Infectious Disease and Microbiology – Haemophilus Species

Overview

Non-influenzae Haemophilus species are small, fastidious Gram-negative coccobacilli that occur worldwide. Many colonize the upper respiratory and oral mucosa, but they can occasionally cause invasive disease, particularly bacteremia, endocarditis, pneumonia, meningitis, brain abscess, and soft-tissue infection.

Certain species have especially important clinical associations. Haemophilus aegyptius is associated with conjunctivitis and historically with a severe purpuric septic syndrome, while some species formerly classified as Haemophilus are important causes of HACEK endocarditis.

Important Species

The source lists:

• Haemophilus aegyptius

• Haemophilus aphrophilus

• Haemophilus haemolyticus

• Haemophilus parahaemolyticus

• Haemophilus parainfluenzae

• Haemophilus paraphrophilus

• Haemophilus segnis

Several of these organisms have undergone taxonomic reclassification.

Important Taxonomic Changes

Older microbiology references may use Haemophilus names that are no longer preferred.

Notably:

Haemophilus aphrophilus → Aggregatibacter aphrophilus

Haemophilus paraphrophilus → now included within Aggregatibacter aphrophilus

Haemophilus segnis → Aggregatibacter segnis

These changes are particularly important when studying HACEK organisms and infective endocarditis.

Microbiologic Characteristics

Haemophilus species are generally:

• Gram-negative coccobacilli

• Fastidious organisms

• Facultatively anaerobic, although older sources may describe them as aerobic

• Associated with human mucosal surfaces

Different species have different requirements for X factor (hemin) and V factor (NAD), which can assist laboratory identification.

Epidemiology

These organisms have a worldwide distribution.

Many species colonize the:

• Oropharynx

• Upper respiratory tract

• Oral cavity

Infection frequently develops when organisms invade beyond their normal mucosal habitat.

Bacteremia

Non-influenzae Haemophilus species can occasionally cause bacteremia.

Bloodstream infection may occur:

• With endocarditis

• During severe respiratory infection

• In immunocompromised patients

• As part of systemic sepsis

Persistent bacteremia should raise concern for an endovascular focus such as infective endocarditis.

Upper Respiratory Tract Infection

Some Haemophilus species can cause or participate in:

• Pharyngitis

• Other upper respiratory infections

• Respiratory tract colonization with subsequent invasive disease

Because several species may colonize the respiratory tract, culture results should be interpreted together with the clinical syndrome.

Epiglottitis

Although H. influenzae type b is the classic Haemophilus associated with epiglottitis, other Haemophilus species have occasionally been implicated.

Epiglottitis remains an airway emergency because rapidly progressive swelling can cause upper-airway obstruction.

Pneumonia and Chronic Bronchitis

These organisms may cause:

• Pneumonia

• Exacerbations of chronic bronchitis

• Other lower respiratory tract infections

Respiratory disease is particularly relevant in patients with underlying pulmonary abnormalities.

Soft-Tissue Infection

Rare soft-tissue infections may occur when organisms gain access through disrupted mucosal or skin barriers.

Deep specimens are generally more useful than superficial cultures for determining whether an isolate represents true infection.

Endocarditis

Important Clinical Association

Some organisms historically classified as Haemophilus are particularly important causes of infective endocarditis.

This includes organisms now classified within Aggregatibacter.

These organisms belong to the clinically important HACEK group.

HACEK Organisms

HACEK refers to a group of fastidious Gram-negative organisms associated particularly with infective endocarditis:

H – Haemophilus species traditionally included in the group

A – Aggregatibacter species

C – Cardiobacterium hominis

E – Eikenella corrodens

K – Kingella species

Because of taxonomic changes, many organisms historically placed under the “H” component are now classified as Aggregatibacter.

HACEK Endocarditis

The characteristic pattern is:

Oropharyngeal flora

• ●

Bacteremia

• ●

Cardiac valve infection

→ Consider a HACEK organism

Endocarditis may have a relatively indolent or subacute presentation.

