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Intensive care


General considerations


Every blood culture that reveals growth of yeasts, together with clinical signs of infection, represents an infection that needs prompt management, including the initiation of antifungal therapy and the removal of central venous lines. When cultures of catheter tips grow yeasts, while blood cultures remain sterile, systemic antifungals are not indicated in every case, depending on the clinical condition of the patient. Important considerations when choosing the antifungal agent and the mode of application (IV versus oral) in candidaemia and systemic candidiasis include the localisation of the infection, the severity of disease (for example, sepsis, severe sepsis, and septic shock), impairment of organ functions (especially in liver and kidney), previous exposure to antifungals, the identified fungal strain, local resistance patterns and patient characteristics, such as age. Most importantly, antifungal treatment for uncomplicated


candidaemia is recommended for 14 days after the first negative blood culture and resolution of all clinical signs of infection. Ophthalmoscopy is recommended prior to the discontinuation of antifungal chemotherapy to rule out endophthalmitis or chorioretinitis. De-escalation strategies (switch from IV echinocandin therapy after initial response to oral therapy with an azole antifungal drug) are commonly used in clinical practice but criteria for early switch (for example, after three-to-five days) are not clearly established and need further clinical evaluation. After improvement of clinical signs, sterilisation of blood cultures and documented in vitro susceptibility of the causative yeast, step-down therapy after initial treatment with an echinocandin (anidulafungin, caspofungin and micafungin) was shown to be effective with oral fluconazole (or voriconazole) starting on day 10 of antifungal therapy, and may be recommended if oral drug intake and gastrointestinal absorption are possible.1


Therapy Conventional amphotericin


B-deoxycholate (cAmB-D) has served as standard treatment for more than five decades, but its toxicity and limited efficacy have underscored the need for alternative antifungal drugs. Fluconazole is as effective as amphotericin B for the


Treatment for candidaemia in non-neutropenic patients Treatment duration is at least 14 days after the first negative blood culture


YES AIII AII Echinocandin


anidulafungin (200→ 100mg/day), caspofungin (70→ 50mg/day), or micafungin (100mg/day)


Responding + stable?


Step-down BIII Figure 1: Therapy of (proven) candidaemia/Candida infections (IDSA)1


treatment of candidaemia and has superior safety, although the reduced susceptibility of some species, such as C. glabrata and C. krusei, may limit its use in settings where these species are prevalent. Newer options for patients with candidaemia or invasive candidiasis include broad-spectrum azoles (such as voriconazole), and the echinocandins (caspofungin, micafungin and anidulafungin), all of which have excellent activity in vitro against a range of common Candida species. Most importantly, the immediate start of antifungal therapy in a clinically compromised patient with candidaemia after receipt of the culture results from the laboratory is mandatory in order to improve the overall survival of the patient. In daily practice, the time for blood cultures to become positive takes up to 96 hours. This may lead to a substantial delay in the initiation of antifungal therapy in many patients. In addition, it is assumed that only 50–60% of blood cultures may detect disseminated Candida infection. According to this


Guideline recommendations The 2009 clinical practice guidelines of the Infectious Diseases Society of America (IDSA) reflect significant changes in the management of candidaemia and invasive candidosis with respect to the appropriate use of echinocandins and expanded spectrum azoles.1


The expert panel of the


IDSA favours an echinocandin for first-line treatment of candidaemia in non-granulocytopenic patients with moderately severe-to-severe illness, as first-line treatment for granulocytopenic patients, patients recently exposed to azole, candidaemia caused by C. glabrata, and/or suspected invasive candidosis (empirical therapy) caused by C. glabrata or C. krusei (Figure 1). The three echinocandins are regarded as equally effective for treatment of candidaemia and invasive candidosis. Fluconazole may be considered in less-critically ill patients. According to the IDSA, amphotericin B is recommended as an alternative therapy in patients with limited tolerance to echinocandins or fluconazole, or in situations where availability of other


“The immediate start of antifungal therapy in a clinically compromised patient with candidaemia is mandatory in order to improve the overall survival of the patient.”


diagnostic dilemma, empirical or pre-emptive antifungal therapy is increasingly used, in particular in severely ill patients with sepsis in the ICU. Despite the lack of prospective, randomised trials, some guidelines have published recommendations for empirical treatment of suspected Candida infections.1


antifungals is limited.1 Amphotericin


B-induced nephrotoxicity is associated with increased mortality in at-risk individuals, and patients with more than two risk factors for nephrotoxicity are potential candidates for alternative antifungal therapy. Consequently, according to the European guideline,


www.hospitalpharmacyeurope.com


Moderately-to-severely ill patients and/or C. glabrata/krusei and/or recent azole exposure?


AIII


Fluconazole (C. albicans)


(800→ 400mg/day) Voriconazole


(non-C. albicans) (6→ 3mg/kg/day)


NO


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