AHFS Class:

• Antibacterials 52:04.04

Generic Name(s):

• Erythromycin

Erythromycin is a macrolide antibiotic.139,140

Bacterial Ophthalmic Infections

Erythromycin 0.5% ophthalmic ointment is used for the topical treatment of superficial infections of the eye involving the conjunctiva and/or cornea caused by susceptible bacteria.139,140

Although mild, acute bacterial conjunctivitis often resolves spontaneously without anti-infective treatment,135,136,137,141 topical ophthalmic anti-infectives may shorten the time to resolution and reduce severity and risk of complications.135,136,137,141 Treatment of acute bacterial conjunctivitis generally is empiric and use of a broad-spectrum topical ophthalmic antibacterial usually is recommended;135,136,141 however, indiscriminate use of topical anti-infectives should be avoided.135,141 In vitro staining and/or cultures of conjunctival material is indicated in the diagnosis and management of all cases of suspected infectious conjunctivitis in neonates,135,136,141,292,344 all cases of suspected gonococcal or chlamydial conjunctivitis,292,344 and may be indicated in the management of recurrent, severe, or chronic purulent conjunctivitis or when acute conjunctivitis does not respond to initial empiric topical treatment.135,136,141

Because bacterial conjunctivitis caused by Neisseria gonorrhoeae is associated with a high risk for corneal involvement and subsequent corneal perforation,136,141,344 such infections require treatment with systemic anti-infectives (e.g., IM or IV ceftriaxone)135,136,141,292,344 with or without topical anti-infectives.135,136,141 Topical anti-infectives alone are inadequate for the treatment of ophthalmia neonatorum caused by N. gonorrhoeae and some experts state that adjunctive use of topical anti-infectives is unnecessary when recommended systemic anti-infectives are used.292

Chlamydial Ophthalmic Infections

Although erythromycin has been used topically in the treatment of conjunctivitis secondary to trachoma caused by Chlamydia trachomatis †,127,128,129,130,131,134,136 systemic anti-infective therapy (usually oral azithromycin) is recommended for the treatment of ocular trachoma.136,292

Systemic anti-infective therapy (e.g., oral azithromycin, doxycycline, or erythromycin) is necessary for the treatment of chlamydial conjunctivitis, including chlamydial ophthalmia neonatorum.135,136,292,344 Data to support use of topical anti-infectives in conjunction with systemic therapy for treatment of chlamydial conjunctivitis are not available.135,136 Some experts state that topical anti-infective therapy alone is inadequate for the treatment of chlamydial ophthalmic infections and is unnecessary when appropriate systemic anti-infective therapy is used.292,344

Erythromycin 0.5% ophthalmic ointment has been used for topical prophylaxis of ophthalmia neonatorum caused by C. trachomatis .139,140 Infants born to women with untreated chlamydial infection are at high risk for infection;292,344 however, efficacy of topical prophylaxis for the prevention of chlamydial neonatal conjunctivitis has not been established and such prophylaxis does not eliminate nasopharyngeal colonization with C. trachomatis .101,102,103,104,106,107,109,114,116,292,344 Some experts state that erythromycin 0.5% ophthalmic ointment used for topical prophylaxis of gonococcal ophthalmia neonatorum will not prevent chlamydial ophthalmia neonatorum.292

Prophylaxis of Gonococcal Ophthalmia Neonatorum

Erythromycin 0.5% ophthalmic ointment is used for topical prophylaxis of ophthalmia neonatorum caused by N. gonorrhoeae .139,140,292,344 Efficacy of topical erythromycin for the prevention of ophthalmia neonatorum caused by penicillinase-producing N. gonorrhoeae is not established.139,140

The US Centers for Disease Control and Prevention (CDC) and American Academy of Pediatrics (AAP) recommend topical prophylaxis against gonococcal ophthalmia neonatorum in all neonates as soon as possible after birth (regardless of whether they are delivered vaginally or by cesarean section), and such prophylaxis is required by law in most states.292,344 Although diagnosis and treatment of gonococcal infections in pregnant women is the best means of preventing neonatal gonococcal disease, not all women receive prenatal care.344 CDC states that universal topical prophylaxis is warranted since it can prevent sight-threatening gonococcal ophthalmia and because it is safe, easy to administer, and inexpensive.344

CDC and AAP recommend use of erythromycin 0.5% ophthalmic ointment for topical prophylaxis of gonococcal ophthalmia neonatorum.292,344 If erythromycin ophthalmic ointment is not available, CDC states that neonates at risk for exposure to N. gonorrhoeae (especially those born to women who are at risk for gonococcal infection or received no prenatal care) should receive systemic prophylaxis with a single dose of ceftriaxone (IM or IV).344 Although silver nitrate and tetracycline have been used in the past for topical prophylaxis of gonococcal ophthalmia neonatorum, ophthalmic preparations of these drugs are no longer commercially available in the US.292,344

Infants born to women with untreated gonorrhea are at high risk of infection with N. gonorrhoeae , and CDC and AAP recommend that such neonates receive systemic prophylaxis with a single dose of ceftriaxone (IM or IV) instead of the usual topical erythromycin prophylaxis.292,344

For systemic use of erythromycin, see the Erythromycins General Statement 8:12.12.04. For other topical uses of erythromycin, see Erythromycin 84:04.04.

