Fungal and Yeast Flashcards

Question

Hepatosplenic candidiasis history and PE

Answer 1

Form of systemic candidiasis with underlying hematologic malignancy and neutropenia Occurs during the recovery phase of a neutropenic episode History & PE: Fever unresponsive to broad-spectrum antimicrobials Right upper quadrant pain Abdominal pain and distension Jaundice (rare) Right upper quadrant tenderness & hepatosplenomegaly (< 40%)

Answer 2

4th most commonly isolated organism in blood cultures Generally considered a nosocomial infection History Several days of fever that is unresponsive to broad-spectrum antimicrobials; frequently the only marker of infection Prolonged intravenous catheterization A history of several key risk factors Possibly associated with multiorgan infection Physical examination Fever Macronodular skin lesions (approximately 10%) Candidal endophthalmitis (approximately 10-28%) Occasionally, septic shock (hypotension, tachycardia, tachypnea)

Answer 3

Frequently associated with multiple deep organ infections or may involve single organ infection Blood cultures are negative in up to 40-60% of patients with disseminated candidiasis History Fever unresponsive to broad-spectrum antimicrobials Negative results from blood culture Physical examination Fever (may be the only symptom) with an unknown source Sepsis and septic shock

Answer 4

Candida endophthalmitis Exogenous (trauma/postoperative) and endogenous (hematogenous, 10-28% with candidemia) Classic lesions are large and off-white, similar to a cotton-ball, with indistinct borders covered by an underlying haze form Renal candidiasis Consequence of candidemia or disseminated candidiasis History includes fever that is unresponsive to broad-spectrum antimicrobials, otherwise asymptomatic lacking renal symptoms CNS infections due to Candida species Rare and difficult to diagnose Exogenous (trauma/postoperative) and endogenous (hematogenous with multiple small abcesses)

Answer 5

Wet mount for hyphae, pseudohyphae, or budding yeast cells Potassium hydroxide smear, Gram stain, or methylene blue is useful for direct demonstration of fungal cells Cultures from affected nails may help identify the etiologic agent responsible for onychomycosis versus other noninfectious causes treatment.

Answer 6

Blood cultures yield positive results in only 50-60% of cases of disseminated infection Urinalysis may be helpful and may show either colonization or renal candidiasis Cultures of nonsterile sites can be considered for initiating antifungal therapy in patients with fever unresponsive to broad-spectrum antimicrobials; interpretation is key Positive blood cultures and cultures from other sterile sites always imply the presence of invasive disease; should always be considered significant and treated Gastrointestinal, respiratory, and urinary tract cultures may not always represent invasive disease, but demonstrate colonization

Answer 7

Synthetic compounds in 2 groups, imidazoles and triazoles Triazoles (fluconazole, itraconazole, econazole, terconazole, butoconazole, and tioconazole) have 3 atoms of nitrogen in the azole ring Imidazoles (miconazole, ketoconazole, and clotrimazole) have 2 nitrogen atoms MOA - inhibition of lanosterol 14-alpha-demethylase, an enzyme required for the synthesis of ergosterol, the main component of fungal cell membranes

Answer 8

Newer - excellent clinical efficacy, low incidence of adverse events, good safety profile & ease of use MOA - inhibit the formation of fungal cell wall Caspofungin, micafungin, and anidulafungin

Answer 9

Broad-spectrum fungicidal agents; MOA - insertion into fungal cytoplasmic membrane, causing increases in permeability; membrane channel activity is increased at lower doses, and pores are formed at higher concentrations Amphotericin B, Amphotericin B, lipid formulations, Nystatin (Mycostatin)

Answer 10

Cause deficiency of ergosterol within the fungal cell wall, causing fungal cell death Terbinafine (Daskil, Lamisil)

Answer 11

Cryptococcus neoformans is an encapsulated yeast > 50 species of Cryptococcus, only primarily pathogenic to humans C neoformans (mostly immunocompromised hosts) found in U.S and temperate regions in pidgin poop C gattii * (mostly immunocompetent hosts) found in the tropics not associated in birds

Answer 12

Inhalation with yeast spores deposited in pulmonary alveoli, Spores must survive the neutral-to-alkaline pH and physiologic concentrations of carbon dioxide before they are phagocytized by alveolar macrophages (glucosylceramide synthase (GCS) is an essential factor in the survival outside alveolar macrophage) Host response to cryptococcal infection includes both cellular and humoral components

