Introduction

People with hematological cancer, patients treated with chemotherapy or irradiation, and those with an HIV infection are liable to develop oropharyngeal candidiasis. This is an opportunistic mucosal infection caused, in most cases, by Candida albicans. There are four types:

• pseudomembranous candidiasis (thrush), consisting of white discrete plaques on the buccal mucosa, and the mucosa of the throat, tongue or gingivae.
• erythematous candidiasis, in which there are smooth red patches on the hard or soft palate, dorsum of the tongue, or buccal mucosa.
• hyperplastic candidiasis, comprising white adherent patches or plaques, usually bilaterally on the buccal mucosa.
• denture-related stomatitis often associated with angular cheilitis.

Candida is found in the mouth of 30-60% of healthy people, without producing symptoms. The organism can be transmitted directly, or on fomites.

Symptomatic oropharyngeal candidiasis occurs in persons with local or systemic immunosupression, hematological disorders, broad spectrum antibiotic use, inhaled or systemic steroid use, diabetes, xerostomia, and wearing dentures.

The frequency of occurrence varies according to the cause and the general condition of the patient. It is seen in 7-48% of people with HIV infection, and in over 90% of those with advanced disease. Relapse rates in HIV infected patients are high (30-50%), and occur within 14 days of stopping specific treatment.

Prevention of oropharyngeal candidiasis

Two systematic reviews of the published literature and an additional randomized clinical trial show that antifungal prophylaxis significantly reduces the risk of oropharyngeal candidiasis compared with placebo in patients receiving chemotherapy or radiation. Systemic or topical drugs that were found effective included; amphotericin B, clotrimazole, miconazole, ketoconazole, fluconazole, and itraconazole. There were no adequate trials comparing nystatin with placebo.

In three studies, azoles were found to be somewhat superior to polyenes (amphotericin B, nystatin). Chlorhexedrine oral rinses were found to be effective in two studies of patients with neutropenia after bone marrow transplant.

In people with HIV infection, daily or weekly oral antifungal prophylaxis with fluconazole, itraconazole, or nystatin significantly reduces the incidence of oropharyngeal candidiasis, compared with placebo. Fluconazole was shown to be superior to clotrimazole in one study.

Is there a difference between once-weekly and daily fluconazole prophylaxis, apart from convenience? One 11-month study showed that continuous treatment was better at preventing relapses, but that there was no difference in the emergence of antifungal resistance.

Adverse effects of prophylactic therapy were not remarkable. Frequencies of 5.6% and 5.2% were reported for fluconazole and oral polyenes, respectively. The most common adverse effects were abdominal pain, nausea, vomiting, and rash. Hepatotoxicity was not encountered.

Treatment of oropharyngeal candidiasis

One systematic review encompassed 8 randomized clinical trials in patients given chemotherapy and/or irradiation, in which antifungal treatment was compared with placebo, or another active intervention. Ketoconazole was shown to be superior to placebo, while clotrimazole was not found to be more effective than placebo in one trial, although higher doses of clotrimazole were more effective than lower doses in another study.

There were no differences in effectiveness between drugs that were well-absorbed (fluconazole, ketoconazole, itraconazole) versus those that were partially (clotrimazole) or poorly absorbed (amphotericin B, nystatin).

Topical preparations of itraconazole, fluconazole, and clotrimazole have been shown to treat oropharyngeal candidiasis effectively in HIV patients.
Suspensions or pastilles were compared with orally effective antifungal agents; in most studies, the topical was as effective, or better than, the oral antifungal, but in one, oral fluconazole was superior to nystatin liquid.

Adverse events associated with antifungal treatments of candidiasis were not reported in this review.

Oropharyngeal candidiasis in infants and children

Randomized clinical trials in children are not common. One large un-blinded study in immunocompromised children aged 6 months to 17 years showed that fluconazole was significantly superior to oral polyenes in reducing the incidence of oropharyngeal candidiasis.

Oropharyngeal candidiasis (clinical oral thrush) occurs occasionally in immuno-competent infants. In such cases, miconazole gel was shown to be significantly superior to nystatin suspension or gel.

In immunocompromised children (HIV infection, malignancy, immunosuppressive treatment), fluconazole suspension was more effective than nystatin in producing a clinical cure. Relapse rates were similar with both drugs after 2 weeks - 18% and 24%, respectively. Vomiting was seen with both drugs in 4.5% of children.

Comment

This review of evidence from clinical studies shows that oropharyngeal candidiasis can be treated quite effectively with oral or systemic azole derivatives, although clotrimazole is less effective than the others (fluconazole, ketoconazole, miconazole, and itraconazole). Of the polyenes, amphotericin B was superior to nystatin when used systemically.

Perhaps more importantly, these drugs can be used to prevent the occurrence of symptomatic candidiasis in patients at high risk. Daily or once-weekly fluconazole were almost equally effective, but itraconazole was less so. Locally, chlorhexidine or nystatin oral rinses may be used.

The review contains little information on drug doses, which should be obtained from prescription manual or the manufacturers' approved labeling. It also contains no reference to alternative therapies (such as ThreeLac, Hydroxygen Plus, and Paracan) that are widely advertised. Apart from a pilot study of melaleuca solution, there are no adequate clinical trials showing efficacy of such substances reported in the medical literature.