Meningitis

Non-influenzae Haemophilus species can rarely cause meningitis.

Diagnosis requires appropriate examination and culture or molecular evaluation of cerebrospinal fluid.

Brain Abscess

Rare cases of brain abscess have also been associated with these organisms.

Because many originate from the oral or upper respiratory flora, CNS infection may occasionally follow contiguous spread or hematogenous dissemination.

Urinary Tract Infection

Although uncommon, some Haemophilus species have been associated with urinary tract infection.

Because these organisms require specialized culture conditions, routine urine culture techniques may occasionally fail to detect them.

Haemophilus aegyptius

Conjunctivitis

H. aegyptius is classically associated with:

Acute conjunctivitis

Historically, the organism has also been called the Koch-Weeks bacillus in association with acute conjunctival disease.

Brazilian Purpuric Fever

An especially important historical association is:

H. aegyptius → Brazilian purpuric fever

This is a severe systemic illness described particularly in children and characterized by:

• Acute fever

• Sepsis

• Purpuric skin lesions

• Rapid clinical deterioration

It was associated with particular invasive strains related to H. aegyptius.

High-Yield H. aegyptius Pattern

Child

• ●

Recent conjunctivitis

• ●

Acute fever and sepsis

• ●

Purpuric lesions

→ Think Brazilian purpuric fever associated with H. aegyptius

Diagnosis

The source lists:

Culture

as the primary diagnostic method.

Because these organisms are fastidious, appropriate media and incubation conditions are important.

For invasive disease, specimens may include:

• Blood

• Cerebrospinal fluid

• Respiratory specimens

• Abscess material

• Conjunctival specimens

Treatment

The source lists:

Ampicillin

as a treatment option.

For endocarditis or severe sepsis, the older source describes combining ampicillin with an:

Aminoglycoside

However, treatment of serious infection should account for modern susceptibility patterns and the specific organism identified.

Additional Treatment

The source lists:

• Third-generation cephalosporins

• Imipenem

• Meropenem

For invasive disease, antimicrobial selection should be guided by species identification, susceptibility testing, infection site, and severity.

High-Yield Clinical Pattern – Endocarditis

Fastidious Gram-negative coccobacillus

• ●

Normal oral/oropharyngeal flora

• ●

Subacute endocarditis

→ Consider a HACEK organism, including organisms historically classified among Haemophilus species.

Species Associations

H. aegyptius

→ Conjunctivitis

→ Brazilian purpuric fever

H. parainfluenzae

→ Respiratory infection

→ Occasionally bacteremia/endocarditis

Former H. aphrophilus / H. paraphrophilus

→ Now Aggregatibacter aphrophilus

→ Particularly important in invasive disease, including endocarditis and brain abscess

Former H. segnis

→ Now Aggregatibacter segnis

Exam Essentials

Genus: Haemophilus

Morphology: Gram-negative coccobacilli

Distribution: Worldwide

Typical habitat: Oral and upper respiratory flora

Major infections: Bacteremia, respiratory infection, pneumonia, endocarditis

Other infections: Meningitis, brain abscess, UTI, soft-tissue infection

Important species: H. aegyptius

H. aegyptius infection: Conjunctivitis

Severe H. aegyptius association: Brazilian purpuric fever

Purpuric fever pattern: Conjunctivitis followed by fever, sepsis, and purpura

Endocarditis association: HACEK organisms

Taxonomic change: H. aphrophilus → Aggregatibacter aphrophilus

Diagnosis: Culture

Treatment in source: Ampicillin

Additional treatment: Third-generation cephalosporin or carbapenem

Modern principle: Species identification and susceptibility-guided therapy

Key clinical pearl: Non-influenzae Haemophilus species are uncommon but important causes of invasive infection. Remember two particularly high-yield associations: fastidious oral Gram-negative organisms with endocarditis → think HACEK, and H. aegyptius with conjunctivitis followed by fulminant sepsis and purpura → Brazilian purpuric fever.