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Guidelines


Table 2: Choice of antifungals for treatment of candidaemia depending on patients’ characteristics Previous azole


Liposomal


amphotericin B Fluconazole Voriconazole


Recommended


Severe renal failure Not recommended


Not recommended Not recommended Moderate


recommendation Echinocandins Recommended Recommended


recommendation as a first-line therapy for candidaemia.18


Its use could be considered


as an alternative to other therapies (BI) or as a step-down therapy for C. krusei or voriconazole-susceptible C. glabrata. Despite more emphasis having been given to newer molecules, fluconazole still represents a well-known and well- tolerated antifungal that has a significantly lower acquisition cost compared with echinocandins and polyenes. In the ICU, its use is often limited to clinically stable patients with C. albicans or C. parapsilosis and to de-escalation therapy, generally considered after seven to ten days of IV therapy (BII) and, according to patients’ stability, the possibility of a switch to oral therapy, and strain susceptibility. In the other instances, echinocandins or L-AmB are recommended in critically ill patients.3,14


Fluconazole is indicated as prophylaxis for immunocompetent patients in the event of recent abdominal surgery with recurrent gastrointestinal perforations or anastomotic leakages (BI) or, with a lower strength of recommendation (CI), for empiric therapy in critically ill patients with fever, risk factors (for example, Candida colonisation) and expectation to be hospitalised or ventilated over 72 hours.


Both fluconazole and echinocandins are indicated in the treatment of intra- abdominal candidiasis. Recent recommendations from an international multidisciplinary panel of experts suggested empirical antifungal treatment with echinocandins or L-AmB in critically ill patients or in cases of previous exposure to azoles. Fluconazole was recommended for de-escalation therapy and for empirical or targeted therapy of non-critically ill patients without previous exposure to azoles, unless colonised with a Candida strain with reduced susceptibility to azoles.19


4


In order to avoid organ involvement, the current guidelines for candidaemia recommend a 14-day treatment after BC


www.hospitalpharmacyeurope.com Only oral formulation Shock Recommended


Microbiol Infect 2012;18 Suppl 7:19–37.


Hepatic failure Moderate


recommendation


Not recommended Not recommended Moderate


Not recommended


recommendation Recommended


Recommended


negativisation (BII), along with ophthalmologic fundus examination to exclude disseminated endocular infection, and trans-oesophageal echocardiography to rule out endocarditis in case of persistently positive BC, known valve pathology or any other sign or symptom suggestive of endocardial involvement.3 Central venous catheters (CVCs) should be removed in case of candidaemia, even though there are yet no data from properly randomised, controlled trials. In fact, in CVC-related BSI, biofilm production contributes to Candida pathogenicity and can result in persistent infections, generation of antifungal resistance and severe invasive infections.


Conclusions


In conclusion, the choice of the antifungal strategy has to take into account various factors, including the local knowledge of the epidemiology (proportion of C. albicans versus NAC) and the individual characteristics of the patient (for example, renal and hepatic functions, severe sepsis versus stability) (Table 2). Recommendations from the most recent guidelines are based on studies comparing old and novel AR among various clinical settings, considering drug efficacy, toxicity and pharmacokinetic properties in various patients populations, with the aim to improve the clinical outcomes of a life-threatening infection that often targets fragile patients. ●


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2. Pappas PG et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009,48:503–35.


3. Cornely OA et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin


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12. Kollef M et al. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012;54:1739–46.


13. Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 2005;49:3640–5.


14. Bassetti M, Mikulska M, Viscoli C. Bench-to- bedside review: therapeutic management of invasive candidiasis in the intensive care unit. Crit Care 2010;14:244.


15. Reboli AC et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007;356:2472–82.


16. Choi HW et al. Species-specific differences in the susceptibilities of biofilms formed by Candida bloodstream isolates to echinocandin antifungals. Antimicrob Agents Chemother 2007;51:1520–3.


17. Kuse ER et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007;369:1519–27.


18. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009;53:24–34.


19. Bassetti M et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med 2013;39:2092–106.


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