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ID exam 2
Antifungal Ramsinghani and Shah
| Question | Answer |
|---|---|
| What is the definition of Mycoses? | Infectious diseases caused by fungi |
| Drugs for the treatment of fungi are also referred to as? | anti-mycotic drugs |
| Fungal infections can be | superficial, cutaneous, subcutaneous, or systemic |
| Fungi have _______ ________ while mammalian cells don not | cell walls |
| Fungal cell membrane contains _______ while mammalian cells membrane contains _______ | ergosterol; cholesterol |
| What are your polyene antifungals? | Amphotericin B; Nystatin |
| What are your azole anti-fungal derivatives? | Imidazole derivatives and Triazole derivatives |
| What are your Imidazole derivatives azole anti-fungals? | Ketoconazole, Miconazole, Clotrimazole |
| What are your triazole derivative azole antifungals? | Fluconzaole, Itraconazole, Voriconazole, Posaconazole, Isavuconzaorium sulfate |
| What is your allylamine anti-fungal? | Terbinafine |
| List your Echinocandin antifungals? | Caspofungin, Anidulafungin, Micafungin, Rezafungin, Ibrexafungerp |
| What are your miscellaneous anti-fungals? | Flucytosine, Griseofulvin |
| In the synthesis of Ergosterol, what are the 2 reactions we can target? | 1. Target the conversion of Squaline to Squalene Epoxide (Terbinafine) 2. Conversion of Lanosterol to de-methyl lanosterol (Azole Anti-fungals) |
| Inhibition of DNA synthesis in the fungal cell is done by which anti-fungal? | Flucystosine |
| What is the target of Echinocandin anti-fungals? | Beta glucan synthesis |
| Polyene antifungals have selective toxicity, why? | higher affinity to cell membranes with ergosterol than cholesterol |
| What is the MOA of Polyene anti-fungals? | bind to membrane sterole--> aggreagate to form a pore, and cause cell membnrane disorganization and loss of cellular contents |
| Porperties of Amphotericin B | contains a conjugated system of double bonds in large lactone rings; Its not very soluble contains a cyclic ester (lactone); the COOH on the right side of the moecule allows for the site to form an ACIDIC salt whereas the mycosamine (amino sugar linked to the glycosidic bond) contains an NH2 where the site can form a BASIC salt; |
| The color of Amphotericin B is due to the: | conjugated double bonds next to each other (deep yellow crystals insoluble in water) |
| Polyenes differ in the number of double bonds present in the lactone ring: Natamine is a _______ so it has ___ double bonds; Nustatin is a ______ so it has ___ double bonds; amphotericin B is a ____ so it has __ double bonds. | tetraene, 4; hexaene, 6; heptaene, 7 |
| The number of double bonds of the polyene antifungals co-relates directly to: | antifungal activity and inversely to host toxicity; so the more the nymebr of double bonds the higher the activity. the lower the db, the more toxic |
| Amphotericin B has the most ____ anti-fungal activity | potent |
| Natamine has the most ______ anti-fungal activity | toxic |
| This anti-fungal is BIPHASIC (first phase is 15-48 hours and terminal half-life is for 15 days; has to be used IV since it doesnt penetrate the CSF so given intrathecally for meningitis; also used for systemic infections caused by most fungi but NOT for non-invasice fungal infections | Amphotericin B |
| In order to create a solution using AMB since it lipophilc, a complex was made using _______, also known as the conventional AMBD; however the issue was that its very nephrotoxic | deoxycholate (Brand name: Fungizone) |
| When AMBD is made, it forma. colloid in water and creates particles that are less than 0.4 microns in size. Typical IV filter lines are ___ microns. Filters for IV lines need to be ____ micron when using AMBD due to the drug getting filtered out and not being delivered to the pt | 0.22 microns; 1 micron |
| what was the rationale for making a lipid formulation? | wanted the drug to get to the areas that the fungal target would be aggregating at. -Lipid formualtion delivers into reticuloendothelial system --> lymphatic delivery to fungal concentrated locations (lipid rich organs) |
| What lipid formulations are less Nephrotoxic thn AMBD? | Lipid complex (Abelcet) (ABLC); Colloidal dispersion w/ cholesteroyl sulfate (Aphotec) (ABCD); Liposome (L-AMB) (Ambisome) |
