Infectious Disease and Microbiology - Actinobacillus Species

Basics

Actinobacillus is a genus of gram-negative bacteria that was historically associated mainly with animal disease but can occasionally cause human infection. Several species are clinically relevant, including Actinobacillus equuli, A. hominis, A. suis, and A. ureae.

An important historical species, Actinobacillus actinomycetemcomitans, is no longer classified within this genus. It is now known as Aggregatibacter actinomycetemcomitans. Despite the taxonomic change, older medical literature may still use the former name.

Microbiologic Characteristics

Actinobacillus species are aerobic, gram-negative bacilli that are nonmotile. Their morphology may vary from short rods to coccoid or coccobacillary forms.

Some species are relatively fastidious and may require enriched culture conditions. Their growth characteristics can therefore help distinguish them from other gram-negative organisms.

Epidemiology

Actinobacilli were first recognized as pathogens of cattle, but they have also been isolated from other animals and humans.

Human infection is uncommon and often occurs after direct exposure to animals. Animal bites, particularly horse bites and other traumatic inoculations, are important routes of transmission for several species.

Because of this zoonotic association, a history of recent animal exposure can be an important diagnostic clue.

Important Species

Clinically important species include:

• Actinobacillus equuli

• Actinobacillus hominis

• Actinobacillus suis

• Actinobacillus ureae

The organism formerly called Actinobacillus actinomycetemcomitans is now classified as:

Aggregatibacter actinomycetemcomitans

This organism remains medically important because of its association with endocarditis and periodontal disease.

Aggregatibacter actinomycetemcomitans

Although no longer classified as Actinobacillus, Aggregatibacter actinomycetemcomitans remains strongly associated with the historical Actinobacillus literature.

It is part of the HACEK group of organisms associated with endocarditis.

HACEK traditionally includes:

• Haemophilus species

• Aggregatibacter species

• Cardiobacterium species

• Eikenella species

• Kingella species

These organisms are gram-negative bacteria that can cause indolent infective endocarditis and may require prolonged culture incubation or modern molecular methods for detection.

Endocarditis

Aggregatibacter actinomycetemcomitans is a recognized cause of infective endocarditis.

The disease may have a relatively subacute course, with symptoms such as:

• Fever

• Malaise

• Weight loss

• New or changing cardiac murmur

• Embolic manifestations

• Signs of heart failure in advanced disease

Blood cultures are the major diagnostic tool.

Because HACEK organisms are associated with endocarditis, persistent bacteremia with one of these organisms should prompt careful cardiac evaluation.

Periodontitis

Aggregatibacter actinomycetemcomitans is strongly associated with periodontal infection.

It may be isolated in conjunction with other oral organisms, including Actinomyces israelii.

Clinical disease may include:

• Gingival inflammation

• Periodontal pocket formation

• Loss of periodontal attachment

• Alveolar bone destruction

The organism is particularly associated with aggressive forms of periodontitis in some patients.

Wound Infections

Actinobacillus species can produce localized wound infection following traumatic inoculation.

Animal bites are especially important.

Clinical findings may include:

• Pain

• Erythema

• Swelling

• Purulent drainage

• Cellulitis

• Occasionally deeper soft-tissue involvement

Culture of wound material is useful when infection is clinically significant.

Animal Bite-Associated Disease

Actinobacillus suis and Actinobacillus equuli are particularly associated with animal bite-related wound infections.

Horse bites are a classic exposure.

Infection can result from direct inoculation of organisms present in the animal’s oral flora into damaged human tissue.

Because animal bite wounds are often polymicrobial, other aerobic and anaerobic organisms may also be present.

Actinobacillus hominis

A. hominis has been associated with bacteremia, particularly in patients with significant underlying illness.

Reported risk factors include:

• Chronic pulmonary disease

• Hepatic failure

• Debilitating medical conditions

Bloodstream infection may therefore be a marker of severe underlying disease.

Actinobacillus ureae

A. ureae can occasionally cause invasive infection.

Reported manifestations include:

• Bacteremia

• Meningitis

Central nervous system infection is rare but potentially severe.

Endophthalmitis

Actinobacillus-related ocular infection has occasionally been reported.

Endophthalmitis may occur after:

• Trauma

• Surgery

• Hematogenous spread

Symptoms can include severe eye pain, redness, photophobia, and visual loss.

Urgent ophthalmologic treatment is necessary because intraocular infection can rapidly threaten vision.

Diagnosis

Diagnosis is based primarily on culture.

