Candida is a fungus present in the mouths of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics, and corticosteroid use. In most people, untreated candidiasis persists for months or years unless associated risk factors are treated or eliminated. In neonates, spontaneous cure of oropharyngeal candidiasis usually occurs after 3 to 8 weeks.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent and treat oropharyngeal candidiasis in: adults undergoing treatments that cause immunosuppression; infants and children; people with dentures; and people with HIV infection? Which antifungal regimens reduce the risk of acquiring resistance to antifungal drugs? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 47 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antifungals (absorbed, partially or topically absorbed, or non-absorbed; for example, imidazole [ketoconazole, clotrimazole, toiconazole, miconazole], polyene [amphotericin B, nystatin], triazole [fluconazole, itraconazole], melaleuca and posaconazole), intermittent or continuous prophylaxis, or treatment, and denture hygiene.
Opportunistic infection with the fungus Candida albicans causes painful red or white lesions of the oropharynx, which can affect taste, speech, and the act of eating.
Candida is present in the mouth of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics, corticosteroid use, haematinic deficiencies, and denture wear.
In people with immunosuppression following cancer treatment, absorbed (ketoconazole, itraconazole, or fluconazole) or partially absorbed antifungal drugs (miconazole, clotrimazole) prevent oropharyngeal candidiasis compared with placebo or non-absorbed antifungal drugs. We don't know whether antifungal treatment is effective in this group.
Non-absorbed antifungal drugs (nystatin or amphotericin B) may be no more effective than placebo at preventing candidiasis.We don't know whether antifungal prophylaxis is effective in adults having tissue transplants, as we found few studies.
CAUTION: there have been drug safety alerts that oral ketoconazole can cause severe liver injury, adrenal gland problems, can lead to harmful drug interactions (www.fda.gov), and that the benefits do not outweigh the risks in treating fungal infections (www.ema.europa.eu/ema). It has been suspended in some countries and restrictions placed on its use in others.
Prophylaxis with fluconazole is more effective than oral nystatin or amphotericin B at preventing candidiasis in immunocompromised infants and children, while treatment with fluconazole and miconazole increases cure rates compared with nystatin in both immunocompromised and immunocompetent infants and children.
Antifungal drugs may increase clinical improvement or cure in people with oropharyngeal candidiasis caused by wearing dentures.
We don't know whether denture hygiene or removing dentures at night reduces the risk of developing oropharyngeal candidiasis.
Daily or weekly prophylaxis with fluconazole or itraconazole reduces the incidence of candidiasis in people with HIV infection. Prophylaxis with nystatin may not be effective.
Topical treatments with clotrimazole lozenges and miconazole buccal slow-release tablets may be as effective as oral tablets/suspensions of oral antifungals (fluconazole/itraconazole/ketoconazole) at reducing symptoms of candidiasis in people with HIV infection.A single dose of fluconazole (750 mg) may be as effective as a 14-day course of fluconazole in reducing symptoms of candidiasis in people with HIV infection.
Resistance to antifungal drugs, particularly azole drugs, is an increasing problem. Continuous prophylaxis with antifungal agents may not increase the risk of developing antifungal resistance compared with intermittent prophylaxis, but it may be no more effective at reducing the number of attacks in people with HIV infection, the majority of whom were receiving highly active antiretroviral treatment (HAART).