Neonatal eye infections

• A red, sticky eye in a newborn is most often ophthalmia neonatorum, an inflammation of the conjunctiva in the first month of life from chemical, bacterial or viral causes.
• The timing of the onset is the fastest clue: chemical in the first day; gonococcal on days 2 to 5; herpetic from day 1 to 14; chlamydial on days 5 to 14; other bacteria in the second to fourth weeks.
• Gonococcal disease is the emergency: it can ulcerate and perforate the cornea within hours, so a hyperacute, purulent eye needs same-day Gram stain and parenteral ceftriaxone.
• Chlamydial disease is the commonest infection worldwide and is treated with oral, not topical, antibiotics; untreated it can reach the lungs and cause pneumonia.
• Prophylaxis (erythromycin 0.5% ointment in each eye once, within 24 hours of birth) plus prenatal screening and treatment of the mother is what prevents sight-threatening infection; it does not cover chlamydia, so maternal screening matters.

By the end of this page you should be able to:

1. List the main causes of a red, sticky newborn eye and use the day of onset to rank them.
2. Recognise gonococcal, chlamydial and herpetic ophthalmia neonatorum and state why each is dangerous.
3. Choose and interpret Gram stain, culture and nucleic acid amplification tests for a neonatal eye swab.
4. Prescribe first-line treatment and dose for gonococcal, chlamydial and herpetic disease, including alternatives.
5. Explain why prophylactic erythromycin ointment prevents gonococcal but not chlamydial infection, and what else is needed.
6. Build an approach to the newborn with conjunctivitis and know which babies must be admitted or referred.

A useful bedside classification separates four groups, because each has a different clock and a different urgency:

1. Chemical conjunctivitis - an irritant reaction to prophylactic drops or ointment, common and self-limited.
2. Gonococcal ophthalmia neonatorum - from Neisseria gonorrhoeae, acquired from the maternal birth canal; the sight-threatening form.
3. Chlamydial ophthalmia neonatorum - from Chlamydia trachomatis; the commonest infectious cause worldwide.
4. Herpes simplex virus (HSV) conjunctivitis - usually HSV-1 or HSV-2, from direct contact with infected secretions at delivery or afterwards.
5. Other bacterial and viral causes - Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus species, Pseudomonas aeruginosa, and adenovirus, among others.

Presentation and treatment differ, so these groups should not be managed identically.

Gonococcal disease has become uncommon where mothers are screened for gonorrhoea in pregnancy, which is the main reason cases have fallen. Neisseria gonorrhoeae now accounts for under 1% of reported neonatal conjunctivitis in settings with prenatal screening.^[1]

Chlamydia is the most common single infectious cause. It accounts for 2 to 40% of all cases of ophthalmia neonatorum, and between 1.6 and 12% of all newborns develop conjunctivitis of any cause depending on setting.^[1][6] An infant born vaginally to a mother with untreated chlamydial cervicitis has a 50 to 75% chance of acquiring the organism in the conjunctiva, nasopharynx, rectum or vagina, and 30 to 50% of those with proven exposure develop conjunctivitis.^{[6] [5] [3]}

Herpes simplex neonatal disease is rare but disproportionately severe. Up to 30 to 50% of babies exposed to maternal genital herpes near delivery can become infected, and disease limited to the skin, eye and mouth still needs prompt treatment because it can become disseminated.^[4]

Ophthalmia neonatorum as a whole affects 1.6 to 12% of newborns; the figure can reach 23% in developing countries where screening and prophylaxis are not routine.^[1] It remains one of the leading preventable causes of blindness in low-resource settings. ^[2]

The three major infections are acquired vertically. The baby passes through a cervix colonised by N. gonorrhoeae, C. trachomatis or shedding herpes simplex virus, and the organisms are inoculated directly into the conjunctival sac. Risk factors are:

• Untreated maternal genitourinary infection (the dominant factor), particularly in women under 25 years or with a new or multiple sex partners, a partner who has a sexually transmitted infection, or residence in a high-prevalence community.
• No prenatal care, or prenatal screening that was done but not followed up.
• Ruptured membranes, which allows earlier exposure and a shorter incubation.
• Delivery by a person with infected secretions on their hands (herpes, adenovirus).
• Prematurity and low birth weight, because thinner epithelium and poorer local immunity worsen disease.

