NAPLEX - Invasive fungal infections McGraw Hill

Which of the following agents is recommended as therapy for invasive aspergillosis? Select all that apply.

A

Amphotericin B deoxycholate

B

Fluconazole

C

Voriconazole

D

Liposomal amphotericin B

E

Terbinafine

ACD

Amphotericin B is a drug of choice for Aspergillus species.

Answer c is correct.Voriconazole is a drug of choice for Aspergillus species.

Answer d is correct. Lipid formulations of amphotericin B are a drug of choice for Aspergillus species.

Answer b is incorrect.Fluconazole lacks activity against molds such as Aspergillus.

Answer e is incorrect.Terbinafine is used for cutaneous infections.

TI is a 44-year-old patient with an aspergillosis infection. She is to receive treatment with amphotericin B. Which one of the following adjunctive measures is used to lessen the occurrence of nephrotoxicity associated with amphotericin B?

A

Test dose of amphotericin B

B

Diphenhydramine premedication

C

Normal saline boluses

D

Furosemide

C

Although not proven via large-scale controlled trials, data from animal and small human studies suggest a decrease in nephrotoxicity. Patients will often receive a 500-mL IV bolus of normal saline solution before starting the amphotericin B infusion. Saline doses are also often administered after the dose of amphotericin B.

Answer a is incorrect. This may help identify patients who might develop an infusion-related adverse effect (fevers, chills, rigors, or hypotension) or anaphylaxis. Most experts do not advocate this anymore due to the poor predictive value. However, during initial dosing, the drug should be administered under close monitoring.

Answer b is incorrect. This is believed to reduce the occurrence of infusion-related adverse effects (fevers, chills, and rigors). Other medications that might be used to treat/prevent the infusion-related reactions include acetaminophen, nonsteroidal anti-inflammatory medications, and hydrocortisone. If the patient continues with severe rigors despite the premedication, meperidine may be used.

Answer d is incorrect. Use of furosemide can often contribute to renal insufficiency in patients receiving amphotericin B.

Which antifungal preparation carries a relative contraindication against use in patients with severe renal insufficiency (due to risk of renal complications from a carrier molecule). Select all that apply?

A

IV posaconazole

B

IV voriconazole

C

Oral itraconazole

D

IV caspofungin

E

Oral voriconazole

AB

IV voriconazole and IV posaconazole use a cyclodextrin carrier molecule. Related cyclodextrins have been associated with nephrotoxicity in some animal studies.

Answers d and e are incorrect. No carrier molecule is contained in these formulations.

Answer c is incorrect. Oral itraconazole solution uses a cyclodextrin carrier molecule, but it does not enter the systemic circulation.

BB is receiving initial therapy for Cryptococcus. His provider has been monitoring for toxicity and identified that BB has a low granulocyte count (previously within normal limits). Which of the following antifungal agents is associated with bone marrow suppression?

A

Fluconazole

B

Amphotericin B

C

Voriconazole

D

Flucytosine

D

5-Flucytosine is known to cause blood dyscrasias. Bone marrow toxicity (as well as hepatic) is dose-related; monitor levels closely and adjust dose accordingly.

Answers a and c are incorrect. The azoles have not been identified as a common cause of blood dyscrasias. Note: Be careful about using drug information resources when looking up or studying adverse reactions. Azole antifungals have hematologic side effects listed, but they are extremely rare.

Answer b is incorrect.Amphotericin B may cause a normocytic-normochromic anemia. The drug has been rarely associated with neutropenia.

A patient with a QTc interval of 460 ms needs an azole antifungal agent that can be used to treat invasive candidiasis and will not prolong the QTc interval. Which one would be the safest?

A

Itraconazole

B

Isavuconazole

C

Posaconazole

D

Fluconazole

B

Isavuconazole does not prolong the QTc interval. As a matter of fact, it can actually cause a shortening of QTc.

A patient with a histoplasmosis infection is to be discharged from the hospital and started on oral itraconazole capsules. Which one of the following statements would you tell the patient about his medication to maximize the oral absorption?

A

Take with food and avoid concomitant use of antacids.

B

Take on an empty stomach.

C

Food will not affect the oral absorption.

D

Do not take this with cola.

A

For optimal dissolution and absorption of itraconazole capsules an acidic pH is desired.

