Candida albicans
Candida albicans is a medically important pathogenic yeast-like fungus. It is called ‘yeast-like fungus’ due to its ability to form pseudohyphae. Pseudohyphae formation is a phenotypic ‘switch over’ that the yeast undergoes whenever there is tissue invasion. Hence the presence of pseudohyphae in microscopy of tissue specimens indicates invasiveness of the yeast and can be considered an infection by the organism. This is especially important in clinical settings where C.albicans can be a part of the commensal flora like the oral cavity or the gastrointestinal tract. Fungal diarrheas due to Candida albicans are well known in hospital settings. Thus pseudohyphae can be considered to be one of the virulence factors for Candida albicans. Other virulence factors like proteases, adhesions to extracellular matrix proteins and complement binding receptors further contribute to increased infectious capability of Candida albicans.
Candida albicans is capable of causing superficial infections of the skin and mucosae as well as invasive blood stream infections. In the community, Candida albicans commonly causes vaginitis in women, particularly pregnant women, due to the low pH of the vagina during pregnancy. Paronychia and onychomycosis are seen in occupations involving frequent immersion of hands in water. Additionally, oral thrush is seen in bottle fed infants. Infants may also develop candidial skin lesions in the groin and perineal region frequently called ‘nappy rash’ due to maceration of the skin by urine or sweat. Mucocutaneous candidiasis in the form of oral thrush and denture stomatitis is common in advanced age due to the local mechanical irritation of the oral mucosa caused by dentures.
Predisposing Factors
Candida albicans is an notable pathogen in healthcare settings. Among the fungi, it is the most common nosocomial pathogen. Despite antifungal therapy, mortality involving invasive fungal disease with Candida albicans can be as high as 40%. The risk factors predisposing to candidiasis in healthcare settings are
- Extremes of age such as in very low birth weight babies and the elderly
- Patients with hematological malignancies who are on chemotherapy or those who have undergone transplants and have been prescribed immunosuppressive drugs
- Diabetes
- Prolonged hospitalization
- Patients with invasive devices such as central venous catheters, umbilical catheters and urinary catheters
- Prolonged use of broad spectrum antimicrobial agents
Advances in medical technology have reduced mortality markedly. The down fall of this has been the increasing incidence of nosocomial infections, more so with opportunistic yeasts, of which Candida albicans is the most common. The origin of infection is frequently endogenous. Candida albicans is a part of the commensal flora of the gastrointestinal tract. Studies have indicated that fungal sepsis in critically ill patients can be traced to the colonizing flora of the gastrointestinal tract. Colonization of the various indwelling devices is also an important source of continuing fungal sepsis in critical care settings.
A large variety of broad spectrum antibacterial drugs are now available and are frequently misused, either by prolonged administration or by administration to patients who do not require broad spectrum coverage. This is of concern as prolonged administration of antibacterial agents is a critical risk factor for developing invasive candidiasis. With broad spectrum antimicrobial coverage, the yeast grows rapidly and can invade the blood stream. Additionally, it has been observed that drug resistance in yeasts can develop when antifungal agents are administered for a prolonged period of time. With fluconazole being used commonly as a prophylactic antifungal agent, some strains of Candida albicans have developed resistance to fluconazole. This has also led to the emergence of invasive infections caused by non-albicans Candida species which are intrinsically resistant to the azoles e.g. Candida glabrata. This is not only true in hospital settings but also outpatient services where the use of over-the-counter (OTC) antifungal agents has also produced resistance.
Candida albicans and biofilms
Colonization of indwelling medical devices occurs prior to invasion of the blood stream. Candida albicans is known to colonize invasive devices within 72 hours of placing the device, especially in critically ill patients. The material of the indwelling medical device serves as a substrate for the growth of biofilms produced by Candida albicans. The biofilm is a ‘slimy’ extracellular matrix (ECM) within which large colonies of C.albicans persists. Studies have shown that in patients with fungal sepsis, up to 88% of central venous catheters show biofilm formation of yeasts. The biofilm serves as the nidus through which yeast cells are constantly thrown out into the circulation to continue sepsis. It is interesting that Candida albicans cells present within the biofilm are phenotypically different from the planktonic cells (cells suspended in the blood stream). Also yeast cells within the biofilm are not affected by the antifungal agent the patient receives. The only treatment is removal of the medical device.
Candida albicans is also known to quantitatively produce large, complex amounts of biofilms as compared to other non albicans Candida species. This biofilm consists of a dense basal layer of yeast cells which anchors the biofilm to the indwelling medical device. A layer of hyphal forms can be seen over the basal layer while the Extracellular matrix (ECM) surrounds the yeast cells within this biofilm. Also of interest is the fact that the genes expressed by planktonic cells and the cells present in the biofilm are different. Therefore they have differing phenotypic properties, the most important being the response to antifungal agents. It has been well documented that the biofilm cells of Candida albicans can be resistant to even Flucytosine and Amphotericin B. Therefore, biofilms now play a critical role in assessing the prognosis of invasive fungal disease and its pharmacotherapy. This can also be deduced from the fact that denture induced stomatitis and oral thrush often recurs soon after the antifungal therapy is stopped. The yeast cells forming the biofilm on the dentures are the culprit.
Diagnosis of invasive candidiasis can be made by submitting blood culture to the laboratory or by demonstrating budding yeast cells with pseudohyphae via tissue microscopy. Candida albicans can easily be cultured on routine microbiological media. Candida albicans is germ tube positive and on chromogenic media yields a bright green color and can hence be easily identified. Newer automated methods of identification and antifungal susceptibility have helped in the early diagnosis and treatment of Candida albicans infections.