| What are the adverse effectsion of AMB formulations? | Infusion-related toxicity (N/V/ chills, fever--> manage with pre-medicate of tyleonol or NSAIDS, slow infusion; Nephrotoxicity (manage with saline loading); HYPOKALEMIA, hypmagnesemia, anemia--> manage with erythropoieten to manage anemia Drug interactions: Increased risk with other nephrotoxic drugs; increased risk of digoxin toxicity |
| Biosynthesis of Ergosterol and Cholesterol--> Where is it that we see the divergence between the 2? | 14-Demehtylllanosterol |
| Which structure of the biosynthesis is it that we see more of a steroid structure? | Squalene epoxide's conversion to LANOSTEROL |
| What are Azoles? | 5 member Nitrogen containing ring |
| If there are 2 Nitrogens in the ring its a and the X contains a C (carbon) | Imidazole |
| If there are 3 Nitrogens in the ring its a and the X contains a N (another Nitrogen) | Triazole |
| Lanosterol (14a(alpha)-demethylase is a ___ enzyme that has a heme structure (iron bound to a PORPHYRIN ring | CYP |
| 14 alpha-demethylase undergoes how many sequential oxidation s? | 3 |
| How do our azole anti-fungals interact with Lanosterol? | our drug doesn't let the iron bind to Oxygen and instead it binds to the iron in the heme and prevents oxidation of the CH3 group. |
| What is the IC50 in C. Albicans for Ketoconazole? | 10^-8 M |
| What is the IC50 in humans for Ketoconazole? | 10^-6 M |
| What are the mechanisms of resistance to Azole Anti-fungals? | Alteration of lanosterol-14-a-demethylase Overexpression of lanosterol-14-a-demethylase Energy-dependent efflux systems Changes in sterol and/or phospholipid composition of fungal cell membrane (decreased permeability) |
| Some of our Azole anti-fungals are too lipophilic and require a _________ vehicle for IV | cyclodextrin (hydrophilic outer surface and hydrophobic guest inside) |
| Which azole anti-fungals require acidic pH and have a drug interaction with antacids | ketoconazole, Itraconazole, Posaconazole |
| Triazole anti-fungals have a _____ ratio between IV and PO | 1:1 |
| Which azole anti-fungal is not available as IV and ONLY PO? | Itraconazole |
| Class activity of azole anti-fungals cause: | Hepatotoxicity, QTc prolongation (except for 1--> QTc shortening) |
| Which Imidazole derivative azole anti-fungal is a PROTOtypical potent inhibitor of CYP3A4; many DI used orally and as a topical shampoo, cream? | Ketoconazole |
| These imidazole derivative azole anti-fungals are used for superficial fungal infections. Their main use is for topical Treatment of TINEA infection and VULVOVAGINAL CANDIDIASES? | Clotrimazole and Miconazole |
| This Azole antifungal is a triazole derivative and has strong inhition of CYP2C9 (warfarin, phenytoin metabolism lowered) with a log P of 0.58? | Fluconazole |
| the logP of 0.58 for Fluconazole means its soluble enough that we dont need to use which vehicle for delivery? | cyclodextrin |
| Which triazole antifungal is NOT INTERCHANGEABLE due to its Bioavailability (LogP: 6) and capsule formulation? This azole is also contraindiciated in patients with CHF | Itraconazole |
| This triazole anti-fungal has NON-linear and saturable kinetics (i.e. if you increase a dose by 50% may see effect of 500% increase); this azole is known to cause VISUAL CHANGES and PHOTOTOXICITY (due to extra fluro group) and cause cause Periostitis (inflammation/pain in bone) | Voriconazole |
| This trazole derivative has a logP value of 5 (requires cyclodextrin) and its metabolism is via PHASE II GLUCORONIDE | Posaconazole |
| This triazole anti-fungal is a pro-drug and was developed to icnreaed solubility w/o using cyclodextrin; half-life is 130 hours, and has AE of causing QTc SHORTENING | Isavuconazonium sulfate; (Isavuconazole is the active form) |
| What is the MOA of your Allylamine anti-fungals? what is the selective toxicity? | inhibition of squalene epoxide Fungal enzyme inhibited at lower conc. (2500-fold lower) Main use: fungal infections of skin and nails |
| Terbinafine unique structure is the? Treatment is for? | allylamine (responsible for drug action); Athlete's foot (fungal infection b/w toes) N-C-C=C |
| Naftifine, Butenadine, Tolnaftate are your ______ allylamine antifungals | topical |
