fungal infections

Question 1

vulvovaginal candidiasis

Answer 1

infection in women with or without sxs who have positive vaginal cultures for candida species
can be sporadic or recurrent depending on frequency
may be defined as uncomplicated or complicated
-uncomplicated - sporadic infection that is susceptible to all forms of antifungal therapy regardless of treatment duration
-complicated - recurrent VVC; severe disease; non-candida albicans infection; host factors (DM, immuno suppression, pregnany)

Question 2

pathophys of VVC

Answer 2

candida albicans - 80-92% of symptomatic VVC
non-albicans 8-20%
cancdida species are dimorphic
candida colonize the vagina and changes in host’s vaginal environment or response is necessy to induce symptomatic infection
no precipitating factors in most cases

Question 3

VVC risk factors

Answer 3

increased when sexually active
oral-genital contact
contraceptives increase risk
OCs
antibiotics
post-menopausal women taking HRT
no association w diet, douching or tight clothing

Question 4

VVC clinical pres

Answer 4

often involves vulva and vagina

sxs: intense itching, soreness, irritation, burning on urination, dyspareunia
signs: erythma, fissuring, curdy “cheese”-like discharge, edema

Question 5

treatment of uncomlicated VVC - OTC/topical vaginal products

Answer 5

butoconazole 2% cream, 1 app x 3
clotrimazole
-1%, 2%, 10% cream 1 app x1
-100 mg tab x7
-200 mg tab x3
-500 mg tab x1
miconazole
-2% cream 1 app x1
-100 mg supp x7
-200 mg supp x3
-1200 mg ovule x1
tioconazole 6.5% ointment 1 app x1

Question 6

treatment of uncomplicated VVC - prescription/topical

Answer 6

nystatin 100,00 units  1 tab x 14
terconazole
-0.4% cream 1 app HS x7
-0.8% cream 1 app HS x3
-80 mg supp HS x3

Question 7

treatment of uncomplicated VVC - prescription/oral

Answer 7

fluconazole 150 mg tab PO x1

Question 8

treatment of complicated VVC

Answer 8

immunosuppressed or have uncontrolled DM
same drugs as uncomp but extend duration of therapy to 10-14 days
fluconazole 150 mg x 2-3 doses 72 h apart
pregnancy: topical are safe throughout, treat for 7 days with topical azole, oral are contraindicated

Question 9

treatment of recurrent VVC

Answer 9

definition: over 4 episodes within a 12-month period

2 stage treatment: topical or oral azole x 10-14 days followed by fluconazole 150 mg PO once weekly x 6 mo

Question 10

antifungal resistant VVC

Answer 10

consider resistance if persistently positive yeast cultures and/or fail to respond to therapy despite adherence
boric acid 600 mg capsule intravaginally daily x14 then 1 cap twice weekly
flucytosine cream 1000 mg intravaginally nightly x7

Question 11

oropharyngeal candidiasis

Answer 11

OPC
infection of the oral mucosa with candida species
most common OI in HIV patients

Question 12

esophageal candidiasis

Answer 12

EC

infection of the esophagus with Candida species

Question 13

oropharyngeal and esophageal candidiasis

Answer 13

primary line of host defenses against C. albicans is cell-mediated immunity (mediated by CD4 T-cells)
prevalence of EC has increased secondary to HIV disease and other severely immunocompromised patients
In patients with HIV, highly-active antiretroviral therapy (HAART) has resulted in significant decline in OPC and EC

Question 14

OPC and EC risk factors

Answer 14

local factors: steroids and antibiotics, dentures, xerostomia due to drugs, chemo, radiotherapy to head/neck, BMT, smoking, disruption of oral mucosa caused by chemo and radiotherapy, ulcers, endotracheal intubation trauma, burns
systemic factors: drugs, neonates or elderly, HIV infection/AIDS, DM, malignancies, nutritional deficiencies