Answer 13

7%-15% of patients with AIDS develop cryptococcal infections 1993 CDC 6% of 274,150 patients with AIDS developed cryptococcal disease Patients with AIDS-associated cryptococcal infections now account for 80%-90% of all cases of cryptococcosis 4% mortality rate in patients with cryptococcal disease treated with amphotericin B plus flucytosine; 28% mortality rate in patients treated with other regimens

Answer 14

Variable presentation from asymptomatic saprophytic airway colonization to acute respiratory distress syndrome (e.g. AIDS, organ transplant recipients May present as a slowly progressive mass that may compress thoracic structures such as the vena cava Pulmonary cryptococcosis may present with mild-to-moderate symptoms, including fever, malaise, cough with scant sputum, pleuritic pain, and hemoptysis (rare) Unusual findings include rales or pleural rub Pleural effusions may be present but are uncommon.

Answer 15

Meningitis/meningoencephalitis are the most common manifestations of CNS cryptococcosis Typically subacute or chronic Invariably fatal without appropriate therapy; death may occur from 2 weeks to several years after symptom onset. Clinical presentation and course variable depending of host immune status (e.g. glucocorticoid use, DM, sarcoidosis) Most common symptoms are headache and altered mental status, including personality changes, confusion, lethargy, obtundation, and coma Nausea and vomiting common (associated with increased intracranial pressure) Fever and stiff neck (symptoms of more aggressive inflammatory response) are less common

Answer 16

Cutaneous lesions occur in 10%-15% of cases; papules, pustules, nodules, ulcers, or draining sinuses Umbilicated papules in patients with AIDS may resemble molluscum contagiosum Cellulitis with necrotizing vasculitis occurs in patients who undergo organ transplantation Bone lesions develop in 5%-10% of patients and are usually osteolytic or resemble cold abscesses (may resemble tuberculosis or neoplasm)Chorioretinitis Hepatitis Peritonitis Renal abscess

Answer 17

Cutaneous lesions – biopsy with fungal stains and cultures Blood and CSF should be cultured for fungi; cryptococcal antigen testing CSF (obtain after CT/MRI to exclude masses) - opening pressures should be measured at each spinal tap; elevated pressures (≥250 mm H2 O) portend a poor prognosis, CSF glucose depresses, protein elevated, lymphocytic cell count @ 20 or higher, positive for India ink or antigen Serologic testing of blood and CSF recommended if cryptococcal CNS infection considered Antigen tests unobtainable in impoverished countries; cryptococcosis often goes undiagnosed (2009, lateral flow assay (LFA) for diagnosing cryptococcosis was developed, may provide a point-of-care assay in resource-poor areas Culturing for Cryptococcus may be appropriate, even when the CSF profile is unremarkable

Answer 18

Cryptococcal meningitis with AIDS (mortality 25-30%; sequelae 40%) Account for more than 80% of the patients with cryptococcosis Initially, administer amphotericin B at 0.7-1 mg/kg/d for 2 weeks, with or without 2 weeks of flucytosine at 100 mg/kg/d in 4 divided doses, followed by fluconazole at 400 mg/d for a minimum of 8-10 weeks Cryptococcal meningitis without AIDS (effective 70-75%) Initial therapy should be amphotericin B (0.7-1 mg/kg/day) alone or in combination with flucytosine (100 mg/kg/day in 4 divided doses). Amphotericin B can be administered alone for 6-10 weeks or in conjunction with flucytosine for 2 weeks, followed by fluconazole for a minimum of 10 weeks Pulmonary cryptococcosis Without concomitant immunosuppression/deficiency; observation possible as the infection may resolve without antifungal therapy Observing allowed if CSF chemistry parameters are normal; the CSF culture, India ink preparation, and serology results are negative; urine culture results are negative; the pulmonary lesion is small and stable or shrinking; and the patient has no predisposing conditions for disseminated disease. Mild-to-moderate cryptococcal pulmonary disease*: fluconazole for 6-12 months, itraconazole for 6-12 months, or amphotericin B Severe pulmonary disease: amphotericin B (0.7-1 mg/kg/d) plus flucytosine (100 mg/kg/d) for 6-10 weeks or same for 2 weeks followed by fluconazole at 400 mg/kg/d for at least 10 weeks (some recommend consolidation therapy for 6-12 months) Treatment of extraneural nonpulmonary disease Without AIDS, cryptococcal lesions of the skin, bones, or other organs treated with amphotericin B plus flucytosine or with amphotericin B alone Patients with cryptococcal infection require lumbar puncture ensure absence of CNS infection

