Opportunistic Mycoses

Guest · **posting in usmle forum about Microbiology**

Opportunistic mycoses are infections due to fungi with low inherent virulence which means that these pathogens constitute an almost limitless number of fungi. These organisms are common in all environments.

The disease equation:

Number of organisms x Virulence = Disease
Host resistance

is tilted in favor of "disease" because resistance is lowered when the host is immunocompromised. In fact, for the immunocompromised host, there is no such thing as a non-pathogenic fungus.

The fungi most frequently isolated from immunocompromised patients are saprophytic (i.e. from the environment) or endogenous (a commensal). The most common species are Candida species, Aspergillus, and zygomycetes.

The upward trend in the diagnoses of opportunistic mycoses reflects increasing clinical awareness by physicians, improved clinical diagnostic procedures and better laboratory identification techniques. Another important factor contributing to the increasing incidence of infections by fungi that have not been previously known to be pathogenic has been the rise in the number of immunocompromised patients who are susceptible hosts for the most uncommon agents. Patients with primary immunodeficiencies are susceptible to mycotic infections particularly when cell-mediated immunity is compromised. In addition, several types of secondary immunodeficiencies may be associated with an increased frequency of fungal infections.

When a fungus is isolated from an immunocompromised patient, the attending physician has to distinguish between:

Colonization (which is of no major concern)

Transient fungemia (often involving C. albicans)

Systemic infection.

A great deal of clinical judgment is required to reach these conclusions, which imply important therapeutic decisions.

The diagnosis of opportunistic infections requires a high index of suspicion. Without this curiosity, the clinician may not consider mycotic infections in the compromised patient because:

Patients present with atypical signs and symptoms

The etiological agent may be considered a saprophyte or contaminant

The systemic mycoses may occur outside the known endemic area

Causes of immunodeficiency commonly encountered are:

Malignancies. (Leukemias, lymphomas, Hodgkin's Disease). In one study of cancer patients, fungal septicemia and pneumonias accounted for almost a third of deaths.

Drug therapies. Anti-neoplastic substances, steroids, immunosuppressive drugs.

Antibiotics. Over-use or inappropriate use of antibiotics can also contribute to the development of fungal infections by altering the normal flora of the host and facilitating fungal overgrowth or by selecting for resistant organisms.

Therapeutic procedures can predispose for fungal infections:

Solid Organ and Bone Marrow transplantation

Open heart surgery

Indwelling catheters (urinary, I.V. drugs or parenteral hyperalimentation). In cases of fungemia, the contaminated catheter must be removed before starting anti-fungal therapy.

Artificial heart valves can be colonized by a variety of infectious agents, including Candida species. In a case of Candida infection of an artificial heart valve, antifungal treatment is only efficient if the infected valve is replaced.

Radiation therapy.

Other factors associated with increased frequency of mycotic infections are:

Severe burns

Diabetes

Tuberculosis

I.V. drug use

AIDS. Virtually all AIDS patients will have a fungal infection sometime during the course of disease.

Certain fungi may be frequently associated with some of the predisposing factors listed above. However, any one of the ubiquitous saprophytes (most of which do not cause disease in immunocompetent hosts) as well as occasional pathogens may cause disease in these patients.

Biofilm Formation

It has long been recognized that in patients with a microbial infection, any artificial device such as an indwelling catheter or prosthetic valve, must be removed prior to initiating antibiotic therapy. The foreign body will act as a nidus, seeding the infection if it remains present. The exact mechanism is not clear. A biofilm is a microcolony of organisms which adhere to a surface (catheter, implant, or dead tissue) and which resist removal by fluid movement and have a decreased susceptibility to antimicrobials. This biofilm phenomenon, which occurs on the rocks in a stream, was first recognized as a public health problem in water pipes and was regarded as a source of coliform contamination of drinking water. Recent work in clinical microbiology has shown that these organisms develop a resistance to therapy because they are contained in a matrix which acts like a tissue to and becomes a barrier to antibodies and antimicrobial agents.

CLINICAL PRESENTATION

In immunosuppressed patients, common fungal infections may have an unusual presentation because of:

1. Atypical signs and lesions.

Malassezia furfur usually causes a rather benign and self-limited disease in normal hosts (Tinea versicolor), but in immunocompromised patients may show a rash with disseminated disease and sepsis. This organism requires long-chain fatty acids for growth. Patients receiving parenteral fat emulsions for nutrition become a walking petri plate.

2. Unusual Organ affinity.

Candida may invade liver, heart valves; Oral thrush occurs in people who are relatively immunocompetent while esophageal candidiasis occurs in those patients who are immunologically compromised. Cryptococcus may cause pulmonary and cutaneous infections.

3. Infections with systemic dimorphic fungi occurring outside endemic areas. These factors complicate the diagnosis and management of these diseases.

4. Unusual Histopathology.

Even the inflammatory reaction may be different in biopsy specimens. The normal host reaction to fungal invasion is usually pyogenic or granulomatous. In the immunodeficient host, the reaction is necrotic.

Some examples of variations from standard fungal clinical presentation, diagnosis and treatment.

Cryptococcosis

Studies show that from 10 % to 30 % of AIDS patients have cryptococcal meningitis and they will require maintenance therapy with fluconazole for the remainder of their life. Fluconazole penetrates the cerebro-spinal fluid

Mortality: Without treatment 100%
With treatment 20%

Relapse : Non-AIDS patients 15-20%
AIDS patients 50%

With relapse there is 60% mortality.

Sporotrichosis

Co-infection with other fungi is frequent

Coccidioidomycosis

Mycelial forms seen in tissue. Occurs in patients outside the endemic area. Patients require fluconazole or itraconazole maintenance therapy.

Histoplasmosis

All cases are disseminated.
Relapse rate is > 50% and the infection is rapidly fatal in 10% of patients. It occurs in patients outside the endemic area and they require fluconazole or itraconazole maintenance therapy

Blastomycosis

More frequently disseminated. All patients have done very poorly.

There has been one report on 15 cases of blastomycosis in AIDS patients. Six patients (40%) had CNS involvement. Usually CNS disease only occurs in 3-10% of the patients.

Aspergillosis

Mortality: With amphotericin B 72%
Without amphotericin B 90%

Penicillium marneffei

This is a dimorphic fungus that produces a red pigment and reproduces by fission. It requires amphotericin B therapy and oral itraconazole maintenance.

Pneumocystis carinii

This was formerly thought to be a protozoan. Presently it is believed to be a fungus.