Question 15

clinical presentation of OPC

Answer 15

“cottage-cheese” appearance, yellowish-white, soft plaques (or milk curds) overlying areas of erythema
plaques are easily removed by vigorous rubbing - erythematous, bleeding when removed
sxs range from none to painful mouth, burning tongue, metallic taste, dysphagia and odynophagia

Question 16

clinical presentation of EC

Answer 16

dysphagia, odynophagia, and retrosternal chest pain
fever, few to numerous white or beige plaques of varying size
plaques can be hyperemic or edematous with ulceration in severe cases
upper GI endoscopy with biopsy - histologic presence of Candida in lesions; culture warranted; concern for drug resistance

Question 17

OPC treatment

Answer 17

should be individualized - underlying immune status, concurrent mucosal and medical diseases, concomitant medications, exogenous infectious sources
minimize predisposing factors
institute proper oral hygiene
treatment options: drug adherence, adequate saliva for dissolution of solid topical medications, drug interactions, location and severity of infection
treat for 7-14 days
topical therapy for MILD infection
-clotrimazole 10 mg troche (hold in mough for 15-20 min for slow dissolution) 5x/day
-nystatin 100,000 U/ml susp, 4-6 ml swish and swallow, QID
-miconazole 50 mg mucoadhesive buccal tablet, apply to upper gum region (canine fossa) daily x 7-14 days - apply in morning after brushing teeth; hold in place 30 seconds to ensure adhesion; gradually dissolves; eat and drink normally but avoid gum; if falls off and swallowed in first 6 hours - apply new tab
systemic therapy needed in patients with refractory OPC, patients who cannot tolerate topical agents, patient with moderate to severe disease and patients at high risk for disseminated disease (neutropenia)
-fluconazole 100-200 mg daily
-itraconazole soln 200 mg daily (on empty stomach)
-posconazole susp 400 mg BID wf

Question 18

treatment of fluconazole-refractory OPC

Answer 18

treat for 14+ days
itraconazole soln 200 mg daily
posconazole susp 400 mg BID x3 then 400 mg daily x28
ampB 1-5 ml swish and swallow QID
voriconazole 200 mg BID (over 40 kg)
caspofungin 70 mg LD then 50 mg IV daily
micafungin 100 mg IV daily
anidulafungin 200 mg LD then 100 mg IV daily
ampB 0.3-0.7 mg/kg/day

Question 19

treatment for esophageal candidiasis

Answer 19

treat for 14-21 days (21-28 if fluconazole refractory)
systemic therapy always required
fluconazole 200-400 mg PO daily
itraconazole soln 200 mg daily
echinocandim (micafungin 150 mg daily; caspofungin 70 mg LD then 50 mg daily; anidulafungin 200 mg daily)
voriconazole 200 mg PO/IV BID
posaconazole susp 400 mg BID or delayed release tablets 300 mg daily
ampB 0.3-0.7 mg/kg/day

Question 20

mycotic infections of skin, hair and nails

Answer 20

dermatophytosis -superficial mycotic infections of the skin
trichophyton, epidermophyton, microsporum
affect both sexes, all races
individuals develop infection if come in contact with organism and have conducive environment for mycotic growth
risk factors: prolonged exposure to sweaty clothes, failure to bathe regularly, many skinfolds, sedentary, confined to bed

Question 21

tinea pedis

Answer 21

athlete’s foot
affects 70% of adults
occurs in hot weather, with exposure to a surface reservoir (locker room floor) and with use of occlusive footwear
treatment with topical therapy for 2-4 weeks is adequate for mild infections
recurrence is common necessitating prolonged therapy

Question 22

tinea manuum

Answer 22

usually involves the palmar surfaces

treatment is similar to tinea pedis

Question 23

tinea cruris

Answer 23

infection of the proximal thighs and buttocks
“jock itch”
more common in males
topical therapy for 1-2 weeks after symptoms resolve
severe infections may require oral therapy

