Amphotericin B (Amb)

AmB is the broadest-spectrum antifungal agent but has significant toxicities, including nephrotoxicity, fever, chills, and nausea.

• AmB has fungicidal activity and is available only for parenteral administration.
• Lipid formulations lack nephrotoxicity and infusion reactions; whether there is a clinically significant difference in efficacy between the deoxycholate and lipid formulations remains controversial.

Azoles

The azoles' mechanism of action is inhibition of ergosterol synthesis in the fungal cell wall, resulting in fungistatic activity. Azoles cause little or no nephrotoxicity and are available in oral preparations.

• Fluconazole: Fluconazole is available in both oral and IV formulations, has a long half-life, and penetrates into most body fluids, including ocular fluids and CSF.
  • Toxicity is minimal but includes (usually reversible) hepatotoxicity and-at high doses-alopecia, muscle weakness, dry mouth, and metallic taste.
  • Fluconazole is useful for coccidioidal and cryptococcal meningitis and for candidemia, but it is notably ineffective against aspergillosis or mucormycosis.
  • This drug is effective as fungal prophylaxis in bone-marrow and high-risk liver transplant recipients.
• Voriconazole: Available in oral and IV formulations, voriconazole is considered the first-line agent against Aspergillus and has a broader spectrum than fluconazole against Candida species (including C. glabrata and C. krusei). It is also active against Scedosporium, Fusarium, and Coccidioides.
  • Disadvantages of voriconazole (compared to fluconazole) include multiple drug interactions, hepatotoxicity, skin rashes (including photosensitivity), visual disturbances, and the need to monitor drug levels.
  • As it is metabolized completely by the liver, dose adjustments are required in pts with liver failure. Dose adjustments for renal insufficiency are not required, but-given the presence of cyclodextrin-the parenteral formulation should be avoided in pts with severe renal insufficiency.
• Itraconazole: Available in oral and IV formulations, itraconazole is the drug of choice for mild to moderate blastomycosis and histoplasmosis. It is approved by the FDA for use in febrile neutropenic pts, although most centers use other azoles for prophylaxis and treatment in these pts. Disadvantages of itraconazole include its poor penetration into CSF, the use of cyclodextrin in both the oral suspension and the IV preparation, the variable absorption of the drug in capsule form, and the need for monitoring of blood levels in pts taking capsules for disseminated mycoses.
• Posaconazole: Approved for prophylaxis of aspergillosis and candidiasis in high-risk immunocompromised pts, posaconazole is also effective against fluconazole-resistant Candida isolates and may be useful as salvage therapy for some other fungal infections.
• Isavuconazole: Approved for aspergillosis and mucormycosis, although clinical experience is still somewhat limited.

Echinocandins

The echinocandins, including caspofungin, anidulafungin, and micafungin, act by inhibiting the β-1,3-glucan synthase that is necessary for fungal cell wall synthesis. These agents are considered fungicidal for Candida and fungistatic for Aspergillus.

• Among the safest antifungal agents, echinocandins offer broad-spectrum fungicidal activity against all Candida species, and caspofungin has been efficacious as salvage therapy for aspergillosis.
• If anidulafungin or micafungin is used in combination with cyclosporine, no dose adjustment is needed for either drug.

Flucytosine

Flucytosine has excellent CSF penetration, but development of resistance has led to its almost always being used in combination with AmB (e.g., for cryptococcal meningitis). Adverse effects include bone marrow suppression.

Griseofulvin and Terbinafine

Griseofulvin is used primarily for ringworm infection. Terbinafine is used for onychomycosis and ringworm and is as effective as itraconazole.

Topical Agents

Many drug classes are used for topical treatment of common fungal skin infections: azoles (e.g., clotrimazole, miconazole), polyene agents (e.g., nystatin), and other classes (e.g., ciclopirox olamine, terbinafine).

Microbiology

• P. jirovecii infects humans, whereas P. carinii-the original species described-infects rats.
• Developmental stages include the small trophic form, the cyst, and the intermediate precyst stage.

Epidemiology

• Pneumocystis is found worldwide, and most people are exposed to the organism early in life.
• Infections resulting from environmental sources and person-to-person transmission have been demonstrated; the role of airborne transmission is unclear.
• Defects in cellular and humoral immunity (e.g., due to HIV infection, malignancy, transplantation, immunosuppressive medications) predispose to PCP. The incidence among HIV-infected pts is inversely related to the CD4⁺ T cell count: ≥80% of cases occur at counts of <200 cells/µL, and most cases develop at counts of <100/µL.

