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52 Cards in this Set
- Front
- Back
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Systemic fungal infections most common in who?
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patients with impaired immune function: AIDS, solid-organ transplants, cancer
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What are the most common fungal infections at UH?
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Candida and Aspergillus
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Candida
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- exists everywhere
- fourth mowst common blood isolate - dissiminated infections difficult to diagnose - has highest mortality rate of any blood isolate |
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Invasive aspergillosis
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- most common pathogens are A.fumigatus and A.flavus
- difficult to diagnose: blood, CSF, and bone marrow rarely grow Aspergillis - difficult to distinguish from other fungi - grows rapidly with affinity for blood vessels = rapidly fatal - mortality if untreated = 100% - mortality if treated = high |
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Name the antifungal drugs
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amphotericin B
nystatin fluconazole, miconazole, itraconazole caspofungin flucytosine (5-FC) terbinafine griseofulvin tolnaftate |
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Name the Polyenes
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ampho B
lipid ampho B nystatin |
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Ampho B MOA?
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-- binds to ergosterol in the fungal cell membrane to create porins
-- porins increase cell permeability causing cell death |
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Ampho B strengths?
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extremely broad spectrum = GOLD STANDARD for antifungal drugs
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Ampho B weaknesses?
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TOXICITY!
- NEPHROTOXIC - dose dependent, transient and exacterbated by other nephrotox drugs; renal wasting of K and Mg - no perm renal damage in patients with normal fxn before trtmt - renal damage lessened by giving 1L saline i.v. prior to treatment - SHAKE AND BAKE - fever and chills syndrome caused by IL-1, IL-6 and TNF release - ANEMIA - hypochromic, normocytic with decreased HCT via decreased release erythropoietin |
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Lipid Ampho B?
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- enclosed in liposomes, but MOA is exactly same
advantage - delayed toxicity disadvantage - still toxic and costs $$$$ |
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Nystatin
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highly toxic -- almost always a topical treatment
Effective against C. albicans; NOT effective against MET bugs |
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Name the azoles and what do they cover?
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fluconazole, miconazole, clotrimazole, itraconazole, voriconazole
Candida albicans Micropsorum M Epidermophyton E Trichophyton T Pitysporum orbiculare = cause of tinea versicolar |
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Azole MOA?
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-- inhibit enzyme CYP450 lanosterol 14a-demethylase which prevents egosterol formation (needed for fungal cell mbrn)
-- accumulated 14-a-methysterols inhib enzymatic activity of ETC; cell growth blocked -- kill slowly and are considered "static" drugs which is okay as long as patient has patent immune system -- don't use ampho B after treatment w/ azole b/c they take away ampho B site of action |
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Azole resistance
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occurs via mutation of their binding to the demethylase
lanosterol can still bind but the -azoles cannot |
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Azole drug-drug interactions?
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- they inhibit CYP450, so it's always a worry with azoles
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Fluconazole strengths and weaknesses?
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- Most commonly used systemic antifungal
STRENGTHS - lacks major toxicity - F is excellent p.o. - extremely active against C.albicans WEAKNESSES - narrow spectrum of activity; only good against C.albicans and a few other species (cryptococcus) - not good against C.crusei or C.glabrata |
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Itraconazole strengths and weaknesses
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Strengths
- active against Aspergillus Weaknesses - oral solution has limited F and tastes like kerosene (now i.v. prep on market) - Drug-drug interactions via inhib CYP450 are big problem in patients with allografts or cancer |
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New azole: Voriconazole spectrum of activity
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- Superior to Ampho B for treatment of Aspergillis
- DOC for systemic Aspergillis because it is fungicidal - covers Fusarium, but patients must have white cells for it to be effective in treatment - Scedosporium apiospermum - Candida including some which are resistant to fluconazole |
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Voriconazole available preps?
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both i.v. and p.o. are available and F=96% so a petient can change from i.v. to p.o. w/o a dose adjustment
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Voriconazole weaknesses
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- possibly hepatotoxic - elevation of LFTs
- drug-drug interactions - altered light perception - Nephrotoxic? - Not effective against C.glabrata? |
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Miconazole
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i.v. and topical
(Monistat) -- candidal infections |
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Clotrimazole
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topical and oral troche
(tastes better than nystatin) - oral and oropharyngeal candida |
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Name an echinocandin.
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caspofungin
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Caspofungin MOA
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-- Inhib synthesis of 1,3-B-D-glucan, a key component of the fungal cell wall in Candida and Aspergillis
-- thus MOA is different from azoles which attack cell mbrn -- drugs will probably replace Ampho B |
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Caspofungin therapeutic use/strengths?
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-- Approved for "salvage therapy" in patients with invasive aspergillosis who have not responded to ampho B
-- rapidly cidal against Candida, even those resistant to fluconazole -- well tolerated with excellent pharmacokinetics and few drug-drug interactions b/c does not induce ir inhibit CYP450 -- No cross resistance with azoles |
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Caspofungin weaknesses?
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- Cost
- No oral formulations available (BIG molecule) - limited spectrum: Candida, Aspergillis, Pneumocystis |
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Flucytosine (5-FC) MOA?