Administration

Ophthalmic Administration

Erythromycin is applied topically to the eye as a 0.5% ointment.139,140

Erythromycin ophthalmic ointment is for topical ophthalmic use only .139,140

Care should be taken to avoid contaminating the tip of the ointment tube with material from the eye, fingers, or other source.139,140

Dosage

Bacterial Ophthalmic Infections

For the topical treatment of superficial infections of the eye caused by susceptible bacteria, a ribbon of erythromycin 0.5% ophthalmic ointment approximately 1 cm in length should be applied directly to the affected eye(s) up to 6 times daily.139,140 Some experts recommend that erythromycin ophthalmic ointment be applied 4 times daily for 1 week for empiric treatment of acute bacterial conjunctivitis.136

Prophylaxis of Gonococcal Ophthalmia Neonatorum

For prophylaxis of gonococcal ophthalmia neonatorum in neonates, a ribbon of erythromycin 0.5% ophthalmic ointment approximately 1 cm in length should be placed into the lower conjunctival sac of each eye.139,140 Following placement of the ointment, the eyelids should be massaged gently to spread the ointment;292 after one minute, excess ointment can be wiped away with sterile cotton.292 The ointment should not be flushed from the eye following application.139,140,292 A new tube or single-use container of erythromycin ointment should be used for each neonate.139,140

Erythromycin topical prophylaxis should be administered as soon as possible (within 1 hour) after birth.292,344 Although efficacy is unlikely to be affected if topical prophylaxis is delayed for up to 1 hour after delivery (e.g., to facilitate parent-infant bonding), efficacy of prophylaxis administered after a longer delay has not been studied.292 Neonates delivered by cesarean section as well as those delivered by the vaginal route should receive erythromycin topical prophylaxis.292,344 (See Uses: Prophylaxis of Gonococcal Ophthalmia Neonatorum.)

Adverse Effects

The most frequently reported adverse effects in patients receiving erythromycin 0.5% ophthalmic ointment are minor ocular irritation, redness, and hypersensitivity reactions.139,140

Precautions and Contraindications

Erythromycin 0.5% ophthalmic ointment is contraindicated in patients with known hypersensitivity to erythromycin.139,140

Prolonged use of erythromycin ophthalmic ointment may result in overgrowth of nonsusceptible organisms, including fungi.139,140 If superinfection occurs, erythromycin ophthalmic ointment should be discontinued and appropriate therapy initiated.139,140

Geriatric Precautions

No overall differences in safety or efficacy have been observed between geriatric and younger patients.140

Pregnancy and Lactation

Pregnancy

In reproduction studies in rats, mice, and rabbits using erythromycin at doses higher than usual human doses, there was no evidence of harm to the fetus.139,140

There are no adequate and controlled studies to date using erythromycin in pregnant women, and the drug should be used during pregnancy only if clearly needed.139,140

Lactation

Erythromycin should be used with caution in nursing women.139,140

Mechanism of Action

Erythromycin is usually bacteriostatic; however, in high concentrations or against highly susceptible organisms, it may be bactericidal.

Erythromycin inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. The site of action of erythromycin is the same as that of clindamycin, lincomycin, and chloramphenicol.

Erythromycin exerts its effect only against multiplying organisms. The drug generally penetrates the cell wall of gram-positive bacteria more readily than that of gram-negative bacteria, and gram-positive organisms may accumulate 100 times more erythromycin than do gram-negative organisms.

Spectrum

Erythromycin is active in vitro and in clinical infections against some gram-positive bacteria, including Staphylococcus aureus (methicillin-susceptible strains only), Streptococcus pneumoniae , S. pyogenes (group A β-hemolytic streptococci; GAS), viridans streptococci (α-hemolytic streptococci), and Corynebacterium diphtheriae .139,140 The drug also is active in vitro and in clinical infections against some gram-negative bacteria, including some strains of Haemophilus influenzae and Neisseria gonorrhoeae .139,140

Erythromycin is active against Chlamydia trachomatis and Mycoplasma pneumoniae .139,140 The drug also has activity against Treponema pallidum .139,140

Resistance

Gram-negative bacilli (e.g., Escherichia coli , Proteus , Pseudomonas ) are usually resistant to erythromycin, as are viruses, yeasts, and fungi.

Erythromycin-resistant strains of Haemophilus influenzae and staphylococci (particularly Staphylococcus aureus ) and, less frequently, Streptococcus pneumoniae and other streptococci have been reported.

