1.
Which of the following statements correctly pair the antifungal drugs with their likely mechanisms of action?
Correct Answer(s)
B. Griseofulvin - interferes with microtubule function
F. Terbinafine - inhibits squalene epoxidase
Explanation
Answer: BF Griseofulvin is effective only against dermatophytes which take up the drug via an active transport system. Its exact mechanism of action is still unclear but the drug appears to disrupt the mitotic spindle trough interaction with microtubules. Terbinafine (also effective mainly against dermatophytes) blocks the conversion of squalene to lanosterol by inhibiting the fungal enzyme squalene epoxidase A) Inhibition of thymidylate synthetase would be the mechanism of action of flucytosine. C) Inhibition of mycolic acid synthesis would be the mechanism of action of isoniazid. D) Inhibition of DNA dependent RNA polymerase would be the mechanism of action of rifampin E) Inhibition of ergosterol synthesis would be the mechanism of action of azoles.
2.
Which of the following statements correctly pairs the antifungal drug with its typical adverse effect?
Correct Answer(s)
A. AmpHotericin B - normocytic anemia
B. Griseofulvin - pHotosensitivity
C. Flucytosine - myelosuppression
D. Ketoconazole - menstrual irregularities
Explanation
Answer: ABCD
Amphotericin B causes nephrotoxicity that can affect up to 80% of patients The decreased
production of erythropoietin frequently leads to a normocytic anemia.
Griseofulvin is an allergenic drugs that can cause many hypersensitivity reactions including
photosensitivity. Flucytosine may be partially converted to 5-fluorouracil by the intestinal flora of
the host ans so can exhibit some characteristic effects of anticancer drugs like
myelosuppression (up to 13% of patients) and alopecia.
Ketoconazole can affect gonadal hormone synthesis by inhibiting the Cytochrome P450 system.
This can cause menstrual irregularities in women and impotence in men.
E) Nystatin is given only topically or by oral route for intestinal candidiasis. In both cases the
drug is not absorbed so central adverse effects are quite unlikely.
3.
Which of the following statements best explain the mechanism of antifungal action of amphotericin B?
Correct Answer
B. Impairment of the normal permeability of fungal cell membrane
Explanation
Answer: B
Amphotericin B binds to fungal cell membrane and causes the formation of artificial pores
through which ions and small molecules are lost. This causes the death of the fungal cell.
A) This would be the mechanism of action of quinolones.
C) This would be the mechanism of action of several antiviral drugs.
D) This would be the mechanism of action of griseofulvin.
E) This would be the mechanism of action of azoles.
4.
Which of the following statements regarding the toxicity of amphotericin B are correct?
Correct Answer(s)
B. A shock-like fall in blood pressure may occur during IV infusion
D. Renal toxicity is common, is dose-dependent and may be severe
E. AmpHotericin B toxicity seems to be lower with the use of lipid formulations the drug
Explanation
Answer: BDE
Amphotericin B is a toxic drug and more than 50% of patients treated with this drug undergo
some adverse effects. These can be :
a) Acute, infusion-related: IV infusion can cause headache, arthralgias, nausea and vomiting,
fever and chills, hyperpnea, and a shock-like fall in blood pressure (concomitant administration
of antipyretics, antihistamines, glucocorticoids and meperidine have all been shown to reduce
these effects)
b) Chronic, organ-related: a dose-limiting nephrotoxicity, with decreased GFR, azotemia, renal
tubular acidosis, and renal wasting of K+ and Mg++ can affect up to 80% of patients. The
decreased production of erythropoietin frequently causes a normocytic anemia.
Amphotericin B toxicity may be reduced by the use of lipid formulations, but the improvement of
clinical efficacy is moderated, at best.
A) Acidosis, not alkalosis, usually occurs
C) Fever, not hypothermia, can actually occur during IV infusion
5.
Which of the following is an antifungal drug that acts by inhibiting fungal DNA synthesis?
Correct Answer
C. Flucytosine
Explanation
Answer: C
Flucytosine is accumulated in fungal cells and is converted by a cytosine deaminase to 5-
fluorouracil (selectivity occurs because mammalian cells do not accumulate and do not
deaminate flucytosine). Fluorouracil is in turn metabolized to 5-deoxyfluorouridylic acid, a
potent inhibitor of thymidylate synthetase, the enzyme responsible for converting deoxyuridine
monophosphate to deoxythimidine monophosphate. This reduces the availability of thymidylic
acid, so impairing DNA synthesis.
