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Questions and Answers
Which of the following are examples of imidazole antifungal drugs?
Which of the following are examples of imidazole antifungal drugs?
Fungal infections are recognized less frequently than bacterial infections.
Fungal infections are recognized less frequently than bacterial infections.
False
Name one factor that contributes to the development of fungal infections.
Name one factor that contributes to the development of fungal infections.
Immunosuppression
The range of antifungal drugs is ______ compared to antibacterial drugs.
The range of antifungal drugs is ______ compared to antibacterial drugs.
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Match the following classes of antifungal drugs with their characteristics:
Match the following classes of antifungal drugs with their characteristics:
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Which of the following triazole drugs is indicated for the treatment of candidiasis?
Which of the following triazole drugs is indicated for the treatment of candidiasis?
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Griseofulvin is more commonly used as a first-line treatment compared to triazoles.
Griseofulvin is more commonly used as a first-line treatment compared to triazoles.
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What is the primary adverse effect associated with voriconazole, particularly in cats?
What is the primary adverse effect associated with voriconazole, particularly in cats?
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Flucytosine is a ______ synthesis inhibitor and is synergistic with amphotericin.
Flucytosine is a ______ synthesis inhibitor and is synergistic with amphotericin.
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Which anticancer drug is noted for having occasional resistance reported?
Which anticancer drug is noted for having occasional resistance reported?
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Match the following antifungal drugs with their respective characteristics:
Match the following antifungal drugs with their respective characteristics:
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Resistance is exclusively reported in the azole class of antifungal drugs.
Resistance is exclusively reported in the azole class of antifungal drugs.
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Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes are classified as ______.
Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes are classified as ______.
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Which of the following is NOT a common non-infectious cause of fever?
Which of the following is NOT a common non-infectious cause of fever?
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Antifungal susceptibility tests are standardized only for yeasts.
Antifungal susceptibility tests are standardized only for yeasts.
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What are the two considerations included in antimicrobial therapy decision-making?
What are the two considerations included in antimicrobial therapy decision-making?
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Antifungal susceptibility tests can be __________ and costly to perform.
Antifungal susceptibility tests can be __________ and costly to perform.
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Match the following non-infectious causes of fever with their classifications:
Match the following non-infectious causes of fever with their classifications:
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Which of the following is a principle to consider when selecting antimicrobial drugs?
Which of the following is a principle to consider when selecting antimicrobial drugs?
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Patients with immune-mediated conditions require no special considerations in antimicrobial therapy.
Patients with immune-mediated conditions require no special considerations in antimicrobial therapy.
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Name one empirical consideration when selecting antifungal therapy.
Name one empirical consideration when selecting antifungal therapy.
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Which route of administration is NOT mentioned for antimicrobial therapy?
Which route of administration is NOT mentioned for antimicrobial therapy?
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Lipophilic drugs penetrate cellular barriers more readily than hydrophilic drugs.
Lipophilic drugs penetrate cellular barriers more readily than hydrophilic drugs.
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What are the three factors that influence the route of administration for drugs?
What are the three factors that influence the route of administration for drugs?
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Drugs that are very lipophilic can penetrate _____ fluids.
Drugs that are very lipophilic can penetrate _____ fluids.
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Match the following groups of drugs with their characteristics:
Match the following groups of drugs with their characteristics:
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Which of the following are considered to be polar (hydrophilic) drugs?
Which of the following are considered to be polar (hydrophilic) drugs?
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Adverse reactions and host considerations do not impact the choice of antimicrobial therapy.
Adverse reactions and host considerations do not impact the choice of antimicrobial therapy.
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What is one route of administration that is considered topical?
What is one route of administration that is considered topical?
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Which of the following antibiotics can effectively penetrate CSF?
Which of the following antibiotics can effectively penetrate CSF?
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All antibiotics can penetrate into intracellular fluids if they are lipophilic enough.
All antibiotics can penetrate into intracellular fluids if they are lipophilic enough.
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What does MIC stand for in pharmacodynamics?
What does MIC stand for in pharmacodynamics?
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Effective concentrations of antibiotics may be achieved in ______, pleural, and peritoneal fluids.
Effective concentrations of antibiotics may be achieved in ______, pleural, and peritoneal fluids.
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Match the following antibiotics with their ability to penetrate specific fluids:
Match the following antibiotics with their ability to penetrate specific fluids:
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What defines a breakpoint in antibacterial therapy?
What defines a breakpoint in antibacterial therapy?
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Inflammation can assist in the penetration of antibiotics into tissues.
Inflammation can assist in the penetration of antibiotics into tissues.
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What is the primary factor affecting penetration into CSF and ocular fluids?
What is the primary factor affecting penetration into CSF and ocular fluids?