Pathogenesis

• The organisms are inhaled into the alveolar space, where they proliferate, provoking a mononuclear cell response. Alveoli become filled with and are damaged by proteinaceous material, with consequently increased alveolar-capillary injury and surfactant abnormalities.
• On histology, alveoli are seen to be filled with foamy, vacuolated exudates.

Clinical Manifestations

• Pts develop dyspnea, fever, and nonproductive cough.
  • HIV-infected pts often have an indolent course that presents as mild exercise intolerance or chest tightness without fever or cough. Over days to months, these pts develop the more typical symptoms of PCP.
  • Some pts with HIV infection and most pts with other types of immunosuppression have more acute disease that progresses over a few days to respiratory failure.
• Physical examination findings are nonspecific and invariably include hypoxemia. Pts may initially have a normal chest examination but later, without treatment, develop diffuse rales and signs of consolidation.
• Serum levels of LDH may be elevated because of pulmonary damage, but this finding is neither sensitive nor specific.
• CXR classically reveals bilateral diffuse interstitial infiltrates that are perihilar and symmetrical, although this finding is not specific for PCP. Cysts and pneumothoraces are common CXR findings, especially in HIV-infected pts. Chest CT shows diffuse ground-glass opacities in virtually all pts with PCP, and a normal chest CT essentially rules out the diagnosis.
• Rare cases of disseminated infection have been described, generally involving lymph nodes, spleen, and liver.

Diagnosis

• Histopathologic staining makes the definitive diagnosis.
  • Cell-wall stains (e.g., methenamine silver) are used for Pneumocystis cysts and Wright-Giemsa stains for the nuclei of all developmental stages.
  • Immunofluorescence with monoclonal antibodies increases diagnostic sensitivity.
• The demonstration of organisms in bronchoalveolar lavage fluid is almost 100% sensitive and specific for PCP in immunocompromised pts.
• While detection of organisms in expectorated sputum or throat swabs has very low sensitivity, detection in an induced sputum sample can be-depending on the experience of the center conducting the test-highly sensitive (up to 90%) and specific.
• DNA amplification by PCR is most sensitive but may not distinguish colonization from infection.

Prognosis

• Factors that influence mortality risk include advanced age, high degree of immunosuppression, preexisting lung disease, low serum albumin level, need for mechanical ventilation, and development of a pneumothorax.

Prevention

• The most effective method for preventing PCP is to eliminate the cause of immunosuppression (e.g., withdraw immunosuppressive therapy, treat HIV infection).
• Prophylaxis is indicated for HIV-infected pts with CD4+ T cell counts of <200/µL. Guidelines for other compromised hosts are less clear, but prophylaxis should be considered for pts receiving >20 mg of prednisone daily (or its equivalent) for ≥30 days.
• For prophylactic regimens, see Table 108-2 Prophylaxis of Pneumocystosis . TMP-SMX is the drug of choice.

Microbiology and Epidemiology

Candida is a small, thin-walled, ovoid yeast that reproduces by budding and occurs in three forms in tissue: blastospores, pseudohyphae, and hyphae.

• Candida is ubiquitous in nature and inhabits the GI tract, the female genital tract, and the skin. Dissemination probably results from fungal entry into the bloodstream from mucosal surfaces after the organisms have multiplied to large numbers as a result of bacterial suppression by antibacterial drugs.
• C. albicans is common, but non-albicans species (e.g., C. glabrata, C. krusei, C. parapsilosis, C. tropicalis) now cause ∼50% of all cases of candidemia and disseminated candidiasis.
  • Candida spp. represent the fourth most common blood-culture isolate from hospitalized pts in the United States.
  • Pts with a compromised immune system, pts with indwelling catheters, pts with severe burns, and neonates of low birth weight are at risk for hematogenous dissemination.

Clinical Manifestations

The severity of candidal infections ranges from mild to life-threatening, with deep organ infections being at the more severe end of the spectrum.