A, B) Fluorouracil and cytarabine can inhibit DNA synthesis in mammalian cells but are not
accumulated in fungal cells and therefore are devoid of antifungal activity.
D, E, F) These antifungal drugs do not inhibit DNA synthesis.
6.
Which of the following statements best explains the mechanism of antifungal action of azoles?
Correct Answer
E. Inhibition of conversion of lanosterol to ergosterol
Explanation
Answer: E
Azoles inhibit cytochrome P450 enzymes. This inhibition impairs the activity of a P450-
dependent lanosterol demethylase that converts lanosterol to ergosterol. The ultimate effect is
an inhibition of ergosterol synthesis in fungal cells. The specificity of azole drugs results from
their greater affinity for fungal than for mammalian cytochrome P450 enzymes. Imidazoles (i.e
ketoconazole) have a lesser degree of specificity than triazoles (i.e. fluconazole).
A) This would be the mechanism of action of terbinafine.
B) This would be the mechanism of action of amphotericin B
C) This would be the mechanism of action of griseofulvin.
D) No antifungal drug can inhibit the synthesis of squalene. In mammalian cells this synthesis
can be inhibited by HMG-CoA reductase inhibitors through an inhibition of the synthesis of
mevalonate.
7.
Which of the following fungal disease is resistant to azole treatment?
Correct Answer
E. Mucormycosis
Explanation
Answer: E
Azoles have a wide antifungal spectrum that includes most fungal species. A notable exception
are the agents of mucormycoses (mucor and rhizopus species) that are usually resistant to
these drugs.
A, B, C, D) (see explanation above)
8.
Which of the following fungi are sensitive to Griseofulvin?
Correct Answer(s)
C. TrichopHyton rubrum
D. EpidermopHyton floccosum
E. Microsporum gypseum
Explanation
Answer: CDE
The antifungal spectrum of griseofulvin only includes dermatophytes (trichophyton,
epidermophyton and microsporum species). The drug has no effect on other fungi or bacteria.
A, B, F, G) (see explanation above)
9.
Recognized clinical indications for the use of terbinafine include which of the following diseases?
Correct Answer
D. Onychomycosis
Explanation
Answer: D
Terbinafine is an antifungal drug that inhibits the synthesis of lanosterol. It is deposited in
keratinized tissue and is used in the treatment of dermatophytoses, mainly onychomycosis. The
drug is fungicidal and is therefore more effective than griseofulvin, which is fungistatic.
A, B, C) The drug is not effective against bacteria (i.e. actinomyces , brucellae) and protozoa
(i.e. toxoplasma)
E) Terbinafine is effective in vitro against many fungi but is not currently used clinically in
pulmonary or systemic mycoses
10.
A 31-year-old man presented to his physician with an annular lesion with raised borders in his left hand. Microscopic examination of skin scrapings revealed branching hyphae. The diagnosis of tinea manus was made and the patient has prescribed appropriate oral treatment. Which of the following skin structures was most likely the site of action of the prescribed drug?
Correct Answer
C. Stratum corneum
Explanation
Answer: C
Tinea manus is a cutaneous mycosis caused by dermatophytes that infect only the superficial,
keratinized tissues. These fungi are probably restricted to the nonviable, keratinized tissues
(stratum corneum, hairs, nails) because most are unable to grow at 37 C. Dermatophytoses can
be treated locally with several antifungal drugs, but the drugs of choice for systemic treatment
are griseofulvin or terbinafine. These drugs have a good oral bioavailability and are deposited
in newly formed keratinized tissues where they exert their antifungal action.
A, B, D, E) (see explanation above)
F) Griseofulvin or terbinafine can be deposited in the hair shaft, where they can cure tinea
capitis, but in the present case the fungus is in the skin stratum corneum, not in the hair.
11.
A 37-year-old man complained of anorexia, nausea, enlargement of his breast, and impotence. The man, recently diagnosed with pulmonary coccidioidomycosis, has been receiving an antifungal treatment for two weeks. Which of the following drugs most likely caused these adverse effects?
