2IntroductionPrimary or “pathogenic” fungi that can cause disease in both healthy and immunocompromised individualsHistoplasmosisCoccidioidomycosiscryptococcosisBlastomycosis,paracoccidioidomycosis,sporotrichosis,
3Introduction Fungi found only in immunocompromised host such as Candida albicans,Aspergillus spp.,Trichosporon,Torulopsis(Candida) glabrata, Fusarium, Alternaria, and Mucor
4Factors that increase the risk of Fungal infections Organ and bone marrow transplantation,Cytotoxic chemotherapy,The widespread use of indwelling IV cathetersThe increased use of potent, broad-spectrum antimicrobial agents
5HISTOPLASMOSISHistoplasmosis is caused by inhalation of dust-borne microconidia of the dimorphic fungus Histoplasma capsulatum.In the United States, most disease is localized along the Ohio and Mississippi river valleys.
6TreatmentAsymptomatic or mildly ill patients and patients with sarcoid-like disease generally do not benefit from antifungal therapy.Therapy may be helpful in symptomatic patients whose conditions have not improved during the first month of infection.
7TreatmentPatients with mild, self-limited disease, chronic disseminated disease, or chronic pulmonary histoplasmosis who have no underlying immunosuppression can usually be treated with either oral ketoconazole or IV amphotericin B.
8Traetment in AIDs Patients Intensive 12-week primary (induction and consolidation therapy)Amphotericin B should be administered in patients who require hospitalization.Itraconazole 200 mg twice daily may be used to complete a 12- week course or for a full 12-week course in patients who do not require hospitalizationfollowed by lifelong suppressive (maintenance) therapy with itraconazole.
9TreatmentOnce the initial course of therapy for histoplasmosis is completed, lifelong suppressive therapy with oral azoles or amphotericin B (1 to 1.5 mg/kg weekly or biweekly) is recommended, because of the frequent recurrence of infection.Relapse rates in AIDS patients not receiving preventive maintenance are 50% to 90%.
10BlastomycosisNorth American blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis.Pulmonary disease probably occurs by inhalation conidia, which convert to the yeast forms in the lungs.It may be acute or chronic and can mimic infection with tuberculosis, pyogenic bacteria, other fungi, or malignancy.
11BlastomycosisBlastomycosis can disseminate to virtually every other body organ, including skin, bones, and joints, or the genitourinary tract, without any evidence of pulmonary disease.
12Clinical Presentation and Diagnosis Acute pulmonary blastomycosis is generally an asymptomatic or self-limited disease characterized by fever, shaking chills, and a productive, purulent cough, with or without hemoptysis in immunocompetent individuals.Sporadic pulmonary blastomycosis may present as a more chronic or subacute disease, with low-grade fever, night sweats, weight loss, and a productive cough resembling that of tuberculosis rather than bacterial pneumonia.Chronic pulmonary blastomycosis is characterized by fever, malaise, weight loss, night sweats, and cough.
13Diagnosisdirect microscopic visualization of the large, multinucleated yeast with single, broad-based buds in sputum or other respiratory specimens, following digestion of cells and debris with 10% potassium hydroxide.Histopathologic examination of tissue biopsies and culture of secretions should be used to identify B. dermatitidis.
14Treatment All immunocompromised patients and patients with progressive disease or with extrapulmonary disease should be treated with antifungals.
15Treatment ketoconazole Self-limited pulmonary disease, with the hope of preventing late extrapulmonary diseaseItraconazole, 200 to 400 mg/day,non–life-threatening, non-CNS blastomycosisketoconazole, 400 mg/day orally for 6 months)disseminated blastomycosis and those with extrapulmonarydiseaseamphotericin BCNS disease should be treated withAmphotericin BHIV patients
16CryptococcosisCryptococcosis is a noncontagious, systemic mycotic infection caused by the ubiquitous encapsulated soil yeast Cryptococcus neoformans.
17Clinical Presentation Primary cryptococcosis in humans almost always occurs in the lungs.Symptomatic infections are usually manifested by cough, rales, and shortness of breath that generally resolve spontaneously.Disease may remain localized in the lungs or disseminate to other tissues, particularly the CNS, although the skin can also be affected.
18Clinical presentation In the non-AIDS patient, the symptoms of cryptococcal meningitis are nonspecific. Headache, fever, nausea, vomiting, mental status changes, and neck stiffness are generally observed.In AIDS patients, fever and headache are common, but meningismus and photophobia are much less common than in non-AIDS patients.