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-- a fluorinated pyrimidine which is converted to 5-FU
-- 5-FU converted to 5-FUMP -- 5-FUMP converted to FdUMP which inhibits thymidylate synthase -- lack of thymidine inhibits DNA synthesis -- fortunately, humans don't convert 5-FC to 5-FU -- resistance emerges rapidly when used as single agent |
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5-FC strengths
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-- admin p.o.
-- rapid absorption and extensive distribution, including penetration into the CSF -- Eliminated renally -- Antifungal activity synergistic w/ azoles and ampho B |
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5-FC weaknesses
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-- Narrow spectrum: Cryptococcus neoformans and some Candida
-- Bone marrow suppression causing leukopenia and thrombocytopenia -- must be dosed QID -- rapid emergence of resistance |
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5-FC clinical uses
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Given with ampho B or itraconazole in selected fungal infections
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What are the dermatophytes?
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microsporum
epidermophyton trichophyton (MET) |
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Common dermal infections
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1. scalp ringworm (tinea capitis)
2. ringworm (tinea corporis) 3. athlete's foot (tinea pedis) 4. jock itch (tinea cruris) |
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griseofulvin MOA
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inhibits fungal mitosis by binding to polymerized microtubules needed for growth of the hyphae
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griseofulvin use?
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p.o.
-- accumulates in keratin cells -- covers all the tineas -- use has decreased as terbinafine and fluconazole have taken its place in the therapy of fungal infections |
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terbinafine MOA
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prevents ergosterol synthesis by inhibiting the enzyme squalene epoxidase
the accumulation of the squalene kills the fungal cell |
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terbinafine use
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p.o. and topical
accumulates in the skin, nails and fat cells pregnancy category B |
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tolnaftate MOA
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unknown
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tolnaftate therapeutic use
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covers MET and P. orbiculare (causes tinnea versicolar)
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Oral candida infections can be contracted by...?
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-- neonates and children = thrush
-- 90% of all HIV patients -- Asthmatic patients using an inhaled steroid can develop oropharyngeal infections - rinse their mouth and throat with water after inhalation - use spacers or reservoirs to decrease likelihood of infection |
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Oral candida treatment
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1. nystatin - oral suspension using "swish and swallow" for 3-4 days followed by use every other day for 2 wks
2. clomitrazole oral troches have less offensive taste and are replacing oral nystatin |
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What is Candidal vulvovaginitis? (CVV)
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Candida colonizes the genital tract of 20-50% of healthy women
Colonization common in: - women taking antibacs - pregnancy - women with DM Most common org is C.albicans, and 70-75% of all healthy women will have at least one episode of CVV |
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Signs, symptoms of CVV?
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- vaginal discharge
- pruritis - discomfort and pain during intercourse - white discharge and erythema on physical exam |
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CVV treatment?
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Three-day topical treatments are a good balance between efficacy and compliance
- clotrimazole 200 mg suppository - miconazole 200 mg suppository One-day topical treatments - clotrimazole 500 mg vaginal tablet --Topical OTC preps usually require 5-7 days treatment vx. prescription preps require 3 days treatment -- Fluconazole systemic therapy (150mg tablet p.o. x 1) effective with few S/Es, but takes 48 hours for symptoms to improve |
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What about women who develop CVV everytime they take an antibiotic?
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Take a single p.o. dose of fluconazole (150mg) after they have been taking the antibiotic drug for 48 h
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What is tinea capitis?
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A fungas, usually Trychophyton, invades the hair shaft and follicle
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Who gets tinea capitis?
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Usually children 4-14 y.o. but should be suspected in chilfren 3+ months with a scaly scalp
VERY contagious. |
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Tinea capitis clinical appearance?
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1. non-inflammed, diffuse, scaly, gray patches (early stage)
2. Inflammed diffuse, pustular kerions 3. "Black dots" from broken hairs (late stage) 4. Infected hairs and follicles appear green under UV light |
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Tinea capitis treatment?
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1. Griseofulvin is the DOC: Treat with 10mg/kg/d p.o. for 6 weeks and ingest with fatty foods to improve absorption
2. Ketoconazole shampoo is a helpful adjunct therapy 3. Oral tx with terbinafine or fluconazole for 2 wks appears equally effective and these drugs have a better S/E profile 4. Topical tx with an azole or naftifine in very young patients |
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What is Onychomycosis?
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A fungal infection of the nails.
- Found in 2-3% of the population and incidence in males is twice that in females - May be caused by dermatophyte, yeast, or mold - Treatment usually not covered by insurance |
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Onychomycosis risk factors?
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1. increasing age
2. male 3. DM 4. nail trauma 5. peripheral vascular disease 6. poor hygiene 7. tinea pedis 8. immunosuppression 9. chronic exposure of the nails to water predisposes to candidal nail infection |
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Onychomycosis treatment
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Terbinafine is the DOC
-- treat with 250mg/d during the same week each month for three consecutive months -- cure rate is 80+% -- Manufact recommended is qd for 6 wks for fingernails and 12 wks for toenails, but prolonged treatments may cause increase LFTs |
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Athlete's foot and jock itch treatment?
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Topical treatment with terbinafine or an azole is effective.
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