Download Coccidioidomycosis

Guidelines for Prevention and Treatment of Opportunistic
Infections in HIV-Infected Adults and Adolescents
Coccidioidomycosis Slide Set
Prepared by the AETC National Coordinating Resource Center based on
recommendations from the CDC, National Institutes of Health, and HIV
Medicine Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is clinicians
involved in the care of patients with HIV.
Users are cautioned that, owing to the rapidly changing
field of HIV care, this information could become out of date
quickly. Finally, it is intended that these slides be used as
prepared, without changes in either content or attribution.
Users are asked to honor this intent.
-AETC National Coordinating Resource Center
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Coccidioidomycosis
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Epidemiology
Clinical Manifestations
Diagnosis
Prevention
Treatment
Considerations in Pregnancy
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Coccidioidomycosis: Epidemiology
 Caused by Coccidioides immitis and C posadasii
 Endemic in southwest United States, parts of Central
and South America
 Increased risk with extensive exposure to soil
 May cause disease via reactivation of previous
infection
 Disease may occur in those with no discernible
immunodeficiency
 Increased risk in HIV patients with CD4 count <250
cells/µL
 Incidence and severity lower after broader
use of ART
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Coccidioidomycosis: Clinical
Manifestations
 Severity associated with lower CD4 counts, lack
of HIV suppression
 In HIV infection, 6 common syndromes:
 Focal pneumonia
 Diffuse pneumonia (presents like PCP)
 Cutaneous involvement
 Meningitis
 Liver or lymph node involvement
 Positive coccidioidal serology tests without evidence of
localized infections
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Coccidioidomycosis: Clinical
Manifestations (2)
 Focal pneumonia most common if CD4 count
>250 cells/µL
 Other syndromes usually occur with more
advanced immunosuppression
 Meningitis: headache, progressive lethargy,
fever, nausea or vomiting, confusion
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Coccidioidomycosis: Manifestations
Chest X ray: disseminated coccidioidomycosis
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Coccidioidomycosis: Diagnosis
 Culture of clinical specimens
 Histopathology
 Blood cultures (positive in <50%)
 Coccidioidal IgM and IgG serology (EIA,
immunodiffusion, classical tube precipitin, complement
fixation): useful but poorer sensitivity in patients with low
CD4 counts
 CSF analysis: typically shows lymphocytic pleocytosis,
CSF glucose <50 mg/dL, CSF protein normal or mildly
elevated; complement fixation usually positive;
culture positive in <1/3
 Newer coccidioidomycosis-specific antigen assay:
detects antigen in urine and serum
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Coccidioidomycosis: Prevention
 Preventing exposure
 In endemic areas, impossible to avoid exposure
completely
 HIV-infected persons: avoid extensive exposure to
disturbed soil in endemic areas (eg, excavation sites,
dust storms)
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Coccidioidomycosis: Prevention (2)
 Preventing disease
 Primary prophylaxis not recommended
 For HIV-infected persons in endemic regions: yearly
serologic testing is reasonable
 If new positive IgM or IgG serologic test and CD4 count <250
cells/µL
 Fluconazole 400 mg PO QD
 Outside endemic regions: routine testing not useful and
should not be done
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Coccidioidomycosis: Treatment
 Treatment consists of 2 phases: induction and
maintenance
 Total duration of therapy ≥12 months
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Coccidioidomycosis: Treatment (2)
 Severe nonmeningeal infection: diffuse pulmonary or
severely ill with disseminated disease
 Acute phase (continue until clinical improvement):
 Preferred:
 Amphotericin B deoxycholate 0.7-1.0 mg/kg IV QD
 Lipid-formulation amphotericin B 4-6 mg/kg IV QD
 Alternative: add fluconazole or itraconazole to amphotericin
B (itraconazole preferred for bone disease)
 Maintenance therapy (continue indefinitely)
 Fluconazole 400 mg PO QD
 Itraconazole 200 mg PO BID
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Coccidioidomycosis: Treatment (3)
 Mild disease: focal pneumonia
 Preferred:
 Fluconazole 400 mg PO QD
 Itraconazole 200 mg PO BID
 Alternative (limited data):
 Posaconazole 200-400 mg PO BID
 Voriconazole 200 mg PO BID
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Coccidioidomycosis: Treatment (4)
 Meningeal infection
 Consult with specialist
 Acute phase
 Preferred: fluconazole 400-800 mg IV or PO QD
 Alternative:
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Itraconazole 200 mg PO BID
Posaconazole 200-400 mg PO BID
Voriconazole 200-400 mg PO BID
Intrathecal amphotericin B if azoles not effective
 Hydrocephalus may develop: may need CSF shunt
 Lifelong therapy required: relapse in 80% of HIV
patients with azole therapy discontinued
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Coccidioidomycosis: ART Initiation
 Start ART as soon as possible after start of
antifungal therapy
 IRIS has been reported (1 case)
 Triazoles have complex, sometimes bidirectional
interactions with certain ARVs; dosage
adjustments may be needed
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Coccidioidomycosis: Monitoring and
Adverse Events
 Monitor complement-fixing antibody every 12
weeks: useful in assessing response to therapy
 Increase in titer suggests recurrence or worsening –
reassess management
 IRIS: 1 reported case
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Coccidioidomycosis: Treatment
Failure
 Failure of fluconazole or itraconazole:
 Severely ill: amphotericin B (deoxycholate or lipid
formulation)
 Not severely ill: consider posaconazole 200 mg PO BID
or voriconazole 200 mg PO BID (limited data for both)
 Note: significant interactions between voriconazole and
NNRTIs or ritonavir
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Coccidioidomycosis: Preventing
Recurrence
 Consider lifelong suppressive therapy if CD4
count remains <250 cells/µL
 Preferred:
 Fluconazole 400 mg PO QD
 Itraconazole 200 mg PO BID
 Alternative (if patient did not initially respond to
fluconazole or itraconazole):
 Posaconazole 200 mg PO BID
 Voriconazole 200 mg PO BID
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Coccidioidomycosis: Preventing
Recurrence (2)
 Discontinuing secondary prophylaxis:
 Focal pneumonia:
 May discontinue after 12 months of therapy if CD4 ≥250 cells/µL
on effective ART
 Monitor for recurrence (serial chest X rays and coccidioidal
serology)
 Diffuse pulmonary or nonmeningeal disseminated
disease:
 Relapses in >25% of cases, even in HIV-uninfected patients
 Some would continue therapy indefinitely; consult with expert
 Meningitis:
 Relapses in 80%
 Continue therapy lifelong
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Coccidioidomycosis: Considerations
in Pregnancy
 More likely to disseminate if acquired during 2nd
or 3rd trimester
 Amphoteracin B or its lipid formulations are
preferred initial regimen
 At delivery, evaluate neonate for renal dysfunction and
hypokalemia
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Coccidioidomycosis: Considerations
in Pregnancy (2)
 Azoles: avoid in 1st trimester--risk of
teratogenicity
 Coccidioidal meningitis:
 Only alternative to azoles is intrathecal amphotericin B
 Choice of treatment should be based on risk/benefit
considerations and in consultation with the mother and with
infectious disease and obstetric experts
 Voriconazole and posaconazole: teratogenic and
embryotoxic in animals: avoid throughout pregnancy
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Access the Guidelines Online
 AIDS Info: http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by Susa Coffey,
MD, for the AETC National Resource Center in
May 2013
 See the AETC NCRC website for the most
current version of this presentation:
http://www.aidsetc.org
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