Infectious Disease and Microbiology - Acremonium Species

Basics

Acremonium is a genus of filamentous fungi that was formerly known as Cephalosporium. The genus contains roughly 100 species, but only a small number are clinically important. Medically relevant species include Acremonium alabamense, A. falciforme, A. kiliense, A. recifei, A. roseogriseum, and A. strictum. Among these, A. kiliense has historically been one of the most frequently encountered pathogenic species.

Microbiologic Characteristics

Acremonium species are molds composed of septate hyphae. Their microscopic appearance may resemble Fusarium, although Acremonium generally grows more slowly.

Colonies are commonly white and may appear velvety, cottony, or fasciculate. They are usually flat or only slightly elevated in the center. Some species are able to tolerate cycloheximide, a feature that can be useful in laboratory identification.

Because morphology can overlap with other hyaline molds, definitive identification may require specialized mycologic methods.

Epidemiology

Acremonium species are widespread environmental fungi. They have been isolated from soil, sewage, insects, plant rhizospheres, and a variety of other organic substrates.

Human infection is uncommon despite frequent environmental exposure. Disease usually develops after direct inoculation, ocular contamination, surgery, implantation of prosthetic material, or in the setting of significant immunosuppression.

Clinical Infections

Acremonium can cause both localized and invasive disease. Superficial and localized infections are more common than disseminated infection.

Important clinical manifestations include:

• Mycetoma

• Onychomycosis

• Fungal keratitis

• Ocular infection

• Soft contact lens colonization

Rarely, Acremonium produces severe invasive or disseminated disease.

Mycetoma

Acremonium can cause chronic infection of the skin and subcutaneous tissues known as mycetoma.

The infection typically develops slowly after traumatic inoculation of environmental material into the skin. Patients may develop swelling, chronic nodules, sinus tracts, and drainage.

Disease can persist for prolonged periods and may eventually involve deeper tissues or bone.

Onychomycosis

Acremonium is an uncommon cause of fungal nail infection.

Clinical features can include:

• Nail discoloration

• Thickening

• Brittleness

• Separation of the nail plate

Because Acremonium may occasionally represent contamination, repeated isolation or compatible direct microscopy is helpful before attributing nail disease to the organism.

Mycotic Keratitis

Acremonium can cause fungal keratitis, particularly after:

• Corneal trauma

• Exposure to contaminated environmental material

• Contact lens use

• Ocular surgery

Symptoms may include pain, redness, photophobia, tearing, and decreased visual acuity.

Prompt ophthalmologic evaluation is important because fungal keratitis can progress to deeper ocular infection and visual loss.

Contact Lens Colonization

Acremonium species can colonize soft contact lenses and lens-care equipment.

Colonization does not always indicate invasive keratitis, but it may create a reservoir for corneal infection, particularly when lens hygiene is poor or contaminated solutions are used.

Proper contact lens cleaning and replacement practices are therefore important preventive measures.

Invasive Pulmonary Disease

Invasive pulmonary Acremonium infection is rare and usually occurs in patients with major immune compromise, especially profound neutropenia.

Clinical manifestations may include:

• Persistent fever

• Cough

• Dyspnea

• Pulmonary infiltrates

• Nodules or cavitary lesions

Because these findings can resemble invasive aspergillosis, fusariosis, or other mold infections, microbiologic confirmation is important.

Central Nervous System Infection

Rare CNS manifestations include:

• Meningitis

• Cerebritis

• Brain abscess

These infections usually occur in severely immunocompromised patients or after direct inoculation or dissemination from another site.

Neurologic disease can be difficult to treat and may require prolonged systemic antifungal therapy together with surgical intervention when feasible.

Endocarditis

Acremonium has been reported as a rare cause of prosthetic valve endocarditis.

Risk factors include:

• Prosthetic cardiac material

• Previous cardiac surgery

• Prolonged intravascular access

• Immunosuppression

Fungal endocarditis often requires both prolonged antifungal therapy and surgical valve intervention.

Osteomyelitis and Arthritis

Acremonium may cause osteomyelitis or post-traumatic septic arthritis, particularly after:

• Penetrating trauma

• Contaminated wounds

• Surgery

• Direct inoculation

These infections may have a chronic and indolent course.

Successful management frequently requires both antifungal therapy and surgical debridement.

Endophthalmitis

Postoperative endophthalmitis caused by Acremonium has been described after ocular surgery.

Symptoms may include:

• Eye pain

• Redness

• Reduced vision

• Intraocular inflammation

This condition requires urgent ophthalmologic management because permanent visual loss may occur.

Peritoneal Dialysis-Associated Peritonitis

Acremonium can rarely cause peritonitis in patients undergoing peritoneal dialysis.

Presentation may include:

• Abdominal pain

• Cloudy dialysate

• Fever

• Peritoneal leukocytosis

Management may require systemic antifungal therapy and, in some cases, removal of the peritoneal dialysis catheter.