Correct Answer
C. Ketoconazole
Explanation
Answer: C
Coccidioides immitis is sensitive to amphotericin B and to antifungal azoles. Amphotericin B is
the drug of choice for severe systemic coccidioidomycosis, but antifungal azoles are often
preferred in case of mild infection because they are orally active and much less toxic. .
Ketoconazole is an azole antifungal drug that can inhibit the cytochrome P450 system both in
fungal and mammalian cells. The inhibition blocks the synthesis of ergosterol in fungal cell
membrane, so leading to an antifungal effect, but can also block the synthesis of adrenal and
gonadal steroids in mammalian cells. Therefore the drug can cause gynecomastia, impotence
and infertility in males. The newer azoles appear to have greater affinity for fungal cytochrome
enzymes and less interference with mammalian enzymes, so the above mentioned adverse
effects seem less frequent.
A, B, D, E, F) The risk impotence with these drugs is negligible.
12.
A 37-year-old woman with AIDS has been recently diagnosed with systemic candidiasis due to Candida cruzii, and an IV antifungal treatment has been prescribed. Four days later the following lab results were obtained: serum creatinine 5.9 mg/dL(normal: 0.6-1.5), blood urea nitrogen 53 mg/dL (normal 7-30), plasma potassium 2.3mmol/L (normal 3.5-5.3). Which of the following drugs was most likely prescribed?
Correct Answer
A. AmpHotericin B
Explanation
Answer: A
The lab results indicate that the patient is suffering from renal insufficiency. Amphotericin B is
the drug of choice for most systemic mycoses, but the drug can cause a serious, dosedependent
renal dysfunction due to direct damage of renal tubules. Azotemia, renal tubular
acidosis and K+ wasting are the most prominent symptoms.
B, C, D) These antifungal drugs do not cause renal toxicity.
E, F) These agents are nephrotoxic but are not antifungal drugs.
13.
A 32-year-old woman presents to her gynecologist with a 4 days history of perineal pruritus and a non-malodorous, thick, cheesy vaginal discharge. The only medication the woman is taking is an oral contraceptive. A wet preparation of vaginal secretion shows budding yeast cells and pseudohyphae. Which of the following drugs, given locally, would be appropriate for this patient?
Correct Answer
C. Miconazole
Explanation
Answer: C
The symptoms of the patient and the lab results strongly suggest that she is suffering from
genital candidiasis, the most common opportunistic mycosis of genital tract in women taking
oral contraceptives. Other predisposing factors include pregnancy, menstruation, diabetes
mellitus, and use of broad-spectrum antibiotics, corticosteroids, or immunosuppressive drugs.
Budding yeast cells and pseudohyphae of Candida albicans ( the most common candida
species causing candidiasis), can be detected by microscopic examination of biologic
specimens.
Candida albicans is sensitive to most antifungal drugs, but for genital candidiasis a topical azole
derivative (miconazole, ketoconazole, etc. ) or topical nystatin are the treatments of choice.
A, B, D) These agents are not antifungal drugs.
E, F) These antifungal drugs are not effective against Candida albicans.
14.
A 68-year-old man is in the hospital because of a prostatectomy performed 4 days before. He is wearing a urinary catheter and is currently treated with a combination of broad-spectrum antibiotics. The patient has been suffering from chronic renal insufficiency for the past two years. Two recent urinalysis show many budding yeasts and cultures were positive for Candida albicans. Which of the following drugs would be appropriate for systemic antifungal treatment of this patient?
Correct Answer
B. Fluconazole
Explanation
Answer: B
The patient is suffering from candiduria, a condition often related to the placement of an
indwelling urinary catheter, especially if the patient is taking brad spectrum antibiotics, like in
the present case. Eradication of candida in the urine includes the removal of the catheter and
an antifungal treatment. Treatment options include amphotericin B or fluconazole. However, in
the present patient, amphotericin B, which directly damages renal tubules, is contraindicated
because of chronic renal dysfunction.
A) (see explanation above)
C, D) These agents are not antifungal drugs.
E) This antifungal drug is not effective against Candida albicans.