Non-infectious risk is simpler: any prophylactic drop or ointment itself, especially silver nitrate, which can irritate the conjunctiva. Nasolacrimal duct obstruction is an anatomical, not infectious, cause of the "sticky eye": a blocked tear duct produces mucoid discharge with little redness and is very common in the first months of life.

Chemical. The prophylactic agent (classically silver nitrate, but any antiseptic or antibiotic ointment) chemically irritates the conjunctival surface. The lid swells mildly and a serous discharge appears; no organism is present, the culture is sterile, and the process resolves on its own.

Gonococcal. N. gonorrhoeae produces an intense acute purulent inflammation. The incubation is short, the organism penetrates the epithelium, and the cornea is threatened quickly. Within 24 hours an untreated infection can cause corneal ulceration, panophthalmitis, perforation of the globe and endophthalmitis. The same organism can spread haematogenously to cause sepsis, meningitis, arthritis and, rarely, death. Topical antibiotics alone cannot treat it, because the organism is not only on the surface. ^[6]

Chlamydial. C. trachomatis has a longer incubation because it replicates intracellularly. The conjunctiva becomes injected and oedematous with mild-to-moderate mucopurulent discharge. Left untreated it produces chronic follicular conjunctivitis, superficial corneal vascularisation and conjunctival scarring. The organism also colonises the nasopharynx; up to 20% of exposed neonates later develop chlamydial pneumonia at 1 to 3 months of age, usually afebrile with a staccato cough.^[5] Herpetic. HSV produces a follicular conjunctivitis with watery, sometimes blood-stained discharge and small vesicles on the lid margin; corneal epithelial defects are common. The virus can spread to the corneal stroma, retina and optic nerve, and beyond the eye to the central nervous system and whole body, which is why neonatal herpes carries a mortality of up to 85% when disseminated.^[1][4] Other bacteria. Non-sexually transmitted bacteria account for 30 to 50% of cases.^[6] Most are mild and respond to topical antibiotics. Pseudomonas aeruginosa is the exception: it can destroy the cornea and cause perforation and endophthalmitis, so it must be treated aggressively. Blocked tear duct. The nasolacrimal duct is narrow in infants and easily obstructed by oedema or mucus. Tears and mucoid secretion collect (a "sticky eye") with only mild or no conjunctival redness, and the problem usually settles with conservative measures; it is not an infection.

The single most useful fact is the first morning (or day) on which the eye looked abnormal. Ask about discharge, redness, swelling, light sensitivity, and whether one or both eyes are involved; and ask about maternal infection, screening, membrane rupture and mode of delivery.

• Chemical: begins within the first 24 hours; mild lid oedema, mild serous discharge; self-limited, lasting 2 to 4 days. Often follows instillation of silver nitrate or other prophylactic agents.^[1][6]
• Gonococcal: begins on days 2 to 5; hyperacute, with severe lid swelling, chemosis and copious purulent (sometimes blood-tinged) discharge. Both eyes are usually affected.^[1][6]
• Chlamydial: begins on days 5 to 14 (earlier if membranes ruptured); lid swelling of variable degree, mild-to-moderate serous or purulent discharge, conjunctival injection that is worse on the palpebral surface.^[1][5][6]
• Herpes simplex: begins any time from day 1 to 14; mild redness and watery or blood-stained discharge; look for epithelial defects on the cornea and for vesicles on the lid margin (often days 6 to 14).^[1][6]
• Other bacteria: usually day 4 onward, with a subacute course and variable discharge.^[1]
• Nasolacrimal duct obstruction: often presents as a watery, mucoid sticky eye with little redness; it usually begins after the first weeks of life and settles without antibiotics.

Examine under good light with a magnifier. Note unilateral or bilateral disease, the character of the discharge (serous, mucoid or purulent), lid oedema, chemosis, corneal clarity and whether fluorescein staining shows epithelial defects. Palpate the lacrimal sac gently for reflux of mucoid material, which supports nasolacrimal obstruction. Check for vesicles on the lids. Inspect the baby generally: hepatosplenomegaly, rash, hypothermia, seizures or poor feeding point to disseminated herpes or sepsis. Perform a red-reflex and anterior-segment check; significant corneal opacity or ulcer needs same-day ophthalmology.

