Candidiasis

Candidiasis is infection caused by Candida species, predominantly Candida albicans. The spectrum ranges from superficial mucocutaneous infection in otherwise healthy individuals to invasive, life threatening candidaemia and disseminated disease in critically ill or significantly immunocompromised patients.

An increasing proportion of infection is attributable to non albicans species. These include Candida glabrata, Candida krusei and Candida auris. Candida auris is of particular concern given frequently reduced susceptibility to standard antifungal agents and significant nosocomial transmission potential.

The specific clinical context and host risk factors fundamentally shape both the likely causative species and the appropriate management approach.

Pathophysiology and risk factors

• Candida species are normal commensal organisms of the gastrointestinal tract, mucous membranes and skin. Disease occurs when normal host defences are disrupted: mucosal barrier integrity, normal competing microbiota, and cell mediated and neutrophil mediated immune function.
• This explains the characteristic association between candidiasis and antibiotic exposure (disrupting normal bacterial flora), central venous catheters (providing a direct portal for bloodstream invasion), neutropenia, and significant immunosuppression.
• Invasive candidiasis, encompassing candidaemia and deep tissue or organ involvement, carries substantial associated mortality. It is one of the commonest healthcare associated bloodstream infections in critically ill patients, and prompt recognition and treatment directly influence outcome.

• Oropharyngeal candidiasis (thrush) presents with white, adherent plaques on the buccal mucosa, tongue and palate. They can be scraped off to reveal an erythematous, sometimes bleeding, underlying surface.
• Oropharyngeal candidiasis occurs characteristically in infants, denture wearers, those using inhaled corticosteroids without adequate mouth rinsing, and significantly immunocompromised patients. In advanced HIV infection, extensive or recurrent oropharyngeal candidiasis is a recognised marker of significant immunosuppression.
• Oesophageal candidiasis presents with odynophagia and dysphagia, typically in the context of significant immunosuppression. It is an AIDS defining condition, so it should prompt HIV testing where status is not already established.
• Vulvovaginal candidiasis presents with vulval itching, soreness and a characteristic thick, white, curd like discharge. It is extremely common in the general female population and not necessarily indicative of any underlying immunocompromise in isolated, infrequent episodes.
• Recurrent vulvovaginal disease (four or more episodes annually) warrants consideration of predisposing factors including diabetes.
• Cutaneous candidiasis includes intertrigo and candidal paronychia. Intertrigo affects skin folds, particularly in obese or diabetic individuals given the warm, moist, occlusive local environment.
• Cutaneous candidiasis presents with erythematous, macerated, often satellite pustule associated lesions in the affected skin folds or periungual tissue.
• Invasive candidiasis (candidaemia and disseminated disease) presents with fever and sepsis, frequently indistinguishable clinically from bacterial sepsis. It occurs in the specific high risk populations.
• Specific organ involvement reflects haematogenous dissemination: endophthalmitis, presenting with visual disturbance and requiring specific ophthalmological screening in every episode of confirmed candidaemia; endocarditis; and hepatosplenic candidiasis in the context of prolonged neutropenia.

• Superficial mucocutaneous candidiasis (oropharyngeal, vulvovaginal, cutaneous) is generally diagnosed clinically based on the characteristic appearance. Microscopy of a swab or scraping (demonstrating characteristic budding yeast and pseudohyphae) supports diagnosis where confirmation is required or the clinical picture is atypical.
• Blood cultures remain the mainstay for diagnosing candidaemia, though sensitivity is imperfect (estimated at only fifty to seventy five percent even in confirmed invasive disease). A negative blood culture does not reliably exclude invasive candidiasis in a patient with a compatible clinical picture and significant risk factors.
• Beta D glucan, a fungal cell wall component, offers a useful adjunctive serum biomarker with reasonable sensitivity for invasive candidiasis. It lacks specificity for the particular fungal species and can be falsely positive in various other clinical contexts.
• Every confirmed episode of candidaemia warrants ophthalmological examination to screen for endophthalmitis.
• Echocardiography is also warranted where endocarditis is a clinical concern (particularly with prosthetic valves or prolonged candidaemia).
• Remove or exchange any implicated central venous catheter. This is both a diagnostic measure (culture of the removed catheter tip) and an essential therapeutic one (source control).
• Species identification and susceptibility testing of any confirmed isolate is essential, given significant variation in susceptibility to specific antifungal classes between different Candida species. It directly guides definitive treatment selection.

• Oropharyngeal candidiasis is treated with topical nystatin suspension (100,000 units four times daily) or, for more extensive disease, oral fluconazole 50 to 100 mg once daily for seven to fourteen days.
• Recurrent or fluconazole refractory disease (particularly relevant in advanced HIV infection) warrants consideration of an alternative agent and assessment for underlying non albicans or resistant species.
• Oesophageal candidiasis requires systemic treatment given inadequate topical drug delivery to this site. Standard first line therapy is fluconazole 200 to 400 mg once daily for fourteen to twenty one days.
• Vulvovaginal candidiasis is treated with a single oral dose of fluconazole 150 mg, or topical azole preparations (clotrimazole pessary or cream).
• Recurrent vulvovaginal disease (four or more episodes annually) is managed with an induction course followed by maintenance suppressive fluconazole (150 mg once weekly for six months). Assess for and manage any identified predisposing factor.
• Cutaneous candidiasis is treated with topical azole or nystatin preparations, together with measures to reduce moisture and friction in affected skin folds. Manage any underlying predisposing factor such as diabetes.
• Candidaemia and invasive candidiasis require prompt initiation of systemic antifungal therapy. First line empirical treatment is an echinocandin (caspofungin, given as a 70 mg loading dose then 50 mg once daily; or micafungin 100 mg once daily; or anidulafungin).
• Echinocandins have broad activity across Candida species including several azole resistant strains, and a superior safety profile in critically ill patients. Current guidelines prefer them over fluconazole for initial empirical therapy of suspected or confirmed invasive disease.
• Transition to fluconazole (400 mg once daily, following an initial loading dose) may be appropriate once the patient is clinically stable and the specific species is confirmed susceptible. It offers the practical advantage of oral administration to complete the treatment course.
• Remove any implicated central venous catheter promptly where feasible, given clear evidence of improved outcomes with early source control in catheter associated candidaemia.
• Treatment duration for uncomplicated candidaemia is a minimum of two weeks from the first negative blood culture and resolution of symptoms attributable to candidaemia. Extend it substantially for deep seated or disseminated disease (endophthalmitis, endocarditis, hepatosplenic candidiasis) according to the specific site and extent of involvement, guided by specialist infectious disease input.
• Candida auris infection or colonisation requires specific enhanced infection control precautions given significant nosocomial transmission potential and frequently reduced antifungal susceptibility.
• Guide treatment by specific susceptibility testing, given the variable and sometimes extensive resistance pattern characteristic of this emerging pathogen.