F) Nystatin is effective against Candida albicans but is too toxic to be used systemically.
15.
A 30-year-old Filipino man, who is a lifelong resident in the San Joaquin Valley, California, presented to the hospital with a 4-day history of low-grade fever (99.8 F°), severe headache, irritability, and fatigue. Physical examination showed a stiff neck and Kerning’s sign. Microscopic analysis of the spinal fluid revealed spherules filled with endospores.
Which of the following drugs would be appropriate for this patient?
Correct Answer
D. AmpHotericin B
Explanation
Answer: D
The signs and symptoms of the patient suggest the diagnosis of meningitis and the lab results
confirms that tha man is suffering from meningeal coccidioidomycosis. The infection is caused
by Coccidioides immitis, a soil mold that lives in semiarid regions of the globe (southwestern
USA, Argentina, etc.). Inhalation of the arthrospores leads to a primary infection that is
asymptomatic in 60% of individuals. The others develop a flu-like self limited illness called
valley fever or desert rheumatism. Following inhalation the arthrospores forms spherules that
contain endospores. In biologic specimens these spherules are diagnostic of Coccidioides
immitis infection. In less than 1% of individuals a secondary or disseminated infection evolves
within a year after the primary one. This secondary infection is often life-threatening and can
affect many tissues but the most frequent organs are the bone and joints, and the meninges.
Untreated meningitis is always fatal.
Coccidioides immitis is sensitive to amphotericin B and to antifungal azoles. Amphotericin B is
the drug of choice and is usually administered intrathecally in meningeal coccidioidomycosis,
since the drug penetration into the CNS is limited.
A) Flucytosine can easily enter the brain but is not effective against Coccidioides immitis.
B, C, E, F) These agents are not antifungal drugs.
16.
A 31-year-old homosexual male with AIDS presents to the emergency room with fever(102.3 F°), headache, confusion, muddled thinking, and vomiting. Physical examination reveals nuchal rigidity, diplopia, and loss of vision. An agglutination test of the spinal fluid for capsular polysaccharide antigen is positive. Which of the following drugs would be an
appropriate treatment for this patient?
Correct Answer
D. AmpHotericin B and flucytosine
Explanation
Answer: D
The history, symptoms an signs of the patient strongly suggest the diagnosis of cryptococcal
meningitis. In fact after toxoplasmosis, cryptococcosis is the most common CNS infection
associated with AIDS. Cryptococcus neoformans is a yeast that is characterized by a thick
polysaccharide capsule. During infection the capsular polysaccharide is solubilized in spinal
fluid and can be detected by an agglutination test which is diagnostic of cryptococcosis.
Cryptococcus neoformans is sensitive to amphotericin B, flucytosine and antifungal azoles. The
current treatment recommended for acute cryptococcal meningitis is amphotericin B plus
flucytosine. Synergism between the two drugs has been demonstrated in vitro and in vivo. It
may be related to enhanced penetration of flucytosine through the amphotericin-damaged
fungal cell membrane.
A, B, C) These agents are not antifungal drugs.
E, T) These antifungal drugs are not effective against Cryptococcus neoformans.
17.
A 7-year-old girl is brought to the physician by her mother because she has several small hairless patches on her scalp. Upon close physical examination, patches look like black dots on the skin surface. Microscopic examination reveals a dense sheath of spores around the hair. Which of the following drugs given orally would be an appropriate treatment for this patient?
Correct Answer
C. Griseofulvin
Explanation
Answer: C
The microscopic examination of the hair strongly suggests the diagnosis of ‘black dots’ tinea
capitis, a cutaneous mycosis cause by Trichophyton tonsurans. Cutaneous mycoses are
caused by fungi (mainly dermatophytes) that infect only the superficial keratinized tissues.
Dermatophytes are sensitive to griseofulvin, terbinafine, antifungal azoles and amphotericin B ,
but the first two agents are the drugs of choice in cutaneous mycoses since they are deposited
in newly forming skin where they bind to keratin, so protecting the skin from the infection.
Antifungal azoles are also used orally (they have good affinity for keratin) or topically. A, B, D) These agents are not antifungal drugs.
E) rarely) Amphotericin B is given only topically in cutaneous mycoses.