Pharmacokinetics

Topical application of erythromycin to the eye probably does not produce significant antibacterial concentrations in deep layers of the cornea or in the aqueous humor. It is not known if erythromycin is absorbed to any substantial extent from mucous membranes.

Chemistry and Stability

Chemistry

Erythromycin is a macrolide antibiotic produced by a strain of Streptomyces erythreus .139,140 Erythromycin 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 pK_a of 8.9.

For topical ophthalmic use, erythromycin is commercially available as an ophthalmic ointment containing 5 mg of erythromycin per g in a vehicle consisting of mineral oil and white petrolatum.139,140

Stability

Commercially available erythromycin 0.5% ophthalmic ointment should be stored at 15-25°C.139,140 The ointment should not be exposed to excessive heat and should not be frozen.140

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.

101. Anon. Neonatal gonococcal ophthalmia—California. MMWR Morb Mortal Wkly Rep . 1983; 32:518-9. [PubMed 6412066]

102. Zola EM. Evaluation of drugs used in the prophylaxis of neonatal conjunctivitis. Drug Intell Clin Pharm . 1984; 18:692-6. [PubMed 6383753]

103. Hammerschlag MR, Chandler JW, Alexander ER et al. Erythromycin ointment for ocular prophylaxis of neonatal chlamydial infection. JAMA . 1980; 244:2291-3. [PubMed 7431552]

104. Rettig PJ, Patamasucon P, Siegel JD. Postnatal prophylaxis of chlamydial conjunctivitis. JAMA . 1981; 246: 2321-2. [PubMed 7299949]

106. Dillon HC Jr. Prevention of gonococcal ophthalmia neonatorum. N Engl J Med . 1986; 315:1414-5. [PubMed 3773967]

107. Sandstrom I. Ophthalmia neonatorum with special reference to Chlamydia trachomatis : diagnosis and treatment. Acta Paediatr Scand . 1986; 330:3-27.

109. Hammerschlag MR. Neonatal ocular prophylaxis. Pediatr Infect Dis J . 1988; 7:81-2. [PubMed 3344174]

114. Fransen L, Klauss V. Neonatal ophthalmia in the developing world: epidemiology, etiology, management and control. Int Ophthalmol . 1988; 11:189-96. [PubMed 3047073]

116. Bell TA, Sandstrom KI, Gravett MG et al. Comparison of ophthalmic silver nitrate solution and erythromycin ointment for prevention of natally acquired Chlamydia trachomatis . Sex Transm Dis . 1987; 14:195-200. [PubMed 3438783]

127. Roy FH. Trachoma. Ann Ophthalmol . 1974; 6:1167-71. [PubMed 4429322]

128. Vastine DW, Dawson CR, Daghfous T et al. Severe endemic trachoma in Tunisia: I. Effect of topical chemotherapy on conjunctivitis and ocular bacteria. Br J Ophthalmol . 1974; 58:833-42. [PubMed 4451650]

129. Maichuk YF. Some aspects of rational trachoma therapy. Am J Ophthalmol . 1972; 74:684-703.

130. Dawson CR, Daghfous T, Whitcher J et al. Intermittent trachoma chemotherapy: a controlled trial of topical tetracycline or erythromycin. Bull World Health Organ . 1981; 59:91-7. [PubMed 7020973]

131. Dawson CR, Daghfous T, Messadi M et al. Severe endemic trachoma in Tunisia. II. A controlled therapy trial of topically applied chlortetracycline and erythromycin. Arch Ophthalmol . 1974; 92:198-203. [PubMed 4137188]

134. Dawson CR, Schachter J. Strategies for treatment and control of blinding trachoma: cost-effectiveness of topical or systemic antibiotics. Rev Infect Dis . 1985; 7:768-73. [PubMed 4070912]

135. American Academy of Ophthalmology. Preferred practice pattern (PPP) guidelines: conjunctivitis PPP - 2013. From American Academy of Ophthalmology website. Accessed 20 Dec 2017. [Web]

136. Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA . 2013; 310:1721-9. [PubMed 24150468]

137. Sheikh A, Hurwitz B, van Schayck CP et al. Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database Syst Rev . 2012; :CD001211. [PubMed 22972049]

139. Bausch & Lomb Inc. Erythromycin ophthalmic ointment, USP 0.5% prescribing information. Bridgewater, NJ; 2016 Jul.

140. Akorn, Inc. Erythromycin ophthalmic ointment USP, 0.5% prescribing information. Lake Forest, IL; 2016 Jun.

141. Barnes SD, Kumar NM, Pavin-Langston D et al. Microbial Conjunctivitis. In: Bennett JE, Dolin R, and Blaser MJ, eds. Mandell, Douglas, and Bennett's principles and practices of infectious diseases. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:1392-1401.

292. Committee on Infectious Diseases, American Academy of Pediatrics. Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.

344. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2015. MMWR Morb Mortal Wkly Rep . 2015; 64(No. RR-3):1-135. [Fulltext MMWR]