Recommendations for the assessment and treatment of oral candidal infection are in line with expert opinion from a textbook [Hay and Moore, 2004] and narrative reviews [Akpan and Morgan, 2002; Gonsalves et al, 2007; Samaranayake et al, 2009].

First line treatment

• Miconazole
• Miconazole has a broad spectrum of activity against fungal and yeast species, and has some additional activity against some Gram-positive bacteria, making it useful in the treatment of angular cheilitis (which is sometimes caused by Staphylococcal aureus) [Pappas et al, 2009; Samaranayake et al, 2009].
• There is a lack of direct evidence from randomized controlled trials (RCTs) to support the use of topical miconazole in the treatment of oral candidiasis in otherwise healthy adults. However, its use is supported by pharmacological principles, historical use, and extrapolation of clinical data from trials in other groups (such as infants and people who are immunosuppressed).
• Nystatin
• There is a lack of evidence from RCTs to support the effectiveness of nystatin suspension in the treatment of oral candidal infection in otherwise healthy adults. However, data extrapolated from trials in infants and immunosuppressed people suggest it is not as effective as topical miconazole or fluconazole, and therefore not suitable as first-line treatment.
• Fluconazole
• Fluconazole has a broad range of antifungal activity, including against candida species [Pappas et al, 2009; Samaranayake et al, 2009]. Although there is a lack of evidence from RCTs to show the efficacy of oral fluconazole in otherwise healthy people, data extrapolated from trials in infants and immunosuppressed people suggest it is an effective option. Fluconazole is not routinely recommended for first-line treatment of mild and localized candidiasis because:
• It is systemically absorbed, and may cause adverse effects.
• Its use is associated with increasing levels of candidal resistance (especially Candida glabrata or C. krusei) [Laudenbach and Epstein, 2009].

Dental hygiene and smoking

• Poor dental hygiene has been identified as a risk factor for oral candidal infection [Samaranayake et al, 2009], although there is a lack of evidence to show improved hygiene is beneficial.
• Smoking is regarded as a significant cause of oral candidal infection, particularly median rhomboid glossitis. Smoking cessation alone may clear infection in these people [Akpan and Morgan, 2002].

Diabetes and oral candidal infection

• There is conflicting evidence from several observational studies as to whether diabetes is a cause of oral candidal infection.
• The presence of Candida has been associated with poor glycaemic control by some studies [Hill et al, 1989; Aly et al, 1992; Guggenheimer et al, 2000]. However, other studies found no relationship between oral candidal carriage/growth and antidiabetic therapy or glycaemic controls [Bartholomew et al, 1987; Belazi et al, 2005; Kumar et al, 2005].
• The discrepancies between studies may reflect differences in methodology, such as variation in sampling techniques and selection of control populations [Soysa et al, 2006].
• It is generally accepted that an association between diabetes and oral candidal infection is plausible, and most experts agree that good control of blood glucose is important in the long-term management of oral candidiasis [Soysa et al, 2006]. This will also have other wide-reaching benefits.

Drugs not recommended for initiation in primary care

• Oral itraconazole should be reserved for people with fluconazole-resistant candidiasis [BNF 57, 2009]. Specialist advice should be obtained before initiating itraconazole therapy because of the increased risk of drug interactions and adverse effects.
• Oral ketoconazole should only be prescribed for the treatment of chronic mucocutaneous candidiasis that cannot be treated topically because of the site, extent of the lesion, or deep infection of the skin, in people resistant to or intolerant of both fluconazole and itraconazole [MHRA, 2008].
• Oral amphotericin is not recommended as there is a lack of trial evidence to show its efficacy in the treatment of oral candidal infection. It is sometimes used as adjunct to other systemic antimycotic drugs.

Inhaled corticosteroids and oral candidiasis

• Deposition of inhaled corticosteroids in the mouth is thought to have a localized immunosuppressive effect on the mucosa, leading to an increased risk of oral candidiasis.
• A systematic review and meta-analysis of randomized controlled trials (RCTs) found that inhaled corticosteroids significantly increased the incidence of oral candidal infection, dysphonia, and pharyngitis compared with placebo at all doses studied, and regardless of the device used [Rachelefsky et al, 2007].

Management of inhaled corticosteroids

• The recommendation to use good inhaler technique and wash the mouth after use aims to minimize the exposure of corticosteroid on the oral mucosa [Rachelefsky et al, 2007].
• A large-volume spacer device reduces oropharyngeal deposition by filtering out larger particles, and is useful for use with pressurized metered-dose inhalers [DTB, 2000; RPSGB, 2006].

Recommendations for denture hygiene measures are based on expert opinion from narrative reviews [Wilson, 1998; Akpan and Morgan, 2002].

• Chlorhexidine is an antiseptic that has broad-spectrum activity, including antimycotic activity against candida species. It can be used as an effective disinfectant for dentures and inhibits adhesion of candida [Ellepola and Samaranayake, 2001].
• A small, open-label, comparative, randomized controlled trial in 61 people found that twice-daily rinses with the antiseptic hexetidine resulted in a significant reduction in the amount of Candida albicans present in saliva, compared with pretreatment levels (no control group was included) [Koray et al, 2005].

Follow-up recommendations for people with oral candidal infection are pragmatic, and reflect what CKS considers to be good clinical practice.

• Oral candidiasis is unusual in otherwise healthy people, but anecdotal and extrapolated evidence indicates that treatment is effective, and follow up is rarely necessary for mild, localized candidal infection. However, it is reasonable to follow up extensive or severe candidiasis to ensure the infection has cleared and complications have not developed.
• There are no clinical data on which to base decisions if initial treatment is not fully effective. However, extending treatment or switching to nystatin (which may be effective against resistant organisms) or oral fluconazole (which has a systemic effect) are reasonable options before expert advice or referral are sought [Samaranayake et al, 2009].

Admission

• Systemic candidiasis, or candidal infection spreading to the oesophagus, is a life-threatening infection requiring immediate intervention by specialists [Pappas et al, 2009]. Systemic candidiasis has an estimated mortality rate of 71–79% [Akpan and Morgan, 2002].

Referral

• The British National Formulary recommends referral for investigation if candidal infection fails to respond to 1–2 weeks of treatment [BNF 57, 2009].
• Severe, extensive, widespread, or recurrent episodes of oral candidiasis are unusual in otherwise healthy people, and may indicate underlying immunocompromise that requires further investigation.
• Infection that is unresponsive to fluconazole may indicate the development of resistance, the presence of a resistant organism (such as Candida glabrata or Candida krusei), or bacterial superinfection [Samaranayake et al, 2009]. It may be reasonable to swab for the presence of resistant organisms in this group [Akpan and Morgan, 2002].
• Chronic plaque-like oral candidiasis may be a feature of premalignant change [Samaranayake et al, 2009]. Biopsy may be indicated, especially if the candidiasis is unresponsive to treatment.