Candida: Pathogenesis, Symptoms and Diagnosis

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Questions and Answers

A researcher is investigating a novel antifungal drug. They observe that the drug effectively inhibits the formation of germ tubes in a culture suspected to contain Candida albicans. However, the culture still shows abundant pseudohyphae. What can the researcher conclude?

  • The drug is specifically targeting chlamydoconidia formation, and is thus ineffective.
  • The drug is effective against _Candida albicans_ by specifically inhibiting germ tube formation, a key virulence factor, while other morphological forms persist. (correct)
  • The culture likely contains a mixture of _Candida_ species, some of which are resistant to the drug's mechanism of action on germ tube formation.
  • The antifungal drug is ineffective against _Candida albicans_ because it does not eliminate pseudohyphae.

A patient with leukemia undergoing chemotherapy develops disseminated candidiasis initially treated with fluconazole. After several days, there is no improvement, and subsequent species identification reveals Candida glabrata. What is the MOST appropriate next step in managing this patient's infection?

  • Initiate treatment with caspofungin or amphotericin B. (correct)
  • Switch to topical nystatin since it is a disseminated infection.
  • Continue fluconazole treatment at a higher dose.
  • Administer a skin test with _candida_ antigen to assess the cellular immune response.

In a research laboratory, calcofluor white staining is performed on a sample from a patient suspected of having a Candida infection. While fluorescence microscopy confirms the presence of fungal elements, further testing is needed to differentiate between species. Which of the listed methods would be MOST effective in rapidly distinguishing Candida albicans from other common Candida species?

  • PNA-FISH (Peptide Nucleic Acid Fluorescent In Situ Hybridization) assay on the sample.
  • Culture on Sabouraud dextrose agar to observe colony morphology.
  • Gram staining to observe the gram-positive characteristics of _Candida species_.
  • Germ tube formation assay in serum at 37°C. (correct)

A researcher is evaluating the efficacy of a new antifungal agent against Candida tropicalis in a mouse model of disseminated candidiasis. Which in-vitro diagnostic result would most strongly suggest that the new drug is likely to be effective in vivo?

<p>The drug exhibits a minimum inhibitory concentration (MIC) significantly lower than that of fluconazole. (C)</p> Signup and view all the answers

A 6-month-old infant presents with a persistent diaper rash that is unresponsive to standard topical treatments. Microscopic examination of skin scrapings reveals budding yeast and pseudohyphae. The infant's pediatrician suspects diaper candidiasis and advises the parents to use topical nystatin. What aspect of the infant's condition MOST likely prompted the suspicion of a Candida infection over other causes of diaper rash?

<p>The rash is characterized by white patches and inflamed skin, prominently located in the folds of the diaper area. (C)</p> Signup and view all the answers

A patient with a history of recurrent vaginal yeast infections reports using over-the-counter miconazole cream with initial relief of symptoms, but experiences a resurgence within a few weeks. Suspecting a resistant strain or alternative etiology, which diagnostic approach would provide the MOST definitive information to guide further treatment?

<p>Obtain a vaginal culture and perform antifungal susceptibility testing. (D)</p> Signup and view all the answers

A hematologist is monitoring a neutropenic patient undergoing intensive chemotherapy. The patient develops disseminated candidiasis, and imaging reveals subcutaneous nodules. Which statement BEST explains the significance of the subcutaneous nodules in the context of disseminated candidiasis in a neutropenic patient?

<p>Subcutaneous nodules are a typical manifestation of disseminated candidiasis in neutropenic patients, reflecting fungal invasion of the skin due to immune compromise. (D)</p> Signup and view all the answers

A researcher is investigating the host immune response to Candida albicans in individuals with chronic mucocutaneous candidiasis (CMC). Given the pathogenesis of CMC, which immunological finding is MOST likely to be observed in these patients?

<p>Impaired Th1 cell function and reduced production of gamma interferon. (D)</p> Signup and view all the answers

A patient undergoing treatment for oropharyngeal thrush with fluconazole shows no improvement after one week. A swab is taken, cultured, and identified as Candida krusei. What is the MOST appropriate change in management based on this finding?

<p>Discontinue fluconazole and initiate treatment with an alternative antifungal such as caspofungin or amphotericin B. (C)</p> Signup and view all the answers

A clinician is using PNA-FISH to identify Candida species directly from a positive blood culture. The fluorescence microscopy results show a yellow signal. Which Candida species is MOST likely present in the blood culture?

<p><em>Candida tropicalis</em>. (B)</p> Signup and view all the answers

Flashcards

Candida

A fungus that is part of the normal flora in the upper respiratory tract, gastrointestinal tract, and female genital tract. All species exist as oval, yeast-like forms that produce buds.