Answer b is incorrect.Itraconazole should be taken with food. Soln w/o food, cap/tab WF

Answer c is incorrect. Studies have shown that food can significantly improve oral absorption.

Answer d is incorrect. Administration with cola has been one way to provide some acidic fluid to increase dissolution and absorption.

Lipid-based or liposomal amphotericin B formulations have what advantage over conventional amphotericin B (deoxycholate)?

A

Less expensive than conventional amphotericin B

B

Decreased mortality

C

Decreased rates of nephrotoxicity

D

More efficacious than conventional amphotericin B

C

Changes in serum creatinine are less pronounced with lipid-based formulations.

Answer a is incorrect. Liposomal formulations are considerably more expensive.

Answer b is incorrect. This has not been shown in well-designed trials.

Answer d is incorrect. This has not been shown in well-designed trials.

Which antifungal agent now comes in a delayed-release tablet?

A

Itraconazole

B

Isavuconazole

C

Posaconazole

D

Fluconazole

C

.Posaconazole now comes in a delayed-release tablet that provides more reliable oral absorption than the original oral liquid product.

Which one of the following antifungal agents is most often monitored by therapeutic drug monitoring (TDM)?

A

Amphotericin B

B

Amphotericin B lipid complex

C

Fluconazole

D

Voriconazole

D

TDM is often employed when using voriconazole, due to metabolic variability and drug interaction risk.

Answer a is incorrect. TDM is not performed with amphotericin B.

Answer b is incorrect. TDM is not performed with amphotericin B.

Answer c is incorrect. TDM is rarely, if ever performed with fluconazole. This azole is well-absorbed and has less pharmacokinetic variability than other azoles.

Which antifungal agents require renal dosage adjustment when CrCl is significantly reduced Select all that apply?

A

Liposomal amphotericin B

B

Fluconazole

C

Flucytosine

D

Caspofungin

BC

About 80% of a fluconazole dose is eliminated unchanged in the urine. Dosage adjustments are recommended in the package insert.

Answer c is correct.Flucytosine is excreted primarily by the kidneys; renal impairment may lead to accumulation of the drug. Dosage recommendations and TDM are recommended if the drug is used in renal insufficiency.

Answer a is incorrect. Although amphotericin B formulations can cause nephrotoxicity, dosage adjustments are not routinely recommended.

Answer d is incorrect. Echinocandins do not undergo significant renal elimination and do not have renal dosage adjustments.

The fungal cell wall component (1, 3) β-D-glucan is not a key structure in C. neoformans and therefore explains the poor activity of what class of antifungal agents for Cryptococcus?

A

Triazoles

B

Amphotericin B

C

Echinocandins

D

5-Flucytosine

C

Echinocandins inhibit (1, 3) β-D-glucan synthase enzyme that makes (1, 3) β-D-glucan fibrils. They lack activity for cryptococcal infections.

Answer a is incorrect. Triazoles inhibit 14-α-demethylase. They are usually effective for cryptococcal infections.

Answer b is incorrect.Amphotericin B binds to ergosterol. It usually is effective for cryptococcal infections.

Answer d is incorrect. 5-Flucytosine causes defective fungal protein synthesis. It can be effective for cryptococcal infections.

A 54-year-old man with leukemia developed neutropenia 10 days ago after a chemotherapy course. His absolute neutrophil count (ANC) is 200, and he has been febrile for 7 days despite empiric bacterial therapy with imipenem and vancomycin. He was ordered amphotericin B deoxycholate 5 days ago. His CrCl has diminished to less than 30 mL/min. Which one of the following antifungal agents would be an option for a febrile neutropenic patient with renal insufficiency? The provider would like a broad-spectrum antifungal that covers yeasts and molds and an agent that does not affect the kidneys as much as conventional amphotericin B.

A

Liposomal amphotericin B

B

Fluconazole

C

Posaconazole

D

Ketoconazole

A

Although liposomal amphotericin B can still contribute to continued renal failure it affects renal function less. This agent is a broad-spectrum antifungal (yeasts and molds).

Answer b is incorrect. This agent is not advised due to narrow spectrum of activity and fungistatic killing rate.

Answer c is incorrect. This agent is primarily used in the prophylaxis of invasive fungal infections, not treatment. Furthermore the cyclodextrin carrier is relatively contraindicated with his current CrCl.