F) Flucytosine is a systemic antifungal drug, but is not effective against dermatophytes.
18.
A 32-year-old man suffering from a non-Hodgkin’s lymphoma presented with fever, cough, increasing dyspnea, and hemoptysis. The man was in the hospital for the second cycle of chemotherapy. Chest radiograph disclosed diffuse alveolar infiltrates on the right lobe and multiple small cavitary lesions on the left lobe. Bronchoalveolar lavage revealed fungal forms are typical of the Aspergillus genus. Which of the following drug was mostlikely given IV to this patient?
Correct Answer
D. AmpHotericin B
Explanation
Answer: D
Fungi of the genus Aspergillus usually coexist with man in harmless symbiosis. In special
circumstances, however, some species may play an opportunistic role in producing disease in
humans. Patients with chemotherapy-induced neutropenia or impaired immune responses by
any cause are at high risk for invasive pulmonary aspergillosis, like in the present case. Recent
studies indicate that the isolation of Aspergillus in bronchoalveolar lavage fluid correlates
strongly with histologic evidence of parenchymal invasion. The disease is treated with
amphotericin B, but most patient die within few weeks of the diagnosis.
A) Flucytosine is effective in vitro against Aspergillus species, but is not used clinically alone
and even the addition to amphotericin B does not seem to add significant benefit.
B, C) These antifungal drugs are not effective against Aspergillus species.
E) Nystatin is too toxic for parenteral administration and is only used topically.
19.
A 33-year-old, HIV positive homosexual man living near the Mississippi River, was admitted to the hospital with a 3-week history of cough, productive yellow sputum, progressive dyspnea of exertion, and 14-pound weight loss. Pertinent lab results on admission were: CD4+ lymphocyte counts 320 cells/mm, lactate dehydrogenase 5000
IU/L (normal < 600). A bloodstain showed neutrophils containing small, uninucleated, and encapsulated microorganisms. Which of the following statements correctly pairs the most likely disease of the patient with the appropriate treatment?
Correct Answer
A. Progressive disseminate histoplasmosis - ampHotericin B
Explanation
Answer: A
The fact that uninucleated, encapsulated microorganisms are found intracellularly suggests an
infections with Histoplasma Capsulatum. Other intracellular microorganisms are either
multinucleated, like Blastomyces, or not encapsulated, like the intracellular stage of several
pathogenic protozoa. Infection with Histoplasma Capsulatum is extremely common. In the vast
majority of cases it is subclinical, or may manifest itself as a mild, self-limited pneumonia.
Progressive disseminate histoplasmosis usually occurs in people with suppressed cell-mediated
immunity, especially if they are from endemic areas (Mississippi river valleys and Carribean
basin), like in the present case. Most laboratory findings are nonspecific but the lactate
dehydrogenase level can reach ten times over normal. the Progressive disseminate
histoplasmosis has a high fatality rate. Amphotericin B remains the drug of choice but mild
cases can be treated initially with parenteral azoles.
B) Progressive disseminate coccidioidomycosis may have symptoms and sings similar to those
of the present case but microscopic finding is different .
C) Blastomyces dermatitidis is a multinucleate fungus without capsule.
D) Meningeal cryptococcosis is one of the most common opportunistic infection in AIDS
Patients and is treated with Amphotericin B. However clinical and laboratory findings are quite
different from those of the present case.
E) Sporothrix schenckii may cause a disseminate infection from a cutaneous or a pulmonary
lesion. However it does not grow intracellularly.
20.
Which of the following microorganisms are sensitive to amphotericin B?
Correct Answer(s)
A. Coccidioides immitis
C. Histoplasma capsulatum
D. Aspergillus fumigatus
E. Cryptococcus neoformans
Explanation
Answer: ACDE
The activity spectrum of amphotericin B includes most fungal species. The drug is effective
against fungi causing endemic mycoses (like Coccidioides immitis and Histoplasma
capsulatum), as well as opportunistic mycoses (like Aspergillus fumigatus and Cryptococcus
neoformans). The drug is also effective against fungi causing cutaneous mycoses
(epidermophyton, trichophyton an microsporum species) and mucormycoses (mucor and
rhizopus species).
B, F, G) Amphotericin B is not effective against bacteria.