Transcript Presentation - Direct Relief

Esophageal Candidiasis
in Patients with AIDS
Case
• 32-year-old male with AIDS
• CD4 50 cells/mm3
• Reports severe pain and difficulty
swallowing
• “It feels like food gets stuck below my
throat”
• Denies other symptoms
• Reports history of oral candidiasis
What is the most likely diagnosis?
Esophageal Candidiasis
Objectives
• Upon completion of this activity,
participants should be able to:
– Recognize symptoms of esophageal
candidiasis
– Review methods for diagnosing esophageal
candidiasis
– Discuss treatments for esophageal candidiasis
Overview
• Candida ssp is an
opportunistic fungus
(yeast)
• Candida albicans is
the most common
etiology of esophagitis
in patients with AIDS
• Candida tropicalis,
Candida Krusei,
Candida glabrata,
and Candida
parapsilosis can also
cause esophagitis
Overview
• Occurs in 20–40% of patients with AIDS
• Patients usually have CD4 <100 cells/mm3
Esophagitis – Other Causes
• Less common causes: HSV, CMV and
aphthous ulcerations
• Rare causes: lymphoma, KS, PCP,
Cryptosporidia, TB, histoplasmosis, M.
avium
• Consider non-HIV-related causes if CD4
>200 cells/mm3 (e.g., gastro esophageal
reflux disease—GERD, medication- and
food-induced)
Clinical Presentation
• Odynophagia (painful swallowing)
• Dysphagia (difficulty swallowing)
• Diffuse retrosternal pain
• Occasional nausea and vomiting
• Oral candidiasis often present but not
required
Diagnosis
• Usually made clinically based on
symptoms
• Endoscopy only if empirical azole therapy
fails
• Response to empiric treatment precludes
need for endoscopic esophageal
candidiasis diagnosis
• When needed, diagnosis by endoscopy is
made based on visual appearance of
white pseudomembranous plaques in the
esophagus
Diagnosis
• Brushings or biopsy can be taken during
endoscopy for microscopy or culture
• Fungal culture of esophageal
pseudomembranous plaques is useful for
identification of Candida species and
resistance testing (when available)
Treatment – Basic Principles
• No place for topical treatment
• Treat empirically with systemic drugs
• Azoles are first-line of therapy
– Fluconazole included in class
• HAART reduces relapses
First Line Therapy
• Fluconazole 200 mg po daily (preferred)
x 14–21 days
• Itraconazole solution 200 mg po daily
x 14–21 days
– Itraconazole also available in capsule but
better absorption with liquid formulation
– Ketoconazole rarely used due to erratic
absorption
Second Line Therapy
• Amphotericin B 0.3-0.7 mg/kg IV daily
– Or lipid formulations of amphotericin
• If available, can also use
– Echinocandins
• Caspofungin, micafungin
– Alternative azoles with increased activity
against fluconazole-resistant Candida
• Voriconazole, posaconazole, itraconazole
Treatment
• Assess response to therapy within 5–7
days
• Continue therapy for 14–21 days after
clinical improvement
• Use intravenous drugs for patients unable
to swallow
If no Response to Fluconazole
• Check medication adherence
• Reconsider diagnosis
• Refer for endoscopy
• Consider resistance to azole therapy –
especially if repeated courses of azole
treatment or if maintenance therapy used
Other Treatment Considerations
• Azoles prone to drug interactions through
the cytochrome P450 (CYP450) pathway
• The CYP450 enzymes are involved in the
metabolism of most commonly prescribed
drugs
• Check package insert for drug
interactions when prescribing azoles
Other Treatment Considerations
• Absorption of itraconazole capsules is pH
dependent. Absorption affected by:
1. Antipeptic Ulcer Drugs
• H2 blockers
• Proton pump inhibitors
• Antacids
2. Antiretroviral Drugs
• Buffered didanosine
• Liquid formulation better absorbed but
must be taken on an empty stomach
(preferred)
Other Treatment Considerations
• Fluconazole absorption is not affected by
food or gastric pH
