European and US guidelines differ with regard to the use of fluconazole. In the ESCMID Candida guideline, fluconazole is regarded as drug of second choice only, but in the IDSA guideline as a potential alternative. In granulocytopenic patients, an echinocandin or liposomal amphotericin B is recommended as initial therapy based on the fungicidal mode of action. Indwelling central venous catheters serve as a main source of infection independent of the pathogenesis of candidemia in the individual patients and should be removed whenever feasible. l
References 1. 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(5):503–35.
voriconazole are supported with moderate strength. A direct comparison between fluconazole and anidulafungin showed a similar safety profile, a superior treatment response and a trend toward better survival in patients treated with anidulafungin. This was evaluated in a randomised, double-blind, multicentre, multinational, phase III study of patients with candidaemia and/or other forms of invasive Candida infections.7
success at the end of IV therapy for anidulafungin was 75.6% compared with 60.2% for fluconazole-treated patients. The results of this study led to the decision of the ESCMID/EFISG to give fluconazole a marginal recommendation only5
(see Figure 3).
An unmet medical need, with respect to candidaemia and invasive Candida infections, is the development of treatment strategies with echinocandins in specific ICU patient populations, in order to improve their outcome and survival. Most recently, anidulafungin was studied in a non-comparative trial in high-risk patients treated in the ICU.8
transplant and neutropenic patients. A direct comparison of caspofungin and micafungin showed similar efficacy and safety. In addition, no difference in safety or efficacy was seen in patients treated with two different dosages of micafungin (100mg/day or 150mg/day).9
patients required at least one of each cofactor/underlying illness to be included in this trial (post-abdominal surgery, elderly individuals >65 years, renal insufficiency/failure or dialysis, solid tumour, solid organ (liver, kidney, lung, heart, pancreas) transplant recipients, hepatic insufficiency, or neutropenia (neutrophil count <500/mm3
haematology/oncology patients). Anidulafungin was equally effective in all subgroups, but to a lesser extent in
studies comparing different echinocandins are lacking. Higher dosages of caspofungin (150mg/day versus 70/50mg/day) and micafungin (150mg/day versus 100mg/ day) showed a trend toward improved efficacy in subgroups of patients (APACHE-II score >20, granulocytopenia) and might be used in selected patients.9,10 Owing to increased minimal inhibitory concentrations and a higher rate of persistent fungaemia, the use of echinocandins in fungal infections from C. parapsilosis may not be recommended. In this clinical situation, fluconazole is the preferred antifungal drug. However, it has to be stressed that only the combined strategy using an echinocandin together with the removal of an infected catheter may improve Candida-related mortality in severely ill patients with candidaemia/ invasive candidosis.11
In summary, it may be concluded that options for initial therapy of candidemia and other invasive Candida infections in non-granulocytopenic patients include one of the three approved echinocandin compounds; liposomal amphotericin B and voriconazole are secondary alternatives because of their less favourable pharmacological properties.
2. Ruhnke M et al. Diagnosis and therapy of Candida infections: joint recommendations of the German Speaking Mycological Society and the Paul-Ehrlich- Society for Chemotherapy. Mycoses 2011;54(4):279–310.
3. Pappas PG et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 2003;37(5): 634–43.
4. Ruhnke M, Kujath P, Vogelaers D. Aspergillus in the Intensive Care Unit. Curr Fungal Infect Rep 2012;6:63–73.
5. Cornely OA et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012;18 Suppl 7:19–37.
6. Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis – review of the literature. Eur J Med Res 2011;16(4):159–66.
7. Reboli AC et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007;356(24):2472–82.
8. Ruhnke M et al. Anidulafungin for the treatment of candidaemia/invasive candidiasis in selected critically ill patients. Clin Microbiol Infect 2012;18(7):680–7.
9. Pappas PG et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 2007;45(7): 883–93.
10. Betts RF et al. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 2009;48(12):1676–84.
11. Andes DR et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis 2012;54(8):1110–22.
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