• Mucocutaneous candidiasis
  • - Thrush is characterized by white, adherent, painless, discrete or confluent patches in the mouth, on the tongue, or in the esophagus.
  • - Vulvovaginal candidiasis presents as pruritus, pain, and a vaginal discharge that may contain whitish “curds.”
  • Other cutaneous infections include paronychia, balanitis, and intertrigo (erythematous irritation with pustules in skin folds).
  • - Chronic mucocutaneous candidiasis is a heterogeneous infection of hair, nails, skin, and mucous membranes that persists despite therapy and is associated with a dysfunctional immune system.
• Deeply invasive candidiasis: These infections are most commonly due to hematogenous seeding of organs during candidemia, but they can also be due to contiguous spread of organisms after disruption of normal anatomic barriers (e.g., kidney infection associated with an indwelling urinary catheter).
  • Nearly any organ can be infected, but the brain, chorioretina, heart, and kidneys are most commonly involved. Except in neutropenic pts, the liver and spleen are less often infected.
  • Skin involvement manifests as macronodular lesions.
  • Chorioretinal or skin involvement predicts a high probability of abscess formation in deep organs from generalized hematogenous seeding.

Diagnosis

The most challenging aspect of diagnosis is determining which pts have hematogenously disseminated disease; recovery of Candida from sputum, urine, or peritoneal catheters may reflect colonization rather than deep infection.

• The diagnosis of Candida infection is established by visualization of pseudohyphae or hyphae in the presence of inflammation in appropriate clinical samples.
• The β-glucan test has a negative predictive value of ∼90% and can help exclude disseminated disease.

Prevention

Allogeneic stem cell and high-risk liver transplant recipients typically receive prophylaxis with fluconazole (400 mg/d). Some centers also use antifungal prophylaxis for neutropenic pts.

Microbiology and Epidemiology

Aspergillus, a mold with septate hyphae branching at 45° angles, has vast numbers of conidia (spores). It has a worldwide distribution and typically grows in decomposing plant materials and in bedding. A. fumigatus is responsible for most cases of invasive aspergillosis, almost all cases of chronic aspergillosis, and most allergic syndromes.

• Inhalation is common; only intense exposures cause disease in healthy, immunocompetent individuals.
• The primary risk factors for invasive aspergillosis are profound neutropenia, glucocorticoid use, therapy with immune modulators (e.g., TNF-α inhibitors, ibrutinib), severe liver disease, influenza infection, and extracorporeal membrane oxygenation therapy.
• Pts with chronic pulmonary aspergillosis have a wide spectrum of underlying pulmonary diseases (e.g., tuberculosis, sarcoidosis).

Clinical Manifestations

More than 80% of invasive disease cases involve the lungs; in pts who are significantly immunocompromised, virtually any organ can be affected.

• Invasive pulmonary aspergillosis: Pts can be asymptomatic or can present with fever, cough, chest discomfort, hemoptysis, and shortness of breath.
  • Acute and subacute forms have courses of ≤1 month and 1-3 months, respectively.
  • Early diagnosis requires a high index of suspicion, screening for circulating antigen (in leukemia), and urgent CT of the chest.
• Invasive sinusitis: Pts have fever, nasal or facial discomfort, and nasal discharge. The sinuses are involved in 5-10% of cases of invasive aspergillosis; sinus involvement is especially likely in leukemic pts and hematopoietic stem cell transplant recipients.
• Bronchitis: Pts present with recurrent chest infections that only partially improve with antibiotics, significant dyspnea, and cough productive of thick sputum plugs. Pts typically have bronchiectasis or cystic fibrosis but are not significantly immunocompromised.
• Disseminated aspergillosis: Aspergillus disseminates from lung to brain, skin, thyroid, bone, and other organs, after which pts develop skin lesions and deteriorate clinically over 1-3 days, with fever and signs of mild sepsis. Blood cultures are usually negative.
  • Cerebral aspergillosis: Single or multiple lesions, hemorrhagic infarction, and cerebral abscess are common. The presentation can be acute or subacute, with mood changes, focal signs, seizures, and a decline in mental status. MRI is the most useful investigation.
  • - Cutaneous aspergillosis: Dissemination of Aspergillus occasionally results in cutaneous features, usually an erythematous or purplish nontender area that develops into a necrotic eschar.
• Chronic pulmonary aspergillosis: Pts develop one or more cavities that expand over months or years, with pulmonary symptoms (including hemoptysis), fatigue, and weight loss. Pericavitary infiltrates and multiple cavities are typical, and Aspergillus nodules may be present. Without treatment, pulmonary fibrosis can develop.
  • - Aspergillomas (fungal balls) are a late manifestation of chronic pulmonary aspergillosis. Pt presentations range from no symptoms to significant complications (e.g., hemoptysis). Roughly 10% of fungal balls resolve spontaneously.
• Chronic sinusitis: Pts develop one of three presentations: a fungal ball in the maxillary sinus; chronic invasive sinusitis that is slowly destructive; or chronic granulomatous sinusitis, which is most common in the Middle East and India and is often caused by A. flavus.
• Allergic bronchopulmonary aspergillosis (ABPA): A hypersensitivity reaction leads to bronchial plugging, coughing fits, and dyspnea, primarily affecting asthmatics and pts with cystic fibrosis. Total IgE levels are usually >1000 IU/mL.

