Exam 5 Flashcards
What are clinical manifestations of oropharyngeal candidiasis?
-painless, creamy white, plaque-like lesions on the buccal mucosa, hard or soft palate, oropharyngeal mucosa, or tongue surface
-dry mouth
-taste alterations
What are the treatment options for oropharyngeal candidiasis?
-fluconazole 200 mg PO once, then 100-200 mg PO QD for 7-14 days
-topical agents (nystatin or clotrimazole)
What are clinical manifestations of esophageal candidiasis?
-fever
-retrosternal burning pain or discomfort
-dysphagia
-odynophagia
-whitish plaques with superficial ulceration of esophageal mucosa with white surface exudates
What is the treatment for esophageal candidiasis?
fluconazole 200 mg IV or PO QD for 14-21 days
What are clinical manifestations of vulvovaginal candidiasis?
-white, thick vaginal discharge
-vaginal itching
-vaginal burning
-vulvar erythema
What are the treatment options for uncomplicated vulvovaginal candidiasis?
-fluconazole 150 mg PO once
-topical azole for 3-7 days
-ibrexafungerp 300 mg PO BID for 1 day
What are the treatment options for severe vulvovaginal candidiasis?
-fluconazole 100-200 mg PO QD
-topical antifungals
What is the duration of therapy for severe vulvovaginal candidiasis?
7 days
What is the treatment for azole-refractory C. glabrata vaginitis?
boric acid 600 mg vaginally QD for 14 days
When is prophylaxis recommended for candidiasis?
frequent or severe recurrences of esophagitis or vaginitis (QD treatment)
What are the clinical manifestations of cryptococcal meningitis?
-fever
-malaise
-headache
-nausea
-dizziness
-lethargy
-irritability
-impaired memory
-behavioral changes
What is the treatment for the induction phase of cryptococcal meningitis?
amphotericin B 3-4 mg/kg IV QD and flucytosine 25 mg/kg PO QID for 2 weeks
What is the treatment for the consolidation phase of cryptococcal meningitis?
fluconazole 800 mg PO QD for 8 weeks (400 mg if patient is stable with sterile CSF and on ART)
What is the treatment for the maintenance phase of cryptococcal meningitis?
fluconazole 200 mg PO QD ≥ 1 year
When should ART be initiated when treating cryptococcal meningitis?
between the induction and consolidation phases
When can secondary prophylaxis be discontinued for cryptococcal meningitis?
-duration of therapy ≥ 1 year
-asymptomatic
-CD4 count ≥ 100 cells/mm^3 for 3 months on ART
When should secondary prophylaxis be restarted for cryptococcal meningitis?
CD4 count < 100 cells/mm^3
What are the clinical manifestations of histoplasmosis?
-fever
-fatigue
-weight loss
-hepatosplenomegaly
-cough
-dyspnea
What are treatment options for mild to moderate histoplasmosis?
-itraconazole 200 mg PO TID for 3 days, then BID for ≥ 12 months
-posaconazole
-voriconazole
-fluconazole
What is the treatment for severe histoplasmosis?
amphotericin B 3 mg/kg IV QD for ≥ 2 weeks, then itraconazole 200 mg PO TID for 3 days, then BID for ≥ 12 months
When should primary prophylaxis of histoplasmosis be initiated?
-CD4 count < 150 cells/mm^3
-high risk due to occupational exposure or living in community with hyperendemic rate of histoplasmosis
What is the treatment for primary prophylaxis of histoplasmosis?
itraconazole 200 mg PO QD
When should ART be initiated for treatment of histoplasmosis?
ASAP
When may primary prophylaxis of histoplasmosis be discontinued?
-ART
-CD4 count ≥ 150 cells/mm^3 for 6 months
When should secondary prophylaxis of histoplasmosis be initiated?
-severe disseminated disease or CNS infection after maintenance therapy OR
-relapse
What is the treatment for secondary prophylaxis of histoplasmosis?
itraconazole 200 mg PO QD
When may secondary prophylaxis of histoplasmosis be discontinued?