| Echinochandin antifungals contain a large ____ lipopeptide; In the structure, Ramsinghani wants you to know that R-5 is for the ______ ____ | cyclic; glycopeptide tail or lipophilc tail) |
| Rezafungin differs from the other Echinocandin anti-fungals in that it has a substituted; Rezafungin is dosed once daily, so how long is its half-life? | quaternary amine group which increases stability and solubility; 123-181 hours |
| MOA of Echinocandins? Use? | inhibit fungal cell wall synthesis (inhibit the fungal enzyme B-1,3- glucan synthase); Use: invasive candidasis, refractory aspergillosis |
| Resistance to Echinocandins can occur if their are mutations in which gene? | FKS (mutating the expression enzyme) |
| Echinocandins have limited oral absorption so are given as? They do not penetrate the CSF so therefore cannot be used for meningeal infections; They are ___-CYP mediated so therefore have minimal ___ | IV infusions; NON-CYP; minimal DI |
| Why are Echinocandins less toxic than AmB and azole anti-fungals? | They target the cell wall, and since their is no cell wall in host cell, its a unique target. Azole and AmB are targeting something that also exists within the host cell |
| This Echinocanin is a NON-LIPOPEPTIDE (actually more steroidal structure). Oral form. ; high conc in VAGINAL TISSUE; classified as a TRITERPENOID; use is vulvovaginal candidiasis (VVC) and contraindicated in pregnancy | Ibrexafungerp (Brexafemme) |
| This miscellaneous antifungal is a pro-drug; its MOA is inhibition of Fungal DNA synthesis; has selective toxicity since humans lack cytosine deaminase; MOR: loss of cytosine deaminase activity | Fluctyosine |
| Flucytosine is similar to cytosine but with a Fluro group. Action steps to inhibtion of DNA synthesis--> | 1. takeaway amino ggroup and form oxidative product (5-FU) aka 5-fluro-uracil (this is also a potent anti-cancer drug; 2. Attachment of a deoxyribose sugar (5-FdUMP) which inhibits DNA synthesis |
| This miscellaneous Anti-fungal is a natural product obtained from P. griseofulvum and used for the treatment of superficial fungal infections (fingernail and toenail); more effective orally and available in MICRONIZED/ULTRAMICRONIZED form (increases surface area); MOA: disrupts microtubule spindle apparatus (aka prevent multiplication) | Griseofulvin |
| What are the 3 Fungal Classifications? | Yeasts (Candidia spp, Cryptococcus spp), Mold Aspergillus spp, Zygomycetes, Fusarium spp, Scedosporium spp) Dimorphic (Coccidioides spp, Histoplasma spp, Blastomyces spp) |
| What are superficial fungal infections? What are invasive fungal infections? | skin, hair/follicles, Subcutaneous tissues; Bloodstream, Eyes, Visceral organs |
| What is vulvovaginal candidiasis? | Fungal infection of the vagina (symptomatic or asymptomatic); could be caused by any changes to the sensitive environment that allows for the overgrowth of organisms that are usually suppressed |
| What is the most common pathogen in VVC (Vulvovaginal candidiasis) | Candida spp; candida albicans (80-92% of VVC); C. glabrata (7-16%) |
| What are the risk factors for VVC? | -Contraceptive agents (i.e. diaphragms w/ spermicide, sponges, IUD, vaginal rings, high dosed OCs; -Increased Estrogen levels (pregnancy, post-menopausal) -Prior antibiotic use -Sexual activity (though not sexually transmitted)* -Genetics -Chronic Conditions (immunosuppressed, uncontrolled Diabetes) |
| What are signs of VVC? | Vaginal/vulvar erythema, "Curdy-cheese like discharge", Edema, Fissuring |
| What are sympotoms of VVC? | Intense, valvular itching, soreness, irritation, burning on urination, Dyspareunia |
| What are the goals of therapy for VVC? | Complete resolution of symptoms |
| By week 6, 25-40% of women will have (+) yeast cultures, but remain ______ | asymptomatic |
| Asymptomatic colonization with candida species does not require ______ | treatment; only treat if symptomatic |
| What are examples of uncomplicated infections? | mild-moderate s/sx; sporadic, infrequent episdodes (<3 per year); immunocompetent; non-pregnant pts |
| What are examples of complicated infections? | immunocompromised pts; pts with uncontrolled diabetes or pregnant pts; infection caused by NON-ALBICANS species; severe signs or symptoms |
