This is a 4 week old male infant born to a 26 year old G2P2 O+, rubella immune, group B strep negative, HBsAg negative, VDRL negative, GC and Chlamydia negative married female at 40 weeks gestation via spontaneous vaginal delivery with Apgar scores of 8 and 9 at 1 and 5 minutes. Pregnancy, delivery and postpartum hospital course were uncomplicated. He presents with his mother to your office with a two day history of bilateral eye drainage. He had been in good health until two days ago when he developed yellow drainage and mild periorbital swelling. Review of systems is negative except for the recent development of a cough that he "probably caught from his older brother".
Exam: VS T37.5, P 120, RR 60, BP 60/40, oxygen saturation 94% in room air, weight 4.0 kg (50%ile) He is a well developed, well nourished, non-toxic male infant with mild tachypnea and staccato cough, but in no acute distress. His upper and lower eyelids are edematous. There is mild conjunctival injection with moderate amounts of mucopurulent drainage bilaterally. Pseudomembranes are seen with eversion of the upper eyelids. Coarse breath sounds are appreciated bilaterally with occasional rales and fine expiratory wheezes. The remainder of his exam is unremarkable.
You swab the conjunctiva for gram stain, culture and chlamydia direct fluorescence antibody staining. Complete blood count is remarkable for eosinophilia. Chest radiograph reveals bilateral patchy infiltrates with hyperinflation. After receiving positive chlamydia DFA results, you inform the mother of the diagnosis. Initially shocked, she admits that six months ago she and her husband had separated briefly, but are now back together.
Ophthalmia neonatorum is the most common ocular disease in the newborn, occurring in 2-12% of neonates (includes chemical conjunctivitis). The major causative agents of neonatal conjunctivitis are chemical, chlamydial and bacterial. Viral ocular infection, usually by herpes simplex virus, occurs infrequently. The mode of infectious transmission is believed to be acquisition during passage through a colonized or infected birth canal (1,2). While nearly every bacterial species has been implicated, ocular infection with Neisseria gonorrhoeae is felt to be one of the most serious because of its potential to damage vision and cause blindness (1,3).
Gonococcal ophthalmia prompted the widespread use of silver nitrate for prophylaxis in the neonate since the 1880's. Consequently, Chlamydia trachomatis is now the most common infectious agent causing neonatal conjunctivitis in approximately 0.4%-2.8% births in this country (4,5). Recognizing the irritant effects of silver nitrate (frequently causes chemical conjunctivitis), 0.5% erythromycin ointment, 1% tetracycline ointment and 2.5% povidone-iodine solution have all been suggested and utilized as less chemically irritating alternatives in preventing neonatal gonococcal conjunctivitis. However, none have been shown to consistently prevent chlamydial conjunctivitis or nasopharyngeal colonization (1-4,6-9).
The presentation of ophthalmia neonatorum varies with the causative agent. Inflammation due to chemical irritation (usually silver nitrate drops) is first appreciated 6-12 hours after birth with spontaneous resolution by 24-48 hours. In contrast, the incubation period for N. gonorrhoeae is 2-5 days (sometimes longer) with the appearance of symptoms seen from birth to beyond 5 days of age. Beginning with a mild inflammation and serosanguinous drainage, gonococcal ophthalmia soon results in thick, profuse purulent discharge and tense eyelid edema with marked chemosis (swelling of the conjunctiva) (2,10).
Chlamydial conjunctivitis in the neonate can present from 3 days to beyond 6 weeks postnatal age, but most commonly occurs during the 2nd week of life. Infants present with conjunctival inflammation, mucopurulent discharge (that may be profuse), eyelid edema and pseudomembranes in the palpebral conjunctiva (5,10).
A distinct pneumonia occurs in 10-20% of infants exposed to C. trachomatis (2,5). Patients typically present with a history of afebrile illness for several weeks. The infant usually appears well with tachypnea and prominent "staccato" cough. Auscultation of the chest often reveals rales and wheezing. Fifty percent of these patients also have concomitant conjunctivitis. Chest radiograph reveals bilateral, diffuse, patchy infiltrates and hyperinflation. CBC commonly reveals moderate eosinophilia (5).
