From the Guidelines
For a young adult with persistent oral candidiasis despite 14 days of fluconazole treatment, the next step would be to switch to an alternative antifungal agent such as itraconazole solution, 200 mg daily, or voriconazole, 200 mg (3 mg/kg) twice daily either intravenous or oral, for 14–21 days. This recommendation is based on the 2016 clinical practice guideline for the management of candidiasis by the Infectious Diseases Society of America 1. Before changing therapy, it's essential to confirm medication adherence and rule out underlying immunosuppression by checking HIV status, complete blood count, and possibly blood glucose levels.
Some key considerations in managing this patient include:
- Obtaining fungal cultures with susceptibility testing to identify potential fluconazole-resistant Candida species, as recommended by the guideline 1.
- If the patient has dentures, these should be thoroughly disinfected or replaced as they can harbor fungi.
- Adding chlorhexidine mouthwash twice daily as an adjunctive treatment can help reduce the fungal burden.
- Persistent thrush despite adequate fluconazole therapy may indicate resistance, which is increasingly common in certain Candida species, or may suggest an underlying immunodeficiency that requires further investigation and management. The guideline recommends considering de-escalating to oral therapy with fluconazole once the patient is able to tolerate oral intake, but this may not be suitable for a patient with fluconazole-refractory disease 1.
Alternative treatments for fluconazole-refractory disease, as outlined in the guideline, include an echinocandin or AmB deoxycholate, but these are generally considered less preferred options due to potential side effects and lower efficacy compared to itraconazole or voriconazole 1. Posaconazole suspension could also be considered, but the evidence supporting its use is weaker compared to other alternatives 1.
From the FDA Drug Label
CLINICAL STUDIES Oropharyngeal Candidiasis ... In an uncontrolled, open-label study of selected patients clinically unresponsive to fluconazole tablets (n = 74, all patients HIV seropositive), patients were treated with itraconazole oral solution 100 mg b.i.d. Approximately 55% of patients had complete resolution of oral lesions.
The next step in managing a young adult with persistent thrush (oral candidiasis) despite 14 days of fluconazole treatment could be to consider alternative antifungal therapy, such as itraconazole oral solution.
- The dosage used in the study was 100 mg b.i.d.
- Treatment duration was 14–28 days based on response 2. However, it is essential to note that all relapsed within 1 month when treatment was discontinued.
From the Research
Next Steps in Managing Persistent Thrush
The next step in managing a young adult with persistent thrush despite 14 days of fluconazole treatment involves considering alternative antifungal therapies.
- Assessing Treatment Failure: Before switching treatments, it's essential to confirm that the initial treatment was taken as directed and that the diagnosis of thrush is correct 3.
- Alternative Antifungal Agents: Studies have shown that itraconazole oral solution can be an effective alternative for treating oropharyngeal candidiasis, with clinical response rates comparable to or even superior to fluconazole in some cases 4.
- Posaconazole as an Option: Posaconazole has been demonstrated to be as effective as fluconazole in treating oropharyngeal candidiasis, with the added benefit of sustaining clinical success after treatment cessation 5.
- Consideration of Underlying Conditions: The management approach may also depend on the patient's immune status and the presence of any underlying conditions that could be contributing to the persistence of thrush.
- Resistance and Relapse: The possibility of antifungal resistance or relapse should be considered, especially in immunocompromised patients, and may require the use of different antifungal agents or combination therapy 6, 7.