Candidiasis Pathogenesis

Impairment of local or systemic host defenses leads to disease.

PNA-FISH

A method for detecting bacteria and yeast species directly from positive blood cultures. Uses hybridization of PNA probes to organism-specific ribosomal RNA, detected via fluorescent microscopy.

Sabouraud Dextrose Agar

Uses serum at 37°C, colonies typically form.

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Oral Thrush

Overgrowth of Candida albicans in the mouth causes white patches.

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Vaginal Candidiasis

Vaginitis with itching and discharge due to Candida overgrowth.

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Chronic Mucocutaneous Candidiasis

Persistent infection of the skin, oral mucosa, genital mucosa, and nails. Common in immunocompromised individuals.

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Candida Esophagitis

Infection involving the stomach and small intestine, common in patients with leukemia and lymphoma.

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Treatment for Candidiasis: disseminated

Fluconazole is the usual treatment (may require caspofungin or amphotericin B)

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Study Notes

  • Candida exists as an oval, yeast-like form that produces buds, with small daughter cells called blastoconidia.
  • Candida is part of the normal flora of mucous membranes in the upper respiratory tract, gastrointestinal tract, and female genital tract.

Pathogenesis

  • The first line of defense against Candida is intact skin and mucous membranes.
  • The second line of defense requires cell-mediated immunity via Th1 cells producing gamma interferons, which activate macrophages for efficient killing.
  • Neutrophils are important in host defense.
  • Impaired local or systemic host defenses can lead to candidiasis.

Clinical Symptoms

  • Candidiasis manifests differently based on the site of infection.

Diagnosis

  • Samples are taken from fluid in infected tissue and scrapings from mucosal or skin lesions.
  • Candida appears as budding yeast and pseudohyphae, stains gram-positive, and can be visualized with calcofluor white staining.
  • Sabouraud dextrose agar is commonly used for culture, where yeast colonies typically form.
  • Candida albicans forms germ tubes in serum at 37°C, unlike most other Candida species, and produces chlamydoconidia.
  • Skin tests with Candida antigen are positive in immunocompetent adults and assess cellular immune response.
  • Rapid blood cultures can identify Candida species within 3-5 hours.
  • PNA-FISH (Peptide Nucleic Acid Fluorescent In Situ Hybridization) is an FDA-approved method for detecting bacteria and yeast species directly from positive blood cultures, using hybridization of PNA probes to organism-specific ribosomal RNA, which is detected via fluorescent microscopy.
  • Fluorescence microscopy results:
    • Candida albicans and Candida parapsilosis fluoresce green.
    • C. glabrata and Candida krusei fluoresce red.
    • Candida tropicalis fluoresces yellow.

Treatment

  • Treatment depends on the specific species and site of infection.
  • Oropharyngeal or esophageal thrush is treated with fluconazole.
  • Skin infections (cutaneous candidiasis, diaper rash) are treated with topical antifungals like clotrimazole or nystatin, or with itraconazole and voriconazole.
  • Candida vaginitis is treated with topical (intravaginal) clotrimazole or miconazole, or with oral fluconazole.
  • Chronic mucocutaneous candidiasis is treated with fluconazole or itraconazole.
  • Disseminated candidiasis is treated with either fluconazole or an echinocandin such as caspofungin.
  • C. glabrata (more resistant species) is treated with caspofungin or amphotericin B.

Candida Species and Infections

  • Candida glabrata causes infection in immunocompromised patients.
  • Most Candida species (except Candida glabrata) can form pseudohyphae and true hyphae.
  • Candida albicans produces pseudohyphae, true hyphae, germ tubes, and terminal, thick-walled chlamydoconidia.
  • Candida glabrata cannot form pseudohyphae, germ tubes, or true hyphae under most conditions.
  • In culture, most Candida species form smooth, white, creamy, domed colonies.
  • Thrush (oral candidiasis) is an overgrowth of Candida albicans in the mouth, causing white patches.
  • Diaper candidiasis (diaper rash) occurs when diapers are not changed promptly.
  • Vaginal candidiasis (yeast infection) causes vaginitis with itching and discharge and grows in high pH environments, in people with diabetes, or with frequent antibiotic use.
  • Chronic mucocutaneous candidiasis occurs in immunocompromised individuals with T-cell immunity deficiencies and causes a persistent infection of the skin, oral mucosa, genital mucosa, and nails.
  • Disseminated candidiasis is most commonly caused by Candida albicans, but Candida tropicalis and Candida parapsilosis are also important pathogens, and subcutaneous nodules are often seen in neutropenic patients.
  • Candida esophagitis involvement with the stomach and small intestine is common in patients with leukemia and lymphoma.

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