-azole therapy for ≥ 1 year
-negative fungal blood cultures
-serum or urine histoplasma antigen below level of quantification
-ART
-CD4 count ≥ 150 cells/mm^3 for ≥ 6 months
When should secondary prophylaxis of histoplasmosis be restarted?
CD4 count < 150 cells/mm^3
What are clinical manifestations of mycobacterium avium complex (MAC)?
-disseminated multi-organ infection if not on ART
-fever
-night sweats
-weight loss
-diarrhea
-abdominal pain
-malaise/fatigue
What are treatment options for MAC?
-clarithromycin 500 mg PO BID and ethambutol 15 mg/kg PO QD
-azithromycin 500-600 mg PO QD and ethambutol 15 mg/kg PO QD
What drug can be added to a treatment regimen for severe MAC?
rifabutin 300 mg PO QD
When should more antibiotics be added to a treatment regimen for MAC?
-high risk of mortality
-likely drug resistance
-CD4 count < 50 cells/mm^3
-high mycobacterial loads in blood
-ineffective ART
What antibiotics can be added to a treatment regimen for MAC?
-levofloxacin or moxifloxacin
-amikacin or streptomycin
-linezolid, tedizolid, or omadacycline
When can duration of therapy for MAC be shorter?
CD4 count > 100 cells/mm^3 for ≥ 6 months
When should ART be initiated for treatment of MAC?
ASAP
When is prophylaxis not recommended for MAC?
if ART is initiated immediately after HIV diagnosis
When should primary prophylaxis of MAC be initiated?
-CD4 count < 50 cells/mm^3
-no ART or high viral load
What is the treatment for primary prophylaxis of MAC?
azithromycin 1,200 mg PO QW
When should primary prophylaxis of MAC be discontinued?
ART
When should primary prophylaxis of MAC be restarted?
CD4 count < 50 cells/mm^3
When should secondary prophylaxis of MAC be discontinued?
-completed ≥ 12 months
-asymptomatic
-CD4 count > 100 cells/mm^3 for > 6 months
When should secondary prophylaxis of MAC be restarted?
CD4 count < 100 cells/mm^3
What are clinical manifestations of pneumonitis jirovecii pneumonia (PJP)?
-dyspnea
-fever
-non-productive cough
-chest discomfort
-hypoxemia
What are treatment options for mild to moderate PJP?
-Bactrim 15-20 mg/kg/day PO TID
-Bactrim DS 2 tablets PO TID
-dapsone and trimethoprim
-primaquine and clindamycin
-atovaquone
For what drugs in the treatment of PJP do G6PD levels need to be checked?
-dapsone
-primaquine
-clindamycin
What are treatment options for moderate to severe PJP?
-Bactrim 15-20 mg/kg/day IV divided Q6-8H for 21 days
-primaquine and clindamycin
-pentamidine
When should adjunctive corticosteroid therapy be initiated for PJP?
pO2 < 70 mm Hg (within 72 hours of PJP therapy initiation)
What is the adjunctive corticosteroid treatment for PJP?
prednisone 40 mg PO BID for 5 days, then QD for 5 days, then 20 mg PO QD for 11 days
When should ART be initiated for treatment of PJP?
within 2 weeks of PJP diagnosis
When should primary prophylaxis of PJP be initiated?
-CD4 count 100-200 cells/mm^3 (if high viral load) OR
-CD4 count < 100 cells/mm^3
When should secondary prophylaxis of PJP be initiated?
all patients with acute episode of PJP
When can secondary prophylaxis of PJP be discontinued?
CD4 count ≥ 200 cells/mm^3 for > 3 months
When should secondary prophylaxis of PJP be restarted?
CD4 count < 100 cells/mm^3
What are clinical manifestations of toxoplasmosis?
-headache
-focal neurologic deficits
-fever
What are the treatment options for acute treatment of toxoplasmosis?
-pyrimethamine 200 mg PO once, then weight-based dosing
-Bactrim 5 mg/kg IV or PO BID
What is the duration of therapy for acute treatment of toxoplasmosis?
≥ 6 weeks
What are the treatment options for maintenance therapy of toxoplasmosis?