19Diagnosis latex agglutination. C. India ink smear of CSF and cultured in more than 96% of patients.CSFreveals an elevated opening pressureCSF pleocytosis (usually lymphocytes),leukocytosis,a decreased CSF glucose,an elevated CSF protein,a positive cryptococcal antigen.
20TreatmentFor asymptomatic, immunocompetent persons with isolated pulmonary disease and no evidence of CNS disease, careful observation may be warranted.With symptomatic infection, fluconazole or amphotericin B is warranted.
21Treatment Cryptococcal meningitis amphotericin B with flucytosine for 6 weeksAn alternative is amphotericin B for 2 weeks followed by fluconazole for an additional 8 to 10 weeks.Suppressive therapy with fluconazole 200 mg/day for 6 to 12 months is optional.
22HEMATOGENOUS CANDIDIASIS Hematogenous candidiasis describes the clinical circumstances in which hematogenous seeding to deep organs such as the eye, brain, heart, and kidney occursCandida is generally acquired via the GI tract, although organisms may also enter the bloodstream via indwelling IV catheters.Immunosuppressed Patients are at high risk for invasive fungal infections
23Clinical presentation Three distinct presentations of disseminated C. albicans have been recognized:(1) the acute onset of fever, tachycardia, tachypnea, and occasionally chills or hypotension (similar to bacterial sepsis);(2) intermittent fevers;(3) progressive deterioration with or without fever;(4) hepatosplenic candidiasis manifested only as fever while the patient is neutropenic.
24TreatmentAmphotericin B may be switched to fluconazole (IV or oral) for completion of therapy.Azoles and deoxycholate amphotericin B are similarly effective; however, fewer adverse effects are observed with azoles.Echinocandins are at least as effective as amphotericin B or fluconazole in nonneutropenic adult patients with candidemia.In patients with an intact immune system, removal of all existing central venous catheters should be considered.
25ASPERGILLUS INFECTIONS Of more than 300 species of Aspergillus, three are most commonly pathogenic: A. fumigatus, A. flavus, and A. niger.Aspergillosis is generally acquired by inhalation of airborne conidia that are small enough (2.5 to 3 mm) to reach the alveoli or the paranasal sinuses.Superficial InfectionSuperficial or locally invasive infections of the ear, skin, or appendages can often be managed with topical antifungal therapy.
26Allergic Bronchopulmonary Aspergillosis Allergic manifestations of Aspergillus range in severity from mild asthma to allergic bronchopulmonary aspergillosischaracterized by severe asthma with wheezing, fever, malaise, weight loss, chest pain, and a cough productive of blood-streaked sputum.
27treatment of Allergic Bronchopulmonary Aspergillosis Therapy is aimed at minimizing the quantity of antigenic material released in the tracheobronchial tree.Antifungal therapy is generally not indicated in the management of allergic manifestations of aspergillosis,Itraconazole 200 mg twice daily for 16 weeks resulted in reduced corticosteroid dose and improvement in exercise tolerance and pulmonary function
28AspergillomaIn the nonimmunocompromised host, Aspergillus infections of the sinusesmost commonly occur as saprophytic colonization (aspergillomas, or fungus balls)
29Treatment removal of the aspergilloma. Therapy with glucocorticoids and surgery is generally successful.Although IV amphotericin B is generally not useful in eradicating aspergillomas, intracavitary instillation of amphotericin B has been employed successfully in a limited number of patients.
30Invasive Aspergillosis Patients often present with classic signs and symptoms of acute pulmonary embolus: pleuritic chest pain, fever, hemoptysis, a friction rub, and a wedge-shaped infiltrate on chest radiographs.Demonstration of Aspergillus by repeated culture and microscopic examination of tissue provides the most firm diagnosis.In the immunocompromised host, aspergillosis is characterized by vascular invasion leading to thrombosis, infarction, and necrosis of tissue
31Antifungal therapy should be instituted in any of the following conditions persistent fever or progressive sinusitis unresponsive to antimicrobial therapy;(2) an eschar over the nose, sinuses, or palate;(3) the presence of characteristic radiographic findings, including wedge-shaped infarcts, nodular densities, or new cavitary lesions; or(4) any clinical manifestation suggestive of orbital or cavernous sinus disease or an acute vascular event associated with fever.
32TreatmentVoriconazole is the drug of choice for primary therapy of most patientsamphotericin B second lineThe lipid-based formulations may be preferred as initial therapy in patients with marginal renal function or in patients receiving other nephrotoxic drugs.The optimal duration of treatment is unknown.Caspofungin is indicated for treatment of invasive aspergillosis in patientswho are refractory to or intolerant of other therapies such as amphotericin B.