Question 24

tinea corporis

Answer 24

infection of the skin of the trunk and extremities

similar treatment to tinea pedia

Question 25

tinea capitis

Answer 25

infection involving the scalp, hair follicles and adjacent skin usually affects children treatment with oral therapy (terbinafine 250 mg daily x 4-8 weeks clean combs and brushes

Question 26

tinua barbae

Answer 26

infection of the hairs and follicles of the beard and moustache treatment same as tinea capitis removal of beard or moustache recommended

Question 27

treatment of tinea pedis, manuum, cruris, corporis

Answer 27

topical - butenafine cream, ciclopirox BID, clotrimazole BID, econazole, haloprogin, ketoconazole, miconazole, oxiconazole, sulconazole, terbinafine oral - fluconazole 150 mg once weekly for 1-4 weeks; itraconazole 200-400 mg QD x7; terbinafine 250 mg QD x14

Question 28

treatment of tinea capitis or barbae

Answer 28

topical - shampoo in conjugation with oral therapy, ketoconazole twice weekly x28, selenium sulfide daily x14 oral - terbinafine 250 mg QD x 4-8 weeks itraconazole 100-200 mg QD x 4-6 weeks

Question 29

tinea (pityriasis) vesicolor

Answer 29

hyper or hypopigmented scaly patches on trunk and extremities more common in adults and tropical environments topical therapy adequate unless extensive skin area or recurrent infection

Question 30

treatment of tinea (pityriasis) versicolor

Answer 30

topical - clotrimazole BID, econazole QD, haloprogin BID, ketoconazole QD, miconazole BID, oxiconazole BID, sulconazole BID oral - fluconazole, itraconazole 200 mg QD x 3-7 days

Question 31

onychomycosis (tinea unguium)

Answer 31

fungal infection of the toenails (more common) and fingernails risk factors: increasing age (esp over 40), family hx, genetic factors, immunodeficiency, DM, psoriasis, PVD, smoking, tinea pedis, frequent nail trauma, sporting activities treatment: -terbinafine 250 mg QD x 6 weeks (fingers), 12 weeks (toes) -itraconazole 200 mg BID x 1 week/month for 2 months (fingers); 200 mg QD x 12 weeks (toes) -fluconazole 50 mg QD or 300 mg once weekly for 6+ months (fingers) or 12 months (toes)

Question 32

terbinafine

Answer 32

fungicial against dermatophytes most common AE: -GI: diarrhea, dyspepsia, nausea, abd pain -derm: rash, urticaria, pruritus -HA -may cause transient decrease in lymphocyte count - monitor CBC -rare severe hepatotoxicity - avoid in liver disease -does not inhibit CYP3A4 but potent inhibitor of CYP2D6

Question 33

prophylaxis of invasive fungal infections

Answer 33

administration of antifungal agents prior to and throughout periods of neutropenia (ANC under 1000)

Question 34

early empiric therapy of invasive fungal infections

Answer 34

administration of systemic antifungal agents at the onset of fever and neutropenia

Question 35

empiric therapy of invasive fungal infections

Answer 35

administration of systemic antifungal agents to neutropenic patients with persistent or recurrent fever despite appropriate antimicrobial therapy

Question 36

secondary prophylaxis (suppressive therapy) of invasive fungal infections

Answer 36

administration of systemic antifungal agents to prevent relapse of a documented invasive fungal infection treated during a previous episode of neutropenia

Question 37

histoplasmosis

Answer 37

causative pathogen: histoplasma capsulatum endemic in the ohio and mississippi river valleys infection caused by inhalation of dust-borne microconidia of the organism (activities that disturb the soil) conida aerosolized - inhaled and reach bronchioles and alveoli - germinate - organisms phagocytized but not killed - migrate to lymph nodes and other sites in the body via bloodstream - onset of specific T-cell immunity in non-immune host activated macrophages - fungicidal - over 2-4 mo, tissue granulomas form with central caseastion (necrotic degeneration of bodily tissue into a soft, cheese-like substance) and necrosis these areas become encapsuated and calcified over several years with viable organisms trapped within the necrotic tissue (unable to multiply except in immunocompromised patients) cell-mediated immunity wanes over time in absence of re-exposure re-infection occurs frequently in endemic areas in immune host, host response begins in 24-48 hours - milder infection, no proliferation of organism

