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Candidiasis

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Candida laryngitis
Candida peritonitis
Candida pneumonia
Candiduria in critically ill
Prophylaxis

Updated August 2009 by Charles Gomersall

Candidaemia & acute disseminated candidiasis

Epidemiology

  • fungi 4th most common cause of nosocomial bloodstream infection in USA
  • high proportion of patients with fungaemia are critically ill
  • proportion of critically ill patients infected with candida varies considerably depending on the group being studied and their prior length of stay in ICU

Treatment

Proven candidaemia or acute disseminated candidiasis

  • remove all central intravenous catheters if possible
    • greater benefit in non-neutropaenic patients
    • particularly important for C. parapsilosis infection - more frequently associated with CVC infection
  • drug treatment options:
    • critically ill patients (regardless of whether they are neutropaenic or not) should be treated with an echinocandin (eg caspofungin, micafungin, anidulafungin) initially until sensitivities or species are known. Patients infected with C parapsilosis should be switched to fluconazole unless their condition is clearly improving
      • doses:
        • caspofungin 70 mg loading then 50 mg/day
        • micafungin 100 mg daily
        • anidulafungin 200 mg loading then 100 mg daily
        • fluconazole 12 mg/kg then 6 mg/kg/day
    • less severely ill, non-neutropaenic patients who have not previously received azoles can be treated with fluconazole until sensitivities or species are known
  • duration of treatment
    • at least 2 weeks after last positive blood culture and resolution of clinical features of infection. Longer treatment is required for those with metastatic complications
  • treatment failure
    • breakthrough or persistence of candidaemia despite on-going antifungal therapy suggests:
      • infected intravascular device
      • significant immunosuppression
      • drug resistance
    • management
      • start different class of anti-fungal immediately
      • identify species of Candida and consider susceptibility testing
      • remove infected intravascular device
      • ameliorate immunosuppression if possible
  • ophthalmological examination for candida enophthalmitis
    • within 1 week of initiation of therapy

Species-specific treatment

Species Drug of choice Comments
C. parapsilosis Fluconazole If patient is already on an echinocandin and is improving clinically it is reasonable to continue the same therapy
C. glabrata Echinocandin Use of fluconazole or voriaconazole not recommended with confirmation of susceptibility. If patient is already on azole and is improving clinically it is reasonable to continue the same therapy
C. krusei Echinocandin If amphotericin is used a higher dose (up to 1 mg/kg/day) should be considered

Probable disseminated candidiasis in non-neutropaenic patients

  • Data suggests that, in those patients who subsequently prove to have candidaemia delaying treatment by more than 12 hours results in a substantial increase in mortality. The difficulty is in determining who is at high risk.
  • In general disseminated candidiasis or candidaemia are less common during the first week of ICU admission but this is not universally true and it is, therefore, important to know the pattern in your own ICU
  • The following rule has been used to predict invasive candidiasis or candidaemia in patients that have been admitted to the ICU for ≥4 days:
     
    ONE of
    • Any systemic antibiotic during ICU admission
    • Central venous catheter during  ICU admission
    AND TWO of
    • TPN during ICU admission
    • Dialysis during  ICU admission
    • Major surgery in week prior to ICU admission
    • Pancreatitis in week prior to ICU admission
    • Any use of steroids in week prior to or during ICU admission
    • Other immunosuppresson in week prior to ICU admission

     

  • The Candida rule has been used to predict invasive candidiasis in patients admitted to ICU for ≥ 7 days who are colonized with candida
     
    Clinical feature Score
    Severe sepsis 2
    Colonization of multiple sites 1
    Parenteral nutrition 1
    Post operative 1

    Score ≥3 associated with greater risk of invasive candidiasis
    Note that this score cannot be used to identify patients with low risk of candida infection unless routine surveillance cultures for candida are carried out (faeces/rectal swab, urine, axillae, tracheal aspirate, gastric or pharyngeal aspirate).
     

  • neither of these scores/rules has high positive predictive value and of greater use in identifying patients unlikely to have invasive candidiasis. Nevertheless in ICUs with high incidence of invasive candidiasis it may be reasonable to treat patients who meet these criteria
  • (1®3) β-D-glucan may be useful in identifying patients with invasive fungal infection, although the test is not specific for Candida
  • Candida PCR is promising but is not yet a mainstream investigation
  • expert opinion is that empirical antifungal therapy should be considered in patients with risk factors for invasive candidiasis and no other known cause of fever. The recommended drugs are identical to those recommended for proven infection

Empirical therapy for neutropaenic patients with prolonged fever despite anti-bacterials

  • ~20 % of neutropaenic patients with persistent fever despite broad-spectrum antibiotics develop an overt invasive fungal infection
  • Antifungals appropriate for neutropaenic patients with:
    • persistent unexplained fever
    • 4-7 days of appropriate antibacterial therapy
  • Regimes:
    • echinocandin eg caspofungin, micafungin or anidulafungin
    • lipid formulation amphotericin B
    • voriaconazole (not for patients who have received prophylaxis with an azole)

Candida endocarditis

  • high morbidity and mortality
  • lipid formulation amphotericin B 3-5 mg/kg/day ± flucytosine 25 mg/kg 4 times daily
  • alternatives: high dose amphotericin B or high dose echinocandin
  • consider stepping down to fluconazole 6-12 mg/kg for patients infected with susceptible species who are clinically stable and whose blood cultures have become negative
  • valve replacement recommended
    • drug treatment should be continued for for at least 6 weeks after surgical replacement of infected valve

Candida endopthlamitis

  • Amphotericin B 0.7-1 mg/kg/day with flucytosine 25 mg/kg 4 times daily for advancing lesions or lesions threatening macula
  • Less severe cases: fluconazole 12 mg/kg loading then 6-12 mg/kg daily
  • Voriaconazole or enchinocandin for patients who are intolerant of or failing therapy
  • Severe cases consider partial vitrectomy and intravitreal amphotericin

Candida meningitis

  • high morbidity and mortality
  • lipid formulation amphotericin B 3-5 mg/kg/day ± flucystosine 25 mg/kg 6 hourly for initial several weeks of treatment
  • step down to fluconazole 400-800mg/day after patient responds
  • continue treatment until all clinical features, CSF and radiological abnormalities have resolved
  • remove prosthetic devices

Further reading

Pappas PG. Guidelines for treatment of candidiasis: 2009 update by Infectious Diseases Society of Ameria. Clin Infect Dis 2009; 48:503-535

Potential conflict of interest

The Dept of Anaesthesia & Intensive Care, Chinese University of Hong Kong has received educational grants and payment for research from Pfizer Corporation Hong Kong Ltd and educational grants from Merck Sharp & Dohme.

Dr Gomersall has received a speaker's honorarium from Pfizer Corporation


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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