| Defnition of a recurrent infection? | 3 or more infections in 12 months |
| Which of the following would be defined as an uncomplicated infection? | 42 yo female with her 2nd episode of VVC this year |
| Which of the following would be defined as a complicated infection? | 28 yo pregnant female presenting with VVC; 38 yo female with SEVERE VVC symptoms |
| Which of the following would be defined as a recurrent infection? | 19 yo female presenting with her 4th VVC infection this year |
| What are non-pharm recommendations for VVC? | -avoid harsh soaps and perfumes in vaginal areas -genital area should be kept clean and dry -avoid constrictive clothing -avoid douching -cool baths (avoid hot baths) |
| What are recommended treatment options for uncomplicated VVC? | Topical azole or PO fluconazole 150 mg x 1 (no difference in cure rates b/w PO and topical) |
| What are recommended treatment options for complicated VVC? | Topical azole daily for 7-14 days; PO fluconazole: 150 mg q72h for 2-3 doses (day 1, 4, 7); **oral azoles contraindicated in pregnant patients |
| What are recommended treatment options for recurrent VVC? | Topical azole daily for 7-14 days; PO fluconazole: 150 mg q72h for 2-3 doses (day 1, 4, 7) THEN 100-200 mg once weekly for 6 months **induction followed by maintenance therapy |
| Epidemiologic studies indicate a single 150 mg dose of fluconazole might be associated with ______ _____ and _____ _______ | spontaneous abortion; congenital anomalies; Shah: "so for pregnant pts give topical and send home" |
| What are some examples of OTC vaginal products? | -Butoconazle (Femstat-3) -Clotrimazole (Gyne-Lotrimin 7/ Mycelex-7/ Gyne-Lotrimin-3) -Miconazole (Monistat 1/3/7 Cure and Itch relief) -Ticonazole (Monistat 1 Simple Therapy) |
| What are some examples of Rx topical vaginal products for VVC? | Butoconazole (Gynazole-1) -Terconazole (Terazol 3/7) (Zazole) |
| What are some examples of Rx oral prescriptions for VVC? | Fluconazole (Diflucan) |
| What are some counseling points for topical azoles? | -use applicator from manufacturer -laying down when applying may reduce leakage -Insert as far into vagina w/o causing damage -Do not use diaphragms or latex condoms w/in 72h of tx -Do not use tampons concomitantly -Pts may benefit from nighttime administration -Pts can use utilize pads to prevent leakage into underwear |
| Oropharyngeal & Esophageal Candidiasis are? most common candida? | fungal infection or oral or esophageal mucosa; candida albicans |
| Local and systemic factors that increase risk for Oropharangeal and Esophageal candidiasis? | Local: inhaled corticosteroid use, dentures, smoking, xerostmia Systemic: PPI use, HIV infection, diabetes, malignancy |
| Other s/sx of OPC include: | Symptoms: Sore painful mouth, burning tongue, metallic taste, Dysphagia, Odynophagia Signs: Diffuse erythema, white patches on the surface of the bucal mucosa, throat, tongue, or gums Diagnosis: scraping of lesions for culture |
| Other s/sx of EC: | Symptoms: Dysphagia, Odynophagia, RETROSTERNAL CHEST PAIN; EPIGASTRIC pain Signs: Consitutional symptoms are common (fever); white or beige plaques of variable sizes; plaques can be hyperemic or edematous and can have ulceration Diagnosis by upper GI endoscopy |
| Treatment for OPC: | Can be treated with either topical or systemci anti-fungal agents; Topical therapy for mild disease Systemic therapy for moderate-severe disease |
| Treatment for EC: | CANNOT be treated with topical (topical wont get to SOA) -Always treat with a systemic agent: 1st line (Fluconazole) -Other agents may be used if pt is unable to tolerate PO therapy |
| OPC Initial treatment: | -Clotrimazole troches 10 mg 5x/day -Miconazole buccal tablets 50 mg daily -Alternative: Nystatin suspension 100,000 U/mL 4-6 mL QID -Duration 7-14 days |
| OPC severe/refractory/recurrent infection treatment: | Severe: Fluconazole PO 100-200 mg daily for 7-14 days Fluconazole-refractory: Itraconazole/ Posaconazole/ Voriconazole for up to 28 days **Refractory (Plaque didn't go away) |
| EC Initial treatment: | -Fluconazole 200-400 mg PO daily for 14-21 days -If cannot tolerate PO--> IV fluconazole 400 mg (6mg/kg) daily (**IV Echinocandins have a higher relapse rate so are not ideal) -Switch to PO Fluconazole when aple to tolerate PO |
