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Efficacy and utility of a protocol for pre-emptive antimycotic therapy


Invasive candidiasis (IC) is associated with increasing morbidity and mortality in critically ill patients. This, in conjunction with difficulties in diagnosis, underscores the need for novel treatment strategies based on the identification of significant risk factors for IC. The aim of the study was to evaluate the efficacy and safety of a protocol for pre-emptive antimycotic treatment.


A randomized prospective controlled trial was carried out in a general ICU for 2 years. After the implication of the inclusion and exclusion criteria, patients were submitted to block randomization and stratified on the basis of their initial SAPS II expanded score. We have developed a protocol for pre-emptive antimycotic treatment. Having reviewed the current literature, we combined the most significant risk factors for IC with tree major clinical criteria for persistent nonbacterial sepsis and assumed this algorithm as an indication for starting pre-emptive therapy. According to the protocol, antimycotic therapy was started on the day of inclusion in the treatment group and only with proven IC in the control group. Initial data were gathered on demographic characteristics of the patients, proven risk factors for IC-related mortality (malnutrition, non-albicans colonization, creatinine clearance) and severity of inflammatory response and organ dysfunction. Dynamics of SIRS and SOFA, subsequent Candida isolates, ventilator-free days, length of ICU stay, outcome and eventual adverse reactions were followed.


A total of 110 patients (equal in both groups) were enrolled. No statistically significant differences in the basal characteristics of the patients, length of ICU stay and the number of ventilator-free days were found. The delta SOFA score was significantly lower in the treatment group (P = 0.019). The in-hospital mortality was 38.2% in the treatment group vs 61.8% in the control group (P = 0.013). The associated with pre-emptive therapy relative risk was 0.62 (95% CI = 0.4 to 0.94). Significant differences between the Kaplan-Meyer estimates of survival were found (log-rank test P = 0.007). A total of 15 (13.6%) adverse reactions were observed among treated patients in both groups which was not associated with higher mortality risk.


The implementation of the developed protocol reduced the degree of organ dysfunction severity and was associated with significant survival benefit.

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Correspondence to SG Milanov.

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Milanov, S., Georgiev, G., Todorova, V. et al. Efficacy and utility of a protocol for pre-emptive antimycotic therapy. Crit Care 14, P70 (2010).

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  • Organ Dysfunction
  • Significant Risk Factor
  • Invasive Candidiasis
  • Sofa Score
  • Significant Survival Benefit