Antibiotic therapy plays an important role in the treatment of acne, especially moderate and severe acne. In recent years, improper selection or irregular use of antibiotics has resulted in the development of bacterial resistance and an increase in drug-induced adverse reactions, causing many problems for acne treatment. In order to re-evaluate the rational application of antibiotics in acne treatment, this article briefly discusses the following issues.
I. Basis of antibiotic selection in acne treatment
Different antibacterial drugs can be chosen in acne treatment, but the choice of drugs must take into account the pathogenesis of acne and the different pathological and physiological conditions of patients. Overall, the following four aspects are important bases for antibiotic selection.
1. Antibacterial effect is the key to ensure efficacy
Antibiotics for the treatment of acne mainly rely on their antibacterial effect and non-specific anti-inflammatory effect, especially the tetracyclines. The non-specific anti-inflammatory effects include inhibition of neutrophil chemotaxis, reduction of cytokine secretion, reduction of matrix metalloproteinase activity and direct inhibition of lymphocyte mitosis, which can effectively reduce the inflammatory response of acne. However, as mentioned above, only live Propionibacterium acnes (P. acnes) is associated with inflammatory response formation, and the live bacteria can amplify the inflammatory response process by secreting bacterial extracellular enzymes to induce cytokine production. It was found that if P. acne isolated from the lesion site was resistant to tetracycline or macrolide antibiotics, switching to other therapies was equally ineffective, suggesting that effective inhibition of live bacteria is a prerequisite to ensure the effectiveness of antibiotic therapy. Therefore, effective antimicrobial effect is necessary to control the inflammatory process of acne fundamentally, while nonspecific anti-inflammatory response is of secondary importance.
Currently, the antimicrobial drugs available for clinical use are tetracyclines, macrolides, clindamycin, cotrimoxazole and quinolones, among which tetracyclines and macrolides are commonly used. Given that macrolide antibiotics, especially erythromycin, have significantly increased resistance, and that increased resistance is closely related to reduced efficacy and cross-resistance with clindamycin, their use is restricted. The first generation of tetracyclines such as tetracycline resistance has also increased significantly, while the second generation such as minocycline, doxycycline and lymecycline, which have high antibacterial activity, low resistance and also have clear non-specific anti-inflammatory effects, are recommended as the first choice in the global consensus for the treatment of acne, and the first and second generations should not be substituted for each other.
2. The effective penetration of antibiotics into the hair follicles and sebaceous glands is a prerequisite to ensure the antibacterial effect
Antibiotics need to effectively penetrate the hair follicles and sebaceous glands in order to obtain a high antibacterial effect. In vitro studies found that tetracyclines, erythromycin, cephalosporins, quinolones and other drugs have strong antibacterial activity on cultured P. acne, but the molecular quality and lipophilicity of the drugs differ greatly, resulting in differences in the distribution concentration in hair follicles and sebaceous glands. It was found that minomycin had the highest concentration in hair follicles and sebaceous glands, followed by erythromycin, while penicillins, including cephalosporins, had difficulty penetrating into hair follicles and sebaceous glands. Therefore, even though cephalosporin antibiotics have been shown to significantly inhibit the growth of P. acne in vitro, the clinical application of cephalosporins is ineffective in the treatment of acne. It is also noted that the same tetracyclines, oral first generation such as tetracycline requires fasting due to low absorption rate to prevent its bioavailability from being taken with other drugs or food, while the second generation such as minomycin does not have the above problems.
3. Adverse drug reactions limit antibiotic treatment of acne
It is well known that tetracyclines have more adverse reactions, the common ones are gastrointestinal discomfort, dysbiosis, liver function damage, photosensitivity reaction, etc. Common adverse reactions of minomycin can cause nausea, vomiting, diarrhea, dizziness, ataxia, increased intracranial pressure, pigmentation, etc. Serious adverse reactions include serum sickness-like syndrome and hypersensitivity reaction syndrome, which manifests as fever, rash, arthralgia, enlarged lymph nodes, etc. In addition, long-term use of minomycin may occasionally induce autoimmune reactions, such as lupus erythematosus and autoimmune hepatitis. Most of the general adverse reactions can be relieved after stopping the drug, and most of the serious adverse reactions are reversible. It is recommended that patients taking minocycline for a long time should be tested regularly for relevant immunological indicators under the guidance of a doctor. Macrolide antibiotics also have gastrointestinal discomfort, liver toxicity, tinnitus, hearing loss and drug metabolic reactions. Therefore, when tetracyclines and macrolide antibiotics are clinically applied to treat acne, it is mostly advocated to take them after meals and pay attention to their toxicity to the liver, especially since China is a country with a high incidence of hepatitis B. Care must be taken to ask if there is a history of hepatitis B, and to avoid alcohol during medication to avoid aggravating liver damage. Patients with a history of hepatitis B or with impaired liver function should be used with caution or prohibited. Also, because tetracyclines affect the development of teeth and bones, they should be prohibited for children under 14 years of age, and erythromycin can be used instead.