Diagnosis

Culture, molecular testing, antigen detection, and histopathology usually confirm the diagnosis; ∼40% of cases of invasive aspergillosis are diagnosed only at autopsy.

• Culture may be falsely positive (e.g., in pts with airway colonization) or falsely negative; only 10-30% of pts with invasive Aspergillus have a positive culture at any time.
• Galactomannan antigen testing of serum from high-risk pts is best done prospectively, as positive results precede clinical disease; false-positive results can occur (in association, for example, with certain β-lactam/β-lactamase inhibitor antibiotic combinations).
• A halo sign on high-resolution thoracic CT scan (a localized ground-glass appearance representing hemorrhagic infarction surrounding a nodule) suggests the diagnosis.

Outcome

• Invasive aspergillosis is curable if immune reconstitution occurs, whereas allergic and chronic forms are not. The overall mortality rate is 30-70% with treatment, but the disease is uniformly fatal without therapy.

Microbiology and Epidemiology

Cryptococcus is a yeast-like fungus. C. neoformans and C. gattii are pathogenic for humans and can cause cryptococcosis; most clinical laboratories do not routinely distinguish between these species.

• Worldwide, there are ∼1 million cases of cryptococcosis, with >600,000 deaths annually. Most cases are in pts with AIDS.
• Cryptococcosis due to C. neoformans is rare in the absence of impaired immunity; in contrast, C. gattii-related disease often occurs in immunocompetent pts.
• C. neoformans is found in soil contaminated with pigeon droppings, whereas C. gattii is associated with eucalyptus trees. Most cases are acquired via inhalation, which results in pulmonary infection.

Clinical Manifestations

The clinical manifestations of cryptococcosis reflect the site of fungal infection, usually involving the CNS and/or the lungs.

• CNS involvement most commonly presents as chronic meningoencephalitis, with headache, fever, lethargy, sensory and memory deficits, cranial nerve paresis, visual deficits, and meningismus (absent in some cases) lasting for weeks.
• Pulmonary cryptococcosis is generally asymptomatic but can present as cough, increased sputum production, and chest pain. Cryptococcomas are granulomatous pulmonary masses associated with C. gattii infections.
• Skin lesions are common in pts with disseminated cryptococcosis and can be highly variable, including papules, plaques, purpura, vesicles, tumor-like lesions, and rashes.

Diagnosis

Diagnosis requires the demonstration of C. neoformans in normally sterile tissue (e.g., positive cultures of CSF or blood).

• India ink smear of CSF is a useful rapid diagnostic technique but may yield negative results in pts with a low fungal burden.
• Cryptococcal antigen testing of CSF and/or serum provides strong presumptive evidence for cryptococcosis; such testing often yields negative results in pulmonary cryptococcosis and is of limited utility in monitoring response to therapy.

Microbiology and Epidemiology

Mucormycosis is caused by fungi of the order Mucorales, most commonly Rhizopus oryzae and R. delemar; despite the name of the disease, Mucor species are only rarely the cause.

• Mucorales have characteristic wide (≥6- to 30-µm), thick-walled, ribbon-like, aseptate hyphal elements that branch at right angles.
• These ubiquitous environmental fungi primarily affect pts with diabetes, solid organ or hematopoietic stem cell transplants, prolonged neutropenia, malignancy, and deferoxamine treatment for iron overload syndromes.

Clinical Manifestations

Mucormycosis is highly invasive and relentlessly progressive, with a mortality rate of >40%. The disease is usually categorized by the anatomic site involved.

