Dr. Baldwin is the Medical Director of the Acne Treatment and Research Center in Brooklyn, New York and is with Rutgers Robert Wood Johnson Medical Center in New Brunswick, New Jersey.
ABSTRACT: Acne vulgaris is the most common dermatological disease in the United States, affecting up to 85 percent of teenagers. While the American Academy of Dermatology has established guidelines regarding acne treatment in general, the variability among acne treatments, even within a given class, prevents establishment of a straightforward regimen. For example, moderate to severe acne is generally treated with an oral antibiotic, although several options are available—both across and within antibiotic classes. The aim of this review is to report the efficacy and safety data available for commonly prescribed oral antibiotics. While there are currently no data to support superiority of one drug over another, there are substantial differences in safety profiles and brand-specific features that may make one antibiotic preferable over another.
Acne vulgaris is the most common skin disorder encountered in dermatology practice in the United States, affecting approximately 85 percent of teenagers and sometimes persisting into and throughout adulthood.
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Many patients with acne report feelings of depression, anxiety, emotional stress, or poor self-image, and severe acne can lead to permanent scarring in up to 20 percent of cases.
Acne is a disease of the pilosebaceous unit with a complex pathology. Currently, there are thought to be at least four synergistic, biological mechanisms that contribute to acne pathogenesis, which is primarily inflammatory in nature.
These include increased sebum production, follicular hyperkeratinization, local inflammatory cascades, and microbial proliferation of Cutibacterium acnes (or C. acnes, formerly Propionibacterium acnes).
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The complex interplay of these biological pathways makes effective treatment of acne difficult. Nonetheless, there are a variety of therapeutics available, each targeting one or more of these pathogenic processes.
Pharmacological treatments for acne include a variety of topical and systemic agents. Topical treatment (e.g., benzoyl peroxide, antibiotics, and retinoids) is generally used as first-line treatment in cases of mild-to-moderate acne with comedonal lesions and inflammatory lesions.
Systemic treatment (e.g., oral antibiotics and hormonal therapy) can be used as first-line treatment in cases of moderate-to-severe acne, in combination with a topical agent.
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While it is outside the scope of this review to discuss each treatment type in detail, Table 1 provides a summary of recommended treatment options. This review will focus on the efficacy and safety of oral antibiotics that are commonly used or available to treat acne.
The American Academy of Dermatology supports the use of oral antibiotics for treating moderate and severe acne, and oral antibiotics have been a mainstay of acne treatment for over 50 years.
As such, some previously employed antibiotics (e.g., erythromycin and clindamycin) are no longer used clinically because of their high rates of resistance.
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The concern is serious enough that the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) now actively promote campaigns aimed to confront antibiotic resistance.
The CDC encourages antibiotic stewardship, which asserts that physicians must act responsibly when prescribing antibiotics, with the hope that this will limit the development and/or expansion of antibiotic resistance.
The WHO’s “global action plan” has five strategic objectives, aimed both at the community (e.g., improving awareness and understanding) and providers (e.g., optimizing use).
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Apart from the tetracycline class of antibiotics (doxycycline, minocycline and sarecycline), the potential benefit of oral antibiotics often outweighs the potential risks, and they remain a mainstay of moderate-to-severe acne treatment. With currently available clinical studies and data, there is a consensus that no one antibiotic is superior to another regarding efficacy.
In this article, we will review previous research for several antibiotics currently used, including doxycycline, minocycline, azithromycin, and trimethoprim-sulfamethoxazole, and one recently introduced to the market, sarecycline. Studies included were those that evaluated treatment response in patients with acne.
Perhaps most frequently used is the change in inflammatory lesions from baseline to endpoint, expressed as either absolute change or percent change. Similarly, the absolute or percent change in non-inflammatory lesions (i.e., open or closed comedones) might be recorded, although this is less common in studies of oral antibiotics, as they are generally more effective for inflammatory lesions. A common subjective measure is the investigator’s global assessment (IGA), which considers the quality and quantity of acne lesions. While the IGA is a five-point scale based on acne severity (ranging from 0=clear to 4=severe), results are generally dichotomized in trials such that a participant has IGA “success” (score of 0 or 1; clear or almost clear, respectively) or IGA “failure” (score >1). Change in inflammatory lesions will be the emphasis of efficacy results for this review.