Question 38

histoplasmosis clinical presentation

Answer 38

depends on host, pathogen and environment host factors - degree of immunosuppression, presence of immunity (from prior infection) environmental factors - inoculum size, exposure within closed area, duration of exposure acute pulmonary histoplasmosis -low inoculum exposure results in mild or asymptomatic pulmonary infection -high inoculum exposure - acute, self-limited illness with flu-like pulm sxs -pateints w diffuse pulm histoplasmosis can have diffuse radiographic changes, become hypoxic, and require mechanical ventilation chronic pulmonary histoplasmosis -presents as an opportunistic infection imposed on a pre-existing medica condition (emphysema) -chronic pulm sxs with apical lung lesions that progress with inflammation, calcified granulomas and fibrosis -patients with early, non-cavitary disease usually recover without treatment -progressive disease develops over several years in 25-30% of patients; associated with cavitation, pulm insufficiency and death disseminated histoplasmosis -may be seen in patients exposed to large inoculum or immunocomp -successful containment of organism with macrophages may not occur - progressive illness characterized by persistent yeast-filled macrophages and inability to form granulomas -most adults have mild, chronic form of the disease; untreated patients may be ill for 1-20 years with long periods of asymptomatic periods interrupted by clinical illness characterized by weight loss, weakness and fatigue HIV infected patients -progressive disseminated histoplasmosis (PDH) can occur as a direct result of initial infection or reactivation of a dormant foci -in endemic areas, 50% of AIDS patients will develop PDH as first manifestation -sxs: fever, chills, fatigue, weight loss, night sweats, hepatosplenomegaly, cough, chest pain, dyspnea -CNS histoplasmosis - fever, HA, seizure, mental status changes -GI disease - diarrhea, fever, abd pain

Question 39

Histoplasmosis diagnosis

Answer 39

direct exam or histology of blood tissues DNA probes culture of blood. sputum and bone marrow serologic testing - detect histoplasma antigen -complement fixation -immundiffusion -latex agglutination in patient with HIV/AIDS - bone marrow biopsy and culture; antigen detection

Question 40

histoplasmosis treatment - immunocompetent host - acute pulmonary histoplasmosis

Answer 40

asymptomatic or mild-moderate disease with sxs under 4 weeks - no therapy required mild-moderate disease with sxs 4+ weeks -itraconazole 200 mg TID x3, then 200 mg QD or BID x 6-12 weeks -alt - posaconazole and fluconazole moderately severe-severe disease -lipid ampB 3-5 mg/kg/day x 1-2 weeks, then itraconazole 200 mg TID x 3 then 200 mg BID for a total of 12 weeks -methylprednisolone 0.5-1 mg/kg daily for first 1-2 weeks

Question 41

histoplasmosis treatment - immunocompromised host - disseminated histoplasmosis

Answer 41

therapy required for all patients moderately severe-severe disseminated disease -liposomal ampB 3 mg/kg/day x 1-2 weeks then itraconazole 200 mg TID x3 then 200 mg BID for at least 12 months*** -obtain itraconazole conc after 2 weeks (random conc over 1.0) less severe disease -itraconazole 200 mg TID x3 then 200 mg BID x 12 mo alternatives - posaconazole, voriconazole; fluconazole less effective than itraconazole

Question 42

blastomycosis

Answer 42

causative pathogen: blastomyces dermatitides endemic in SE, south central and MW US pulmonary infection occurs secondary to inhalation of conidia - inflammatory response with neutrophilic recruitment to lungs - dissemination - cell-mediated immunity - granuloma formation