• Rhino-orbital-cerebral mucormycosis: In this, the most common form of the disease, pts initially have nonspecific symptoms that include eye or facial pain and facial numbness followed by the onset of conjunctival suffusion, blurry vision, and soft tissue swelling.
  • If untreated, the infection can spread from the ethmoid sinus to the orbit (affecting extraocular muscle function and being associated with proptosis and chemosis) and then to the brain (frontal lobe or cavernous sinus).
  • The visual appearance of infected tissue may progress from normal to erythematous to violaceous to a black necrotic eschar.
• Pulmonary mucormycosis: In this second most common manifestation, pts typically present with fever, dyspnea, cough, and chest pain. Angioinvasion results in necrosis, cavitation, and/or hemoptysis. Differentiation from aspergillosis is critical as treatment regimens differ; the presence of ≥10 pulmonary nodules, pleural effusion, or concomitant sinusitis makes mucormycosis more likely.
• Cutaneous mucormycosis: Caused by external implantation or hematogenous dissemination, necrotizing fasciitis due to mucormycosis has a mortality rate of ∼80%.
• Gastrointestinal mucormycosis: Classically a disease of premature infants, GI mucormycosis is increasing in incidence among immunocompromised adults. Adult pts present with GI bleeding and fungating masses in the stomach, with possible progression to visceral perforation.
• Hematogenously disseminated mucormycosis: Infection can disseminate from any primary site of infection to any organ (most commonly the brain), and widely disseminated disease has a mortality rate of >90%.

Diagnosis

Although definitive diagnosis requires a positive culture from a sterile site, a positive culture from a nonsterile site (e.g., sputum or bronchoalveolar lavage [BAL] fluid) or the detection of Mucorales on the surface of histopathology samples from a pt with a consistent clinical history should prompt treatment pending confirmation of the diagnosis.

• The fact that only ∼50% of pts have positive cultures is due, in part, to the organisms' being killed by the tissue homogenization required for preparation of culture.
• The laboratory should be notified that mucormycosis is being considered so that tissue sections instead of tissue homogenates can be cultured.

Microbiology and Epidemiology

Histoplasma capsulatum, a dimorphic fungus, causes histoplasmosis.

• Mycelia are infectious and have microconidial and macroconidial forms. Microconidia are inhaled, reach the alveoli, and are transformed into yeasts with occasional narrow budding. A granulomatous reaction results; in pts with impaired cellular immunity, infection may disseminate.
• Histoplasmosis is the most prevalent endemic mycosis in North America and is also found in Central and South America, Africa, and Asia. In the United States, histoplasmosis is endemic in the Ohio and Mississippi river valleys.
• The fungus is found in soil, particularly that enriched by droppings of birds and bats.

Clinical Manifestations

Depending on the intensity of exposure, the immune status of the exposed individual, and the underlying lung architecture of the host, disease can range from asymptomatic to life-threatening.

• Immunocompetent pts usually have asymptomatic or mild and self-limited disease.
  • Approximately 1-4 weeks after exposure, some pts develop a flu-like illness with fever, chills, sweats, headache, myalgia, anorexia, cough, dyspnea, and chest pain; 5-10% of pts with acute histoplasmosis develop arthralgia or arthritis, often associated with erythema nodosum.
  • Hilar or mediastinal lymphadenopathy may occur and can cause vascular or tracheoesophageal compression.
• Immunocompromised pts, who are more likely to develop progressive disseminated histoplasmosis (PDH), account for ∼70% of cases.
  • The clinical spectrum ranges from a rapidly fatal course with diffuse interstitial or reticulonodular lung infiltrates, shock, and multiorgan failure to a subacute course with focal organ involvement, hepatosplenomegaly, thrombocytopenia, fever, and weight loss.
  • Meningitis, oral mucosal ulcerations, GI ulcerations, and adrenal insufficiency can occur.
• Chronic cavitary histoplasmosis most often affects smokers with structural lung disease (e.g., emphysema) and presents as productive cough, dyspnea, low-grade fever, night sweats, and weight loss.

Diagnosis

Fungal culture remains the gold standard (Table 108-4 Recommendations for the Diagnosis and Treatment of Histoplasmosis ), but cultures are often negative in less severe cases and may take up to 1 month to become positive.

• In PDH, the culture yield is highest for BAL fluid, bone marrow aspirate, and blood; cultures of sputum or bronchial washings are usually positive in chronic pulmonary histoplasmosis.
• Fungal stains of cytopathology or biopsy materials may be helpful in diagnosing PDH.
• Histoplasma antigen assay of body fluids (e.g., blood, urine, CSF, BAL fluid) is useful in diagnosing PDH or acute disease and in monitoring the response to treatment.
• Serology can be helpful in diagnosis but requires ≥1 month for antibody production.

Microbiology and Epidemiology

Coccidioidomycosis is caused by the two species of the dimorphic soil-dwelling fungus Coccidioides: C. immitis and C. posadasii. These organisms exist as branching, filamentous molds.