-pyrimethamine 25-50 mg PO QD and sulfadiazine 2,000-4,000 mg PO BID-QID and leucovorin 10-25 mg PO QD
-Bactrim DS 1 tablet PO BID
When should primary prophylaxis of toxoplasmosis be initiated?
toxoplasma IgG positive with CD4 count < 100 cells/mm^3
What is the treatment for primary prophylaxis of toxoplasmosis?
Bactrim DS 1 tablet PO QD
When can primary prophylaxis of toxoplasmosis be discontinued?
-CD4 count > 200 cells/mm^3 for > 3 months in response to ART
-CD4 count 100-200 cells/mm^3 and low viral load for ≥ 3-6 months
When should primary prophylaxis of toxoplasmosis be restarted?
-CD4 count < 100 cells/mm^3
-CD4 count 100-200 cells/mm^3 and high viral load
When can secondary prophylaxis of toxoplasmosis be discontinued?
-CD4 count > 200 cells/mm^3 for > 6 months
-completed initial therapy
-asymptomatic
When should secondary prophylaxis of toxoplasmosis be restarted?
CD4 count < 200 cells/mm^3
What are risk factors for infections in immunocompromised patients?
-neutropenia
-immune system defects
-destruction of protective barriers
-environmental contamination/alteration of microbial flora
neutropenia
ANC < 1000 cells/mm^3
What are the most common causative bacteria for neutropenia?
-Staphylococcus aureus
-Enterobacterales
-Pseudomonas aeruginosa
cell-mediated immunity
-T-lymphocytes
-primary defense against intracellular pathogens
humoral immunity
-B-lymphocytes
-primary defense against extracellular pathogens
What can cause immune system defects?
-underlying disease
-immunosuppressive drugs
What are protective barriers or methods that protective barriers can destroy?
-skin
-mucous membranes
-surgery
How can mucous membranes be destructed?
-chemotherapy
-radiation
What type of bacteria does oropharyngeal flora rapidly change to in hospitalized patients within the first 48 hours?
Gram-negative bacilli
fever in neutropenic cancer patients
-single oral temperature of ≥ 38.3ºC OR
-oral temperature ≥ 38ºC for ≥ 1 hour
What are the characteristics of low-risk neutropenia patients?
-anticipated neutropenia ≤ 7 days
-clinically stable
-no medical comorbidities
-outpatient at fever onset
What is the outpatient treatment for low-risk neutropenia?
PO fluoroquinolone and Augmentin
When are IV antibiotics indicated for low-risk neutropenic patients?
-inadequate outpatient infrastructure OR
-not candidate for oral regimen
What IV antibiotics are used for neutropenia?
-Zosyn
-antipseudomonal carbapenem
-cefepime
-ceftazidime
What are the characteristics for high-risk neutropenia patients?
-anticipated neutropenia > 7 days
-clinically unstable
-medical comorbidities
-HSCT
-inpatient at fever onset
-ANC ≤ 100 cells/mm^3
When can IV vancomycin be added to a drug regimen for neutropenia?
-cellulitis
-pneumonia
-severe sepsis or shock
-Gram-positive bacteria
-suspected IV catheter infection
-MRSA
-resistant Streptococci
What antibiotics can be added to a neutropenia drug regimen for septic shock, Gram-negative bacteremia, or pnuemonia?
-aminoglycoside
-antipseudomonal fluoroquinolone
What bacteria should always be covered by antibiotics for the treatment of neutropenia?
Pseudomonas
What can be used as a high-risk neutropenia drug regimen for patients with a penicillin allergy?
-ciprofloxacin
-aztreonam
-vancomycin
What antibiotic is used for MRSA?
vancomycin
What antibiotics are used for VRE?
-daptomycin
-linezolid
What antibiotic is used for ESBL?
carbapenems
What antibiotics are used for KPC?
-meropenem/vaborbactam
-imipenem/cilastatin/relebactam
-ceftazidime/avibactam
When should targeted therapy be re-evaluated after empiric therapy for the treatment of neutropenia?
