Page 916 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 70: Fungal Infections 647

In most patients, candiduria represents colonization of the urinary tract, specificity of 74%. A prospective multicenter study compared the use-
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and further studies are necessary to establish a diagnosis of Candida fulness of the Candida Score to the Candida Colonization Index to iden-
urinary tract infection. On the other hand, culture of Candida species tify ICU patients at greatest risk of invasive candidiasis and found that
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from normally sterile sites, characteristic skin lesions, and involved tis- the Candida Score was more sensitive in predicting the development of
sues implies invasive infection. invasive candidiasis than the Candida Colonization Index. 69
It takes 1 to 3 days for yeasts to grow in blood culture bottles and for
the laboratory to notify the clinician of this event. In most laboratories, ■ CLINICAL PREDICTION RULES
subculture onto solid media is required to determine the species of The potential use of colonization indices and scores seems obvious, but
Candida, adding an additional few days until a final identification is they are not utilized by many ICUs because it is quite costly to perform
reported. Several studies have shown increased mortality when anti- repeated surveillance cultures from multiple different sites in all patients
fungal therapy is delayed more than 48 hours after blood is taken for in an ICU when, for most units, the risk of developing invasive candi-
culture. 53,54 An increasing number of laboratories use a rapid specific diasis is less than 5%. Because of this, others have proposed prediction
fluorescence-based assay, PNA-FISH, that can identify C albicans and rules based solely on clinical risk factors. 70,71 One such rule identified
C glabrata within 1 to 2 hours of finding yeasts in a blood culture bottle. 58,59 several factors that, if present within a few days of ICU admission, were
■ NONCULTURE TECHNIQUES highly predictive of invasive candidiasis. These factors included systemic
antibiotic therapy, presence of a central venous catheter, parenteral
Many years have been spent trying to develop an antigen assay for the nutrition, dialysis, major surgery, pancreatitis, corticosteroids, and other
diagnosis of invasive candidiasis. The most promising target is an assay immunosuppressive agents. Currently, none of these rules or indices is
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for (1,3)-β-D-glucan, a component of the cell wall of fungi. 60-63 This widely used, and the benefit appears to be greatest for those units that
assay is not specific for Candida because the antigen is present in the cell have high rates of candidiasis. 71
wall of many fungi. However, it could be used as an indirect test for the
possibility of candidiasis in appropriate high-risk hosts, such as those STRATEGIES TO PREVENT INVASIVE CANDIDIASIS
in the ICU. In one multicenter study in the United States and another
single center in Japan (using a different assay), approximately 80% of Several strategies have been developed to reduce the risk of develop-
patients with documented invasive candidiasis had a positive test, and ment of invasive candidiasis in patients in the ICU setting. These strate-
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the sensitivity was 70% to 85%. 62,63 However, a study conducted specifi- gies include prophylaxis, preemptive therapy, and empirical therapy
cally in ICU patients found a sensitivity of only 52%. At this point, it (Table 70-4).
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is not clear that this assay will prove to be more useful than obtaining ■
cultures of blood. PROPHYLAXIS
PCR technology appears to hold promise for the diagnosis of invasive Prophylaxis has been used for patients who are at risk for invasive candi-
candidiasis and for identification of the infecting Candida species, but diasis, but who do not have documented colonization. 66,67 In some stud-
has yet to be developed as a commercially available, standardized assay. ies, prophylaxis was given to most patients at the time of their admission
In some studies, but not in others, PCR facilitated earlier diagnosis. 64,65 to the ICU; other studies selectively used prophylaxis only for those
patients felt to be at the highest risk for invasive candidiasis. 74-81 Two pla-
IDENTIFYING PATIENTS AT RISK cebo-controlled studies have shown that fluconazole, 100 mg or 400 mg
FOR INVASIVE CANDIDIASIS daily, given on admission to the ICU can prevent invasive candidiasis, but
in both studies, there was no decrease in mortality. 74,77 In a small placebo-
Because of the difficulty in quickly establishing a diagnosis of invasive controlled blinded trial that specifically targeted patients at high risk for
candidiasis, strategies to determine which patients are at greatest risk Candida intra-abdominal infections, fluconazole prophylaxis was able
for invasive candidiasis have been developed with the intent of allowing to prevent both intra-abdominal Candida colonization and infection. 78
therapy for invasive candidiasis to begin as early as possible in appropri- In an attempt to obviate the issue of selection of fluconazole-
ate patients. 66,67 A number of prediction rules have been formulated to resistant yeasts, such as C glabrata, the use of an echinocandin, caspo-
identify high-risk patients. The prediction rules are of two types: one fungin, as prophylaxis in the ICU setting has been studied. A small
type uses the presence of Candida colonization as one component of the
rule and is more commonly used in European medical centers 36,68,69 ; the
other does not use Candida colonization in formulating the rule and is TABLE 70-4 Strategies for Prevention of Candidemia and Invasive Candidiasis
more common in North American medical centers. 70,71 in the ICU
■ COLONIZATION INDEX AND CANDIDA SCORE Empirical antifungal therapy Begin antifungal therapy when patient develops signs

The initial studies by Pittet et al utilized daily cultures of multiple and symptoms of possible invasive Candida infection, but
no organism has been identified
body sites for Candida in patients in a surgical ICU and showed that
a Candida Colonization Index (number of body sites yielding same Example: the patient who is febrile, on broad-spectrum
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Candida species/number body sites tested) that was >0.5 was able to antibiotics, with CVC, APACHE II >16
identify those patients who developed invasive candidiasis. A modifi- Preemptive antifungal therapy Begin antifungal therapy when the patient has Candida
36
cation of this index is the Corrected Candida Colonization Index, which colonization and certain risk factors for invasive candidiasis
takes into account the density and degree of colonization as determined Example: the patient with Candida Score >3, calculated
by semiquantitative cultures of each body site. Piarroux et al used a as follows: parenteral nutrition = 1, surgery = 1, severe
36
Corrected Candida Colonization Index ≥0.4 to determine the need sepsis = 2, multifocal Candida colonization = 1 69
for early antifungal therapy and showed that the Corrected Candida
Colonization Index performed better than the Candida Colonization Prophylactic antifungal Antifungal therapy given to all patients with certain
Index to identify patients at risk for invasive candidiasis. 72 therapy risk factors for invasive candidiasis without evidence for
Other prediction rules integrate colonization with clinical risk factors Candida colonization
to try to increase specificity. The Candida Score is a bedside scoring Example: the patient with antibiotics or CVC on day 1-3
system that combines evidence of multifocal colonization with Candida and at least two of the following: parenteral nutrition,
with other risk factors (total parenteral nutrition, recent surgery, pancreatitis, dialysis, immunosuppressive agents, surgery 71
and sepsis) and has been reported to have a sensitivity of 81% and a APACHE II, acute physiology and chronic health evaluation; CVC, central venous catheter.

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