| EC Severe/refractory/recurrent infection treatment: | Fluconazole-refractory: Itraconazole/ Posaconazole/ Voriconazole for 14-21 days Recurrent: chronic suppressive therpay with Fluconazole 100-220 mg 3x/week |
| Pt counseling for OPC/EC therapy | -Clean the oral cavity prior to admin the topical anti-fungal agent -Use the topical antifungal over 15 min, not chewed, or swallowed whole, and swallow saliva -swish susp. around mouth to cover all areas for as long as possible (gargle and swallow) -remove dentures while med is being applied to oral tissue -disinfect dentures -Complete tx course -Maintain good oral hygeine |
| Tell me about Fluconazole: | PO or IV AE: headache, N/V/D, hepatotoxicity, liver failure, ALOPECIA, QTc prolongation -Clicnal pears: CYP2C9/3A4 inhibitor--> watch for DDI; greater than 90% BA; -Does not require TDM |
| Tell me about Posaconazole: | Best tolerated; no PO suspensionsl Variable BA AE: rash, HA, N/V/D, hepatotxicity, liver failure, CNS depression, QTc prolongation; Clinical pearls: CYP3A4 inhibitor; Avoid PO suspension due to many admin requirements (high fat and acidic food) that causes drastic absorption variability) -Requires TDM |
| Tell me about Voriconazole: | Remember V for vision -hepatoxicity, PHOTOSENSITIVITY, reversible visual changes, bone toxicity, QTc prolongation; Clinical Pearls: Strong CYP2C19 inhibitor and substrate, and CYP3Ar substrate--> watch for DDI; -INDEPENDENT RISK FACTOR FOR SKIN CANCER in LUNG TRANSPLANT pts -Requires TDM |
| Tell me about Itraconazole: Brand name: Sporanox (PO/Solution); Tolsura (Capsule) | AE: rash, HA, GI upset, hepatotoxicity, liver failure, delirium, QTc prolongation; Clinical Pearls: CYP 3A4 inhibitor/substrate--> watch for DDIs; Avoid PPIs/H2Ras -BBW for pts with HEART FAILURE; for BA: Tolsura > solution > Sporanox (**Formulations are NOT INTERCHANGEABLE); -Requires TDM |
| Tell me about Isavuconazole: | AE: Headache, Hepatotoxicity, QTc SHORTENING; Clinical Pearls: CYP 3A4 substrate--> watch for DDIs; Prodrug converted from isavuconazonium -DOES NOT REQUIRE TDM |
| What is tinea pedis? Treatment? | "Athlete's foot, generally presents with scaly rash b/w toes Tx: topical anti-fungals |
| What is Tinea Cruris? Treatment? | "Jock Itch", invovles the proximal thigh or buttocks Tx: topical antifungals; systemic therapy if extensive involvement, recurrent infection, or failure of topical therapy |
| What is Tinea Corporis? Treatment? | "Ring-worm", infection of the trunk, extremities, or face Tx: Topical antifungals; systemic therapy in widespread infection |
| What is Tinea Unguium? Treatment? | "Onychomycosis", infection of the fingernails or toenails Tx: Terbinafine is first line *Systemic anti-fungals are greater than topical antifungals |
| What are OTC products for Tinea infections? | -Terbinafine cream/gel/spray -Butenafine cream -Clotrimazole cream/ solution -Miconazole spray -Tolnaftate crea/spray/powder |
| What are some Rx products for Tinea infections? | -Naftatine cream/gel -Econazole cream/Foam -Luliconazole cream -Oxiconazole cream/lotion -Sertaconazole cream |
| What is the cure rate for oral antifungal drugs for onychomycosis? (Fingernails) | Terbinafine cure rate: 59% at 24 weeks Itraconazole cure rate: 46% at 24 weeks Fluconazole cure rate: 76% at 9 months |
| What is the cure rate for oral antifungal drugs for onychomycosis? (Toenails) | Terbinafine cure rate 46% at 72 weeks; 28% at 18 months (500 mg PO Itraconazole (200 q24--> 14% at 72 weeks; relapse: 21% at 5 yrs; 200 mg q12 23% at 72 weeks; relapse: 48% at 5 yrs Fluconazole: 28% at 12 months; relapse: 7% at 12 months |
| Topical Antifungal drugs for Onychomycosis: | Cicopirox 7% at 48 weeks; relapse 40% at 15 months Efinaconazole: 17% at 52 weeks Kerasal nail: 27% at 24 weeks Tavaborole: 10% at 52 weeks Vicks Vaporub: 22% at 48 weeks Tea tree oil: 18% at 6 months |
| Topcial vs Oral for Onychomycosis: | cure rates are higher for PO terbinafine; relapse rates are lower for PO terbinafine -Multiples nails can be treated with PO terbinafine -PO terbinafine requires a shorter duration of use -PO terbinafine is most affordable option **We love terbinafine for onychomycosis |