Question 43

blastomycosis clinical presentation

Answer 43

acute pulmonary blastomycosis - asymptomatic or self-limited disease characterized by fever, chills, and productive cough (with or without hemoptysis) in immunocompetent host chronic pulmonary blastomycosis - fever, malaise, weight loss, night sweats, chest pain, productive cough disseminated blastomycosis

Question 44

blastomycosis diagnosis

Answer 44

direct microscopic exam of sputum or other respiratory specimen histopathologic exam of tissue biopsy culture no reliable skin test or serologic tests

Question 45

pulmonary blastomycosis treatment - immunocompetent

Answer 45

moderately severe-severe disease -lipid ampB 3-5 mg/kg IV daily or ampB 0.7-1 mg/kg IV daily (total dose 1.5 - 2.5 g) x 1-2 weeks or until improvement, followed by itraconazole 200 mg PO TID x3 then 200 mg PO BID for 6-12 months total mild-moderate disease -itraconazole 200 mg PO TID x3 then 200 mg PO BID x 6 mo total -monitor serum conc after 2 weeks

Question 46

disseminated or extrapulmonary blastomycosis - immunocompetent

Answer 46

CNS disease -induction: lipid ampB 5 mg/kg IV daily x 4-6 weeks, followed by an oral azole as consolidation therapy -consolidation: fluconazole 800 mg PO QD; itraconazole 200 mg PO BID-TID; voriconazole 200-400 PO BID; treat for 12+ months moderately severe-severe and mild-moderate disease -treatment same as pulmonary disease -osteoarticular disease - treat for 12 months

Question 47

blastomycosis - treatment immunocompromised host

Answer 47

acute disease -lipid ampB 3-5 mg/kg IV daily or ampB 0.7-1 mg/kg IV daily x 1-2 weeks or until improvement then suppressive therapy for 12+ months total suppressive therapy -itraconazole 200 mg PO TID x3 then 200 mg BID for 12+ total -lifelong suppressive therapy with oral itraconazole 200 mg daily may be required for immunosuppressed patients in whom immunosuppression cannot be reversed and in patients who experience relapse despite appropriate therapy

Question 48

coccidioidomycosis

Answer 48

caused by coccidioides immitis endemic in the SW and western US (CA to TX) - limited rainfall, hot summers, sandy alkaline soil increased prevalence due to increased tourism and population growth in endemic areas, increased use of immunosuppressive therapy and HIV inhalation of conidia into lungs initiates infection

Question 49

coccidioidomycosis clinical presentation

Answer 49

initial or primary infection with C. immitis almost always involves the lungs asymptomatic disease in 60% primary coccidioidomycosis ("valley fever") -non-specific sxs: fever, couhg, HA, sore throat, myalgies and fatigue occur 1-3 weeks after exposure -diffuse maculopapular rash appears in first few days -primary pneumonia can be the first manifestation of disease - characterized by productive cough (blood-streaked); single or multiple soft or dense homogeneous hilar or basal infiltrates on chest x-ray persistent pulmonary coccidioidomycosis -primary disease lasting more than 6 weeks -complicated by hemoptysis and pulmonary scarring; necrosis of pulmonary tissue with drainage and cavity formulation occurs commonly disseminated coccidioidomycosis -most common sites for dissemination: skin, lymph nodes, bone and meninges -CNS infection - HA, weakness, changes in mental status (lethargy and confusion), neck stiffness, low-grade fever, weight loss

Question 50

coccidioidomycosis treatment - primary respiratory infection

Answer 50

most patients with symptomatic primary pulmonary disease recover without therapy treat patients with large inocula, severe infection or concurrent risk factors (e.g HIV infection, organ transplant, pregnancy, or high doses of CS) severe infection - weight loss, intense night sweats persisting 3+ weeks, infiltrates involving more than 1/2 of one lung or portions of both lungs, prominent or persistent hilar adenopathy, complement fixation antibody titers > 1:16, failure to develop dermal sensitivity to coccidial antigens, inability to work or sxs that persist 2+ months treat 3-6 months -itraconazole 200-300 mg PO BID-TID -fluconazole 400-800 mg PO/IV daily (up to 1200 mg) diffuse pneumonia with bilateral or miliary infiltrates - ampB for several weeks followed by an azole for 12 mo total