• Hepatotoxicity and gastrointestinal
intolerance can occur with azole therapy
Other Treatment Considerations
• Amphotericin B is renally eliminated
• Amphotericin B is not a substrate, inhibitor
or inducer of the CYP450 enzymes
• Thus, amphotericin B is not prone to drug
interactions through the CYP450 enzymes
Other Treatment Considerations
• Common side effects of amphotericin B
–
–
–
–
–
Nephrotoxicty
Electrolyte abnormalities
Infusion-related chills
Injection site pain and irritation
Phlebitis
• Increased risk for amphotericin B-induced
nephrotoxicity when given concurrently
with other nephrotoxic drugs
Prophylaxis
• Prophylaxis/maintenance not generally
recommended, but consider if frequent
recurrences
• Fluconazole 100–200 mg po daily
Itraconazole liquid 200 mg po daily can
be used as an alternative
Additional Considerations
• Use analgesic therapy for pain relief
• Reinforce importance of maintaining
adequate nutrition
• Avoid foods that are hot/cold/spicy to
avoid exacerbating discomfort caused by
dysphagia and odynophagia
• Favor pureed/mashed foods and liquids
served at room temperature
Summary
• Candida albicans is the most common etiology
of esophagitis in patients with AIDS
• Treat empirically with fluconazole
• If no response to treatment, consider alternative
etiology, inadequate adherence, drug
resistance
• Azoles are prone to drug interactions through
the CYP450 pathway
• Azoles can cause gastrointestinal and hepatic
toxicity
Summary
• Amphoterycin B for second line therapy
• Amphoterycin B is not prone to drug
interactions through the CP450 pathway
• Common side effects include
nephrotoxicity, infusion-related chills and
fever, phlebitis and electrolyte
abnormalities
Summary
• Prophylaxis usually not recommended
• Reinforce the importance of adequate
nutrition
• Pain management is crucial
• HAART reduces relapses
References
• Ally R, Schurmann D, Kreisel W, et al. 2001. A
randomized, double-blind, double-dummy, multicenter
trial of voriconazole and fluconazole in the treatment of
esophageal candidiasis in immunocompromised
patients. Clin Infect Dis. 33:1447-1454.
• Arathoon EG, Gotuzzo E, Noriega LM, et al. 2002.
Randomized, double-blind, multicenter study of
caspofungin versus amphotericin B for treatment of
oropharyngeal and esophageal candidiasis. Antimicrob
Agents Chemother. 46:451-457.
• Bonacini M, Young T, Laine L. 1991. The causes of
esophageal symptoms in human immunodeficiency
virus infection. A prospective study of 110 patients. Arch
Intern Med. 151:1567-1572.
References
• Clinical Infectious Diseases 2004; 38:165-89.
• Connoly GM, Hawkins D, Harcourt-Webster JN et al.
Oesophageal symptoms, their causes, treatment, and
prognosis in patients with the acquired
immunodeficiency syndrome. Gut. 1989;30:1033-1039.
• de Wet N, Llanos-Cuentas A, Suleiman J, et al. 2006. A
multicenter randomized trial evaluating posaconazole
versus fluconazole for the treatment of oropharyngeal
candidiasis in subjects with HIV/AIDS. Clin Infect Dis.
42:1179-1186.
• de Wet N, Llanos-Cuentas A, Suleiman J, et al. 2004. A
randomized, double-blind, parallel-group, doseresponse study of micafungin compared with
fluconazole for the treatment of esophageal candidiasis
in HIV-positive patients. Clin Infect Dis. 39:842-849.
References
• Maenza JR, Keruly JC, Moore RD, et al. 1996. Risk
factors for fluconazole-resistant candidiasis in
human immunodeficiency virus-infected
patients. J Infect Dis. 174:219-221.
• Vazquez JA. 2000. Therapeutic options for the
management of oropharyngeal and
esophageal candidiasis in HIV/AIDS patients.
HIV Clin Trials. 1:47-59.
• Villanueva A, Arathon EG, Gotuzzo, et al. 2001. A
randomized double-blind study of caspofungin
versus amphotericin for the treatment of
candidal esophagitis. Clin Infect Dis. 33:15291535.