Answer 19

Histoplasmosis is the most common endemic fungal infection seen in humans Central river valleys in the midwestern and south central United States are endemic for histoplasmosis ~ 250,000 individuals are infected annually Clinical manifestations of histoplasmosis occur < 5% of the population Most infections are sporadic, although large outbreaks of histoplasmosis may occur

Answer 20

Most individuals with histoplasmosis are asymptomatic Clinical disease is usually in immunocompromised or are exposed to a high quantity of inoculum Histoplasma species may remain latent in healed granulomas and recur, resulting in cell-mediated immunity impairment Conversion from the mycelial to the pathogenic yeast form occurs intracellularly. After phagocytosis by macrophages, the yeast replicates in approximately 15-18 hours Despite fusion with lysosomes, multiplication continues within the phagosomes (possible inhibition of lysosomal proteases) As the host immunity response develops, yeast growth ceases within 1-2 weeks after exposure

Answer 21

Approximately 90% of patients are asymptomatic If symptoms develop, onset occurs 3-14 days after exposure Fever, headache, malaise, myalgia, abdominal pain, and chills are common symptoms; usually, histoplasmosis is self-limited With exposure to a large inoculum patient may develop severe dyspnea resulting from diffuse pulmonary involvement Joint pain and skin lesions occur in 5-6% of patients, mostly in females Enlarged hilar and mediastinal lymph nodes are present in 5-10% of patients Cough, hemoptysis, dyspnea, and/or chest pain may be present and are related to the degree of compression on the pulmonary airway and circulation Paratracheal involvement may cause cough or dyspnea because of compression on the trachea or bronchi Rarely, compression of the esophagus occurs, which causes dysphagia

Answer 22

This form occurs mostly in older patients with underlying pulmonary disease and is associated with cough, weight loss, fevers, and malaise Generally, infection involves the apical segments and occurs near emphysematous bullae Pleural thickening is often seen If cavitations are present, hemoptysis, sputum production, and increasing dyspnea are common symptoms

Answer 23

Acute form - fever, worsening cough, weight loss, malaise, and dyspnea; 5-20% of patients have CNS involvement Subacute form - wide spectrum of symptoms Constitutional symptoms GI involvement may produce diarrhea and abdominal pain Cardiac involvement resulting in valvular disease, cardiac insufficiency, or vegetations may produce dyspnea, peripheral edema, angina, and fever CNS involvement may produce headache, visual and gait disturbances, confusion, seizures, altered consciousness, and neck stiffness or pain Mucous membrane lesions are common in disseminated histoplasmosis

Answer 24

CBC – anemia in chronic histoplasmosis & pancytopenia and thrombocytopenia in disseminated Alkaline phosphatase - elevated in acute disseminated and chronic pulmonary histoplasmosis Lactate dehydrogenase increases in AIDS patients with disseminated histoplasmosis Sputum culture - positive in ~ 15% from patients with acute and 60-85% from patients with chronic pulmonary histoplasmosis Blood cultures – positive in 50-70% of patients with progressive disseminated histoplasmosis, usually negative otherwise Complement-fixing antibodies Immunoprecipitating antibodies – detects anti-M and anti-H glycoproteins, vary in duration and presence with acute infection Serum and urine antigen detection - useful in immunocompromised when antibody production may be impaired Angiotensin-converting enzyme – may be elevated with acute infection Third-generation antigen assays – 100% disseminated histoplasmosis antigenemia; antigenuria has variable senstivities for acute and subacute infections CXR – may detect healed lesions, hilar LN reactivity and disseminated disease CT/MRI – considered for CNS or abdominal presentations Pulmonary function tests – determine extent of disease

Answer 25

No treatment is required for individuals who are asymptomatic, monitor symptoms Prolonged symptoms (>4 wk) or those with overwhelming pulmonary involvement, initiate medical therapy with itraconazole for 6-12 weeks; CXR to monitor response to therapy; then followed for several years after treatment for possible relapse Patients with severe infection should be treated with amphotericin B for 1-2 weeks; once stable, amphotericin B may be changed to itraconazole and should be continued for 1 year Patients with acute respiratory distress symptoms may require methylprednisone for 1-2 weeks

Answer 26

Often fatal if not treated (mortality rate ~ 50% without treatment; 28% with treatment) May have progressive loss of pulmonary function Cavitary lesions must be treated; itraconazole given for one year; relapse in 15% Persistent cavitations despite medication warrant surgical consideration

