Lecture 6

A fungal infection that takes advantage of impaired host defenses, disrupted mucosal barriers, or altered microbiota. Classic examples include Candida albicans in patients on broad-spectrum antibiotics or corticosteroids, and Aspergillus in neutropenic patients. Most fungi causing human disease are opportunists rather than true pathogens.

A group of keratinophilic fungi (Trichophyton, Microsporum, and Epidermophyton species) that infect the superficial keratinized layers of skin, hair, and nails. They cause tinea infections and are the most common fungal problem encountered in community pharmacy practice.

The clinical name for a superficial dermatophyte infection, classified by anatomic site: tinea pedis (foot, athlete’s foot), tinea corporis (body, ringworm), tinea capitis (scalp), tinea cruris (groin, jock itch), and tinea unguium (nail, onychomycosis)

Dermatophyte infection of the nail plate, most often caused by Trichophyton rubrum. Topical antifungals generally fail because of poor nail penetration; oral terbinafine is the standard of care, with liver function monitoring.

A subcutaneous mycosis caused by the dimorphic fungus Sporothrix schenckii. Classically acquired by traumatic inoculation from thorns, sphagnum moss, or plant debris (the “rose-gardener’s disease”). After inoculation, the organism tracks up regional lymphatics, producing a chain of nodular lesions.

A pattern of infection in which organisms travel from a primary skin inoculation site along lymphatic channels, producing a linear chain of nodular lesions. The classic example is sporotrichosis tracking up the forearm after a thorn prick.

The most common Candida species causing human disease. A commensal yeast present in 30–50 percent of the oropharyngeal, gastrointestinal, and female genital microbiota. Causes mucocutaneous disease (thrush, vulvovaginitis), cutaneous candidiasis, and invasive disease (candidemia) in immunocompromised and critically ill patients. Responsible for approximately 70 percent of nosocomial fungal infections.

Superficial infection of the tongue, buccal mucosa, and oropharynx by Candida, presenting as white plaques that can be scraped off to reveal erythematous base. Treated with topical nystatin or clotrimazole for mild disease; oral fluconazole for moderate or refractory disease, especially in poorly controlled diabetes.

Bloodstream infection caused by a Candida species. Risk factors include central venous catheters, total parenteral nutrition, broad-spectrum antibiotics, and intensive care unit admission. Empiric therapy is an intravenous echinocandin, with source control (catheter removal or exchange) a critical component of care.

An emerging multidrug-resistant Candida species first identified in 2009. Persists for weeks on environmental surfaces, is frequently misidentified by standard clinical microbiology labs, and is intrinsically resistant to fluconazole with emerging echinocandin resistance. Designated a CDC urgent antimicrobial resistance threat. Echinocandins are first-line; liposomal amphotericin B is second-line.

A fungus that exists in two morphologic forms depending on environment: typically a mold with hyphae in the environment at ambient temperature, and a yeast form inside the human body at 37ºC. The thermal shift from mold to yeast is central to virulence. The endemic dimorphic fungi include Histoplasma, Coccidioides, Blastomyces, and Sporothrix.

Systemic fungal infections with a characteristic geographic distribution tied to specific environmental reservoirs. The three North American endemic mycoses discussed in lecture are histoplasmosis (Ohio/Mississippi River Valleys), coccidioidomycosis (Southwestern United States), and blastomycosis (Great Lakes, Ohio/Mississippi Valley, Southeastern United States). Geography is the primary diagnostic clue.

The most common true systemic fungal pathogen in the United States. A dimorphic fungus whose environmental reservoir is moist soil enriched with bird or bat guano. Causes histoplasmosis after inhalation of spores

The disease caused by Histoplasma capsulatum. Primary infection is pulmonary and often asymptomatic or self-limited. In immunocompromised hosts or with heavy inoculum, it disseminates to the reticuloendothelial system. Treated with itraconazole for mild to moderate disease and amphotericin B followed by itraconazole for severe disease.

A localized collection of macrophages, often with fibrosis, forming in response to persistent antigenic stimulation that the immune system cannot clear. Chest imaging findings of granulomas in a patient with appropriate exposure history raise suspicion for tuberculosis, histoplasmosis, or other chronic granulomatous infections.

The network of phagocytic cells in the liver, spleen, lymph nodes, and bone marrow. Disseminated histoplasmosis characteristically involves this system, producing hepatosplenomegaly, lymphadenopathy, and pancytopenia.

Dimorphic fungi endemic to the arid Southwestern United States (Arizona, California Central Valley, Nevada, New Mexico, Utah). Cause coccidioidomycosis. Incidence is rising with climate change and the endemic range is expanding.

The disease caused by Coccidioides species. Approximately 60 percent of infections are asymptomatic. Symptomatic disease presents as community-acquired pneumonia that fails to respond to standard antibacterial therapy. Can disseminate to skin, bone, and meninges

The airborne infectious spore of Coccidioides, released from environmental mycelia during soil disturbance (dust storms, construction, agriculture). Inhalation of a single arthroconidium is sufficient to cause infection

A severe disseminated form of coccidioidomycosis affecting the central nervous system. Requires lifelong fluconazole therapy because discontinuation is associated with relapse. A defining pharmacy-practice example of chronic antifungal therapy and lifelong CYP450 interaction management.