Answer d is incorrect. This drug is only available in an oral formulation with poor absorption. There is limited data on using this drug in this indication.

When preparing an IV formulation of amphotericin B deoxycholate, the lyophilized amphotericin B powder must first be reconstituted with sterile water. What type of IV fluid must the reconstituted amphotericin B be placed in for IV administration?

A

0.9% Sodium chloride

B

5% Dextrose in water

C

Lactated Ringer solution

D

Any of the above solutions

B

This solution will maintain the micellular distribution that is required for IV amphotericin B deoxycholate.

What drug interaction would be exhibited by adding fluconazole to a person's medication regimen that includes warfarin (stabilized at an international normalized ratio [INR] of 2.5)?

A

Fluconazole and warfarin concentrations would both be reduced.

B

An increase in INR would be expected.

C

Warfarin cytochrome P-450 metabolism would be induced.

D

An interaction would not be expected.

B

.Fluconazole can interact with warfarin primarily through CYP 2C9 and some CYP 3A4 inhibition, increasing warfarin concentrations and therefore the patient's INR.

A patient is to receive home infusion therapy with amphotericin B. What laboratory values should be monitored? Select all that apply.

A

Serum creatinine

B

Serum potassium

C

Serum magnesium

D

Serum Creatine phosphokinase (CPK)

ABC

Amphotericin B is nephrotoxic.

Answer b is correct. Due to nephrotoxicity the kidney loses ability to maintain potassium.

Answer c is correct. Due to nephrotoxicity the kidney loses ability to maintain magnesium.

Answer D is incorrect. Although myopathies are reported rarely, CPK is not routinely monitored for amphotericin B.

What is the generic name for Cresemba?

A

Itraconazole

B

Isavuconazole

C

Posaconazole

D

Ketoconazole

B

.Itraconazole is the generic name of Sporanox.

Answer c is incorrect.Posaconazole is the generic name of Noxafil.

Answer d is incorrect.Ketoconazole is the generic name of Nizoral.

A 58-year-old febrile woman in the surgical intensive care unit has one out of two blood culture bottles growing yeast and is hemodynamically unstable. Initial culture reveals C. glabrata. What is the best empiric decision for this patient?

A

Start fluconazole 400-800 mg IV daily.

B

Wait for a susceptibility report and then start with a sensitive antifungal agent.

C

The one out of two blood bottles and the urine culture do not require therapy.

D

Initiate caspofungin 70 mg × 1 dose, then 50 mg daily.

D

Echinocandins such as caspofungin would be active against C. glabrata, and would be preferred over fluconazole in this case due to potential dose-dependent resistance as well as hemodynamic instability.

Answer a is incorrect. This option could be used, but many C. glabrata strains may require higher doses of fluconazole based on in vitro susceptibilities (S-DD). Additionally, the patient is hemodynamically unstable which would then indicate a preference for echinocandin therapy. Fluconazole could be used after susceptibilities become known if the patient clinically stabilizes.

Answer b is incorrect. Generally antifungal therapy is initiated and changed if needed based on the susceptibility results or clinical situation.

Answer c is incorrect. All positive blood cultures growing yeast should receive treatment.

A 55-year-old man is to be treated for invasive aspergillosis. He weighs 100 kg. What amphotericin B formulation dose(s) would be appropriate for this patient? Select all that apply.

A

Amphotericin B deoxycholate 80 mg

B

Amphotericin B deoxycholate 400 mg

C

Liposomal Amphotericin B 400 mg

D

Liposomal Amphotericin B 80 mg

E

Liposomal Amphotericin B 800mg

AC

The recommended dose of amphotericin B deoxycholate is 0.5 to 1.5 mg/kg.

Answer c is correct: The recommended dose for liposomal amphotericin B is 3 to 5 mg/kg.

Which of the following antifungal agents has been shown to cause visual acuity side effects?

A

Amphotericin B

B

Flucytosine

C

Fluconazole

D

Voriconazole

E

Caspofungin

D

About 30% of patients in clinical trials reported some degree of reversible changes in visual acuity with voriconazole.

Genetic variability in cytochrome P-450 CYP 2C19 has been linked to significant interpatient pharmacokinetic differences for which antifungal agent?

