Q3
LONG ANSWER
10M
★ High-yield
Describe candidiasis with its predisposing factors, clinical forms, laboratory diagnosis and treatment.
The Organism
- Candida albicans is the commonest species, but non-albicans species are increasing — C. Glabrata, C. Tropicalis, C. Parapsilosis, C. Krusei and C. Auris
- A yeast-like fungus — oval budding cells with pseudohyphae, and true hyphae in invasive disease. It forms smooth creamy colonies on Sabouraud agar
- A normal commensal of the mouth, gastrointestinal tract and vagina in a large proportion of healthy people — so infection is nearly always endogenous, arising when the balance shifts rather than on acquisition from outside
- Virulence factors — adhesins; the yeast-to-HYPHA transition, which is required for tissue invasion; secreted aspartyl proteases and phospholipases; biofilm formation on catheters and prostheses; and phenotypic switching
Predisposing Factors
| Category | Factors |
|---|---|
| Local | Moisture, occlusion, maceration and obesity (intertrigo); dentures; inhaled corticosteroids without rinsing the mouth |
| Physiological | Extremes of age; pregnancy (raised oestrogen and vaginal glycogen) |
| Endocrine | Diabetes mellitus — recurrent vaginal or oral candidiasis may be the presenting feature of undiagnosed diabetes |
| Iatrogenic | Broad-spectrum antibiotics (removing competing bacteria), corticosteroids, cytotoxic drugs, central venous catheters, parenteral nutrition, abdominal surgery, dialysis |
| Immunological | HIV, neutropenia, transplantation; and inherited defects of Th17 immunity causing chronic mucocutaneous candidiasis |
CLINICAL PEARL
Recurrent thrush in an adult is a symptom, not a diagnosis. Candida is a commensal, so disease means the host has changed — and the commonest reasons are diabetes, HIV, antibiotics and corticosteroids. Oral candidiasis in an adult who is not on inhaled steroids, wearing dentures or recently treated with antibiotics should prompt a blood glucose and an HIV test rather than simply a prescription for nystatin.
Clinical Forms
| Form | Features |
|---|---|
| Oral (thrush) | Creamy white plaques on the tongue and buccal mucosa that can BE scraped off leaving a raw bleeding surface — which distinguishes it from oral hairy leukoplakia and from lichen planus, neither of which rubs off. Also angular cheilitis, denture stomatitis and an atrophic erythematous form |
| Oesophageal | Dysphagia and retrosternal pain; an AIDS-defining illness at CD4 below 200 |
| Vulvovaginal | Intense itching with a thick "cottage cheese" discharge and vulval erythema; the pH remains normal (below 4.5), unlike bacterial vaginosis and trichomoniasis, which is a useful bedside discriminator |
| Cutaneous | Intertrigo in warm moist flexures with characteristic satellite lesions; napkin dermatitis, which involves the skin folds where irritant dermatitis spares them; paronychia and onychomycosis in those with wet hands |
| Chronic mucocutaneous | Persistent disfiguring infection of skin, nails and mucosae from a defect of T-cell immunity; may be associated with endocrinopathy |
| Urinary | Usually catheter-associated colonisation, which needs no treatment; candiduria in a non-catheterised patient may indicate disseminated disease |
| Candidaemia and disseminated candidiasis | Usually from a central line or the gut; a leading cause of hospital bloodstream infection with high mortality. Seeds to eye (endophthalmitis), kidney, liver, spleen, bone, heart valves and brain |
| Hepatosplenic (chronic disseminated) | Multiple lesions appearing as neutrophil counts recover after chemotherapy — an immune reconstitution phenomenon |
Laboratory Diagnosis
- Microscopy — Gram stain or KOH mount showing budding yeasts with pseudohyphae. In tissue, seeing hyphae indicates invasion, whereas yeasts alone may represent colonisation
- Culture on Sabouraud agar at 37°C, giving creamy colonies within 24 to 48 hours; CHROMagar distinguishes species by colony colour, which matters because species predicts susceptibility
- Germ tube test (Reynolds-Braude phenomenon) — incubation in serum at 37°C for 2 to 3 hours produces germ tubes without a constriction at the point of origin, identifying C. Albicans and C. Dubliniensis rapidly and cheaply
