What is the most likely infectious agent in a 6-month-old infant with fever, neck rigidity, seizures, and cerebrospinal fluid showing an encapsulated Gram-negative rod that requires heme and NAD to grow, treated with ceftriaxone (third-generation cephalosporin)?

Haemophilus influenzae

The most likely infectious agent is Haemophilus influenzae type b (Hib), an encapsulated Gram-negative coccobacillus that requires heme (X factor) and NAD (V factor) for growth, causing meningitis in this incompletely vaccinated 6-month-old infant.

Microbiological Identification

The cerebrospinal fluid findings definitively point to Haemophilus influenzae:

• Encapsulated Gram-negative rod requiring both heme (X factor) and NAD (V factor) for growth is pathognomonic for H. influenzae 1
• This growth requirement distinguishes it from all other answer choices 1
• H. influenzae is specifically listed as a causative agent of meningitis in the FDA label for ceftriaxone 1

Epidemiological Context and Vaccination Status

The critical detail is the missed vaccinations at 2 and 4 months due to intercurrent colds:

• Historically, H. influenzae type b was one of the three main pathogens causing bacterial meningitis in children beyond neonatal age, along with N. meningitidis and S. pneumoniae 2
• After Hib vaccination was introduced in the 1990s, this pathogen has virtually disappeared as a major cause of bacterial meningitis in vaccinated children 2
• H. influenzae meningitis currently occurs incidentally in unvaccinated children or may be due to serotypes other than type b 2
• In the pre-vaccine era, H. influenzae type b accounted for 7.4-10% of occult bacteremia cases 2
• No H. influenzae was isolated in post-vaccine era studies of occult bacteremia 2

Age-Specific Pathogen Distribution

At 6 months of age, this infant falls into a transitional epidemiological category:

• Neonatal meningitis (0-6 weeks) is primarily caused by Streptococcus agalactiae (58%) and Escherichia coli (21%) 2
• Beyond neonatal age, the classic triad was H. influenzae type b, N. meningitidis, and S. pneumoniae 2
• In the post-vaccine era, S. pneumoniae is now as common as meningococcal meningitis in children beyond neonatal age 2

Elimination of Other Answer Choices

Bordetella pertussis: Not an encapsulated organism, does not cause meningitis, and does not require heme and NAD for growth 1

Escherichia coli: While a Gram-negative rod that can cause meningitis, it does not require heme and NAD for growth, and is primarily a neonatal pathogen (21% of neonatal meningitis) rather than affecting 6-month-olds 2

Neisseria meningitidis: A Gram-negative diplococcus (not a rod), does not require heme and NAD for growth 2

Streptococcus agalactiae (Group B Streptococcus): A Gram-positive coccus (not Gram-negative rod), primarily causes neonatal meningitis (58% of cases), and does not require heme and NAD for growth 2

Clinical Sequelae and Treatment Response

The partial hearing loss outcome is consistent with H. influenzae meningitis:

• Childhood bacterial meningitis may result in permanent hearing loss (17%), mental retardation (19%), seizure disorders (15%), paralysis (11%), and death (7.7%) 2
• Ceftriaxone is specifically indicated for meningitis caused by H. influenzae 1
• Third-generation cephalosporins (ceftriaxone or cefotaxime) are now the preferred drugs for bacterial meningitis caused by H. influenzae, meningococci, and pneumococci 3

Critical Clinical Pitfall

The most important lesson from this case is that routine childhood vaccinations should not be deferred for minor illnesses like uncomplicated upper respiratory infections. This infant's incomplete vaccination status directly led to susceptibility to a vaccine-preventable disease that has been virtually eliminated in properly vaccinated populations 2.