A dimorphic fungus endemic to the Great Lakes region, the Ohio and Mississippi River Valleys, and the Southeastern United States. The reservoir is moist soil near waterways. Causes blastomycosis.

The disease caused by Blastomyces dermatitidis. Primary infection is pulmonary; the classic extrapulmonary manifestation is verrucous skin lesions. Bone and genitourinary involvement also occur. Treated with itraconazole for mild to moderate disease and amphotericin B for severe or central nervous system disease

An encapsulated yeast with worldwide distribution. Environmental reservoir is soil contaminated with pigeon droppings. Classic opportunist in advanced HIV infection, typically with CD4 counts below 100 cells per cubic millimeter. Causes pulmonary cryptococcosis and cryptococcal meningitis.

A related encapsulated yeast with a more geographically restricted distribution, including the Pacific Northwest of North America. Unlike C. neoformans, it can cause serious disease in apparently healthy, immunocompetent adults. Reportable to public health authorities in Oregon and Washington. Requires a longer induction phase (at least six weeks) than C. neoformans.

Central nervous system infection caused by Cryptococcus neoformans or gattii. Presents with headache, fever, and meningeal signs. Treatment is staged: induction with amphotericin B plus flucytosine, consolidation with high-dose fluconazole, and maintenance with lower-dose fluconazole. Uses three different antifungal drug targets in sequence

A yeast surrounded by a polysaccharide capsule visible on microscopy. Cryptococcus species are the classic example. The capsule is anti-phagocytic and is a major virulence factor; it also provides the basis for the cryptococcal antigen diagnostic test.

A simple negative-stain microscopy technique that visualizes the polysaccharide capsule of Cryptococcus as a clear halo around the yeast cell against a dark background. Used for rapid bedside diagnosis of cryptococcal meningitis from cerebrospinal fluid.

A serologic or cerebrospinal fluid assay that detects the polysaccharide capsular antigen of Cryptococcus. More sensitive than India ink and now the primary diagnostic test for cryptococcal meningitis.

A three-phase treatment strategy used for certain severe infections, including cryptococcal meningitis and invasive dimorphic mycoses. Induction delivers intensive, often combination therapy to rapidly control disease; consolidation continues therapy at reduced intensity once the patient is stable; maintenance provides long- term suppression in patients with ongoing immunosuppression

The most common invasive mold pathogen. Spores are ubiquitous in the environment. Causes invasive disease primarily in neutropenic patients and in those receiving corticosteroids, hematologic malignancy therapy, or solid organ or hematopoietic stem cell transplantation.

Angioinvasive pulmonary infection with Aspergillus in an immunocompromised host. Mortality ranges from 30 to 95 percent depending on the patient population. First-line therapy is voriconazole; isavuconazole is an alternative; amphotericin B is second-line.

A hypersensitivity reaction to Aspergillus antigens in patients with asthma or cystic fibrosis. Distinct from invasive aspergillosis: the fungus is not invading tissue, but the immune response produces eosinophilia, elevated IgE, and bronchiectasis. Treated with corticosteroids and sometimes itraconazole.

A patient with an absolute neutrophil count below 500 cells per cubic millimeter (or expected to drop below that within 48 hours), most commonly as a result of chemotherapy for hematologic malignancy or following hematopoietic stem cell transplantation. The canonical setting for invasive mold infection.

Resistance to medical triazoles in Aspergillus fumigatus caused by environmental exposure to structurally related triazole fungicides used on crops. Because agricultural and medical azoles share the CYP51 target, environmental selection produces resistant fungal spores that patients subsequently inhale. Patients can therefore present with azole-resistant infection without ever having received antifungal therapy. Covered in detail in Lecture 5; revisited here as the leading stewardship concern for Aspergillus.

A lipid formulation of amphotericin B in which the active drug is incorporated into small unilamellar vesicles. Reduces nephrotoxicity and infusion reactions compared with the conventional deoxycholate formulation. Now standard for most systemic amphotericin B indications despite higher cost.

Fungicidal drugs kill the organism; fungistatic drugs inhibit growth and rely on host immune clearance. Amphotericin B is fungicidal. Azoles are generally fungistatic. Echinocandins are fungicidal against Candida but fungistatic against Aspergillus. The distinction matters most in immunocompromised hosts and in deep-seated infections, where cidal therapy is preferred

Physical removal or drainage of the nidus of infection — for example, removal or exchange of a central venous catheter in candidemia, or debridement of infected tissue. Often as important as antimicrobial therapy itself, and sometimes more important, especially for candidemia and other device-associated infections.

The thoughtful selection, dosing, and duration of antifungal therapy to maximize clinical cure while minimizing resistance, toxicity, and cost. More urgent than antibacterial stewardship in some respects because the antifungal pipeline is shallower and cross-resistance (for example, agricultural azole exposure driving medical azole resistance) is an ecological problem without an easy fix