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What does it mean if an isolate's MIC is below the susceptible breakpoint concentration?
What does it mean if an isolate's MIC is below the susceptible breakpoint concentration?
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Isolate MIC values help determine if a bacterium is susceptible, intermediate, or resistant to an antimicrobial agent.
Isolate MIC values help determine if a bacterium is susceptible, intermediate, or resistant to an antimicrobial agent.
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What are two factors that establish breakpoints in microbiology?
What are two factors that establish breakpoints in microbiology?
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The main condition when an isolate is classified as intermediate is if the MIC is between the _____ and resistant breakpoint concentrations.
The main condition when an isolate is classified as intermediate is if the MIC is between the _____ and resistant breakpoint concentrations.
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Match the following terms with their definitions:
Match the following terms with their definitions:
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Which of the following is a pathologic cause that can influence drug disposition?
Which of the following is a pathologic cause that can influence drug disposition?
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Host considerations do not play a role in antimicrobial therapy decisions.
Host considerations do not play a role in antimicrobial therapy decisions.
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Name one key pharmacokinetic parameter that may be altered due to physiologic changes.
Name one key pharmacokinetic parameter that may be altered due to physiologic changes.
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Study Notes
Antifungal Drugs
- Antifungal drugs are discussed in two parts: drug types and approach to prescribing.
- Learning objectives include contrasting antifungal and antibacterial agents' activity spectra, explaining mechanisms of action for common antifungal classes, comparing antimicrobial drug resistance in fungi and bacteria, providing examples of drugs for common fungal diseases, understanding antimicrobial prescribing facets (microorganisms, pharmacokinetics, pharmacodynamics, host considerations, toxicity/adverse effects, cost), and giving examples of prescribing guides.
- Fungal infections are increasingly recognized as a cause of hospital-acquired infections, often exacerbated by immunosuppression, malnutrition, or indwelling catheters. Broad-spectrum antibacterial drug use can contribute.
- Antifungal drugs have a limited range compared to antibacterial drugs. Mammals and their fungal pathogens share common cellular characteristics.
Antifungal Drugs: Overview
- Antifungal drugs target various fungal cell components.
- Flucytosine inhibits DNA/RNA synthesis.
- Griseofulvin disrupts microtubule function.
- Naphthoquinones inhibit mitochondria function.
- Polyenes disrupt membranes.
- Imidazoles and allylamines inhibit ergosterol synthesis.
- Echinocandins inhibit the synthesis of β(1-3) glucans.
- Nikkomycins and polyoxins inhibit chitin synthesis.
Antifungal Drugs 1: Azoles
- Azoles, like fluconazole, voriconazole, and posaconazole, target ergosterol synthesis in the fungal cell membrane.
- The drug inhibits ergosterol synthesis, disrupting the membrane, leading to toxic sterol production.
Imidazole Drugs
- Ketoconazole is lipophilic, has good oral bioavailability, but limited distribution. It's inexpensive but has common adverse effects and is less effective than triazoles. It is synergistic with amphotericin and flucytosine. Resistance is reported.
- Miconazole is effective for dermatophytosis, especially for Malassezia species and Microsporum species. Frequently used as a topical treatment and is frequently combined with other medications.
Triazole Drugs
- Fluconazole is water-soluble, has good oral bioavailability, short half-life, a narrow spectrum, and few adverse effects. Used for candidiasis.
- Itraconazole is lipophilic, has a short half-life, wide distribution, binds keratin, shows few adverse effects, and is used for blastomycosis.
- Voriconazole has excellent tissue penetration, is a broad-spectrum drug, but adverse effects (mostly neurological symptoms) can occur, especially in cats.
Antifungal Drugs 2: Flucytosine & Griseofulvin
- Flucytosine is a pyrimidine synthesis inhibitor, has good oral bioavailability and tissue penetration, synergistic with amphotericin, and treats, among other conditions, cryptococcosis. Resistance to it is observed in Candida and Cryptococcus.
- Griseofulvin is a benzofuran antibiotic that is orally bioavailable, but absorption varies. It is preferentially deposited in keratin, requiring prolonged therapy. Occasional resistance is reported, and the drug is teratogenic in cats.
Antifungal Drugs 3: Polyenes
- Polyenes, such as amphotericin B and nystatin, are broad-spectrum antifungal drugs. They have a long half-life and extensive distribution. They are frequently nephrotoxic and cause thrombophlebitis.
- Amphotericin B and related drugs target ergosterol.
- Common clinical uses include systemic fungal infections.
Antifungal Drugs 4: Allyl amines
- Terbinafine is a lipophilic drug with good oral absorption and urinary excretion. It penetrates keratinized tissues, leading to prolonged persistence in hair and synergism with azoles. Broad-spectrum, rare resistance, and some gastrointestinal side effects have been reported.
