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Table 1: Strength of recommendations and quality of evidence of the IDSA and ESCMID guidelines IDSA

Category, grade




Good evidence to support a recommendation for or against use

Moderate evidence to support a recommendation for or against use

ESCMID Strength of recommendation Strongly supports a recommendation for use Moderately supports a recommendation for use

Poor evidence to support a recommendation Marginally supports a recommendation for use ND

Supports a recommendation against use Quality of evidence Evidence from at least one properly designed randomised controlled trial

Evidence from at least one well-designed clinical trial, without randomisation; from cohort or case- controlled analytic studies (preferably >one centre); from multiple time series; or from dramatic results of uncontrolled experiments

Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

In the past years, mainly due to the widespread use of fluconazole-based prophylaxis, the epidemiology of Candida spp distribution has shifted from Candida albicans to non-albicans (NAC) species, thus posing possible problems in terms of antifungal treatment.9

In fact, C. krusei

and C. glabrata can display resistance to fluconazole, whereas C. parapsilosis can be difficult to eradicate because of its biofilm production.5,10

A delay in the antifungal therapy has been linked to high mortality rates in different clinical contexts.8,11–13

The lack

of both adequate and timely antifungal treatment and source control have been linked to increased mortality in patients with septic shock due to Candida infection.13

Guidelines and management strategies

To minimise the negative impact of this infection, several management strategies have been developed and detailed in the recent European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines. These are: ● Prophylaxis ● Empirical therapy ● Pre-emptive therapy ● Culture-based treatment.3

Prophylaxis and empirical therapy Both prophylaxis, based on universal antifungal treatment, and empirical therapy, based on the persistence of fever non-responsive to antibacterials and a combination of risk factors, might overexpose the patients to treatment, potentially increasing the rates of

Evidence from opinions of respected authorities, based on clinical experience, descriptive case studies

resistance to antifungals. Although the benefit of antifungal prophylaxis is well established in neutropenic patients (for example, haematological and recipients of bone marrow transplant), the utility in non-neutropenic, critically ill patients is still controversial.14

Also, the empirical

approach has limitations due to confounding features related to specific patients populations, being the risk factors associated to candidaemia that are common in IMW and ICU patients.

Diagnosis-based approach The pre-emptive, diagnosis-based approach, instead, aims to target the patients at risk for candidaemia relying not only on risk factors but also on serological techniques (for example, beta-D-glucan and mannan-antimannan), reducing the

criteria highlighted in Table 1.

Compared with the IDSA, the ESCMID recommendations detail empiric and pre-emptive treatments, describe specifically the management of candidaemia in the ICU and endorse the use of echinocandins as first-line treatment for candidaemia (grade AI). The rationale of this statement is that, compared with fluconazole,

echinocandins showed broader spectrum of activity, limited selection of resistance, fungicidal activity, a better safety profile and fewer drug–drug interactions. Specifically, anidulafungin demonstrated superiority versus fluconazole in the treatment of severe infections.15

In the

IDSA guidelines, fluconazole was the drug of choice for the targeted treatment of candidaemia, unless the patients were unstable, or previously treated with fluconazole (AIII), or at risk for less susceptible NAC (for example, C. kruzei, C. glabrata) (BIII). Regarding C. parapsilosis, either fluconazole or echinocandins are recommended. Although fluconazole is fungistatic and displays a reduced activity against sessile forms in the biofilm, failures owing to emergence of resistance have been reported with echinocandins, thus suggesting continuation of treatment with echinocandins only if clinical improvement is maintained after the initial therapy.2

Both echinocandins and

amphotericin B have good penetration into the biofilm formed on vascular devices. Specifically, liposomal amphotericin B (L-AmB) was more effective against C. parapsilosis and C. tropicalis biofilms compared with

“Antifungal therapy delay has been linked to high mortality rates in different clinical contexts”

antifungal exposure and avoiding a therapy delay until Candida is identified in BCs.3 Although BCs are characterised by low sensitivity and a prolonged time to positivisation (usually >72 hours) from the time of blood sample collection, they remain the essential investigation to assess candidaemia. Targeted treatment is mandatory in case of yeast detection from BC.2,3

The 2009 Infectious Diseases Society of America (IDSA) guidelines and the 2012 ESCMID recommendations present a review of the different strategies for Candida infection rated according to the

caspofungin and micafungin.16 Among polyenes, both liposomal (BI) and lipid complex (CII) amphotericin B are considered as alternatives in the targeted treatment of candidaemia, although studies have demonstrated higher toxicity compared with echinocandins.17

Due to toxicity, amphotericin B deoxycholate is no longer recommended by ESCMID, as well as itraconazole and posaconazole, due to limited data proving efficacy and the absence of an intravenous (IV) formulation, respectively.3 Voriconazole has a moderate


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