A

Fluconazole

B

Voriconazole

C

Micafungin

D

Flucytosine

B

Studies indicated that CYP 2C19 is significantly involved in the metabolism of voriconazole. This enzyme exhibits genetic polymorphism. About 3% to 5% of Caucasians and 12% to 23% of Asians are expected to be poor metabolizers.

Answer a is incorrect.Fluconazole is not a significant substrate for CYP 2C19.

Answer c is incorrect.Micafungin is not a CYP-450 substrate.

Answer d is incorrect.Flucytosine is not a CYP-450 substrate.

BK is a 40-year-old HIV-positive patient. He develops CSF culture-positive cryptococcal meningitis. He has no hepatic or renal insufficiency and his complete blood count is within normal limits. Select the preferred antifungal induction regimen for a patient with cryptococcal meningitis.

A

Amphotericin B deoxycholate + flucytosine

B

Amphotericin B deoxycholate

C

Liposomal amphotericin B

D

Fluconazole

A

This is regarded as the first-line regimen. Flucytosine has excellent cerebrospinal fluid (CSF) penetration. Historically, it was used as monotherapy, but resistance quickly developed. It is now used as adjunctive therapy with amphotericin B to avoid failure due to resistance and to optimized killing due to synergistic killing of both agents.

Answer b is incorrect. This would be a second-line alternative. Amphotericin B alone may not be as good during the initial part of the treatment. Amphotericin B does not penetrate the CSF as well as flucytosine.

Answer c is incorrect. This would be a second-line alternative. Liposomal amphotericin B alone may not be as good during the initial part of the treatment. Amphotericin B does not penetrate the CSF as well as flucytosine.

Answer d is incorrect. This would be a second-line alternative. Fluconazole is not fungicidal enough to use for induction therapy. It is, however, used as antifungal consolidation after about 2 weeks of amphotericin B deoxycholate + flucytosine and as a chronic sup

PT is a 33-year-old human immunodeficiency virus (HIV) patient. He has a high HIV viral load and low CD4. He has been nonadherent with medication and provider appointments. PT is admitted to the medical center for a change in mental status. He is undergoing a complete work-up to identify the cause. An India ink stain is reported as positive. Which one of the following organisms is likely to manifest a positive India ink stain on a CSF sample?

A

Candida albicans

B

Candida glabrata

C

Aspergillus fumigatus

D

Cryptococcus neoformans

D

The India ink stain adheres to the capsule around C. neoformans.

Answers a, b, and c are incorrect.Cryptococcus is evaluated via an India ink stain. The other organisms do not respond to the India ink stain.

At the end of initial treatment (with amphotericin B and flucytosine) for cryptococcal meningitis (cerebrospinal fluid (CSF)-sterilized) in an human immunodeficiency virus (HIV)-positive patient, what is generally recommended for consolidation therapy in terms of cryptococcal infection?

A

Once weekly doses of azithromycin.

B

8 weeks of fluconazole oral therapy.

C

Once weekly doses of fluconazole for 4 weeks.

D

No further antifungal therapy is needed.

B

Longer fluconazole therapy may be needed in some cases where CSF is still positive or was slow to sterilize. Higher doses may be used.

Answer a is incorrect. This is used to prevent Mycobacterium avium-intracellulare complex (MAC).

Answer c is incorrect. Daily dosing of fluconazole would be warranted in these infections.

Answer d is incorrect. Consolidation is needed for at least 8 weeks. HIV-positive patients will also receive indefinite therapy (CD4-based) after the patient displays clinical cure and a negative CSF. Dose is 200 mg.

Which antifungal agent is only available as a parenteral formulation?

A

Amphotericin B lipid-complex

B

Voriconazole

C

Posaconazole

D

Fluconazole

A

This is available as IV only.

Answer b is incorrect. This is available as oral and IV.

Answer c is incorrect. This is available as oral suspension, delayed-release tablets, and IV.

Answer d is incorrect. This is available as oral and IV.

_________binds to the fungal cell membrane component ergosterol, forming pores that cause rapid leakage of monovalent ions (K+, Na+, H+ and Cl−) and subsequent fungal cell death.

A

Amphotericin B

B

Voriconazole

C

Flucytosine

D

Micafungin

A