Antifungal Drugs 5: Echinocandins
- Echinocandins, like micafungin and caspofungin, have extensive tissue distribution and are given intravenously. They are often synergistic with azoles, have a narrow spectrum of resistance, and typically cause only rare adverse effects.
Pharmacodynamics of Antifungal Drugs
- Time-dependent effects: %T > MIC is important for flucytosine.
- Concentration-dependent effects: Cmax/MIC and AUC/MIC are key parameters for polyenes, echinocandins, and triazoles.
Antifungal Drug Resistance
- Antifungal drug resistance can result from prolonged treatment. It depends on the drug's mode of action (e.g., reduced drug uptake like azoles, drug export through efflux pumps like azoles, or altered affinity of target enzymes). Unlike bacteria, fungi do not acquire transferable drug resistance.
Antifungal Susceptibility Testing
- Fungi exist in various forms (yeasts, filamentous fungi, dimorphic fungi).
- In vitro tests, standardized for yeasts and filamentous fungi, have technical challenges and high costs. Empirical choices can be used to determine probable susceptibility.
Principles of Antimicrobial Drug Selection and Use
- Antimicrobial therapy considerations are interconnected among microorganisms, pharmacodynamics, pharmacokinetics, host factors, and cost.
- Considerations often include adverse effects along with likely species involved and probable susceptibility in patients.
Routes of Administration
- Routes of administration for drugs can include intravenous, intramuscular, subcutaneous, oral, topical, and regional infusion routes.
- Factors influencing choice include drug type, pharmacokinetics, physicochemical properties, formulation, bioavailability, route of elimination, location, and nature of infection.
Physicochemical Drug Properties
- Polar drugs (hydrophilic, low lipophilicity) have limited ability to cross cell membranes.
- Moderate to high lipophilic drugs readily penetrate membranes.
- Highly lipophilic drugs readily cross barriers and accumulate in lipids.
MICs and Breakpoints
- MIC is the lowest drug concentration that stops bacterial growth.
- Breakpoints describe the concentrations that separate susceptible, intermediate, and resistant isolates.
- Breakpoints are commonly derived from population MIC studies and clinical pharmacology and tissue-dependent.
How are Breakpoints Established
- EUCAST and CLSI provide standardized guidance for breakpoint establishment.
- Breakpoints consider large population MIC distributions, clinical pharmacology, target-species concentrations (cmax & cmin), and AUC24h (dose concentration in 24-hours), and half-life.
Breakpoint Interpretation
- Clinical susceptibility or resistance is ascertained by where the calculated MIC lies relative to the breakpoint.
- Breakpoints are tissue specific.
Duration of Therapy: Clinical Trials in humans
- Stewardship principles emphasize shorter treatment durations whenever possible, as supported by published studies.
Duration of Therapy: Common Infections in humans
- Common infectious treatment durations vary based on the specific infection.
Potential Reasons for Antimicrobial Treatment Failure
- Treatment can fail due to factors like infection absence, insensitivity of the pathogen to the chosen drug, incorrect drug dosing or administration route, or source control issues. Also included are pharmacokinetic, pharmacodynamic, and antagonistic considerations.
Adverse Drug Reactions
- Antifungal drugs can cause adverse reactions in various organs (e.g., CNS/PNS, skin, ocular, renal, bone marrow).
- Relevant drug classes include aminoglycosides, cephalosporins, fluoroquinolones, macrolides, nitroimidazoles, polypeptides, and others.
Cost
- A graph depicts antifungal drug prices over time.
- Drug cost is an important consideration in antimicrobial therapy.
Minimum Withdrawal Times
- Withdrawal times for various antibiotic injectable medications, likely for veterinary use, are listed.
Prescribing Guides
- Many resources provide guidance for antibiotic prescribing.
4 Moments of Antibiotic Decision-Making
- The 4 moments of antibiotic decision-making include assessing for infection, diagnostics, selecting treatment, and patient education, encompassing a systematic approach.
The Antibiotic Decision-Making Process
- The process of prescribing antibiotics involves data gathering (history, physical examination, same-day diagnostics), decision processes, antibiotic selection/formulation, observation of patient response, and communication.
Source Decide Treat Patient Plan
- Use of the acronym SODAPOP aids in the decision-making process, identifying the source of infection, making the decision to treat, considering the patient factors, and developing the treatment plan.
Firstline
- Firstline is a digital resource providing antimicrobial use guidelines.
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Description
This quiz explores the types of antifungal drugs and their prescribing practices. Learn about the differences between antifungal and antibacterial agents, their mechanisms of action, and the considerations for effective antimicrobial prescribing. Understand the growing significance of fungal infections in clinical settings.
