Coccidiomycosis

Question 1

What causes coccidioidomycosis?

Answer 1

Coccidioidomycosis is caused by either of two soil-dwelling dimorphic fungi: Coccidioides immitis and Coccidioides posadasii.

Question 2

In which areas is coccidioidomycosis highly endemic in the United States?

Answer 2

Endemic areas include:
* Lower San Joaquin Valley
* Much of Arizona
* Southern regions of Utah, Nevada, and New Mexico
* Western Texas
* Northern Mexico

Question 3

What is the relationship between CD4 T lymphocyte counts and the risk of symptomatic coccidioidomycosis in people with HIV?

Answer 3

The risk is increased in people with CD4 counts <250 cells/mm3 and who are not virologically suppressed.

Question 4

What are the four common clinical syndromes of coccidioidomycosis?

Answer 4

The four common clinical syndromes are:
* Focal pneumonia
* Diffuse pneumonia
* Extrathoracic involvement (including meningitis, osteoarticular infection)
* Positive coccidioidal serology tests without evidence of localized infection

Question 5

What symptoms are associated with focal pneumonia in coccidioidomycosis?

Answer 5

Symptoms may include cough, fever, and pleuritic chest pain.

Question 6

True or False: Diffuse pneumonia is more common in immunocompromised patients.

Answer 6

True

Question 7

What are the cerebrospinal fluid (CSF) profile characteristics in coccidioidal meningitis?

Answer 7

CSF profile shows:
* Low glucose levels
* Elevated protein levels
* Lymphocytic pleocytosis

Question 8

What is the primary method for diagnosing coccidioidomycosis?

Answer 8

Diagnosis is based on serology, histology, culture, and clinical presentation.

Question 9

What is a significant laboratory biosafety hazard when culturing Coccidioides species?

Answer 9

The risk of inhalation of dislodged arthroconidia.

Question 10

Fill in the blank: The enzyme immunoassay (EIA) is used for detecting _______.

Answer 10

immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies.

Question 11

What should be done if a patient with a new positive serological test for Coccidioides shows no signs of active disease?

Answer 11

Pre-emptive antifungal therapy with fluconazole 400 mg daily is recommended.

Question 12

What is the preferred therapy for mild-to-moderate pulmonary infections caused by coccidioidomycosis?

Answer 12

Fluconazole 400 mg PO once daily or Itraconazole 200 mg PO three times daily.

Question 13

What is the preferred therapy for severe pulmonary or extrapulmonary infection (except meningitis)?

Answer 13

Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily or lipid formulation amphotericin B 3–5 mg/kg IV daily.

Question 14

What is the recommended therapy for coccidioidal meningitis?

Answer 14

Fluconazole 800–1,200 mg PO once daily.

Question 15

What is the recommendation for discontinuation of therapy in focal coccidioidal pneumonia?

Answer 15

Discontinuation can be considered after clinical response to 3-6 months of therapy, CD4 count ≥250 cells/mm3, and virologic suppression on ART.

Question 16

What percentage of patients experience relapse after stopping treatment for coccidioidal meningitis?

Answer 16

Relapse has been reported in 80% of patients.

Question 17

True or False: Routine testing for coccidioidomycosis is recommended for asymptomatic patients who have not lived in or traveled to endemic regions.

Answer 17

False

Question 18

What should be monitored in patients with diffuse pulmonary disease after discontinuation of therapy?

Answer 18

Continued monitoring for recurrence using serial chest radiograph and coccidioidal serology.

Question 19

What type of therapy is not recommended for individuals with HIV and low CD4 counts living in endemic areas?

Answer 19

Primary antifungal prophylaxis or pre-emptive therapy.

Question 20

What is the indication for primary prophylaxis or pre-emptive therapy in coccidioidomycosis?

Answer 20

Previously tested negative with a new positive IgM or IgG test for Coccidioides, CD4 count <250 cells/mm3, and no signs of active disease.

Question 21

What is the preferred therapy for treating coccidioidomycosis in pregnant women during the first trimester?

Answer 21

Lipid formulation amphotericin B 3–5 mg/kg IV daily or Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily.

Question 22

Fill in the blank: Elevated coccidioidal antibody titers can indicate risk of subsequent symptomatic diseases when CD4 count decreases to _______.

Answer 22

10 cells/mm3 or less.

Question 23

What is the significance of a coccidioidomycosis-specific antigen assay?

Answer 23

It detects antigen in urine, serum, and other body fluids from individuals with active coccidioidomycosis.

Question 24

What is the recommended therapy for mild-to-moderate pulmonary coccidioidal infection?

Answer 24

Oral triazole antifungal agent, such as fluconazole 400 mg daily or itraconazole 200 mg three times daily for 3 days followed by 200 mg twice daily

Itraconazole is preferred for those with bone or joint disease.

Question 25

What should be monitored to ensure adequate absorption of itraconazole?

Answer 25

Serum itraconazole concentrations should be measured after 2 weeks ## Footnote Target levels should be between 1.0 to 2.0 mg/mL.

Question 26

What is the preferred initial therapy for severe pulmonary coccidioidal infection?

Answer 26

Amphotericin B ## Footnote Most experience is with the deoxycholate formulation at a dose of 0.7 to 1.0 mg/kg IV daily.

Question 27

What is the recommended treatment for patients with coccidioidal meningitis?