Appropriate specimens depend on the clinical syndrome and may include:

• Blood

• Wound material

• Cerebrospinal fluid

• Ocular specimens

• Periodontal material

• Tissue samples

Species-level identification is useful because clinical associations and antimicrobial susceptibilities vary.

Culture Characteristics

On approximately 1-day-old culture plates, Actinobacillus colonies may appear translucent and measure around 1–2 mm in diameter.

The organism historically called A. actinomycetemcomitans is more fastidious.

It is an obligate capnophile, meaning that increased carbon dioxide improves its growth.

Early colonies may be very small, often less than 0.5 mm in diameter. After several days they may enlarge to approximately 2–3 mm and develop:

• Rough surfaces

• Pitting of the agar

These characteristics can help laboratory identification.

Differential Diagnosis

Depending on the clinical syndrome, the differential may include other gram-negative coccobacilli and HACEK organisms.

For endocarditis, consider:

• Haemophilus

• Cardiobacterium

• Eikenella

• Kingella

• Other causes of culture-positive or culture-negative endocarditis

For bite wounds, consider:

• Pasteurella

• Streptococci

• Staphylococci

• Anaerobic oral flora

• Other zoonotic gram-negative bacteria

Treatment

Treatment depends on the species, infection site, and susceptibility profile.

For HACEK endocarditis, ceftriaxone is a commonly preferred treatment because of its reliable activity and convenient dosing.

Therapy should be guided by current susceptibility data and the specific clinical syndrome.

Ceftriaxone

Ceftriaxone is a major treatment option for HACEK endocarditis.

Its advantages include:

• Reliable activity against many HACEK organisms

• Good bloodstream penetration

• Convenient once-daily dosing

Duration depends on whether native or prosthetic valve endocarditis is present and on current guideline recommendations.

Other Antimicrobial Options

Depending on susceptibility results and the site of infection, other potentially active agents include:

• Ampicillin

• Penicillin G

• Aminoglycosides

• Ciprofloxacin

• Trimethoprim-sulfamethoxazole

• Azithromycin

Azithromycin has demonstrated good in vitro activity against some isolates, although clinical experience varies by syndrome.

Combination Therapy

Older regimens sometimes used:

Ampicillin or penicillin G

plus

An aminoglycoside

particularly for severe invasive disease.

However, modern therapy should be individualized, and susceptibility testing is especially important because resistance patterns can vary.

Management of Bite Wounds

Animal bite-related infections require more than antimicrobial selection alone.

Important management principles include:

• Thorough wound irrigation

• Debridement when necessary

• Evaluation for tendon, joint, or bone involvement

• Tetanus prophylaxis when indicated

• Consideration of rabies risk depending on the animal and epidemiologic setting

Culture is particularly useful when infection is already established.

Prognosis

Most localized wound infections have a good prognosis when treated promptly.

More serious outcomes are possible in:

• Endocarditis

• Bacteremia

• Meningitis

• Endophthalmitis

• Deep bite-related infections

Delayed diagnosis or major underlying disease may worsen prognosis.

High-Yield Taxonomy

Old name:

Actinobacillus actinomycetemcomitans

Current name:

Aggregatibacter actinomycetemcomitans

This taxonomic change is important because older examinations and textbooks may use the former terminology.

High-Yield Endocarditis Association

HACEK organism

• ●

Subacute endocarditis

• ●

Fastidious gram-negative coccobacillus

→ Think Aggregatibacter actinomycetemcomitans among the possibilities.

High-Yield Bite Association

Horse or other animal bite

• ●

Gram-negative coccobacillary wound pathogen

→ Consider Actinobacillus equuli or Actinobacillus suis.

Exam Essentials

Genus:

→ Actinobacillus

Morphology:

→ Aerobic gram-negative coccobacillary or short bacillary organism

Motility:

→ Nonmotile

Important zoonotic association:

→ Animal bites

Former major species:

→ Actinobacillus actinomycetemcomitans

Current classification:

→ Aggregatibacter actinomycetemcomitans

Important disease caused by Aggregatibacter actinomycetemcomitans:

→ Endocarditis and periodontitis

HACEK association:

→ Yes

A. hominis:

→ Bacteremia, especially in patients with serious underlying disease

A. ureae:

→ Bacteremia and meningitis

A. suis and A. equuli:

→ Animal bite-associated wound infection

Diagnosis:

→ Culture

Preferred major therapy for HACEK endocarditis:

→ Ceftriaxone

Other potentially active agents:

→ Ampicillin, penicillin G, ciprofloxacin, TMP-SMX, selected aminoglycosides, and azithromycin depending on susceptibility