotretinoin

Patients with severe recalcitrant nodular acne that is unresponsive to conventional therapy (including topical and systemic antibiotics) have few alternative effective treatment modalities other than the use of oral isotretinoin (Accutane). The cause of acne vulgaris is multifactorial, but the pathogenesis of this disorder of the pilosebaceous follicles arises mainly from endogenous factors. It is usually, but not always, associated with the onset of puberty. Severe acne, defined by the prevalence of facial and truncal inflammatory lesions, is a disfiguring disease that can often result in significant permanent scarring after the healing of deep inflammatory lesions and other disorders, such as systemic bacterial infections. Topical treatments are considered as the first line of therapy for less severe forms of acne, although systemic treatments such as antibiotics or antiandrogen agents are effective for either mild or moderate forms and sometimes effective for severe acne. However, in many patients with large numbers of nodules, longer treatment periods with these agents are required to reduce the count of inflammatory lesions. It has become increasingly evident that (because topical agents and antibiotic or antiandrogenic therapy have a slow onset of action) even mild or moderate acne that is treated in this way can result in scarring. In addition, the excessive use of systemic antibiotics has led to the detection of increasing numbers of antibiotic-resistant bacteria on the skin of patients with acne.(1) Therefore, because of its relatively rapid onset of action and its high efficacy with reducing more than 90% of the most severe inflammatory lesions, Accutane has a role as an effective treatment in patients with severe acne that is recalcitrant to other therapies.