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Q3 LONG ANSWER 10M ★ High-yield

Describe candidiasis with its predisposing factors, clinical forms, laboratory diagnosis and treatment.

Microbiology · 2nd Professional — Para-Clinical

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

CategoryFactors
LocalMoisture, occlusion, maceration and obesity (intertrigo); dentures; inhaled corticosteroids without rinsing the mouth
PhysiologicalExtremes of age; pregnancy (raised oestrogen and vaginal glycogen)
EndocrineDiabetes mellitus — recurrent vaginal or oral candidiasis may be the presenting feature of undiagnosed diabetes
IatrogenicBroad-spectrum antibiotics (removing competing bacteria), corticosteroids, cytotoxic drugs, central venous catheters, parenteral nutrition, abdominal surgery, dialysis
ImmunologicalHIV, 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

FormFeatures
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
OesophagealDysphagia and retrosternal pain; an AIDS-defining illness at CD4 below 200
VulvovaginalIntense 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
CutaneousIntertrigo 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 mucocutaneousPersistent disfiguring infection of skin, nails and mucosae from a defect of T-cell immunity; may be associated with endocrinopathy
UrinaryUsually catheter-associated colonisation, which needs no treatment; candiduria in a non-catheterised patient may indicate disseminated disease
Candidaemia and disseminated candidiasisUsually 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

SpeciesGerm tubeFluconazoleClinical note
C. AlbicansPositiveSusceptibleThe commonest; forms chlamydospores on cornmeal agar
C. GlabrataNegativeDose-dependent or resistantSmall yeasts with NO pseudohyphae; increasingly echinocandin-resistant; commoner in the elderly and after azole exposure
C. TropicalisNegativeUsually susceptibleCommon in neutropenic patients with haematological malignancy
C. ParapsilosisNegativeSusceptibleGrows on catheters and in parenteral nutrition; carried on the hands of staff; reduced echinocandin susceptibility; a major neonatal unit pathogen
C. KruseiNegativeIntrinsically resistantEmerges under fluconazole prophylaxis
C. AurisNegativeUsually resistantMultidrug-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

All questions in Mycology

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