Summary

2016 IDSA update on management of candidiasis covering candidemia, invasive candidiasis, and mucosal disease across neutropenic, nonneutropenic, ICU, neonatal, and special-site populations. Major change from 2009 is the elevation of echinocandins to first-line therapy for most candidemia and invasive candidiasis, with fluconazole reserved for selected stable, azole-naive patients. Adds guidance on β-D-glucan and PCR diagnostics, and updates recommendations for endocarditis, endophthalmitis, CNS, intra-abdominal, and urinary tract candidiasis.

Key Recommendations

Initial therapy for candidemia in both nonneutropenic and neutropenic adults is an echinocandin (caspofungin, micafungin, or anidulafungin).
Transition from echinocandin to fluconazole after 5–7 days if patient is clinically stable, isolate is fluconazole-susceptible, and repeat blood cultures are negative.
All nonneutropenic candidemic patients require dilated ophthalmologic exam within first week; in neutropenic patients delay exam until neutrophil recovery.
Treat candidemia for 2 weeks after documented bloodstream clearance and resolution of symptoms when no metastatic complications.
Remove central venous catheters early in nonneutropenic candidemia when CVC is the presumed source; individualize in neutropenic patients where gut is often the source.
Obtain follow-up blood cultures every 1–2 days to document clearance.
Lipid formulation amphotericin B is reserved for intolerance, resistance, or suspected azole- and echinocandin-resistant Candida.
For Candida endocarditis, use lipid AmB ± flucytosine OR high-dose echinocandin with valve replacement, continuing therapy ≥6 weeks postoperatively; lifelong fluconazole suppression for prosthetic valve or non-operable cases.
Empiric antifungal therapy in critically ill ICU patients with risk factors and unexplained fever or septic shock—preferred agent is an echinocandin.
Neonatal invasive candidiasis: AmB deoxycholate 1 mg/kg/day is first-line; fluconazole 12 mg/kg/day is acceptable alternative; echinocandins reserved for salvage.
Asymptomatic candiduria does not require treatment except in neutropenic patients, very low birth weight infants, or patients undergoing urologic procedures.
Symptomatic Candida cystitis: fluconazole 200 mg daily for 2 weeks; for fluconazole-resistant C. glabrata use AmB deoxycholate or flucytosine; do not use echinocandins or lipid AmB for urinary infections.
Uncomplicated vulvovaginal candidiasis: topical antifungal or single 150 mg oral fluconazole; recurrent disease requires induction then fluconazole 150 mg weekly for 6 months.
Oropharyngeal candidiasis: clotrimazole troches or miconazole buccal tablet for mild disease; fluconazole 100–200 mg daily for moderate-to-severe disease.
Esophageal candidiasis always requires systemic therapy: oral fluconazole 200–400 mg daily for 14–21 days.

Thresholds & Doses

Caspofungin: 70 mg loading dose, then 50 mg IV daily
Micafungin: 100 mg IV daily (no loading dose); 150 mg daily for esophageal/endocarditis
Anidulafungin: 200 mg loading dose, then 100 mg IV daily
Fluconazole for candidemia: 800 mg (12 mg/kg) load, then 400 mg (6 mg/kg) daily
Voriconazole: 400 mg (6 mg/kg) twice daily x2 doses, then 200–300 mg (3–4 mg/kg) twice daily; therapeutic trough 1–5.5 mg/L
Lipid formulation amphotericin B: 3–5 mg/kg daily for most invasive candidiasis; 5 mg/kg for CNS
AmB deoxycholate for neonates: 1 mg/kg daily
Flucytosine: 25 mg/kg 4 times daily; peak <100 mg/L to avoid toxicity
Duration of candidemia therapy: 14 days after blood culture clearance and symptom resolution
Transition from echinocandin to fluconazole: usually within 5–7 days
Ophthalmologic exam timing: within first week after diagnosis (nonneutropenic) or after neutrophil recovery (neutropenic)
ICU fluconazole prophylaxis threshold: invasive candidiasis rate >5%
Neonatal fluconazole prophylaxis: 3–6 mg/kg twice weekly x6 weeks in nurseries with >10% invasive candidiasis rate, birth weight <1000 g
Oral nystatin neonatal prophylaxis: 100,000 units 3 times daily for 6 weeks in infants <1500 g
Vulvovaginal candidiasis: single 150 mg oral fluconazole; severe disease 150 mg every 72 hours x2–3 doses; recurrent disease 150 mg weekly x6 months
C. glabrata vulvovaginitis: intravaginal boric acid 600 mg daily x14 days OR nystatin suppositories 100,000 units daily x14 days
Symptomatic Candida cystitis: fluconazole 200 mg (3 mg/kg) daily x14 days; AmB deoxycholate 0.3–0.6 mg/kg daily x1–7 days for resistant species
AmB bladder irrigation: 50 mg/L sterile water daily x5 days
Oropharyngeal candidiasis: clotrimazole troches 10 mg 5x daily, or fluconazole 100–200 mg daily x7–14 days
Esophageal candidiasis: fluconazole 200–400 mg (3–6 mg/kg) daily x14–21 days
Candida endocarditis: continue therapy ≥6 weeks after valve replacement; chronic fluconazole 400–800 mg suppression for prosthetic valve
Candida osteomyelitis: fluconazole 400 mg daily for 6–12 months; septic arthritis 6 weeks total
Intravitreal AmB deoxycholate: 5–10 μg/0.1 mL; intravitreal voriconazole: 100 μg/0.1 mL
Intraventricular AmB deoxycholate: 0.01–0.5 mg in 2 mL D5W
Fluconazole clinical breakpoint for C. albicans: susceptible ≤2 μg/mL, resistant ≥8 μg/mL

Citations

Section I, Recommendations 1–12 — Treatment of candidemia in nonneutropenic patients
Section II, Recommendation 13 — CVC removal in nonneutropenic candidemia
Section III, Recommendations 14–23 — Candidemia in neutropenic patients
Section V, Recommendations 28–33 — Empiric therapy in nonneutropenic ICU patients
Section VII, Recommendations 37–53 — Neonatal candidiasis and prophylaxis
Section X, Recommendations 59–73 — Candida endocarditis and intravascular infections
Section XII, Recommendations 82–91 — Candida endophthalmitis
Section XIV, Recommendations 97–114 — Urinary tract candidiasis
Section XV–XVII, Recommendations 115–140 — Vulvovaginal, oropharyngeal, and esophageal candidiasis
Table 1 — CLSI clinical breakpoints for antifungal agents against common Candida species