The table above is the working differential. Use time of onset plus three bedside clues:

• Perforation risk in the first 48 hours? Think gonococcus, especially with hyperacute chemosis.
• Vesicles on the lid margin or corneal dendrites? Think herpes simplex.
• Only a "watery, sticky" eye, little redness, no photophobia? Think nasolacrimal duct obstruction and conservative management.

Other conditions to keep in mind:

• Congenital dacryocystocele - a bluish medial canthal swelling in the first days, from a blocked nasolacrimal system; it may become infected (dacryocystitis) and needs treatment.
• Neonatal conjunctival haemorrhage from birth trauma - bright red, no discharge, resolves.
• Metabolic or allergic conjunctivitis - rare in the first month.
• Sepsis with conjunctival injection - in a generally unwell baby do not attribute the eye to a local cause without ruling out systemic infection.

These remain the core tests and should be taken before starting treatment whenever practical.

• Gram stain of conjunctival exudate is read immediately. Intracellular gram-negative diplococci are highly suggestive of gonococcal infection and should trigger presumptive treatment for gonorrhoea while cultures and susceptibility testing are awaited.
• Culture of the conjunctiva gives the organism and antibiotic sensitivities, which matters because gonococcal resistance patterns vary.
• Specimens for culture and non-culture tests should be taken from the everted eyelid, with conjunctival cells (not discharge alone), using a Dacron swab or the swab specified by the test kit. ^[3]
• Pharyngeal, rectal and vaginal swabs, plus blood, cerebrospinal fluid and joint fluid when indicated, detect disseminated infection.

• NAATs are the most sensitive way to detect C. trachomatis in urogenital specimens, but for conjunctival specimens they are not cleared by the regulator in all countries; laboratories must validate the method under their own quality rules (CLIA in the United States). A positive result should be treated; a negative result in a clinically compatible baby does not exclude infection. ^[3]
• Direct fluorescent antibody (DFA) is the only non-culture test cleared for chlamydia on conjunctival swabs in some jurisdictions.
• For HSV, PCR (NAAT) is the test of choice for eye, cerebrospinal fluid, blood and lesion swabs; viral culture has lower sensitivity.

• Culture for herpes has low sensitivity; use PCR.
• Imaging is not routine, but if Pseudomonas or perforation is suspected, an urgent ophthalmology review replaces imaging.
• Maternal testing for gonorrhoea and chlamydia, and HSV assessment where indicated, should be arranged at the same time.
• Blood cultures, urinalysis and lumbar puncture are needed when disseminated infection, sepsis or herpes is possible.

There are no formal scoring systems for neonatal conjunctivitis; diagnosis is clinical plus laboratory. The approach is algorithmic and is summarised in the flowchart.

• Stop any remaining prophylactic medication and do not repeat it.
• Clean the eye gently with sterile saline; do not patch a neonatal eye.
• Send Gram stain, culture and, where validated, NAAT before antibiotics if the eye can wait a short time; in hyperacute disease do not delay treatment.
• Start empiric therapy based on the most dangerous likely cause, then refine.
• Arrange ophthalmology review promptly if there is corneal opacity, ulcer, perforation threat or herpetic disease.
• Treat the mother and her partner(s) for any sexually transmitted infection; otherwise the baby will be re-infected.

• Hospitalise the infant and involve an infectious-disease specialist.
• Ceftriaxone 25 to 50 mg per kg IV or IM in a single dose, not exceeding 250 mg.^[2]
• Give cefotaxime 100 mg per kg IV or IM as a single dose instead if ceftriaxone cannot be given because of simultaneous IV calcium (newborns on calcium-containing fluids). (Systemic alternative cefotaxime is also used in some regions.)^[2]
• Ceftriaxone must be used cautiously in neonates with hyperbilirubinaemia, especially the premature.^[2]
• Add topical therapy only if the ocular surface is heavily colonised; systemic treatment is what cures the eye.^[2]
• Irrigate the conjunctiva frequently to remove pus and protect the cornea.
• Evaluate for disseminated gonococcal infection: blood and cerebrospinal fluid cultures as indicated, and joint aspiration if arthritis is suspected.^[2]
• Presumptive treatment is justified when intracellular gram-negative diplococci are seen on Gram stain; treat the attendant organism from culture and susceptibility testing.

