Treatment of Fungal Infections

The treatment of most fungal infections is primarily the responsibility of physicians (Table 2).5-7 However, the diagnosis and treatment of oropharyngeal candidal infections, to a great extent, falls within the purview of oral healthcare providers. The pathogenesis of candidal infections is based on interplay between host defense mechanisms and the pathogenicity of candida organisms. Patients with compromised immune defenses are at increased risk of infection.

Table 2. Indications for Antifungal Chemotherapy.5-7
Mechanism of action Drugs* Indications*
Inhibitors of β-(1,3)-D-glucan synthase Echinocandins
     Anidulafungin
     Caspofungin
     Micafungin
Candidiasis
Aspergillosis
Inhibitors of squaline synthase Allylamines and benzylamines
     Butenafine
     Naftifine
     Terbinafine
Tinea corporis or tinea cruris (all)
Tinea capitis (terbinafine)
Tinea pedis (butenafine)
Inhibitors of 14α-sterol demethylase Imidazoles
     Butoconazole
     Clotrimazole
     Econazole
     Ketoconazole
     Luliconazole
     Miconazole
     Oxiconazole
     Sertaconazole
Candidiasis
Cryptococcosis
Coccidioidomycosis
Histoplasmosis
Blastomycosis
Triazoles
     Fluconazole
     Itraconazole
     Posaconazole
     Terconazole
     Voriconazole
     Isavuconazole
Candidiasis
Aspergillosis
Blastomycosis
Histoplasmosis
Inhibitors of fungal plasma membrane stability Polyenes
     Amphotericin B
     Nystatin
Most fungal infections (amphotericin B)
Mucocutaneous candidiasis
Inhibitor of fungal nucleic acid synthesis Flucytosine Candidiasis
Cryptococcosis
Inhibitor of fungal mitosis Griseofulvin Fungal infections of the skin, hair, or nail caused by Trichophton, Microsporum, or Epidermophyton
*FDA-approved information on specific antiviral agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3

Primary oropharyngeal candidiasis may appear in a variety of clinical forms. It is often asymptomatic, but patients may relate burning and altered taste. A classification system based on clinical criteria provides a clear distinction between primary forms of oropharyngeal candidiasis (Figures 2‑7) and secondary candidal infection associated with keratinized primary lesions such as leukoplakia, lichen planus, and lupus erythematosus.8

Figure 2.
Acute pseudomembraneous candidiasis as a consequence of the extended use of a broad-spectrum antibacterial agent.
Figure 3.
Chronic pseudomembraneous candidiasis as a consequence of inhaled corticosteroid use in the management of asthma.
Figure 4.
Erythematous candidiasis confirmed by cytology.
Figure 5.
Hyperplastic candidiasis (candidal leukoplakia) confirmed by biopsy.
Figure 6.
Candida-associated erythematous denture stomatitis.
Figure 7.
Granular or papillary Candida-associated denture stomatitis.

Other candidal infections include median rhomboid glossitis and angular cheilitis. The presence of oropharyngeal candidiasis and symptoms of dysphagia or odynophagia are the hallmark of candidal esophagitis. A rare condition observed in patients with an immune defect is chronic mucocutaneous candidiasis accompanied by chronic persistent onychomycosis. At times, hematogenous dissemination may lead to systemic candidal infection.

Oral healthcare providers must recognize oropharyngeal candidiasis and must be familiar with treatment strategies and patient management guidelines (Table 3).6,7 Treatment with an antifungal agent can eliminate oropharyngeal infection and prevent systemic dissemination. Patients who fail to respond to antifungal therapy may have undiagnosed or inadequately treated predisposing conditions and are best managed by their physician.