48-72 hours
What is the median time of dissolution of fever for neutropenia?
5-7 days
When should antifungal therapy be initiated for neutropenia?
-persistent fever OR
-development of new fever with undocumented infection after 4-7 days of broad spectrum antibiotics
What are antifungal treatments for neutropenia?
-amphotericin B (deoxycholate or liposomal)
-azoles
-echinocandins
What azoles can be used to treat neutropenia?
-fluconazole
-voriconazole
-posaconazole
-isavuconazole
What echinocandins can be used to treat neutropenia?
-micafungin
-caspofungin
-anidulafungin
What is the duration of therapy for antifungal therapy for neutropenia?
2 weeks
When should antiviral therapy be initiated for neutropenia?
-vesicular/ulcerative skin or mucosal lesions OR
-presumed or confirmed viral infection
What is the treatment for HSV/VZV?
-acyclovir
-valacyclovir
What patients are eligible for neutropenia prophylaxis?
-moderate- or high-risk patients with expected ANC ≤ 100 cells/mm^3 for > 7 days
-heme malignancies
-allogeneic and autologous hematopoietic stem cell transplants
-graft versus host disease with high-dose steroids
-alemtuzumab
What are treatment options for neutropenia prophylaxis?
-ciprofloxacin
-levofloxacin
-Bactrim
What is the HIV viral protein?
gp120
What are the stages of HIV infection?
-acute retroviral syndrome
-chronic HIV infection
-AIDS
What are the routes of transmission of HIV?
-exposure of mucous membrane or damaged tissue to infected body fluids
-bloodstream exposure to infected body fluids
-mother-to-child
What is the seroconversion window for the OraQuick In-Home test?
3 months
What is the CD4 cell count cutoff for HIV vs. AIDS?
200 cells/mm^3
What is the CD4 percentage cutoff for HIV vs. AIDS?
14%
What is the mechanism of action of nucleoside reverse transcriptase inhibitors?
synthetic purine and pyrimidine analogues resulting in elongation termination of growing proviral DNA chain
What medications are nucleoside reverse transcriptase inhibitors?
-abacavir
-emtricitabine
-tenofovir
-vudine
What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?
bind to allosteric site of reverse transcriptase enzyme (reduces functionality)
What medications are non-nucleoside reverse transcriptase inhibitors?
-vir-
What is the mechanism of action of protease inhibitors?
inhibit viral protease (prevents assembly, maturation, and release of new virions)
What is the suffix of protease inhibitors?
-navir
What is the mechanism of action of integrase strand transfer inhibitors?
inhibit HIV integrase (prevents proviral DNA integration into host cell genome)
What is the suffix of integrase strand transfer inhibitors?
-tegravir
What is the mechanism of action of attachment inhibitors?
binds to gp120
What drug is an attachment inhibitor?
temsavir
What is the mechanism of action of post-attachment inhibitors?
binds to domain D2 of CD4 receptor on T cells and interrupts post-attachment steps required for entry of HIV into host cell
What drug is a post-attachment inhibitor?
ibalizumab-uiyk
What is the mechanism of action of chemokine receptor (CCR5) antagonists?
-binds to CCR5 on CD4 receptors on T cells
-blocks binding of gp120
-prevents entry of HIV into host cell
What drug is a chemokine receptor (CCR5) antagonist?
maraviroc
What is the mechanism of action of capsid inhibitors?
binds to interface between capsid protein (p24) subunits (interferes with multiple steps of viral lifecycle)
What drug is a capsid inhibitor?
lenacapavir
What is the recommended dose of dolutegravir for integrase strand transfer inhibitor-naive?
50 mg PO QD
What is the recommended dose of dolutegravir for integrase strand transfer inhibitor-experienced?
50 mg PO BID
What HIV medication needs to be taken on an empty stomach at bedtime?
efavirenz
What HIV medication needs to be titrated from 200 mg BID to 400 mg QD?
nevirapine
What HIV medications need to be taken with food?