Answer 27

Initiate medical therapy with amphotericin B with progressive disseminated histoplasmosis and meningitis Thoracentesis or pericardiocentesis in patients with severe pleural effusions and pericardial tamponade

Answer 28

Pneumocystis organisms are commonly found in the lungs of healthy individuals Most children have been exposed to the organism by age 3 or 4 years Occurrence is worldwide Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in persons with HIV infection (renamed Pneumocystis jiroveci [pronounced “yee-row-vet-zee”]) Classified as a fungal pneumonia, but PCP does not respond to anti fungal treatment Antibiotics (e.g. trimethoprim-sulfamethoxazole TMP-SMX) are primarily recommended for treatment of mild, moderate, or severe PCP Corticosteroids are used as adjunctive initial therapy only in patients with HIV infection who have severe PCP

Answer 29

HIV infection whose CD4+ cells fall below 200/µL and who are not receiving PCP prophylaxis HIV with opportunistic infections (e.g. oral thrush) increases the risk of PCP, regardless of CD4+ count Primary immune deficiencies, including hypogammaglobulinemia and severe combined immunodeficiency (SCID) Long-term immunosuppressive regimens for connective-tissue disorders, vasculitides, or solid-organ transplantation (e.g. heart, lung, liver, kidney) Hematologic and nonhematologic malignancies, including solid tumors and lymphomas Severe malnutrition

Answer 30

Pneumocystis infection in lung transplant patients was 88% without prophylaxis With routine prophylaxis, PCP is very rare in solid-organ transplant patients and has significantly decreased in patients infected with HIV Prior to the widespread use of highly active antiretroviral therapy (HAART), PCP occurred in 70-80% of patients with HIV infection Mortality rate with HIV and PCP previously 20-40%, presently 10-20%

Answer 31

Symptoms of P carinii pneumonia (PCP) are nonspecific PCP in patients with HIV infection tends to run a more subacute indolent course and tends to present much later, often after several weeks of symptoms, compared with PCP associated with other immunocompromising conditions ``` Symptoms infection can be found in any organ system Fever nonproductive cough chills wt loss ```

Answer 32

Sputum - Pneumocystis organisms are frequently found in sputum induced by inhalation of a hypertonic saline solution; sensitivity varies with technique (< 50% to >90%); specificity is high (99-100%) Lactic dehydrogenase (LDH) - usually elevated (>220 U/L) in patients with P carinii pneumonia (PCP); elevated in 90% of patients with PCP and HIV; high sensitivity (78-100%); but limited specificity LDH levels appear to reflect the degree of lung injury; improving with successful treatment; consistently elevated LDH levels during treatment may indicate therapy failure & poor prognosis Quantitative PCR - useful in distinguishing between colonization and active infection (not yet available for routine clinical use) β-D-Glucan (BDG) - cell-wall component of many fungi, including candida, aspergillus, and pneumocystis Sensitive test to detect PCP, not specific CXR

Answer 33

Treatment of PCP may be initiated before the workup is complete in severely ill high-risk patients Pneumocystis organisms persist in the host for days to weeks after therapy is started, allowing time for completion of the appropriate workup Treatment of PCP depends on the degree of illness at diagnosis, based on alveolar-arterial gradient: Mild (< 35 mm Hg) Moderate/severe (35-45 mm Hg) Severe (>45 mm Hg); also O2 < 70 mm Hg In patients without HIV infection, response to treatment should begin in 4-5 days; patients infected with HIV, the treatment response typically takes longer; within the first 8 days

Answer 34

Antibiotics are primarily recommended for treatment of mild, moderate, or severe P carinii pneumonia (PCP) Trimethoprim-sulfamethoxazole (TMP-SMX) has been shown to be as effective as intravenous pentamidine and more effective than other alternative treatment regimens Recommended duration of treatment for PCP is 21 days in patients with HIV infection and 14 days for all other patients; patients infected with HIV tend to have a higher organism burden and respond to treatment slower than patients without HIV infection requiring a longer duration of therapy Corticosteroids are used as adjunctive initial therapy only in patients with HIV infection who have severe P carinii pneumonia (PCP): RA pO2 < 70 mm Hg or an arterial-alveolar O2 gradient > 35 mm Hg

Answer 35

Smoking cessation Smokers are at an increased risk of P carinii pneumonia (PCP) and have a more complicated treatment course Chemoprophylaxis in patients with HIV Infection Two types of outpatient chemoprophylactic therapies exist: primary prophylaxis in immunocompromised patients without a history of PCP; secondary prophylaxis is used in patients with a prior bout of PCP