What is the most likely antitubercular (anti-tuberculosis) drug to cause blindness in a 5-month-old infant with suspected tuberculosis (TB)?

Ethambutol is the Most Likely Drug to Cause Blindness in This Infant

Ethambutol (option c) is the correct answer, as it is the antitubercular drug most associated with ocular toxicity leading to blindness, particularly through retrobulbar neuritis that can result in permanent vision loss if not promptly discontinued. 1, 2

Clinical Context Supporting TB Diagnosis

This 5-month-old infant presents with classic features suggestive of disseminated/miliary tuberculosis:

• Prolonged fever (10 days) with irritability when handled suggests possible meningeal involvement 3
• Chest X-ray showing "snowflakes appearance" is pathognomonic for miliary tuberculosis 3
• No BCG vaccination increases susceptibility to disseminated disease 3
• Cough for 2 weeks indicates pulmonary involvement 3

Why Ethambutol Causes Blindness

Mechanism of Ocular Toxicity

• Ethambutol causes retrobulbar neuritis (optic neuritis) manifesting as decreased visual acuity, scotomata, color blindness (particularly red-green discrimination), and visual field defects 3, 1
• The toxicity is dose-dependent and can be irreversible if not recognized promptly, with some cases resulting in permanent blindness 1, 4
• Vision loss can be painfully slow to recover or permanent even after drug discontinuation 4, 5

Critical Risk Factors in This Infant

• Young age (<5 years) makes visual monitoring extremely difficult, as the child cannot report visual symptoms 1, 2, 6
• Visual impairment in young children is likely underestimated because they cannot communicate changes in vision 6
• In a study of children <5 years on ethambutol, 27.3% developed visual impairment, which only normalized after drug discontinuation 6

Why Other Options Are Less Likely

Streptomycin (option a)

• Primary toxicity is ototoxicity (hearing loss), not blindness 3
• Causes auditory nerve damage and renal impairment, but not ocular toxicity 3

Pyrazinamide (option b)

• Does not cause ocular toxicity 3
• Main adverse effects include hepatotoxicity and hyperuricemia 3

Ampicillin (option d)

• Not an antitubercular drug and has no association with blindness 3
• Would be ineffective against Mycobacterium tuberculosis 3

Critical Guideline Recommendations for Ethambutol in Young Children

FDA and International Guidelines

• The FDA states ethambutol is not recommended for children under 13 years since safe conditions for use have not been established 7
• However, ethambutol can be used in young children when drug resistance is suspected, but with extreme caution due to inability to monitor visual acuity 2
• The British Thoracic Society states ethambutol should only be used in patients who can appreciate and report visual symptoms 3

Monitoring Requirements That Cannot Be Met in This Infant

• Baseline visual acuity testing by Snellen chart is required before prescribing ethambutol 3, 1
• Monthly monitoring for visual disturbances including blurred vision and scotomata is mandatory 1
• Ishihara charts for color vision testing require patient cooperation, typically from age 5 years 3
• This 5-month-old infant cannot cooperate with any of these tests, making safe use impossible 2, 6

Clinical Pitfall to Avoid

The most dangerous pitfall is prescribing ethambutol to infants and young children who cannot report visual symptoms. 1, 2 Visual-evoked potentials (VEPs) can be used for monitoring in children too young to cooperate with standard vision testing, but this requires specialized equipment and expertise 6. Even with VEPs, visual impairment occurred in over one-quarter of young children in one study 6.

In this clinical scenario, if ethambutol must be used due to suspected drug resistance, the dose should be carefully calculated at 15-20 mg/kg/day (never exceeding this), and VEP monitoring should be arranged if available. 2 However, the risk-benefit ratio must be carefully considered, as permanent blindness has been documented even at recommended doses 4, 5.