Question 51

disseminated coccidioidomycosis treatment

Answer 51

nonmeningeal disease: -itraconazole or fluconazole -ampB meningeal disease: -fluconazole 400-800 mg IV/PO daily (not cure; life long suppression therapy) -itraconazole 200-300 mg PO BID -intrathecal ampB with or without continuation of azole therapy - dose 0.01-1.5 mg daily to weekly (start low and titrate based on response)

Question 52

cryptococcosis

Answer 52

caused by cryptococcus neoformans and cryptococcus gattii - both in immunocomp infection acquired by inhalation of the organism - resists phagocytosis d/t capsule cell-mediated immunity plays a major role in host defense against infection disease may be localized in lungs or disseminate to other areas (CSF)

Question 53

cryptococcosis clinical presentation

Answer 53

pulmonary - cough, rales, SOB meningitis -non-AIDS: HA, fever, NV, mental status changes, nuchal rigidity; less common - photophobia, blurred vision, papilledema -HIV/AIDS - fever, HA

Question 54

cryptococcosis diagnosis

Answer 54

``` meningitis - non-HIV -increased CSF opening pressure -increased CSF WBCs (lymphocytes) -decreased CSF glucose -increased CSF protein -positive CSF cryptococcal antigen -india ink stain -culture reduced inflammatory response in HIV/AIDS with extremely high cryptococcal antigen titer ```

Question 55

cryptococcal meningitis treatment - non-HIV infected, non-transplant host

Answer 55

induction: ampB 0.7-1 mg/kg/day IV plus flucytosine 100 mg/kg/day PO in 4 divided doses for at least 4 weeks - 4 weeks in patients without neurologic complications and negative CSF cultures after 2 weeks of therapy may use lipsomal ampB 3-4 mg/kg/day extend induction phase to 6 weeks if neurologic complications or flucytosine not given consolidation: fluconazole 400 mg PO daily x 8 weeks may use AmpB plus flucytosine for 2 week induction phase in patients with low risk for therapeutic failure - early dx by history, no uncontrolled underlying diseases or immunocompromised states, excellent clinical response to initial 2-week regimen consolidation phase: fluconazole 800 mg PO daily x 8 weeks maintenance therapy: fluconazole 200 mg PO daily x 6-12 months

Question 56

cryptococcal meningitis treatment - HIV-infected patients

Answer 56

preferred: -induction: liposomal AmpB 3-4 mg/kg/day IV plus flucytosine 100 mg/kg/day PO in 4 divided doses for 2+ weeks -consolidation: fluconazole 400 mg PO daily x 8+ weks -maintenance: 200 mg PO daily to complete at least 1 year of azole therapy - may be stopped in patients with CD4 count over 100, who have undetectable viral load on ART for > 3 months, and received at least 1 year of mainentance therapy alternative: -ampB 0.7-1 mg/kg/day IV or lip ampB 3-4 mg/kg/day IV x 4-6 weeks -ampB 0.7 mg/kg/day IV plus fluconazole 800 mg PO daily x 2 weeks then fluconazole 800 mg PO daily x 8 weeks -fluconazole 800-1200 mg daily plus flucytosine 100 mg/kg/day x 6 weeks -fluconazole 1200 mg daily x 10-12 weeks

Question 57

cryptococcal meningitis treatment - organ transplant recipients

Answer 57

induction: lip ampB 3-4 mg/kg/day IV plus flucytosine 100 mg/kg/day PO in 4 divided doses for 2+ weeks consolidation: fluconazole 400-800 mg PO daily x 8+ weeks maintenance: 200-400 mg PO daily x 6-12 months

Question 58

non-meningeal cryptococcosis treatment

Answer 58

immunosuppressed and immunocompetent patients with mild-to-moderate pulmnary disease: fluconazole 400 mg daily x 6-12 months immunosuppresed and immunocompetent patient with severe pulmonary disease: same as CNS x 12 mo cryptococcemia and nonmeningeal, nonpulmonary: same as CNS x 12 mo patients without CNS disease, no fungemia with infection at a single site and no immunosuppressive risk factors: fluconazole 400 mg daily x 6-12 mo

Question 59

candidiasis

Answer 59

caused by candida species yeasts: small, unicellular, thin-walled, ovoid cells that reproduce by budding C. albicans is normal flora of the skin, female genital tract and entire GI tract most common cause of invasive fungal infections in humans

Question 60

candidiasis risk factors

Answer 60

