section name header

Introduction

AHFS Class:

Generic Name(s):

Erythromycin is a macrolide antibiotic.

Uses

[Section Outline]

Acne Vulgaris !!navigator!!

Erythromycin is used topically in the treatment of acne vulgaris. Therapy of acne vulgaris must be individualized and frequently modified depending on the types of acne lesions which predominate and the response to therapy. Topical anti-infectives, including erythromycin, are generally effective in the treatment of mild to moderate inflammatory acne. However, use of topical anti-infectives as monotherapy may lead to bacterial resistance;110,111 this resistance is associated with decreased clinical efficacy.110

Topical erythromycin is particularly useful when used with benzoyl peroxide or topical retinoids. Results of clinical studies indicate that combination therapy results in a reduction in total lesion counts of 50 to 70%.

Skin Infections !!navigator!!

Although erythromycin was previously available for topical use in the treatment of superficial infections of the skin caused by susceptible bacteria, minor skin infections and wounds usually heal without treatment, and systemic anti-infective therapy is required for the treatment of serious or extensive skin infections such as impetigo. The currently available erythromycin ointment is intended for topical use in the treatment of inflammatory acne and not for the treatment of superficial infections of the skin. The US Food and Drug Administration (FDA) advisory panel on over-the-counter antimicrobial drugs has concluded that there is a lack of substantial evidence to demonstrate that topical anti-infectives, including topical erythromycin, are effective as skin wound anti-infectives. In addition, most clinicians state that indiscriminate use of topical erythromycin may result in the emergence of organisms resistant to the drug.

For other uses of erythromycin, see 8:12.12.04 and 52:04.04.

Dosage and Administration

Acne Vulgaris

For the topical treatment of acne vulgaris, erythromycin has been applied to the skin in the form of a solution, gel, or ointment. The solution, gel, or ointment should be applied to all areas of skin prone to acne.110 A thin film of one of the commercially available erythromycin 2% solutions, 2% gel, or 2% ointment should be applied to the cleansed, affected area each morning and/or evening. When pledgets saturated with an erythromycin 2% solution are used, several pledgets may be necessary with each application depending on the size of the affected area. Maintenance therapy is needed to prevent recurrence.110

Cautions

[Section Outline]

Adverse Effects !!navigator!!

Erythromycin has a low order of toxicity. Sensitivity reactions rarely occur following topical application of the drug. Generalized urticaria, which required treatment with systemic corticosteroids, has been reported in a few patients following topical use of erythromycin.

The most frequent adverse reaction to erythromycin topical solutions is local dryness. Erythema, tenderness, burning, pruritus, oiliness, and desquamation have also been reported following topical application of erythromycin solutions or gel. Most of these reactions appear to be caused by the alcohol or other ingredients in commercially available solutions or gel of the drug rather than erythromycin. Irritation of the eye has been reported with topical erythromycin solutions or gel. Skin irritation, such as erythema and peeling, has occasionally been reported with topical application of erythromycin ointment for acne. At least one case of contact dermatitis has been reported following topical application of the ointment for acne, but a causal relationship to the ointment has not been established. A generalized urticarial reaction, which required systemic corticosteroid therapy and possibly was causally related to erythromycin, has been reported during topical use of the gel.

Precautions and Contraindications !!navigator!!

Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with the use of erythromycin. CDAD should be considered in the differential diagnosis of patients who develop diarrhea during or following anti-infective therapy. Mild cases of colitis may respond to discontinuance of the drug alone. If colitis is severe or is not relieved by discontinuance of the drug, appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) should be administered.105,106,107,108

Topical use of erythromycin may result in overgrowth of nonsusceptible organisms including fungi. Gram-negative folliculitis has been reported rarely following topical use of erythromycin in the treatment of acne vulgaris. If superinfection or suprainfection occurs during erythromycin therapy, the drug should be discontinued and appropriate therapy instituted.

Erythromycin topical solutions, including a solution available as saturated pledgets, topical gel, and topical ointments are for external use only and should not be used near the eyes, nose, mouth, or other mucous membranes.

Erythromycin topical preparations are contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulations.

Pregnancy and Lactation !!navigator!!

Pregnancy

Safe use of erythromycin topical preparations during pregnancy has not been established.

Lactation

Safe use of erythromycin topical preparations during lactation has not been established.