Answer 27

Treatment with a triazole antifungal, preferably fluconazole 800 to 1,200 mg daily ## Footnote Intravenous amphotericin B alone is ineffective.

Question 28

What is the significance of monitoring CF antibody titer in therapy?

Answer 28

It assesses response to therapy, with a more than twofold rise suggesting recurrence ## Footnote Should be measured every 12 weeks.

Question 29

True or False: Delaying ART initiation is always necessary when treating coccidioidomycosis in HIV patients.

Answer 29

False ## Footnote In general, delaying initiation of ART may not be necessary.

Question 30

What should be the goal therapeutic concentration of itraconazole in severe coccidioidomycosis?

Answer 30

1.0 mg/mL to 2.0 mg/mL ## Footnote If treatment fails with these concentrations, switch to IV amphotericin B.

Question 31

What is the recommended treatment for non-meningeal coccidioidomycosis during the first trimester of pregnancy?

Answer 31

Intravenous amphotericin B, either deoxycholate or lipid formulation ## Footnote Extensive use has not been associated with teratogenicity.

Question 32

What is the risk associated with fluconazole during the first trimester of pregnancy?

Answer 32

Teratogenic potential ## Footnote Congenital malformations, including craniofacial and limb abnormalities, have been reported.

Question 33

What should be monitored in patients taking posaconazole?

Answer 33

Blood pressure and serum potassium levels ## Footnote A syndrome of mineralocorticoid excess has been reported.

Question 34

What is the recommendation for treating patients who do not respond to fluconazole or itraconazole?

Answer 34

Use posaconazole, voriconazole, or isavuconazole ## Footnote These are recommended for patients with limited data supporting their use.

Question 35

Fill in the blank: Coccidioidomycosis relapse occurs in ______% to ______% of individuals without HIV who have diffuse pulmonary coccidioidomycosis.

Answer 35

25% to 33% ## Footnote Relapses may also occur in people with HIV who have CD4 counts ≥250 cells/mm3.

Question 36

What is the preferred monitoring strategy for patients with coccidioidal meningitis?

Answer 36

Continue treatment doses of azole for life ## Footnote This is necessary even in those with immune reconstitution.

Question 37

What should be done if a patient with coccidioidal meningitis requires intrathecal therapy?

Answer 37

Administer by someone experienced in the technique ## Footnote Intrathecal amphotericin B deoxycholate is recommended.

Question 38

What is the impact of maternal fluconazole use during the first trimester according to meta-analysis?

Answer 38

Increased prevalence of heart defects ## Footnote Associated with both low dose and any dose exposure.

Question 39

What is the preferred dosage form of posaconazole for better tolerability?

Answer 39

Delayed-release tablet formulation ## Footnote Recommended dosage is 300 mg twice on the first day and then 300 mg once daily.

Question 40

What is the recommended duration of antifungal therapy for diffuse pulmonary disease in HIV patients?

Answer 40

At least 12 months ## Footnote Usually much longer based on clinical and immunological response.

Question 41

What is the association of fluconazole exposure during the first trimester with congenital malformations?

Answer 41

Marginal association with increased risk (OR 1.09; 95% CI, 0.99–1.2, P = 0.088) ## Footnote This includes heart defects and spontaneous abortion; exposure to more than 150 mg is associated with an overall increase in congenital malformations.

Question 42

What did a nationwide cohort study in Denmark find regarding fluconazole exposure during pregnancy?

Answer 42

Increased risk of spontaneous abortion (HR 1.48; 95% CI, 1.23–1.77) compared to unexposed pregnancies ## Footnote Higher risk observed with topical azole exposure (HR 1.62; 95% CI, 1.26–2.07).

Question 43

What was the adjusted odds ratio (OR) for spontaneous abortion with fluconazole doses of ≤150 mg?

Answer 43

2.23 (95% CI, 1.96–2.54) ## Footnote This indicates a higher risk of spontaneous abortion compared to unexposed pregnancies.

Question 44

What did the cohort study using Swedish and Norwegian registry data conclude about fluconazole use during pregnancy?

Answer 44

No association with risk of stillbirth or neonatal death ## Footnote This was noted despite other studies showing risks associated with fluconazole.

Question 45

What is the recommendation regarding fluconazole use in the first trimester?

Answer 45

Consider only if benefits clearly outweigh risks ## Footnote This is based on reported birth defects associated with fluconazole.

Question 46

What did a systematic review and meta-analysis of itraconazole exposure during pregnancy find?

Answer 46

No significant difference in overall risk of birth defects compared to non-exposure ## Footnote Limb and congenital heart defects were common but within published rates.

Question 47

What is the finding regarding eye defects in infants exposed to itraconazole?

Answer 47

Rate of eye defects was higher than that published by EUROCAT ## Footnote EUROCAT is the European network for congenital anomalies surveillance.

Question 48

What should be considered when using itraconazole during pregnancy?

Answer 48

Cost-benefit analysis ## Footnote This indicates that itraconazole use should be carefully evaluated.

Question 49

What is the teratogenic status of voriconazole, posaconazole, and isavuconazole in animal studies?

Answer 49

Teratogenic and embryotoxic ## Footnote No adequately controlled human studies have assessed their teratogenicity.

Question 50

What is the recommendation for using voriconazole, posaconazole, and isavuconazole during pregnancy?

Answer 50

Not recommended, especially in the first trimester (AIII) ## Footnote This is due to their teratogenic effects observed in animal studies.