-etavirine
-rilpivirine
-atazanavir
-elvitegravir
What HIV medication requires an oral lead-in phase for ≥ 28 days?
cabotegravir
What HIV medication is administered IV?
ibalizumab
What HIV medication is administered subcutaneous?
lenacapavir
What are adverse effects of nucleoside reverse transcriptase inhibitors?
-mitochondrial toxicity
-lactic acidosis
What is an adverse effect of non-nucleotide reverse transcriptase inhibitors?
rash
What are adverse effects of protease inhibitors?
-GI intolerance
-insulin resistance
-lipodystrophy
What is an adverse effect of integrase strand transfer inhibitors?
weight gain
How long should antacids be separated from PO INSTIs?
6 hours
What HIV medication cannot be administered with aluminum and magnesium?
raltegravir
What HIV medication is contraindicated with PPIs?
rilpivirine
What are the preferred benzodiazepines with protease inhibitors and cobicistat?
-lorazepam
-oxazepam
-temazepam
What is the preferred corticosteroid with protease inhibitors and cobicistat?
beclomethasone
What are the preferred statins with protease inhibitors and cobicistat?
-atorvastatin
-rosuvastatin
-pitavastatin
-pravastatin
What is the dosing of PDE5 inhibitors with protease inhibitors and cobicistat?
low doses Q48-72H
How long should polyvalent cation supplements be separated from integrase inhibitors?
6 hours
What class of HIV medications requires dosing adjustment in renal insufficiency?
nucleoside reverse transcriptase inhibitors
What lab is required prior to initiation of abacavir?
HLA-B*5701 allele genetic testing
What lab is required prior to initiation of maraviroc?
tropism assay
What is the website for HIV treatment guidelines?
https://clinicalinfo.hiv.gov
What are first-line initial treatment regimens for HIV?
-bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy)
-dolutegravir/tenofovir alafenamide or tenofovir disoproxil fumarate/emtricitabine or lamivudine
-dolutegravir/lamivudine (Dovato)
In what patients can dolutegravir/lamivudine not be administered to?
-HIV RNA > 500,000 copies/mL
-HBV co-infection
-ART started before results of HIV genotypic resistance testing or HBV testing available
What viral load is needed for successful resistance test results?
> 500 copies/mL
What HIV drug class has the lowest genetic barrier to resistance?
NNRTIs
What HIV drug class has the highest genetic barrier to resistance?
boosted PIs
What are PEP treatment regimens?
-emtricitabine/tenofovir disoproxil fumarate 200/300 mg PO QD for 28 days AND
-raltegravir 400 mg PO BID OR dolutegravir 50 mg PO QD for 28 days
What are PrEP treatment regimens?
-emtricitabine/tenofovir disoproxil fumarate 200/300 mg PO QD
-emtricitabine/tenofovir alafenamide 200/25 mg PO QD (MSM and transgender women who have sex with men)
-cabotegravir 600 mg IM once, then 1 month later, then Q2M
What do fungal cells contain in the cell membrane instead of cholesterol like in mammalian cells?
ergosterol
What enzyme do allylamines inhibit?
squalene epoxidase
What step does squalene epoxidase catalyze?
squalene –> squalene epoxide
What enzyme do azoles inhibit?
14 alpha-demethylase
What step does 14 alpha-demethylase catalyze?
lanosterol –> ergosterol
What drug class do amphotericin B and nystatin belong in?
polyenes
What is the mechanism of action of polyenes?
-bind to ergosterol to form pores for ions to leak out of cells
-withdraw ergosterol from membrane
What drug class does terbinafine belong in?
allylamines
What is the suffix of echinocandins?
-fungin
What is the mechanism of action of echinocandins?
inhibit synthesis of beta(1-3) glucan synthase
How are echinocandins selective for fungal cells?
mammalian cells lack beta(1-3) glucan synthase
What drug class does flucytosine belong in?
antimetabolites
What is the mechanism of action of flucytosine?
inhibit thymidylate synthase
How is flucytosine selective for fungal cells?
mammalian cells cannot convert flucytosine to active metabolite
What is the mechanism of action of ibrexafungerp?
inhibits glucan synthase
What is the mechanism of action of tavaborole?
inhibits leucyl transfer RNA synthetase (leuRS)
How are amphotericin B and flucytosine synergistic agents?
amphotericin B creates pores to allow flucytosine to enter fungal cells more easily
What is the first step of metabolism of flucytosine?
flucytosine –> 5-FU (catalyzed by cytosine deaminase)
What are the second and third steps of flucytosine metabolism?