The list of causative agents of ophthalmia neonatorum includes, but is not limited to, chemical irritants, Neisseria gonorrhoeae, Chlamydia trachomatis, Staphylococcus aureus, group A or B streptococcus, S. pneumonia, Haemophilus influenzae, Pseudomonas aeruginosa and Herpes simplex virus (1,2).
Shortly after birth, ophthalmic prophylaxis for gonorrhea should be administered to all infants, including those delivered by cesarean section since ascending infection can occur. Two drops of a 1% silver nitrate solution or a 1 cm ribbon of antibiotic ointment (0.5% erythromycin or 1 % tetracycline) are applied to each lower conjunctival sac. The eyes should not be flushed or irrigated (8). Currently, there is no antibiotic agent effective for use as prophylaxis for Chlamydia ophthalmia neonatorum (1-4,6-9). Chemical conjunctivitis is self-limiting and requires no treatment.
Diagnosis of ocular infection with N. gonorrhoeae can be made following identification of gram negative oxidase positive diplococci on gram stain or culture of conjunctival swabbings or eye drainage. Cultures of blood, CSF, or other sites of infection should be obtained in infants with gonococcal ocular infection to rule out disseminated infection. Tests for concomitant C. trachomatis, T. pallidum, and HIV infection should also be performed. For nondisseminated N. gonorrhoeae ophthalmia neonatorum, infants should receive ceftriaxone (25-50 mg/kg IV or IM) once. Alternatively, 100 mg/kg of cefotaxime (IV or IM) can also be given. Therapy is extended to 7 days for septicemia and 10-14 days for meningitis. Frequent saline irrigation of the eyes should also be performed until the discharge is eliminated. Infants born to mothers with untreated gonococcal infection should receive a one-time dose of IM or IV ceftriaxone or cefotaxime (9).
Chlamydia can be detected by PCR, ligase chain reaction (LCR), DNA probe, direct fluorescent antibody (DFA) tests, enzyme immunoassays (EIAs), or by isolating the organism in tissue culture. Diagnosis of chlamydial infection should prompt testing for other STDs in the infant as well as examination of the mother and her sexual partners. Infants who develop chlamydial conjunctivitis with or without pneumonia should be treated with oral erythromycin (50mg/kg/day in 4 divided doses) for 14 days. Treatment with topical antibiotics will not eliminate nasopharyngeal colonization and conjunctivitis may recur (5). In cases where the infant is less than 6 weeks of age, parents should be counseled regarding a reported association between oral erythromycin and infantile hypertrophic pyloric stenosis. Retesting for C. trachomatis is not indicated once treatment has been completed unless symptoms persist (3).
Without prompt treatment, N. gonorrhoeae ocular infection may spread to the deeper layers of the conjunctiva and cornea (2,10). Corneal ulceration and perforation, iridocyclitis, anterior synechiae, and panophthalmitis from untreated gonococcal ophthalmitis may result in permanent vision loss and blindness (1,4,6). Disseminated gonococcal disease can result in scalp abscess, bacteremia, arthritis, meningitis or endocarditis (9).
Left untreated, chlamydia conjunctivitis will subside within 2-3 weeks, but chronic infection is common. Chlamydia pneumonia, not conjunctivitis, is the most serious consequence of neonatal C. trachomatis infection (4). The pneumonia is usually mild and deaths attributed to chlamydial pneumonia have not been reported (5). However, the disease can lead to chronic cough and long term pulmonary impairment (4,5).
1. Which details of this patient's presentation (in the case) distinguish his illness from neonatal N. gonorrhoeae infection?