• Oral erythromycin base or ethylsuccinate 50 mg per kg per day, divided into four doses daily for 14 days. (A 14-day course is the standard recommended by paediatric authorities.)^[3][6]
• Erythromycin cures roughly 80% of cases, so a second course is sometimes required; follow up the infant after treatment to confirm resolution.^[3]
• Azithromycin is sometimes used instead, in small studies at 20 mg per kg once daily for 3 days; one systematic review found microbiological cure of about 60% after a single dose and about 86% after 3 days. Data are limited, so follow local guidance and discuss with the paediatric team.^[5][6]
• Topical antibiotics alone are inadequate and unnecessary if systemic treatment is given.^[3]
• Test and treat for concomitant N. gonorrhoeae and assess for chlamydial pneumonia.^[3]
• Monitor for infantile hypertrophic pyloric stenosis (vomiting, persistent feeds) after oral erythromycin or azithromycin in babies under 6 weeks.^[3]
• Treat the mother and her partner(s) for chlamydia. For pregnancy, azithromycin 1 g orally in a single dose is recommended; doxycycline is avoided in later pregnancy.^[3]

• Systemic acyclovir 20 mg per kg IV every 8 hours for 14 days if disease is confined to skin, eye and mucous membranes, or for 21 days if disease is disseminated or involves the central nervous system.^[4]
• Work with paediatric infectious disease and ophthalmology; HSV in a neonate can be fatal and needs specialist care.^[4]
• Arrange a full evaluation for neonatal herpes: swabs and PCR from eye, mouth, nasopharynx and rectum, blood PCR, chest imaging if needed, and lumbar puncture for HSV PCR in cerebrospinal fluid.^[4][6]
• Ophthalmology may add topical antiviral drops (for example 1% trifluridine) and monitor corneal scarring; systemic treatment is what protects the brain and body.^[6]
• Begin acyclovir early when the mother acquired genital herpes late in pregnancy even if the baby is asymptomatic and surveillance is planned, because risk is high.^[4]

• Most of these infections cause mild-to-moderate disease and respond to topical antibiotics (aminoglycosides, macrolides or fluoroquinolones), with appropriate Gram stain and culture first.
• Pseudomonas infection is an emergency: assume aggressive management with topical and systemic aminoglycosides, subconjunctival antibiotics where needed, ophthalmology assessment and isolation, because it can destroy the cornea and rarely kill.^[6]

• No antibiotic is needed unless there is secondary infection (dacryocystitis, with a red, tender swelling below the medial canthus).
• Conservative measures: warm compress, gentle lacrimal sac massage, lid hygiene; many resolve without treatment in infancy.
• Refer to ophthalmology if obstruction persists or if dacryocystitis recurs.

• Gonococcal: corneal ulceration; perforation of the globe within 24 hours if untreated; endophthalmitis; panophthalmitis; disseminated infection (sepsis, meningitis, arthritis).^[1][2][6]
• Chlamydial: chronic follicular conjunctivitis, superficial corneal vascularisation, conjunctival scarring, pannus, symblepharon; chlamydial pneumonia in up to 20% of exposed neonates at 1 to 3 months.^[1][5]
• Herpetic: recurrent corneal scarring and profound amblyopia, chorioretinitis, optic neuritis, cataract; disseminated central-nervous-system disease with mortality up to 85%.^[1][4]
• Other bacteria: Pseudomonas can cause corneal ulcer, perforation and endophthalmitis.
• Prophylaxis-related: silver nitrate causes chemical conjunctivitis in 50 to 90% of exposed infants; erythromycin and tetracycline cause it in under 10%; topical antibiotics as prophylaxis select resistant strains.^[1]

With prompt, appropriate treatment, gonococcal disease rarely causes blindness today, but the window is short. Chlamydial disease resolves but must be treated systemically to prevent pneumonia. Herpetic disease has the worst prognosis even with treatment, which is why early acyclovir and full evaluation are essential. Chemical and non-sexually transmitted bacterial infections usually resolve without sequelae.

