Approach

The main goal of treatment is to reduce the patient's discomfort, to increase quality of life, and to improve food intake. It is important to facilitate adequate nutrition and hydration of the immunocompromised patient.

In addition, if left untreated in severely immunocompromised or debilitated patients, oropharyngeal candidiasis may become focally invasive or disseminate. Therefore, early diagnosis, management, and follow-up of the infection are important.

For denture-related disease, aggressive disinfection of the denture for definitive cure is often recommended.[59] However, there is weak evidence in support of soaking the dentures in effervescent tablets or enzymatic solutions alone. Manually brushing the dentures with paste has been found to be more efficacious at removing plaque and killing microbes compared to inactive treatment.[60]

Guidelines emphasize careful daily removal of bacterial biofilm on dentures by soaking and manual brushing with an effective nonabrasive denture cleaner as an effective method for controlling denture stomatitis. They also recommend not wearing dentures continuously (i.e., 24 hours per day) in order to reduce the risk of denture stomatitis.[58][61]

Mild to moderate disease (focal tissue involvement, minimal symptoms)

Candida albicans is usually susceptible to most antifungal agents.[54] Most patients initially respond to topical therapy. Using topical agents to treat oropharyngeal candidiasis reduces systemic drug exposure, diminishes the risk of drug-to-drug interactions and systemic adverse events, and may reduce the likelihood of antifungal resistance.[17]​ Mild to moderate cases of oral candidiasis may be treated with azole antifungal agents (e.g., clotrimazole, miconazole), a topical polyene (i.e., nystatin), and gentian violet.[17]​​[54] It should be noted that nystatin suspension has a high sucrose content and its frequent use, especially in a patient with hyposalivation/xerostomia, may increase the risk of dental caries.[62]

Severe disease (generalized tissue involvement, pain, and burning)

For patients with severe disease, especially in patients with HIV who may relapse sooner with a topical agent, treatment with systemic azoles (e.g., fluconazole tablets, itraconazole oral solution, or posaconazole suspension) is recommended.​[17]​[54] Infectious Diseases Society of America guidelines recommend the use of fluconazole in severe disease; other azoles are reserved for fluconazole-resistant cases.[54] However, US guidelines for opportunistic infections in people with HIV recommend fluconazole as first-line treatment but recognize other azoles as acceptable options.​[17]​

Itraconazole oral solution and posaconazole oral suspension are both as effective as fluconazole tablets but have more drug-drug interactions.[17]​ Posaconazole oral suspension is generally better tolerated than itraconazole oral solution.[17]​ Ketoconazole and itraconazole capsules (but not itraconazole suspension) are less effective than fluconazole because of their more variable gastrointestinal (GI) absorption and should be second-line alternatives.[17]​​[54] Fluconazole-refractory oropharyngeal candidiasis will respond to posaconazole oral suspension in 75% of patients, while itraconazole oral solution is considered an alternative treatment.[17]​​[54]

The most common adverse effects associated with the use of posaconazole include headache, fever, nausea, vomiting, and diarrhea.[63] Ketoconazole may cause severe liver injury and adrenal insufficiency. In July 2013, the US Food and Drug Administration recommended that oral ketoconazole should only be used for life-threatening fungal infections where alternative treatments are not available or tolerated, and when the potential benefits of treatment outweigh the risks. Its use is contraindicated in patients with liver disease. If used, liver and adrenal function should be monitored before and during treatment.[64] This recommendation does not apply to topical formulations of ketoconazole.

Patients may experience GI upset with oral azole treatment, and periodic monitoring for hepatotoxicity is recommended for treatment lasting longer than 21 days.​[17]​

Refractory oropharyngeal candidiasis

Further alternative compounds for patients with azole-resistant strains include anidulafungin, caspofungin, micafungin, voriconazole, or amphotericin-B.[17]​​[54] Resistance to caspofungin in albicans and non-albicans strains has been reported.[65][66] Intravenous amphotericin-B is usually reserved for progressive potentially life-threatening fungal infections. Amphotericin-B oral suspension may also be used when treatment with itraconazole has failed; however, it is not available in the US.[17]​​[54]

If intravenous antifungal therapy is being considered, the patient is referred to an infectious disease specialist for management.

Angular cheilitis

Management of angular cheilitis involves the use of topical antifungal agents and sometimes topical corticosteroids. See Angular cheilitis.

Preventive treatment in severely immunocompromised patients

Prophylaxis with antifungal agents may be used to prevent local infection and systemic candidal involvement in patients undergoing radiation or chemotherapeutic cancer treatment, or among patients who have had a bone marrow or organ transplant. [ Cochrane Clinical Answers logo ] There is also some evidence that among very preterm and very low birth weight infants, prophylaxis with oral/topical nonabsorbed antifungal agents reduces the risk for invasive fungal infection.[52] Evidence suggests that antifungal prophylactic drugs absorbed from the GI tract (e.g., fluconazole) prevent oral candidiasis in patients receiving treatment for cancer.[44][45][46] 

Routine primary prophylaxis is not recommended among patients with advanced HIV infection due to the risk of drug-resistant Candidastrains and significant drug-to-drug interactions. The administration of antiretroviral therapy and immune restoration among patients living with HIV is deemed most effective in preventing oropharyngeal candidiasis.[17]​ Most HIV specialists do not recommend secondary prophylaxis of recurrent oropharyngeal candidiasis unless the patient has frequent or severe recurrences.[17]​ In such cases, a daily dose of fluconazole is recommended.[17]​​[54] [ Cochrane Clinical Answers logo ]  

Continuous fluconazole therapy (three times weekly dosing) compared with episodic fluconazole treatment has been shown to be more effective in lowering the number of episodes of recurrences among patients with CD4 counts <150 cells/mm³.[67] There are insufficient data to make recommendations concerning continuous versus intermittent therapy for the use of prophylactic antifungals in patients with diabetes.[15]

The use of continuous suppressive therapy increases the number of Candida isolates with an increased fluconazole minimum inhibitory concentration, but it does not increase the likelihood of developing an infection that does not respond to fluconazole.[48] Patients may experience hepatotoxicity with >7 to 10 days of systemic azole treatment.[16]

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