Advancements In Oral Antibiotic Therapy For The Treatment Of Moderate To Severe Acne Vulgaris (slides With Transcript)
The tetracyclines. Among oral antibiotics used to treat acne, tetracycline has the longest history, having been discovered in the 1940s and FDA-approved in 1953. While effective, its side effect profile, need for frequent dosing, and susceptibility to antibiotic resistance have made it unpopular, and it is no longer considered a standard treatment regimen.
Thus, this review will focus not on tetracycline as a drug, but rather on the individual drugs that fall within the tetracycline class (i.e., doxycycline, minocycline, and sarecycline).
Each of these “second-generation” tetracyclines share the same mechanisms of action (MOA); the chemical is transported into bacterial cells, binds the 30S unit of the ribosome, and inhibits protein synthesis. In addition to their antibacterial action, the tetracyclines demonstrate multiple anti-inflammatory properties.
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The therapeutic effect of tetracyclines in acne might be due, at least in part, to reduction in neutrophil chemotaxis and inhibition of proinflammatory cytokines and matrix metalloproteinases.
While all tetracyclines share these anti-microbial and anti-inflammatory MOAs, there is significant variability regarding side effect profiles, discussed below, that account for the preferential prescription of one over the other.
Doxycycline. The first tetracycline derivative to come to market was doxycycline, approved by the FDA in 1967 and still one of the most commonly used antibiotics in clinical practice.
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Relative to its parent tetracycline, doxycycline is more lipophilic, making it optimal for penetrating and accumulating in the sebaceous gland—where C. acnes resides and proliferates.
Two formulations of doxycycline are available—doxycycline hyclate and doxycycline monohydrate, which are different salt forms of the same active drug. Doxycycline hyclate is more water-soluble than doxycycline monohydrate and might be more ulcerogenic and susceptible to causing gastrointestinal (GI)-associated side effects.
The side effect profile of doxycycline is superior to that of tetracycline, although there are potential adverse events that should be taken into consideration (Table 2). Most of doxycycline’s side effects are mild and/or can be prevented with proper measures.
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Doxycycline is frequently associated with phototoxicity; it interacts with ultraviolet (UV) rays, making an individual more susceptible to severe sunburn. Gastrointestinal disturbance is a common side effect of doxycycline treatment and might present as nausea, vomiting, and/or diarrhea. Doxycycline is amenable to being taken with food—which might lessen GI discomfort—although its absorption is reduced by approximately 20 percent with food.
When it is taken to treat acne, however, this reduction in absorption is believed to have minimal clinical relevance. Pill esophagitis—inflammation or esophageal ulcers—can occur when taking doxycycline. Like other side effects, however, it is largely avoidable if patients take medication with a large glass of water and do not lie down shortly after ingesting medication.
Lastly, there is the potential for permanent tooth discoloration in individuals with developing teeth. This is a side effect shared by all tetracycline derivatives which are not recommended for children younger than eight years of age and women during pregnancy.
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Similarly, all tetracyclines have been shown to impair bone growth by forming a stable calcium complex and thus should be avoided in children and during pregnancy.
(1970) evaluated the efficacy of doxycycline in 62 patients in a double-blind crossover study. A “good” or “excellent” response in the reduction of inflammatory lesions was reported in 33 percent of patients receiving doxycycline. Statistically, improvement from baseline was significant with doxycycline treatment, but not placebo. In a clinical study by Moore et al,
662 patients were randomized to one of three treatments—a 40mg dose of modified-release doxycycline, a 100mg dose of doxycycline, or placebo. After 16 weeks of treatment, reduction in lesion count and success rate were evaluated. For both outcome measures, doxycycline treatment was superior to placebo. Interestingly, the lower dose of modified-release doxycycline was more effective in reducing the number of overall lesions, suggesting that a large part of the efficacy of doxycycline stems from its role as an anti-inflammatory agent.
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A review article that gathered results from tetracycline treatment studies for acne between 1962 and 2006 showed that doxycycline was consistently effective, although results were variable between studies.
Due to the popularity of doxycycline, several brands are available, each boasting additional benefits aside from their efficacy in treating acne. Acticlate is available as a functionally scored tablet, and dosage can be easily modified without requiring a new prescription.
Minocycline. Another tetracycline derivative, minocycline, was FDA-approved after doxycycline, in 1971, and continues to be a popular treatment option for moderate to severe acne.
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Of the tetracyclines, minocycline is the most lipophilic, making it easily accessible for penetrating and accumulating in the sebaceous gland, where C. acnes colonizes.
The high absorption rate of minocycline is beneficial in multiple facets—it may be taken with food, which may increase patient
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