Disseminated Infection

Disseminated Acremonium infection is uncommon but may occur in patients with profound neutropenia or other severe immunosuppressive states.

Possible sites of dissemination include:

• Lungs

• Brain

• Skin

• Bone

• Heart

• Other internal organs

The prognosis is substantially worse when infection is disseminated.

Risk Factors for Invasive Disease

Important predisposing factors include:

• Prolonged neutropenia

• Hematologic malignancy

• Hematopoietic stem-cell transplantation

• Solid-organ transplantation

• Prolonged corticosteroid therapy

• Major immunosuppression

• Indwelling medical devices

• Recent surgery

• Trauma with environmental contamination

Localized superficial infections, however, can occur in immunocompetent individuals.

Diagnosis

Diagnosis is primarily based on culture from the affected site.

Specimens may include:

• Corneal scrapings

• Nail material

• Tissue biopsy

• Blood cultures

• Cerebrospinal fluid

• Respiratory samples

• Peritoneal fluid

• Bone or joint specimens

Because Acremonium can occasionally represent environmental contamination, the clinical context and repeated recovery from appropriate specimens are important.

Histopathology

Tissue examination may show septate hyaline fungal hyphae.

The morphology can resemble other hyalohyphomycetes, particularly:

• Fusarium

• Aspergillus

Therefore, histopathology is useful for demonstrating tissue invasion, but culture or molecular identification may be needed to determine the exact genus or species.

Differential Diagnosis

Important fungal differentials include:

• Fusarium

• Aspergillus

• Scedosporium

• Other hyaline molds

For keratitis, bacterial and herpetic infections must also be considered.

For chronic subcutaneous disease, the differential includes other causes of mycetoma, including bacterial actinomycetoma and infections caused by other filamentous fungi.

Treatment

Treatment can be difficult because antifungal susceptibility varies among Acremonium species.

Historically, amphotericin B has been considered a major therapeutic option, particularly for invasive disease.

However, clinical response may be inconsistent, and susceptibility testing can be helpful in serious infections.

Amphotericin B

Amphotericin B may be used for:

• Invasive infection

• Disseminated disease

• CNS disease

• Severe ocular or deep tissue infection

A lipid formulation may be preferred in many patients when prolonged treatment is needed because of reduced nephrotoxicity compared with conventional amphotericin B deoxycholate.

Azole Therapy

Newer azoles may have activity against Acremonium, although clinical experience is more limited and susceptibility can be variable.

Potential agents include selected triazoles such as:

• Voriconazole

• Posaconazole

The choice should ideally be guided by:

• Site of infection

• Susceptibility testing

• Clinical response

• Drug interactions

• Renal and hepatic function

Surgical Management

Surgical treatment is often important when infection is localized and accessible.

Possible interventions include:

• Drainage of abscesses

• Debridement of infected tissue

• Resection of infected bone

• Removal of infected prosthetic material

• Valve surgery for fungal endocarditis

• Ophthalmologic surgery for severe ocular infection

Antifungal therapy alone may be insufficient when devitalized tissue or infected foreign material remains in place.

General Management Principles

Successful treatment depends on three main factors:

• Appropriate antifungal therapy

• Source control

• Reversal of immunosuppression when possible

Recovery from neutropenia can significantly improve outcomes in patients with invasive mold infection.

Prognosis

Localized superficial infections usually have a better prognosis than invasive disease.

The outcome is worse in patients with:

• Persistent neutropenia

• Disseminated infection

• CNS involvement

• Prosthetic valve infection

• Delayed diagnosis

• Inability to remove infected foreign material

High-Yield Clinical Pattern

Neutropenic patient

• ●

Persistent fever

• ●

Pulmonary or disseminated mold infection

• ●

Slow-growing septate hyaline fungus

→ Consider Acremonium among the differential diagnoses.

High-Yield Ocular Pattern

Contact lens user or patient with corneal trauma

• ●

Painful keratitis

• ●

Filamentous fungus isolated from corneal scraping

→ Consider Acremonium as a possible cause.

Exam Essentials

Former name:

→ Cephalosporium

Organism type:

→ Filamentous mold

Hyphae:

→ Septate and hyaline

Growth:

→ Generally slower than Fusarium

Common environmental sources:

→ Soil, sewage, insects, and plant-associated environments

Important species:

→ A. kiliense among the historically important pathogenic species

Common localized infections:

→ Mycetoma, onychomycosis, and keratitis

Important invasive infections:

→ Pulmonary disease, CNS infection, endocarditis, osteomyelitis, endophthalmitis, and disseminated infection

Major risk factor for dissemination:

→ Profound neutropenia

Diagnosis:

→ Culture, supported by histopathology

Traditional major antifungal:

→ Amphotericin B

Possible alternative agents:

→ Selected newer azoles based on susceptibility

Important additional therapy:

→ Surgical drainage, debridement, or resection when feasible