Drug Interactions

Topical acne preparations containing peeling, desquamating, or abrasive agents (e.g., benzoyl peroxide, tretinoin, salicylic acid, sulfur) should be used cautiously in patients using topical anti-infectives because a cumulative irritant effect could occur. In addition, information on the physical and/or chemical compatibility of topical anti-infectives and other topical acne preparations is not available. Concurrent use of abrasive or medicated soaps or cosmetic products containing alcohol (e.g., astringents, after-shave lotions) may also cause a cumulative irritant or drying effect in patients using topical anti-infectives.

Because of possible competitive binding for the 50S ribosomal subunit (see Mechanism of Action), erythromycin and clindamycin probably should not be used concomitantly.

Other Information

[Section Outline]

Mechanism of Action

Erythromycin is usually bacteriostatic in action, but may be bactericidal in high concentrations or against highly susceptible organisms.

Erythromycin appears to inhibit protein synthesis in susceptible organisms by reversibly binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. The binding sites of erythromycin appear to be the same as or to overlap those of chloramphenicol, clindamycin, lincomycin, and troleandomycin.

Erythromycin exerts its effect only against multiplying organisms. Only un-ionized erythromycin is believed to penetrate susceptible organisms, and penetration increases as the pH of the extracellular environment increases. Erythromycin generally penetrates the cell wall of gram-positive organisms more readily than that of gram-negative organisms, and gram-positive organisms may accumulate 100 times more erythromycin than do gram-negative organisms.

The exact mechanisms by which erythromycin reduces lesions of acne vulgaris have not been fully elucidated; however, the effect appears to partly result from the antibacterial activity of the drug. Following topical application to the skin of a 1-2% solution of erythromycin base in a vehicle containing alcohol and propylene or polyethylene glycol, the drug inhibits the growth of susceptible organisms (principally Propionibacterium acnes ) on the surface of the skin and reduces the concentration of free fatty acids in sebum. The reduction in free fatty acids in sebum may be an indirect result of the inhibition of lipase-producing organisms which convert triglycerides into free fatty acids or may be a direct result of interference with lipase production in these organisms. Free fatty acids are comedogenic and are believed to be a possible cause of the inflammatory lesions (e.g., papules, pustules, nodules, cysts) of acne. However, other mechanisms also appear to be involved because clinical improvement of acne vulgaris with topical erythromycin therapy does not necessarily correspond with a reduction in the bacterial flora of the skin or a decrease in the free fatty acid content of sebum. In one study, erythromycin did not inhibit the growth of P. acnes within open comedones following topical application of a 1% solution of the base in a pyrollidone vehicle (a vehicle which presumably enhances penetration); however, topical application of a 1% solution of clindamycin as the phosphate in the same vehicle did inhibit these organisms within open comedones.

In an in vivo study, topical application of a 5% solution of erythromycin suppressed the local inflammatory response (e.g., erythema, pustules) to patch tests of 40% potassium iodide. In another in vivo study, topical application of a 2% solution of erythromycin in alcohol and polyethylene glycol resulted in fewer local reactions than did topical application of the vehicle alone. Erythromycin also inhibited leukocyte chemotaxis in an in vitro study. It has been hypothesized that these effects could be other mechanisms by which erythromycin suppresses the inflammatory lesions of acne vulgaris.

Spectrum

In general, erythromycin is active in vitro and in vivo against most aerobic and anaerobic gram-positive bacteria, Rickettsia, Chlamydia, Mycoplasma, Entamoeba histolytica, spirochetes, and a few gram-negative bacteria. The drug also has some activity in vitro against Mycobacterium scrofulaceum and M. kansasii. Erythromycin is inactive against Enterobacteriaceae, Pseudomonas, fungi, and viruses.

There is a wide range of minimum inhibitory concentrations (MICs) reported for erythromycin, but generally in vitro concentrations of 0.1-1.6 mcg/mL inhibit most susceptible staphylococci, streptococci, pneumococci, Actinomyces, Clostridium, Erysipelothrix, Listeria, Mycoplasma pneumoniae, Neisseria, and Propionibacterium acnes. Erythromycin concentrations up to 3.1 mcg/mL may be required in vitro to inhibit some susceptible strains of Haemophilus influenzae, Corynebacterium diphtheriae, and Moraxella.

Resistance

Resistant strains of H. influenzae and staphylococci, particularly S. aureus, have developed during systemic therapy with erythromycin. Resistant strains of pneumococci and streptococci have been reported during systemic therapy, although less frequently. Resistant strains of P. acnes have developed during topical therapy with the drug. Resistance may be caused by alterations in the ribosomal binding site which occur as the result of mutation or the presence of an inducible, plasmid-mediated resistance factor which is acquired via conjugation.