5-FU –> 5-FUMP –> 5-FdUMP (catalyzed by PRT and ribonucleotide reductase)
What is the function of dTMP?
extends fungal DNA for cell growth
What activates isoniazid?
KatG
What is the mechanism of action of isoniazid?
-forms products with NAD+ and NADP+
-inhibits enzymes (InhA) that use NAD+ and NADP+
-inhibits mycolic acid synthesis
What is the mechanism of action of rifampin?
-binds to RNA polymerase within DNA/RNA channel
-blocks path of elongating RNA
What is the mechanism of action of ethambutol?
-inhibits mycobacterial arabinosyl transferase
-results in buildup of arabinan (inhibits formation of arabinogalactan and lipoarabinomannan)
What activates pyrazinamide?
low pH and pncA
What is the mechanism of action of pyrazinamide?
inhibits panD which leads to inhibition of coenzyme A synthesis
What is the mechanism of action of bedaquiline?
inhibits ATP synthase
What is a resistance mechanism of bedaquiline?
mutations in atpE
What activates pretomanid?
deazaflavin-dependent nitroreductase (Ddn)
What are the mechanisms of action of pretomanid?
-forms reactive metabolite that inhibits mycolic acid production (aerobic conditions)
-generates reactive nitrogen species (anaerobic conditions)
At what stage of tuberculosis does a tuberculin skin test (TST) become positive?
infection eliminated with acquired immune response
At what stage of tuberculosis does an interferon-gamma release assay (IGRA) become positive?
infection eliminated with acquired immune response
At what stage of tuberculosis does a culture become intermittently positive?
subclinical TB disease
At what stage of tuberculosis does a sputum smear become positive?
active TB disease
At what stage of tuberculosis does a patient become infectious?
subclinical TB disease
At what stage of tuberculosis does a patient present with symptoms?
subclinical TB disease
At what stage of tuberculosis should treatment be initiated?
latent TB infection
What TB drug should be avoided or used with caution if a patient has HIV and latent TB?
rifampin
What drugs are polyresistant TB not resistant to both of?
isoniazid and rifampin
What drugs are used for the intensive phase of a standard six-month treatment of TB?
-rifampin 600 mg
-isoniazid 300 mg
-ethambutol 800 - 1600 mg
-pyrazinamide 1000 - 2000 mg
How long is the intensive phase of a standard six-month treatment of TB?
8 weeks
What drugs are used for the continuation phase of a standard six-month treatment of TB?
-rifampin 600 mg
-isoniazid 300 mg
How long is the continuation phase of a standard six-month treatment of TB?
18 weeks
What drugs are used for the intensive phase of a rifapentine-based four-month treatment?
-rifapentine 1200 mg
-isoniazid 300 mg
-moxifloxacin 400 mg
-pyrazinamide 1000 - 2000 mg
How long is the intensive phase of a rifapentine-based four-month treatment?
8 weeks
What drugs are used for the continuation phase of a rifapentine-based four-month treatment?
-rifapentine 1200 mg
-isoniazid 300 mg
-moxifloxacin 400 mg
How long is the continuation phase of a rifapentine-based four-month treatment?
9 weeks
What type of patients does Aspergillus primarily cause disease in?
immunocompromised hosts
What are the two most common Cryptococcus bacteria?
-Cryptococcus neoformans
-Cryptococcus gattii
What organ does Cryptococcus primarily affect?
CNS
What fungi is amphotericin a first-line agent for?
-Cryptococcus
-Blastomyces
-Histoplasma
-Mucor
What are common adverse effects of amphotericin?
