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| | 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 |
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
- ~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)
- 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
- 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 |