Partial cross-resistance occurs between erythromycin and clindamycin and lincomycin. In vitro, bacteria resistant to erythromycin and susceptible to clindamycin or lincomycin may exhibit a dissociated type of resistance to the latter drugs during susceptibility testing if erythromycin is also present. This phenomenon may be the result of competition between erythromycin and clindamycin or lincomycin for the ribosomal binding site.

Pharmacokinetics

In an in vitro model using human skin, erythromycin was absorbed into the stratum corneum following topical application of 10-20 mg of the drug in a vehicle containing dimethylacetamide and 95% alcohol. The drug does not appear to be absorbed systemically following twice daily application of a 2% solution of the drug in a vehicle containing 77% alcohol and polyethylene glycol and acetone.

It is not known if erythromycin is absorbed from intact or denuded skin, wounds, or mucous membranes following topical application of an ointment containing the drug.

Chemistry and Stability

Chemistry !!navigator!!

Erythromycin is a macrolide antibiotic obtained from cultures of Streptomyces erythreus. Erythromycin base occurs as a white or slightly yellow, odorless or practically odorless, bitter, crystalline powder. The drug has a solubility of approximately 1 mg/mL in water and is soluble in alcohol at 25°C. Erythromycin has a pKa of 8.9.

For the topical treatment of acne vulgaris, erythromycin base is commercially available as solutions in vehicles containing 66-71% alcohol, propylene glycol, and citric acid; as a gel in vehicles containing 92-95% alcohol and hydroxypropyl cellulose; and as an ointment in a base containing petrolatum, mineral oil, paraffin, talc, titanium dioxide, trilaureth-4 phosphate, oleyl oleate, trilaneth-4 phosphate, sorbitol, and cetearyl alcohol. The manufacturer states that the ointment (Akne-mycin®) commercially available in the US differs from the formulation commercially available under the same trade name in Europe.

Stability !!navigator!!

Commercially available erythromycin topical solutions and gels should be stored at 15-30°C; exposure to heat or open flames should be avoided. The topical ointment should be stored at a temperature less than 27°C.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Erythromycin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Topical

Gel

2%*

Erythromycin Gel

Erygel®

Merz

Ointment

2%

Akne-Mycin®

Healthpoint

Solution

2%*

Erythromycin Solution

Erythra-Derm®

Paddock

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Erythromycin Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Gel

3% with Benzoyl Peroxide 5%*

Benzamycin®

Dermik

Erythromycin and Benzoyl Peroxide Gel

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions July 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Fulton JE Jr, Pablo G. Topical antibacterial therapy for acne: study of the family of erythromycins. Arch Dermatol . 1974; 110:83-6. [PubMed 4278511]

101. Fisher AA. Erythromycin “free base”—a nonsensitizing topical antibiotic for infected dermatoses and acne vulgaris. Cutis . 1977 (Jul); 20:17,26,30,35.

102. Fisher AA. The safety of topical antibiotics in the treatment of acne vulgaris. Cutis . 1980 (May); 25:474,476,481.

103. Van Ketel WG. Immediate- and delayed-type allergy to erythromycin. Contact Dermatitis . 1976; 2:363-4. [PubMed 1032135]

104. Fisher AA. Is topical erythromycin base non-allergenic? Contact Dermatitis . 1983; 9:243. Letter.

105. Johnson S, Gerding DN. Clostridium difficile -associated diarrhea. Clin Infect Dis . 1998; 26:1027-36. [PubMed 9597221]

106. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of America. Position paper on Clostridium difficile -associated diarrhea and colitis. Infect Control Hosp Epidemiol . 1995; 16:459-77. [PubMed 7594392]

107. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile -associated diarrhea and colitis. Am J Gastroenterol . 1997; 92:739-50. (IDIS 386628) [PubMed 9149180]

108. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile -associated disease. Am J Health-Syst Pharm . 1998; 55:1407-11. [PubMed 9659970]

109. Wilcox MH. Treatment of Clostridium difficile infection. J Antimicrob Chemother . 1998; 41(Suppl C):41-6. [PubMed 9630373]

110. James WD. Acne. N Engl J Med . 2005; 352:1463-72. [PubMed 15814882]

111. Strauss JS, Krowchuk DP, Leyden JJ et al. Guidelines of care for acne vulgaris management. J Am Acad Dematol . 2007; 56:651-63.