4. Antibiotics commonly used for systemic infectious diseases should be used with caution to treat acne
Acne is a non-infectious inflammatory disease, and P. acne only plays a role in the formation of inflammatory damage in acne. Since numerous antibacterial drugs have good efficacy in the treatment of acne, including new macrolide antibiotics such as clarithromycin, azithromycin, and fluoroquinolones, but since these antibacterial drugs are still used as the primary drug of choice in the treatment of systemic infections, they should not be used as the first choice or routinely for the treatment of acne anti-P. acne therapy, lest frequent use induce resistance to a variety of other bacteria and affect these The efficacy of antibiotics in the treatment of systemic infectious diseases.
In view of these factors, the international consensus for acne treatment recommends second-generation tetracyclines including minomycin, doxycycline, and lymecycline as the drugs of choice for the antimicrobial treatment of acne, followed by first-generation tetracyclines, and erythromycin only in pregnant patients and children under 14 years of age. Other drugs such as cephalosporins, new macrolides and fluoroquinolones are not suitable as routine drugs for the antimicrobial treatment of acne.
P. acne resistance is increasing, requiring more standardized and rational use of antibiotics.
Antibiotics have been used in acne treatment for more than 40 years and have shown definite efficacy. However, in recent years, studies have found a significant increase in P. acne resistance, leading to a decrease in efficacy. Analysis of drug-resistant P. acne carriage in acne patients found that the most common was erythromycin resistance, followed by tetracycline resistance. The resistance rate among tetracyclines was in the order of tetracycline > doxycycline > minocycline. The important factors causing P. acne resistance you see poor compliance of patients with medication, variable doses, insufficient regimen and recurrent disease. Also topical antibiotics are one of the important factors causing P.acne resistance, especially the drug concentration around the lesion is significantly lower than the central lesion, which can easily induce drug resistance.
The mechanisms leading to drug resistance of P. acne at the site of skin lesions mainly include decreased drug binding to the receptor or target bacteria, production of antibiotic-modifying enzymes, decreased bacterial cell wall permeability and active drug translocation out of the bacterial cytosol. It has been found that the resistance of P. acne to erythromycin depends on the occurrence of point mutations in the 23SrRND peptide acyltransferase gene of the bacterium, and the incidence of such mutations is related to the density of sensitive bacteria on the skin surface, the duration of antibiotic administration, and the patient’s compliance with the drug. Similarly P. acne can be resistant to tetracycline by a mechanism that is primarily a protein encoded by the tetracycline K and L genes that actively transports the antibiotic out of the bacterium, but this mechanism does not cause resistance to minomycin.
In response to the increasing severity of P. acne resistance, the standardization and rational application of antibiotics in acne treatment is particularly important. In order to effectively reduce the generation of antibiotic resistance in P. acne and improve the effectiveness of antibiotic therapy, the following principles should be followed in its use.
① Antibiotics alone should not be used for acne treatment, especially to avoid long-term topical application alone.
(ii) Treatment should begin with adequate doses of tetracycline at 1.0 g daily, doxycycline and minocycline at ≥100 mg daily, and erythromycin at 1.0 g, and should not be reduced for maintenance once effective.
(iii) Antibiotics should be discontinued or replaced promptly when ineffective 1-3 weeks after treatment, with attention to patient compliance and gram-negative bacillary folliculitis.
(iv) Adequate duration of therapy should be ensured, usually more than 6 weeks of continuous use, but not more than 12 weeks, and intermittent use should be avoided.
⑤ P. acne is a parasitic bacterium of normal skin, and treatment is aimed at effective inhibition of its reproduction, not complete eradication; therefore, the dose of antibiotics used should not be increased or the course of treatment extended unprincipled, much less as a maintenance treatment or even as a measure to prevent recurrence.
(6) To emphasize to the patient the importance of medication compliance and the correct method of medication administration.
(vii) In case of poor efficacy of commonly used antibiotics such as macrolides, tetracyclines or doxycycline, consideration should be given to the development of resistance and timely replacement of antibiotics such as minocycline.
(⑧ Combined with other antibiotic therapy, especially anti-drug resistant P. acne and other treatments, such as intermittent topical peroxybenzoyl capsules for 5-7 d, or oral isotretinoin, or combined with phototherapy can inhibit P. acne reproduction, remove drug-resistant bacteria, and reduce drug-resistant production.
In conclusion, acne antibiotic therapy should follow the principles of antibiotic application in general anti-infection treatment, be used in a reasonable and standardized manner, prevent abuse, and reduce the generation of drug resistance and the incidence of adverse drug reactions.