| Tinea corporis/Cruris/pedis are generally responsive to topical creams such as ________ (Lamisil) and ________ (Lotrimin) | terbinafine/ butenafine |
| ___ ________ agents may be indicated for extensive disease, failed topical treatment, immunocompromsed pts, or severe moccasin-type tinea pedis | PO anti-fungal |
| Oral terbinafine is preferred in those with ___________. In those with CI to oral ________, topical therapy may be given, but is less likely to result in cure and must be given for a longer duration | onychomycosis, terbinafine |
| Although oral contraceptives hafve been associated with increased risk for VVC, this has only been seen with ___ -____ regimens | high-dose |
| OPC may be treated with _____ agents, however EC should always be treated with ______ agents | topical; systemic |
| Dermatophyte infections can occur in various areas of the body, and risk factors for dermatophyte infections are prolonged exposure to ____, soaking in water, maceration, intertriginous ____, sharing personal belongings, and close living quarters | sweat; folds |
| Risk factors for development of skin, hair, and nail mycotic infections include: | prolonged exposure to sweat, soaking in water, maceration, intertriginous folds, sharing personal belongings such as combs, and close living quarters |
| Usual pathogens for skin, hair, and nail mycotic infections include: | Dermatophytes, Trichophyton, Epidermophyton, Microsporum, and Malassezia |
| Topical allylamine anti-fungal drugs are preferred for those with _____ infections given their short duration | tinea |
| What is an endemic fungal infection and provide examples? | can be seen in previously helathy pts, although immunocompromised pts tend to ahve HIGHER rates of severe infections or dissemination; examples include: Histoplasmosis, Coccidioidomycosis, Blastomycosis |
| What is an opportunistic fungal infection and provide examples? | Occur almost EXCLUSIVELY in immunocompromised pts with extensive underlying disease (i.e. critically ill pts) Examples include: Candidiasis, Aspergillus, Mycormycosis |
| Risk factors for Endemic and opportunistic infections include: | -Recent chemotherapy -Immunosuppressive therapy -Solid organ or bone marrow transplantation -Critically-ill pts -Extensive broad-spectrum antibiotic use -Home parenteral nutrition -Abdominal surgery/burns |
| Diagnosis of endemic or opportunistic infections include: | -Evaluation of clinical symptoms -Serological tests (Beta-D-glucan for candidasis; Aspergillus galactomannan for aspergillosis; antibodies against endemic fungi -Histopatholigic evaluation -Culture of specimens |
| Tell me about the (1,3)-B-D Glucan (BDG) ASSAY: | AKA: FUNGITELL -The most abundant polysaccharaide contained in the cell wall of most fungi -"Pan-fungal" biomarker: which include candida spp, Aspergillus spp, Fusarium spp., P. Jirovecii -Excludes: Zygomycetes, Blastomyces, and Cryptococcus spp. |
| Tell me about the Galactomannan (GM) ASSAY: | The major polysaccharide component of Aspergillus spp. cell walls, released during growth, produced by other fungi as well; -Most sensitive for: Aspergillus spp., Penicillium spp., Paecilomyces spp., Histoplasma spp. |
| Histoplasmosis Capsulatum: What is Histo? | Dimorphic fungi endemic to OHIO and Mississippi river valleys, central and south america Grows in soul, and bird and bat droppings |
| Histoplasmosis Capsulatum: What are some manifestations? | Symptomatic pts are usually entirely immunosuppressed; commonly stays below the neck (NO CNS diseases (neck down only) |
| Histoplasmosis Capsulatum: What is the first-line treatment option? | Itraconazole (PO only (we like Tulsera when it comes to BA) BBW: can't use in pts with existing HEART FAILURE; Alternatives: AmB or Fluconazole |
| Blastomycosis: What is Blasto? | B. dermatitidis is endemic to the midwestern, southwestern, and south-central US. Found in soli and decaying vegetation, particularly near lakes and rivers |
| Blastomycosis: What are some manifestations? | usually localized to the LUNGS--> pneumonia Mild and self-limiting in immunocompetent hosts |
| Blastomycosis: What is the first-line treatment option? | Itraconazole Alternatives: AmB or Fluconazole |