``` broad-spectrum ABs use of central venous catheters and urinary catheter parenteral nutrition hemodialysis and renal replacement therapy in ICU patients neutropenia (ANC under 500) implantable prosthetic devices immunosuppressive agents surgery ICU length of stay ```

Question 61

candidiasis pathophys/clinical presentation

Answer 61

candida usually acquired via GI tract or can enter bloodstream via IV catheter intact skin is critical for prevention on invasive candidiasis PMNs play a major role in patient's host defense acute onset of fever, tachycardia, tachypnea, chills and hypotensions

Question 62

candidemia - treatment in nonneutropenic adults

Answer 62

echinocandin (caspofungin 70 mg LD, then 50 mg QD; micafungin 100 mg daily; anidulafungin 200 mg LD then 100 mg daily) - recommended initial therapy fluconazole 800 mg LD then 400 mg IV or PO daily - alternative in patients who aren't critically ill and unlikely to have fluconazole-resistant candida azole susc testing recommended on all bloodstream and other clinically relevant isoaltes transition from echinocandin to fluconazole for patients who are clinically stable , have susc isolates and have negative repeat blood cultures after initiation of therapy remove all IV catheters if possible repeat blood cultures QD or QOD treat for 14 days after 1st negative blood culture

Question 63

candidemia - treatment in neutropenic adults

Answer 63

echinocandin (caspofungin 70 mg LD then 50 mg daily; micafungin 100 mg daily; anidulafungin 200 mg LD then 100 mg daily) - initial therapy lipid formulation of amp B 3-5 mg/kg/day if not critically ill and no prior azole exposure: -fluconazole 800 mg LD then 400 mg daily -voriconazole 400 mg BID x1 then 200-300 mg BID if needed C. glabrata - echinocandin preferred C. papapsilosis - fluconazole or lipid ampB preferred C. krusei - echinocandin, lipid amp B or voriconazole treat for 14 days after documented clearance of candida from blood, resolution of sxs, and resolution of neutropenia consider removing IV catheters

Question 64

chronic disseminated (hepatospelnic) candidiasis

Answer 64

lipid ampB 3-5 mg/kg/day OR an echinocandin x several weeks followed by fluconazole 400 mg PO QD continue therapy until documentation of lesion resolution on repeat imaging (several months) if debilitating persistent fevers, short-term treatment with NSAID or CSs

Question 65

empiric treatment of suspected invasive candidiansis in ICU - nonneutropenic adults

Answer 65

echinocandin (caspofungin 70 mg LD then 50 mg daily; micafungin 100 mg daily; anidulafungin 200 mg LD then 100 mg daily) - preferred alt: fluconazole 800 LD then 400 QD if no recent azole exposure and not colonized w azole resistant candida; lip ampB 3-5 mg/kg/day duration: 14 days

Question 66

empiric treatment of suspected invasive candidiansis in ICU - neutropenic adults

Answer 66

lipid ampB 3-5 mg/kg/day echinocandin vorionazole 6 mg/kg IV BID x1 then 3 mg/kg IV BID alt: flucon 800 LD then 400 QD; itraconazole 200 BID azoles should not be used in patients who received azole prophylaxis