- Chlamydospore formation on cornmeal agar with Tween 80 — thick-walled terminal chlamydospores are characteristic of C. Albicans
- Sugar assimilation and fermentation, automated identification systems, and MALDI-TOF
- Blood culture is positive in only about 50% of invasive candidiasis, so a negative result does not exclude it; beta-D-glucan and T2Candida assays and PCR help in that gap
- Interpretation is the difficulty — because Candida is a commensal, isolating it from sputum, a wound swab or catheter urine usually means colonisation, and only isolation from a normally sterile site proves infection
Differentiating the Candida Species
| Species | Germ tube | Fluconazole | Clinical note |
|---|---|---|---|
| C. Albicans | Positive | Susceptible | The commonest; forms chlamydospores on cornmeal agar |
| C. Glabrata | Negative | Dose-dependent or resistant | Small yeasts with NO pseudohyphae; increasingly echinocandin-resistant; commoner in the elderly and after azole exposure |
| C. Tropicalis | Negative | Usually susceptible | Common in neutropenic patients with haematological malignancy |
| C. Parapsilosis | Negative | Susceptible | Grows on catheters and in parenteral nutrition; carried on the hands of staff; reduced echinocandin susceptibility; a major neonatal unit pathogen |
| C. Krusei | Negative | Intrinsically resistant | Emerges under fluconazole prophylaxis |
| C. Auris | Negative | Usually resistant | Multidrug-resistant, environmentally persistent and transmitted patient to patient; frequently misidentified |
Treatment and Applied Aspects
- Topical for mucocutaneous disease — nystatin, clotrimazole or miconazole; oral fluconazole for oesophageal, recurrent or extensive disease
- Invasive candidiasis — an echinocandin (caspofungin, micafungin, anidulafungin) is first-line, being fungicidal, well tolerated and active against most species; fluconazole where the isolate is susceptible and the patient stable; liposomal amphotericin B as an alternative
- Species predicts resistance — C. Krusei is intrinsically resistant to fluconazole, C. Glabrata is often resistant or dose-dependent, and C. Parapsilosis has reduced echinocandin susceptibility — so identification to species level directly changes treatment
- Remove the central line in candidaemia; biofilm on the catheter cannot be sterilised, and retention is associated with persistent fungaemia and death
- Perform fundoscopy in every case of candidaemia to detect endophthalmitis, which is sight-threatening and requires prolonged and different treatment; and take repeat blood cultures to document clearance
- Do not treat asymptomatic candiduria in a catheterised patient; remove or change the catheter instead
- Look for the underlying cause — check the blood glucose, review the antibiotics and steroids, and consider HIV; treating the candidiasis without addressing the reason for it guarantees recurrence
- Seeing hyphae in tissue indicates invasion, whereas yeasts alone may be colonisation — a distinction the histopathology report should be asked for explicitly
- Rinse the mouth after an inhaled corticosteroid and use a spacer; oral candidiasis in an asthmatic is usually a technique problem rather than an immune one
- Oesophageal candidiasis is AIDS-defining, and its diagnosis in an adult should prompt HIV testing without exception
- Vaginal candidiasis has a normal pH, unlike bacterial vaginosis and trichomoniasis; a simple pH strip separates the three at the bedside and avoids inappropriate treatment
- Candidaemia mortality is high and time-dependent, so empirical antifungal treatment is started in a septic patient with risk factors rather than awaiting culture
- Non-albicans species now account for about half of isolates in many Indian units, which is why species identification cannot be treated as an academic refinement
- C. Parapsilosis is carried on the hands of staff and grows in parenteral nutrition, so hand hygiene and line care are the specific preventive measures in neonatal units
- Repeat blood cultures until they are negative, and count the duration of treatment from the first negative culture rather than from the start of therapy
- Do not treat Candida grown from sputum; it essentially never causes pneumonia in an immunocompetent adult and represents oropharyngeal contamination
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