-nephrotoxicity
-hypokalemia
-hypomagnesemia
What is the bioavailability of flucytosine?
high
Does flucytosine penetrate into the CSF?
yes
How much of flucytosine is excreted unchanged in the urine?
85% - 95%
What fungi is flucytosine a first-line agent for?
Cryptococcus
What is a common adverse effect of flucytosine?
bone marrow suppression
What are monitoring parameters for flucytosine?
-CBC
-platelets
-SCr
-BUN
What is the bioavailability of fluconazole?
high
Does fluconazole penetrate into the CSF?
yes
Does fluconazole require dosing adjustment in renal insufficiency?
yes
What body weight is fluconazole dosing based on?
total body weight
What are indications for fluconazole?
-noninvasive candidiasis
-invasive candidiasis
-bone marrow transplant prophylaxis
-Cryptococcal meningitis
What is the dose of fluconazole for invasive candidiasis caused by C. albicans?
800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) QD
What is the dose of fluconazole for invasive candidiasis caused by C. glabrata?
1200 - 1600 mg loading dose, then 800 mg QD
What are common adverse effects of fluconazole?
-headache
-nausea
-anorexia
-QTc prolongation
-elevation of hepatic transaminases
-adrenal insufficiency
What fungi is fluconazole a first-line agent for?
-Candida albicans
-Candida parapsilosis
-Candida tropicalis
-Candida lusitaniae
-Coccidioides
What are itraconazole and voriconazole predominantly metabolized by?
CYP450 enzymes
What is the active metabolite of itraconazole?
hydroxyitraconazole
How does clearance change with higher doses of itraconazole?
decreases
What is absorption of itraconazole dependent on except for oral solutions?
gastric acidity
What are indications for itraconazole?
-histoplasmosis
-blastomycosis
What are common adverse effects of itraconazole?
-hepatotoxicity
-congestive heart failure (boxed warning)
-QTc prolongation
What dosage form of posaconazole is absorption affected by gastric pH?
oral suspension
What is the preferred oral formulation of posaconazole?
delayed release tablets
When should posaconazole and voriconazole be avoided?
CrCL < 50 mL/min
What are common adverse effects of posaconazole?
-N/V
-abdominal pain
-diarrhea
-QTc prolongation
-increased LFTs
-hypokalemia
-rash
-pseudohyperaldosteronism
What dosage form of voriconazole does not require dosing adjustments for renal insufficiency?
oral formulations
What drugs do not affect the oral bioavailability of voriconazole?
-H2RA
-PPI
-antacid
What are indications for voriconazole?
-invasive aspergillosis
-Candida infections
What are common adverse effects of voriconazole?
-visual disturbances
-elevated LFTs
-QTc prolongation
-phototoxic skin reactions
-diffuse painful periostitis
What fungi is voriconazole a first-line agent for?
Aspergillus
Which azole has the least number of drug interactions?
isavuconazole
What is a contraindication for isavuconazole?
familial short QT syndrome
What fungi are echinocandins first-line agents for?
-C. glabrata
-C. krusei
-C. lusitaniae
-C. auris
What are common adverse effects of caspofungin?
-histamine-mediated symptoms
-fever
-phlebitis at infusion site
-N/V
-headache
What is the route of administration for micafungin?
IV
Does micafungin require dosing adjustments for renal insufficiency?
no
What are common adverse effects of micafungin?
-hyperbilirubinemia
-nausea
-diarrhea
-eosinophilia
-rash, pruritis, urticaria
What is the indication for ibrexafungerp?
vulvovaginal candidiasis
What is a contraindication for ibrexafungerp?
pregnancy
When should effective contraception be used for ibrexafungerp treatment?
during and for 4 days after treatment
What is the drug of choice for C. albicans?
fluconazole
What is the drug of choice for C. glabrata?
echinocandin
What is the drug of choice for C. parapsilosis?
fluconazole
What is the drug of choice for C. tropicalis?
fluconazole
What is the drug of choice for C. krusei?
echinocandin
What are the drugs of choice for C. lusitaniae?
fluconazole and echinocandin
What is the drug of choice for C. auris?
echinocandin
What are the drugs of choice for Cryptococcus?