| Coccidiodomycosis: What is Cocci? | aka: VALLEY FEVER Symtoms are very similar to pneumonia (CAP) |
| Coccidiodomycosis: What are some manifestations? | -can cause acute and chronic Pneumonia (Think LUNGS) -can cause pulmonary nodules and cavities -extrapulmonary non-meningeal disease -Meningitis--> more common in HIV pts |
| Coccidiodomycosis: What is the first-line treatment option? | Fluconazole (HIGH-DOSE) Alternatives: Itraconazole In critically-ill pts: start with AmB and step down to Fluconazole (**Remember that AmB is IV only) |
| Cryptococcus: What is Crypto? | C. Neoformans is worldwide and affects immunocompromied pts C.gatti is more regional and affects immunocompetent hosts Cryptococcus can penetrate the BBB and cause CNS symptoms |
| Cryptococcus: What are some manifestations? | Pulmonary infection or Cryptococcal meningitis -can affect any organ of the body--> cutaneous, eye, bone, prostate, etc |
| Cryptococcus: What is the first-line treatment option? | For Cryptococcal meningitis: Liposomal AmB + 5-FC -Cryptococcal pulmonary disease: Fluconazole |
| Histoplamsa camsulatum: 1. Clincal Manifestations? 2. First-line treatments? | 1. Lungs; can cause CNS infection, endocarditis, disseminated disease 2. Itraconazole or AmB |
| Blastomyces dermatitidis: 1: Clinical Manifestations? 2. First-line treatments? | 1. Lungs, Disseminates to skin, bones, prostate, O/P mucosa, abdomen 2. Itraconazole or AmB |
| Coccidioides immitis: 1. Clinical Manifestations? 2. First-line treatments? | 1. Lungs, Disseminate to skin, lymph nodes, bone, meninges, spleen, liver, adrenal gland 2. Fluconazole or Itraconazole or AmB |
| Cryptococcus neoformans or gatti: 1. Clinical Manifestations? 2. First-line treatments? | 1. Lungs--> CNS infections 2. Induction: AmB + Flucytosine Suppressive: Fluconazole |
| Invasive candidiasis can occur in hospitalized pts if Candida infects the ______ (candidemia), organs, bones, or other sterile sites | bloodstream |
| What are the "friendly" types of Candida? | C. albicans, parapsilosis, tropicalis, lusitaniae |
| What are the "more-resistant" types of Candida? | C. glabrata, auris, krusei |
| Invasive candidiasis is usually acquired from the ___ ____ or from skin flora via _____________ catheters | GI tract; indwelling |
| Mortality rates estimated between: | 45-55% |
| What is the gold standard of Invasive candidiasis diagnosis? | blood culture |
| Reminder question: Which serology test can be used for invasive candiasis? | B-D-glucan |
| What are some risk factors for Invasive Candiasis (IC)? | -Renal failure/Hemodialysis -Parenteral nutrition -IV antibiotic use -Immunosuppression -Abdominal trama/ surgery -Central Venous Catethers -Candida colonizaiton -Increasing severity of illness |
| IDSA treatment guidelines include--> in non-neutropenic, critically-ill pts, ________ preferred as initial therapy; step down to _____ if cultures and susceptibilities results allow | Echinocandins; azole (fluconazole usually) |
| IDSA treatment guidelines include---> Echinocandins do not penetrate well into the CNS, so ___________ should be used for CNS infections | IV amphotericin B |
| Candida naturally live in the respiratory tract, so pts with a Candida spp. identified in the _______ ______ might NOT require treatment; MUST think of typical colonization vs infection | respiratory tract **dont want to treat what is naturally there, may make it worse with another infection growth. *remember your sterile and non-sterile sites |
| IDSA treatment guidelines--> Alternate therapies include _______ accepted in select pts (clinically stable, no prior triazole therapy) | Fluconazole |
| IDSA treatment guidelines--> Alternative therapies include ______ (recommended for suspected azole or echinocandin-resistant infection | Liposomal Amphotericin B |
| IDSA treatment guidelines--> Alternate therapies include _______ (effective but not advantage over fluconazole unless fluconazole-resistant strains, such as ________ or _________ | Voriconazole; C. Krusei or C. Glabrata *must remember the Anti-fungal chart |