2. Besides the infant presented in the case vignette, which other family members should be treated for this condition?
3. What etiologies should be considered when a neonate presents with eye drainage?
4. Of 1% silver nitrate solution, 0.5% erythromycin ointment, 1% tetracycline ointment and 2.5% povidone-iodine solution, which is/are considered effective for prophylaxis of ocular chlamydial infection?
5. What is the treatment for C. trachomatis ophthalmia? For N. gonorrhoeae ophthalmia?
6. What are the long-term complications of N. gonorrhoeae ophthalmia neonatorum? Of neonatal C. trachomatis infection?
7. Infants under 6 weeks of age are at increased risk for the development of what disease following treatment with erythromycin?
1. Hammerschlag MR. Neonatal Conjunctivitis. Pediatr Ann 1993; 22(6):346-351.
2. Overall JC. Chapter 9 - The Fetus and the Neonatal Infant. In: Behrman RE, et al (eds). Nelson Textbook of Pediatrics, 14th edition. 1992, Philadelphia: W.B. Saunders Company, pp. 504-505.
3. Chlamydial Infections. In: Pickering LK (ed). 2000 Red Book: Report of the Committee on Infectious Diseases, 25th edition. 2000, Elk Grove Village, IL: American Academy of Pediatrics, pp. 205-212.
4. Schachter J. Why we need a program for the control of Chlamydia trachomatis (editorial). New Engl J Med 1989;320(12):802-803.
5. Phillips CF. Chapter 12 - Infectious Diseases. In: Behrman RE, et al (eds). Nelson Textbook of Pediatrics, 14th edition. 1992, Philadelphia: W.B. Saunders Company, pp. 786-787.
6. Hammerschlag MR. Neonatal ocular prophylaxis. Pediatr Infect Dis J 1988; 7:81-82.
7. Hammerschlag MR, et al. Efficacy of neonatal ocular prophylaxis for the prevention of chlamydial and gonococcal conjunctivitis. New Engl J Med 1989; 320(12):769-772.
8. Prevention of Neonatal Ophthalmia. In: Pickering LK (ed). 2000 Red Book: Report of the Committee on Infectious Diseases, 25th edition. 2000, Elk Grove Village, IL: American Academy of Pediatrics, pp. 735-742.
9. Gonococcal Infections. In: Pickering LK (ed). 2000 Red Book: Report of the Committee on Infectious Diseases, 25th edition. 2000, Elk Grove Village, IL: American Academy of Pediatrics, pp. 254-260.
10. Wagner RS. Eye infections and abnormalities: Issues for the pediatrician. Contemp Pediatr 1997; 14(6): 137-153.
Answers to questions
1. Late presentation, presence of pseudomembranes and accompanying pneumonia.
2. The patient's mother and her sexual contacts should seek medical attention and treatment for urogenital chlamydia and other sexually transmitted diseases.
3. Chemical irritants, Neisseria gonorrhoeae, and Chlamydia trachomatis are the most common causes. However, Staphylococcus aureus, group A or B streptococcus, S. pneumonia, Haemophilus influenzae, Pseudomonas aeruginosa and Herpes simplex virus should also be remembered as potential pathogens.
5. Infants who develop chlamydial conjunctivitis with or without pneumonia should be treated with oral erythromycin (50mg/kg/day in 4 divided doses) for 14 days. For nondisseminated N. gonorrhoeae ophthalmia neonatorum, infants should receive ceftriaxone (25-50 mg/kg IV or IM) once. Alternatively, 100 mg/kg of cefotaxime (IV or IM) can also be given.
6. Without prompt treatment, N. gonorrhoeae ocular infection may result in corneal ulceration and perforation, iridocyclitis, anterior synechiae, and panophthalmitis leading to permanent vision loss and blindness. Left untreated, chlamydia conjunctivitis will subside within 2-3 weeks, but chronic infection is common. Chlamydia pneumonia is the most serious consequence of neonatal C. trachomatis infection. The pneumonia does not appear to be life threatening; however, the disease can lead to chronic cough and long-term pulmonary impairment
7. Infantile hypertrophic pyloric stenosis.