Question 67

prophylaxis of invasive candidiasis in the ICU

Answer 67

fluconazole 800 mg LD then 400 mg QD in high-risk patients in ICUs w high rate of invasive candidiasis echinocandin as alt daily bathing w chlohexidine could be considered

Question 68

treatment of intra-abd candidiasis

Answer 68

consider empiric therapy for patients w clinical eivdence of intra-abd infection and significant risk for candidiasis - recent abd surgery, anastomotic leaks or necrotizing pancreatitis source control w appropraite drainage and debridement treatment - same as candidiasis in nonneutropenic patient

Question 69

treatment of candida UTI - asymptomatic candiduria

Answer 69

not recommended unless high risk of dissemination high risk: neutropenic, low-birth weight infants (under 1500 g) (both: treat as candidemia), patients undergoing urologic procedures (flucon 400 mg QD for several days before and after procedure)

Question 70

treatment of candida UTI - symptomatic candida cystitis

Answer 70

flucon susc: flucon 200 mg PO QD x 14 flucon resistant: -ampB deox 0.3-0.6 mg/kg QD x 1-7 days -amp bladder irrigation 50 mg/L of sterile water for 5 days -flucytosine 25 mg/kg for 7-10 days remove or replave indwelling bladder catheter

Question 71

aspergillosis

Answer 71

caused be aspergillus specis -A. fumigatus*, A. flavus, A. niger, A. terreus generally acquired by inhalation of airbourne conidia that are small enough to reach alveoli or the paranasal sinus use of HEPA filters in ORs and laminar flow rooms and removal of immunocomp patients from hospital renovation sites can be helpful in preventing infection in this population impaired host defenses are required for development of invasive disease phagocytes (neutrophils, monocytes and macrophages) are the primary host defense system against invasive aspergillosis prolonged neutropenia is the most important predisposing factor to the development of invasive aspergillosis uncommon in HIV infection

Question 72

aspergillosis - clinical presentation

Answer 72

lung - most common site characterized by vascular invasion leading to thrombosis, infarction, necrosis of tissue and dissemination to other tissues and organs in the body survival beyond 2-3 weeks is uncommon cavitation of pulmonary lesion generally occurs if bone marrow function returns classic s/sxs: pleuritic chest pain, fever, hemoptysis, friction rubs hyphae invade the walls of bronchi and surrounding parenchyma resulting in an acute necrotizing, pyogenic pneumonitis

Question 73

aspergillosis - diagnosis

Answer 73

demonstration of aspergillus by repeated culture and microscopic examination of tissue identification of aspergillus generally based on appearance of 2- to 4-microm-wide septate hyphae branched at 45 degree angels galatomannan is a cell-wall polysaccharide specific to aspergillus sepcies that is detectable in serum and other body fluids -circulating antigen can be detected at mean of 8 days before diagnosis by other means -use of mold-active AFs can decrease sensitivity -false-positives have been reported in patients receiving pip-tazo and amox-clav CXR - wedge-shaped pleural-based infiltrates or cavities CT scan: -halo sign: area of low attenuation surrounding a nodular lung lesion caused by edema or bleeding surrounding an ischemic area -cresent sign: air cresent near the periphery of a lung nodule caused by contraction of infarcted tissue

Question 74

aspergillosis treatment

Answer 74

invasive pulmonary aspergillosis voriconazole 6 mg/kg q12h x1 then 4 mg/kg q12h; PO: 200 mg q12h alt: -lipid ampB 3-5 mg/kg/day -caspo 70 mg LD then 50 mg QD -mica 150 mg QD -posaconazole 200 mg PO q6h, then 400 mg BID after stabilization of disease primary combination therapy not recommended

Question 75

aspergillosis prophylaxis

Answer 75

posaconazole 300 mg IV q12h x1 then 300 mg QD OR 200 mg susc TID alt: itraconazole 200 mg IV q12h x 2 then 200 mg IV QD or PO BID OR micafungin 50 mg IV QD