| For Candidemia management the goal is to get source control so we can: | 1. Remove offending agent, if possible (Central Venous catheters) 2. Dilated eye exam w/in the 1st week after diagnosis to assess for possibility of endophthamitis 3. Repeat blood cultures DAILY to establish clearance 4. Transistion to Fluconazole if clincally stable, blood cultures have cleared following 5-7 days of therapy, and isolate is susceptible |
| For Candidemia managemen: what is the recommended duration of therapy? | greater than or equal to 2 weeks (up to 6 months) |
| If endophthamitis is diagnosed, which antifungal should not be used due to low/no CNS penetration? | Micafungin **remember your echinocandins do not penetrate the CNS at all For CNS infection you would use an azole such as Voriconazole (remmebr BBW) or use Liposomal AmB |
| Candiemia Algorithm from Shah includes: | 1. initial treatment with Echinocandins 2. Transistion to PO Fluconazole if possible 3. Treat for at least 14 days |
| Aspergillosis is a? | UBIQUITOUS mold that exists everywhere (plants, soil, indoors and exposure is universal |
| what is the most common Aspergillus? most common manifestation? | A. Fumigatus; Pulmonary manifestations |
| What is the disease spectrum for Aspergillus spp.? | Immunocompetent hosts--> allergic reason--> allergic bronchopulmonary aspergillosis (ABPA) -immune imparement--> aspergilloma (Fungal Ball) -Immunocompromised--> acute, invasive aspergillosis |
| What are risk factors for Aspergillosis infection? | Prolonged neutropenia (both degree and duration of neutropenia) -Recipeients of hematopoietic stem-cell transplant or solid organ transplants -HIV/AIDS -Chronic granulomatous disease --> COPD cystic fibrosis |
| What is the drug of choice (DOC) for Aspoergillosis? Alternatives? | Voriconazole Alternatives include: Isavuconazole, Posaconazole, and AmB |
| Mucormycosis: what is mucor? | rare fungal infection that can affect pts with major trauma, birns, diabetes, or that are immunosuppressed (not endemic) -Characterize by infarction and necrosis (BLACK/DEAD TISSUE); Mortality rates are up to 90%!!! |
| Mucormycosis: what are some manifestations of mucor? | RHINO-ORBITAL infection is most common Can manifest in CNS, lungs, cutaneous tissue, or GI tract |
| Mucormycosis: what is the first-line treatment option? | CUT IT OUT + Liposoma AmB (LAmB) -Step down to Posaconazole or Isavuconazole -Duration of therapy is years-lifeling |
| Antifungal Adverse effects and Clinical pearls: Amphotericin B? | AE: Nephrotoxicity, infusion rxn (shake and bake), electrolyte abnormalities, hepatotoxicity Clinical Pearls: Caution w/ different formulations (ABDC, LAmB, ABLC), important pre- and post- fluids and medications (1 Liter of fluids) -Does not require TDM |
| Antifungal Adverse effects and Clinical pearls: Fluctosine (5-FC)? | AE: BMS (bone marrow suppression), (anemia, leukopenia, thrombocytopenia), hepatotoxicity Clinical pearls: Antimetabolite-- similar agents used in chemo, hence BMS -Requires TDM |
| Antifungal Adverse effects and Clinical pearls: Echinocandins? | AE; GI upset, HA, elevated liver enzymes, mild infusion rxn Clinical pearls: Very well tolerated -Does not require TDM |
| Endemic fungal infections can occur in anyone, whereas ______ fungal infections generally ONLY occur in pts with relative immunocompromise | opportunistic |
| Endemic fugal pathogens are _________ spp., __________ spp., _________ spp., and Cryptococcus spp. | Histoplasma; Coccidioides; Blastomyces |
| Opportunistic fungal pathogens include: ______ spp., ________ spp., and __________ | Candida; Aspergillus; Mucormycosis |
| In ________ ________, echinocandins are always preferred as initial therapy, regardless of the infecting Candida spp. | invasive Candidiasis |
| Candida ____ is intrinsically resistant to Fluconazole and Candida _______ has variable Fluconazole susceptibility, while all Candida species are highly susceptible to Echinocandins | krusei; glabrata |
| IDSA guidelines recommend empiric echinocandin therapy in pts with _____ | candidemia |
| Aspergillosis typically affects _______ pts and the drug of choice is ______ | immunosuppressed; voriconazole |
| When is day 1 of treatment for pts candidemia? | when you get the first (-) culture back *remember that blood cultures are DAILY |
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Xander635
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