Non-albicans candida infections

What are non-albicans candida infections?

Non-albicans candida infections are fungal infections caused by the Candida species of yeast other than C. albicans. These include:

• C. dubliniensis
• C. kefyr
• C. krusei
• C. glabrata
• C. guilliermondii
• C. parapsilosis
• C. tropicalis [1].

The incidence of non-albicans candidiasis has been increasing over recent years.

Who gets non-albicans candida infections?

Of the known non-albicans candida species, C. tropicalis, C. parapsilosis, and C. orthopsilosis are considered to be part of normal skin flora [2,3].

Infections typically ensue in the context of wounds or other non-intact skin, pre-existing illness, or immunosuppression.

• Virulence factors such as biofilm formation, hydrolytic enzymes, and adherence to host tissue contribute to the transition from commensal to pathogenic species [4].
• Factors that have led to an increase in non-albicans candida infections include widespread use of broad-spectrum antibiotics, empirical use of antifungal drugs, indwelling catheters, and exposure to medications based on polyenes and azoles [1,4].

What are the clinical features of non-albicans candida infections?

The clinical features and complications of non-albicans candidiasis are indistinguishable from candidiasis caused by C. albicans [4].

Vulvovaginal candidiasis

Vulvovaginal candidiasis is one of the most frequent infections experienced by adult women [5,6]. It presents with vulval irritation, itching, soreness, discomfort with sexual activity (dyspareunia), and a curdy-white vaginal discharge [5,6]. Many non-albicans species have been identified in vulvovaginal candidiasis, with most cases associated with C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis.

• C. glabrata accounts for 50–67% of reported non-albicans vulvovaginal candidiasis [4,7].
• Non-albicans candida species are more often isolated from asymptomatic women than from women with vulvovaginitis [5,8].
• C. glabrata and C. albicans have also been isolated from patients diagnosed with asymptomatic bacterial vaginosis [9].
• Some studies relating non-albicans species to symptomatic vulvovaginitis have shown that non-albicans infections can present with milder symptoms compared with C. albicans [10], while others have reported that C. glabrata and C. krusei are associated with more frequent vaginal soreness and painful intercourse [11].

Oral candidiasis

Oral candidiasis is caused by an overgrowth of Candida species in the mouth. The two main forms are white oral candidiasis (pseudomembranous candidiasis, hyperplastic candidiasis) and erythematous oral candidiasis (atrophic candidiasis, median rhomboid glossitis, angular cheilitis, linear gingival erythema). Other forms are chronic mucocutaneous candidiasis, cheilocandidiasis (candida affecting lips), and chronic multifocal candidiasis [12].

Non-albicans species implicated in oral candidiasis include:

• C. dubliniensis
• C. glabrata
• C. kefyr
• C. parapsilosis
• C. stellatoidea
• C. tropicalis [12].

Candida species are a part of the normal oral flora of healthy individuals [13].

Non-albicans Candida species have been isolated from the oral cavity of patients with oral squamous cell carcinoma. There is no connection between the presence of candida and mortality rate from oral cancer [14].

Systemic candidiasis

Systemic candidiasis refers to invasion and growth of Candida in specific organ systems (also called disseminated candida) or the bloodstream (candidaemia). It is an opportunistic infection.

• Increasing prevalence of C. krusei, C. glabrata, C. tropicalis, and C. parapsilosis causing systemic candidiasis is reported worldwide [15–17].
• Malignancy is one of the major underlying causes; systemic candidiasis is associated with a 30–50% mortality rate in cancer patients [15].
• Other risk factors include exposure to quinolones or b-lactamase inhibitors and the presence of central venous catheters [16].

How are non-albicans candida infections diagnosed?

All candida infections are diagnosed by their typical clinical features and by seeing pseudohyphae and yeast forms on microscopy of swabs and scrapings. See laboratory test for fungal infections.

• Fungal cultures help identify Candida, rule out a bacterial infection, and determine topical or oral antifungal sensitivities [18].
• Non-albicans species identification can be determined using biochemical and molecular biology techniques including polymerase chain reaction (PCR) [1,4].

Microscopy of C. dubliniensis

C. tropicalis in culture

What is the treatment for non-albicans Candida infections?

Candida infections are treated using the three approved classes of antifungals: azoles, echinocandins, and amphotericin B. Resistance to azoles, while rare in C. albicans, is frequent with non-albicans species and may contribute to their increased incidence [1,4].

The most common topical antifungal medications used in cutaneous candidiasis include clotrimazole, nystatin, and miconazole [19].

Boric acid, which prevents the growth of fungi, is used in the form of intravaginal suppositories for vulvovaginal candidiasis caused by C. glabrata [20].

Systemic/oral antifungal medications for cutaneous candidiasis include fluconazole and itraconazole. Voriconazole and posaconazole are reserved for serious systemic candidiasis.

There are few clinical trials reporting the response of non-albicans species to treatment [19].

Candida auris: an emerging species

C. auris is a multidrug-resistant pathogen with a growing incidence since its initial isolation and discovery in 2009 [21–23]. It causes systemic candidiasis, wound infection, and otitis, and is considered to be iatrogenic [22,23].

• Patients with C. auris infection have presented with pericarditis, respiratory infections, or urinary tract infections [24].
• C. auris has been detected in multiple body sites: nares, groin, axilla, and rectum [22]; it was initially isolated from a Japanese patient with an ear infection [21].
• Common risk factors for C. auris infection include contact with infected persons, the presence of catheters, recent antibiotics or surgery, immunodeficiency, and immune suppression [24].

Treatments for C. auris are extremely limited; echinocandins are the most frequently recommended option, though several strains are believed to be resistant to all antifungals. Off-patent or repurposed drugs may be tried in the treatment of C. auris infections, with the anti-inflammatory compound Ebselen showing the most promise [25,26].