fluconazole, amphotericin, and flucytosine
What is the drug of choice for Blastomyces?
itraconazole
What is the drug of choice for Histoplasma?
itraconazole
What is the drug of choice for Coccidioides?
fluconazole
What is the drug of choice for Aspergillus?
voriconazole
What is the drug of choice for Mucor?
amphotericin
What is the primary defense against superficial Candida infections?
cell-mediated immunity
What is the mechanism of action of pyrethrins?
bind to voltage-gated sodium channels in parasite nerve cells
What is the mechanism of action of spinosad?
nicotinic acetylcholine receptor agonist
What is the mechanism of action of benzimidazoles?
inhibit formation of microtubules
What is the mechanism of action of pyrantel pamoate?
depolarizing neuromuscular blocking agent
What are the mechanisms of action of artemisinin?
-forms free radicals
-inhibits PfPI3K
What is the mechanism of action of chloroquine?
-binds to heme to form FP-chloroquine complex
-caps hemozoin molecules to prevent further biocrystallization of heme
What is the mechanism of action of primaquine?
spontaneous oxidation to O-PQm which produces H2O2
What is the mechanism of action of doxycycline in malaria?
blocks protein translation in apicoplast
What are treatment options for malaria prophylaxis in all malaria-endemic regions?
-atovaquone/proguanil
-doxycycline
-tafenoquine
When should atovaquone/proguanil and doxycycline be started for malaria prophylaxis?
1-2 days before departure
How long should atovaquone/proguanil be continued for malaria prophylaxis?
7 days after leaving malaria endemic region
When should be atovaquone/proguanil be avoided?
-CrCl < 30 mL/min
-pregnant women
-women breastfeeding infants < 5 kg
-children < 5 kg
How long should doxycycline be continued for malaria prophylaxis?
4 weeks after leaving malaria endemic region
When should doxycycline be avoided?
-pregnant women
-children < 8 years old
-tetracycline allergy
-women prone to vaginal yeast infections
When should tafenoquine be started for malaria prophylaxis?
3 days before departure
How long should tafenoquine be continued for malaria prophylaxis?
1 week after leaving malaria endemic region
When should tafenoquine be avoided?
-G6PD deficiency or no test results
-pregnant or breastfeeding women
-psychotic disorders
-children
What are treatment options for malaria prophylaxis in regions with chloroquine-sensitive malaria?
-chloroquine
-hydroxychloroquine
When should chloroquine and hydroxychloroquine be started for malaria prophylaxis?
1-2 weeks before departure
How long should chloroquine and hydroxychloroquine be continued for malaria prophylaxis?
4 weeks after leaving malaria endemic region
What treatment is administered for malaria prophylaxis in regions primarily with Plasmodium vivax?
primaquine
When should primaquine be started for malaria prophylaxis?
1-2 days before departure
How long should primaquine be continued for malaria prophylaxis?
7 days after leaving malaria endemic region
When should primaquine be avoided?
-G6PD deficiency or no test results
-pregnant or breastfeeding women
What treatment is administered for malaria prophylaxis in regions with mefloquine-sensitive malaria?
mefloquine
When should mefloquine be started for malaria prophylaxis?
≥ 2 weeks before departure
How long should mefloquine be continued for malaria prophylaxis?
4 weeks
When should mefloquine be avoided?
-mefloquine allergy
-active/recent depression
-recent history of psychiatric disorders or seizures
-cardiac conduction abnormalities
What are treatment options for chloroquine or unknown resistance uncomplicated malaria?
-artemether-lumefantrine
-atovaquone-proguanil
-quinine sulfate AND doxycycline, tetracycline, or clindamycin
What is the treatment option for chloroquine, no mefloquine, or unknown resistance uncomplicated malaria?
mefloquine
What are the treatment options for chloroquine sensitive uncomplicated malaria?
-chloroquine
-hydroxychloroquine
What are the treatment options for anti-relapse treatment for P. vivax and P. ovale infections?
-primaquine phosphate
-tafenoquine
What is the treatment for severe malaria?
IV artesunate