• Coccidioidomycosis is confined to the Western Hemisphere between the latitudes of 40°N and 40°S. The disease is highly endemic in California, Arizona, and other areas of the southwestern United States, with ∼43 cases per 100,000 residents in 2011; northern Mexico and localized regions in Central and South America also account for cases of infection.
• Direct exposure to soil harboring Coccidioides increases risk, but infection, which results from inhalation of airborne arthroconidia, can occur without overt soil exposure and may be related to other climatic factors (e.g., periods of dryness after rainy seasons).

Clinical Manifestations

Approximately 60% of infected pts are asymptomatic; the remaining 40% have primarily pulmonary disease characterized by fever, cough, and pleuritic chest pain.

• Primary pulmonary infection is sometimes associated with erythema nodosum, erythema multiforme, arthralgias, and arthritis.
  • A history of night sweats, profound fatigue, eosinophilia, and hilar or mediastinal lymphadenopathy suggests the disease.
  • Pneumonic complications include pulmonary nodules (resembling pulmonary malignancies) and pulmonary cavities (a thin-walled lesion in a bronchus that is associated with cough, hemoptysis, and pleuritic chest pain).
• Disseminated infection affects <1% of infected pts, most commonly pts with depressed cellular immunity and pregnant women.
  • Common sites for dissemination include bone, skin, joint, soft tissue, and meninges.
  • Pts with meningitis present with persistent headache, lethargy, confusion, mild to moderate nuchal rigidity, and CSF with lymphocytic pleocytosis and profound hypoglycorrhachia. The mortality rate is ∼100% without treatment.

Diagnosis

Clinical findings that suggest coccidioidomycosis include eosinophilia, hilar or mediastinal adenopathy on radiographic imaging, marked fatigue, and failure to improve with antibiotic therapy. Serology and culture are the primary means of diagnosis. The laboratory should be alerted about the possible diagnosis to avoid exposure.

• Tube-precipitin (TP) and complement-fixation (CF) assays, immunodiffusion, and an enzyme immunoassay (EIA) are available to detect IgM and IgG antibodies.
  • TP antibody does not gauge disease progression and is not found in CSF.
  • Rising CF titers in serum are associated with clinical progression, and CF antibody in CSF indicates meningitis.
  • EIA frequently yields false-positive results.
• Examination of sputum or other respiratory fluids after Papanicolaou, Gomori methenamine silver, or calcofluor white staining reveals spherules in many pts with pulmonary disease.

Microbiology and Epidemiology

Blastomyces dermatitidis is a dimorphic fungus that is found in the southeastern and south-central states bordering the Mississippi and Ohio river basins, in areas of the United States and Canada bordering the Great Lakes and the St. Lawrence River, and sporadically in Africa, the Middle East, and India. Infection is caused by inhalation of Blastomyces from moist soil rich in organic debris.

Clinical Manifestations

Acute pulmonary infection can present as abrupt-onset fever, chills, pleuritic chest pain, myalgias, and arthralgias. However, most pts with pulmonary blastomycosis have chronic indolent pneumonia with fever, weight loss, productive cough, and hemoptysis. Skin disease is common and can present as verrucous (more common) or ulcerative lesions. Blastomycosis can include osteomyelitis in one-fourth of infections and CNS disease in ∼40% of pts with AIDS.

Diagnosis

Smears of clinical samples or cultures of sputum, bronchial washings, pus, or tissue are required for diagnosis. Antigen detection in urine and serum may help diagnose infection and monitor pts during therapy.

Microbiology and Epidemiology

Sporothrix schenckii is a dimorphic fungus found worldwide in soil, on plants, and on animals. Infection, which results from inoculation of the organism into the skin, is most common among people who participate in landscaping, gardening, or tree farming.

Clinical Manifestations

Lymphocutaneous sporotrichosis involves secondary lesions (papules that are not very painful and often ulcerate) developing along lymphatic channels proximally from the initial site of inoculation. Other presentations include a fixed lesion (verrucous or ulcerative) at the initial site of inoculation without lymphatic spread, osteoarticular disease (chronic synovitis or septic arthritis in alcoholics), pulmonary disease (most common among pts with chronic obstructive pulmonary disease), and disseminated disease (numerous skin lesions with occasional spread to visceral organs in immunocompromised pts).

Diagnosis

Culture of material from a skin lesion or histopathologic examination of a skin biopsy sample can confirm the diagnosis.