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Internal Medicine

Candidiasis

Fungal infection due to any type of Candida.

Cutaneous, mucosal and deep-seated organ infections caused by fungi of the Candida genus, which can occur at any age and usually occur in the setting of easily identifiable risk factors for infection.

Microbiology

Candida:

Candida spp. are common commensal organisms in the skin and gut microbiota, and disruptions in the cutaneous and gastrointestinal barriers (for example, owing to gastrointestinal perforation) promote invasive disease.

Major pathogenic species:

At least 15 distinct Candida spp. can cause human disease, but the majority of invasive infections are caused by 5 pathogens:
  1. C. albicans
  2. C. tropicalis
  3. C. parapsilosis
  4. C. krusei
  5. C. glabrata

Risk factors:

Candida spp. are commensal yeasts that are part of the normal human skin and gut microbiota, and they are detectable in up to 60% of healthy individuals; thus, invasive disease is usually a consequence of increased or abnormal colonization together with a local or generalized defect in host defences.
  • Prolonged intensive care stay
  • Broad-spectrum antibiotic therapy
  • Renal failure
  • Very low birthweight (VLBW)
  • Immunosuppressive therapies
  • Total parenteral nutrition
    • Especially intralipids
  • Neutropenia
  • Central venous catheters

Clinical features

The spectrum of disease of invasive candidiasis ranges from minimally symptomatic candidaemia to fulminant sepsis with an associated mortality exceeding 70%.

Superficial infections

  • Thrush, vaginitis, paronychia, etc

Invasive infections:

Bloodstream infections with Candida spp. (that is, candidaemia) and deep-seated infection
  • Intra-abdominal abscess
  • Peritonitis
  • Osteomyelitis
  • Candidaemia (candidal sepsis)
Candida spp. can be detected on the mucosal surfaces of ∼50–70% of healthy humans. a | When breaches in the intestinal barriers occur, for example, after gastrointestinal surgery, Candida spp. can disseminate to the abdominal cavity directly and invade the bloodstream (candidaemia). b | Under normal conditions, the fungus behaves as a commensal organism without causing disease. c | Impairment of immune response, among other factors, can promote fungal overgrowth in the gut and candidaemia, which can lead to deep-seated opportunistic infections in various organs (invasive candidiasis). | Pappas, P., Lionakis, M., Arendrup, M. et al. Invasive candidiasis. Nat Rev Dis Primers 4, 18026 (2018). https://doi.org/10.1038/nrdp.2018.26

Diagnosis

Blood culture:

GOLD STANDARD for diagnosis of invasive candidiasis that enables species identification and susceptibility testing.

Antigen detection:

  • Mannan antigen and antimannan antibody.
  • β-D-glucan: Pan-fungal marker of invasive fungal infection
  • C. albicans germ tube antigen (CAGTA) test: Candida spp.-specific antibody test

Management

It is important to differentiate colonization from true infection to avoid overtreatment

  • Fluconazole (Drug of choice)
  • Fluconazole-resistant Candida: Amphotericin B, echinocandins, newer azoles (voriconazole)
For candidaemia, the total duration of therapy is 14 days from the first negative blood culture. *As yet unknown species. ‡Step-down therapy to fluconazole is usually based on documented susceptible minimum inhibitory concentrations to fluconazole (<2 μg/ml for C. albicans, C. parapsilosis and C. tropicalis and <32 μg/ml for C. glabrata) and clinical stabilization of the patient. Higher-dose fluconazole consists of 12 mg/kg per day. | The information in the presented figure is based in part on Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines | Pappas, P. G. et al. Clinical Practice Guideline for the Management of Candidiasis: update by the Infectious Diseases Society of America. Clin. Infect. Dis. 62 1–50 (2016). This is the most recent version of international treatment guidelines for candidaemia and invasive candidiasis. | Cornely, O. A. et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin. Microbiol. Infect. 18, 19–37 (2012).

Summary:

Epidemiological features of invasive candidiasis, a common health-care-associated fungal infection with a high mortality. | Invasive candidiasis. Nat Rev Dis Primers 4, 18027 (2018). https://doi.org/10.1038/nrdp.2018.27

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