Prevention works on two levels, and the distinction between them is a common exam trap.

Maternal level (protects against chlamydia and gonorrhoea alike):

• Screen pregnant women at risk at the first prenatal visit and re-screen in the third trimester or at delivery; women at risk include those under 25 years and those with a new or multiple partner, a partner with a sexually transmitted infection, or residence in a high-prevalence area.
• Test and treat every mother found to be infected, retest after treatment, and treat the partner(s).

Neonatal eye prophylaxis (protects mainly against gonorrhoea):

• The US Preventive Services Task Force recommends erythromycin 0.5% ophthalmic ointment in each eye in a single application for every newborn, within 24 hours of birth, regardless of mode of delivery.^[2]
• Apply ideally in the first hour and no later than 24 hours; if it is delayed, set up a system to ensure it is given.^[2]
• Instil from single-use tubes or ampules rather than multi-use tubes where possible.^[2]
• Erythromycin is the only ophthalmic preparation now recommended for this purpose in the United States: silver nitrate and tetracycline are no longer available there, bacitracin is ineffective, gentamicin ointment has been associated with severe ocular reactions, and povidone-iodine (2.5%) has not been adequately studied in all jurisdictions.^[2]
• Ocular prophylaxis is ineffective against chlamydia. Therefore, in countries where mothers are not routinely screened, chlamydia remains common and maternal screening is the real prevention.^{[1][5] [3]}
• If erythromycin ointment is unavailable, infants at increased risk of gonococcal exposure (mother with no prenatal care or at high risk) can be given ceftriaxone 25 to 50 mg per kg IV or IM once, not exceeding 250 mg as prophylaxis.^[2]
• Povidone-iodine 2.5% has a broad spectrum including viruses, does not select resistance, is cheap and causes less chemical conjunctivitis in several studies; it is widely used where erythromycin is unavailable or costly.^[1]
• Neonates born to mothers with untreated gonorrhoea should be tested at exposed sites and treated presumptively with ceftriaxone even if they have no symptoms.^[2]

• Pregnancy: reducing maternal infection is the whole strategy. Treat chlamydia in pregnancy with azithromycin 1 g orally once^[3]; treat gonorrhoea and retest; suppress recurrent genital herpes with acyclovir 400 mg orally three times daily from 36 weeks.^[4] For women with active herpetic lesions at labour, delivery mode should be managed with obstetrics and sexual health, not by the neonatal team alone.\n- Premature and small infants: chlamydial and gonococcal infection is often more severe; ceftriaxone must be used carefully when bilirubin is high.
• Immunocompromised or HIV-exposed infants: co-infections (syphilis, gonorrhoea, chlamydia) are common; test broadly and manage with an infectious-disease specialist.
• Low birth weight and critically ill neonates: do not delay treatment for test results when gonococcus or herpes is possible.

• Where maternal screening is poor, chlamydia and gonorrhoea remain the major causes, and prophylaxis with whatever single-dose agent is available (erythromycin, tetracycline, or povidone-iodine where these are unavailable and licensed) is better than nothing. Apply it within hours of delivery.
• The single test that changes management is a Gram stain at the bedside: intracellular gram-negative diplococci mean gonococcus and ceftriaxone now. ^[2]
• If erythromycin or ceftriaxone are unavailable, seek local first-line agents for gonococcal and chlamydial disease, and arrange referral; do not rely on topical antibiotics for gonococcal disease.
• Any baby with corneal opacity, severe chemosis or suspected herpes should be referred urgently; these babies often lose vision before they reach a hospital.
• Teach parents (and birth attendants who wash and dry babies) clean handling of eyes; herpes and adenovirus spread this way.

• Paediatric stye, blepharitis and common conjunctivitis
• Gonorrhoea, chlamydia and genital herpes in adults
• Antenatal sexually transmitted infection screening
• Genital herpes in pregnancy and neonates
• Nasolacrimal duct obstruction and dacryocystitis
• Red eye in adults