Diagnosis>Opportunistic Infections>

PATHOGENS

• Candida albicans
• Candida glabrata
• Candida tropicalis
• Candida parapsilosis
• Candida krusei  
• Candida lusitaniae 

CLINICAL

• Generally seen in pts with CD4 <100; AIDS-defining illness
• Sx: retrosternal pain or discomfort, dysphagia and/or odynophagia, usually without fever
• Occurs in 20-40% of all AIDS pts
• Candidiasis is most common cause of esophagitis (EC) with HIV infection, but CMV, HSV and aphthous ulcerations can cause similar Sx.
• Most common cause is C. albicans. Other Candida spp. can cause esophagitis and some are resistant to fluconazole. However azole resistance predominantly due to prior azole exposure (repeated or long-term)
• Approximately half of recurrent cases are caused by same strain of Candida.
• Systemic candidiasis unusual in HIV+ pts
• Refractory EC in 4-5% of HIV+ pts who have CD4 <50 and multiple prior exposures to azole antifungals. Treatment failure defined as EC that persists after 7-14 days of appropriate therapy.
• Increasing recognition of non-albicans spp., especially C. glabrata, as cause of refractory EC

DIAGNOSIS

• Dx typically presumptive based on Sx of retrosternal pain, dysphagia and/or odynophagia and presence of oropharyngeal candidiasis on exam.
• Endoscopy required with unusual presentations or lack of response to azole within several days
• Endoscopy: visible white plaques in esophagus, Bx results, or microscopy from brush samples
• Wet mount microscopy or histopath evaluation useful for evaluation of yeast and/or pseudohyphae. Fungal Cx of esophageal lesions rarely required but allows identification of infecting species and resistance testing if poor response to azole therapy. Cx of limited use in Dx of oral candidiasis due to colonization.
• Resistance testing for yeasts has been standardized with NCCLS M27-A2 methodology, with defined breakpoints for Candida spp. to fluconazole, itraconazole, and flucytosine. Significant decline in resistance to fluconazole (45% to 10%) and itraconazole (37% to 7%) in HAART era among oropharyngeal Candida spp.

TREATMENT

• All therapy should be continued for 14-21 d.
• Fluconazole 100 mg/d (up to 400 mg/d) PO or IV
• Itraconazole 200 mg/d PO (oral solution preferred) or IV
• IV azoles may be needed for pts w/ severe dysphagia/odynoyphagia.
• Empiric trial of azole indicatedif HIV+ CD4<200, oral thrush and/or esophageal symptoms

• All therapy should be continued for 14-21 d.
• Voriconazole 200 mg PO or IV twice-daily
• Caspofungin 70 mg IV x1 then 50 mg IV once-daily
• Amphotericin B 0.6 mg/kg IV once-daily
• Lipid amphotericin formulations
• Other echinocandins: anidulafungin and micafungin approved for EC but generally not used for this indication.

• Voriconazole, caspofungin, or amphotericin should be limited to patients with Cx-confirmed fluconazole-resistant candidiasis or clinical failure on fluconazole or itraconazole.
• Itraconazole solution effective in 55-80% of pts who have inadequate responses to fluconazole.
• Posaconazole 400mg PO twice-daily x28 days also effective in 75% of pts who have inadequate response to azoles, but given broader antifungal spectrum and cost, use should be limited for this indication.
• Amphotericin lipid formulations or amphotericin B also usually effective and can be considered
• Echinocandins (anidulafungin, caspofungin, micafungin) may be considered but little data except small phase 2 study with anidulafungin.

• Primary prophylaxis not recommended due to cost, lack of attributable morbidity, potential for development of resistance, drug interactions, and efficacy of therapy for acute disease.
• Consider chronic (secondary) prophylaxis with daily azole therapy for pts with recurrent esophagitis (at least 3 episodes per year). Best treatment is immune reconstitution with ART.

Drug Comments

FOLLOW UP

• 85-90% respond within 7-14 days
• Endoscopy for Bx and Cx required after failure of empiric antifungal therapy to look for other causes of esophagitis.
• If not responding: can increase fluconazole dose as some Candida spp. have intermediate MIC to fluconazole and respond to higher doses (400-800 mg/d) or use alternative azole (itraconazole or voriconazole) or IV therapy (caspofungin, amphotericin)
• Consider chronic (secondary) prophylaxis w/ daily azole therapy for pts w/ recurrent EC.
• ART important to reduce risk of disease occurrence, relapse.
• No specific data on discontinuation of secondary (chronic maintenance) if instituted. But based on other OI experience, consider discontinuation when CD4 >200 on ART.
• Oral azoles can be associated with nausea, vomiting, diarrhea and transaminase elevations. Consider monitoring if on prolonged azole therapy >3 wks

OTHER INFORMATION

• Pregnant pts should not be treated with azoles or echinocandins.
• IRIS not reported in association with mucosal candidiasis

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Amphotericine
• Candidiasis, oropharyngeal
• Fluconazole