Table 3. Antifungal Agents for the Treatment of Oropharyngeal Candidiasis.6,7
Diagnosis Drugs Adult dosages
Mild disease Clotrimazole* 10 mg torches
5 times daily for 14 days
Miconazole* 50 mg mucoadhesive buccal tablets
Once daily for 7-17 days
Nystatin§ 100,000 U/mL suspension
4 to 5 mL 4 times daily
Nystatin§ 200,000 U pastilles
1 or 2 pastilles 4 times daily for 7-14 days
Moderate-to-severe disease Fluconazole* 100 mg oral tablets
1 to 2 tablets daily (3 mg/kg) for 7-14 days
Fluconazole-refractory disease Itraconazole§ 10 mg/mL oral solution
200 mg once daily for up to 28 days
Posaconazole§ 40 mg/mL oral suspension
400 mg twice daily for 3 days then 400 mg daily for up to 28
Voriconazole§ 200 mg tablets
200 mg twice daily for 7-21 days
Amphotericin B deoxycholate§ 100 mg/mL oral suspension
100 mg 4 times daily
Caspofungin 70 mg loading dose, IV
then 50 mg daily for 7-21 days
Micafungin 100 mg daily IV
Anidulafungin 50 mg, IV, 1x daily for 7-21 days
Amphotericin B deoxylate 0.3 mg/kg daily, IV
Chronic suppressive therapy Fluconazole* 100 mg oral tablets
100 mg 3 times weekly
Denture-related candidiasis Based on moderate-quality evidence it is strongly recommended that in addition to antifungal chemotherapy, with denture-related candidiasis the prostheses be disinfected.
*Strong recommendation - high-quality evidence
§Strong recommendation - moderate quality evidence
Weak recommendation - moderate quality evidence

Clotrimazole troches and miconazole mucoadhesive tablets are topical antifungal agents used to treat superficial candidal infections of squamous mucosa. Strong recommendation for their use to treat mild oropharyngeal candidiasis is based on high-quality evidence.7 Rare ADRs include itching (pruritus), burning, and hypersensitivity (allergic) reactions.3 Miconazole mucoadhesive tablets are contraindicated in patients with hypersensitivity to milk proteins.3

Nystatin oral suspension or pastilles may also be used to treat candidiasis of the oral mucosa. Strong recommendation for their use to treat mild oropharyngeal candidiasis is based on moderate-quality evidence.7 Nystatin formulations are not absorbed systemically from the gastrointestinal tract or across the oral mucosa. Potential ADRs include rare hypersensitivity reactions (allergic contact mucositis) and Stevens-Johnson syndrome.3

Fluconazole has a nearly 100% bioavailability following oral administration and diffuses freely into saliva. Strong recommendation for its use to treat moderate-to-sever oropharyngeal candidiasis and for chronic suppressive therapy in recurrent infections is based on high-quality evidence.7 Potential ADRs include nausea, vomiting, abdominal pain, and diarrhea; CYP3A4-related drug-drug interactions; and rare cases of liver toxicity and Stevens-Johnson syndrome.3

Itraconazole, posaconazole, and voriconazole have broader activity against Candida sp. Strong recommendation for their use to treat fluconazole-refractory moderate-to-severe oropharyngeal candidiasis is based on moderate-quality evidence.7 Itraconazole solution or posaconazole suspension is to be prescribed first; voriconazole tablets are used when treatment with topical itraconazole or posaconazole has failed. ADRs are similar to those with fluconazole.3

Amphotericin B deoxycholate suspension is effective in some patients with moderate-to-severe fluconazole-refractory oropharyngeal candidiasis. Strong recommendation for its use is based on moderate-quality evidence. The suspension must be compounded by a pharmacist.7 Weak recommendation for intravenous amphotericin B deoxycholate to treat moderate-to-severe fluconazole-refractory oropharyngeal candidiasis is based on moderate-quality evidence.7

Serious ADRs with intravenous administration of amphotericin B deoxycholate may include cytokine storm elicited by tumor necrosis factor-alpha (TNF-α) and interleukin-1(IL-1) released by cells of the immune system. Cytokine storm is characterized by fever, chills, rigors, and hypotension.3 Other potential serious ADRs include renal toxicity; anemia, secondary to reduced production of erythropoietin; and Stevens-Johnson syndrome and toxic epidermal necrolysis.3

Intravenous caspofungin, micafungin, or anidulafungin are used primarily to treat esophageal candidiasis. Weak recommendation for their use to treat fluconazole-resistant moderate-to-severe oropharyngeal candidiasis is based on moderate-quality evidence.7 Since human cells lack a cell wall, the echinocandins have no serious systemic adverse effect. Potential ADRs include pruritus, rash, gastrointestinal disturbances, headache, and fever.3