Itraconazole is NOT Recommended for Candida auris Infection
Echinocandins are the strongly recommended first-line therapy for C. auris infections, not itraconazole. 1 Itraconazole has no role in treating C. auris due to extensive azole resistance patterns and lack of clinical efficacy data.
Evidence-Based Treatment Algorithm for C. auris
First-Line Therapy
- Echinocandins are the drugs of choice (caspofungin, micafungin, or anidulafungin) with strong recommendation despite low quality evidence (1C). 1
- C. auris demonstrates 90-98% susceptibility to echinocandins (caspofungin 90%, micafungin 98.2%, anidulafungin 97.2%). 1
- Treatment duration is at least 14 days after documented clearance from bloodstream and resolution of symptoms. 1
Why Azoles (Including Itraconazole) Fail Against C. auris
- Over 90% of C. auris clinical isolates are highly resistant to fluconazole, with overall susceptibility to fluconazole only 10.7%. 1, 2
- Itraconazole shows similarly poor activity, with high biofilm MICs (minimum inhibitory concentrations) even when planktonic MICs appear acceptable. 3
- C. auris exhibits intrinsic and acquired azole resistance through multiple mechanisms including ERG11 mutations and efflux pump overexpression. 2, 4
Second-Line Options (When Echinocandins Fail)
- Liposomal amphotericin B or amphotericin B deoxycholate may be considered for persistent candidemia or clinical unresponsiveness to echinocandins without evidence of amphotericin B resistance (2C). 1
- C. auris susceptibility to amphotericin B is only 43.1%, making this a suboptimal but sometimes necessary alternative. 1
- Deoxycholate amphotericin B shows better activity against C. auris biofilms than liposomal formulations in vitro. 3
Critical Clinical Pitfalls
Avoid These Common Errors
- Never use fluconazole or itraconazole as monotherapy for suspected or confirmed C. auris infection—resistance rates are prohibitively high. 1, 2
- Do not rely on traditional biochemical identification methods, as C. auris can be misidentified; molecular methods are required. 5
- Recognize that C. auris has extraordinarily high mortality (up to 64%) and requires aggressive treatment. 1
Infection Control Considerations
- C. auris is highly transmissible in healthcare settings and requires strict infection control measures beyond standard antifungal therapy. 5
- Nosocomial outbreaks have been reported globally, emphasizing the need for rapid identification and isolation. 5
Experimental Combination Approaches (Not Standard of Care)
While not guideline-recommended, research shows potential synergy:
- Sulfamethoxazole combined with voriconazole or itraconazole restored azole activity in 3/8 and 3/4 resistant isolates respectively, but only when resistance was ERG11-mediated (not efflux pump-mediated). 4
- HIV protease inhibitors (lopinavir/ritonavir) with azoles showed synergy in vitro and reduced fungal burden by 94-97% in mouse models. 6
- These combinations remain investigational and should not replace echinocandin-based therapy in clinical practice. 4, 6
Bottom Line
Itraconazole has no established role in C. auris treatment due to extensive resistance. Start with an echinocandin immediately for any suspected C. auris infection, and escalate to amphotericin B formulations only if echinocandins fail and susceptibility testing supports this approach.