Fungal infections in the intensive care unit? Another approach for defining a target group of patients who benefit from implementing preemptive antimycotic treatment

Introduction

Candida spp. is the third most common reason for sepsis in the ICU, not differentiating our results from the classic pattern of ICU-acquired infection. Prevention of sepsis development and identification of potentially modifiable risk factors are important goals in intensive care patents. Preemptive treatment of Candida sepsis accepted by some authors is defined as an early antifungal treatment given to patients with evidence of substantial colonization in the presence of multiple risk factors for Candida infection prior to establishing the diagnosis by cultures. Our aim was to form a focused group of patients with significant risk for Candida sepsis; to prove the feasibility and efficacy of our preemptive scheme for antimycotic treatment in order to reduce the risk of development of proved Candida sepsis.

Methods

During a 2-year period (2005–2006), a study was performed in a 17-bed general ICU, divided into two phases: a case–control retrospective study in which controls comprising a representative subpopulation with severe bacterial sepsis were compared with cases (patients with Candida sepsis) with respect to multiple demographic and clinical factors in a univariate analysis; and a prospective phase creating a preemptive scheme based on results from the retrospective part followed by progressively implementing it among targeted patients.

Results

Identified were 28 cases with Candida sepsis and 50 controls with severe bacterial sepsis with an all-cause mortality rate of 40.2%. The mortality rate for Candida sepsis was 46.4% with an attributable risk of 10/100 and was associated with a worse score of systemic injury (SAPS II = 51.7 ± 15.0), comparing with a mortality rate of 35.7% and SAPS II = 38.8 ± 13.3 for bacterial sepsis. Candida sepsis was always accompanied by concurrent bacterial sepsis (2.8 ± 1.1 microorganisms/patient isolated from blood cultures). Identified were risk factors with great significance in addition to already known ones: Candida colonization (OR = 3.4), diabetes (OR = 3.2), number of antibiotics used (OR = 2.9), a nothing per os regimen (OR = 2.63), ICU length of stay (OR = 1.97), length of antibiotic use (OR = 1.74), pancreatitis (OR = 1.7), shock at admission (OR = 1.54), ventilator days/ICU stay ratio (days)(OR = 1.4), multiple resistant bacterial strains (OR = 1.5). Patients with gastrointestinal surgery were at risk for development of early fungal sepsis – by the 10th day of admission – compared with the other clinical cases – by the 21st day of admission. The incidence rate of positive blood cultures for Candida in the group exposed to our scheme was calculated as 6.7% vs 18.5% in the control group.

Conclusion

Based on our results, we accepted an algorithm for performing a preemptive therapy for which we observed clinical efficacy and which we considered indicated the following target groups of patients: with presence of clinical features of unresolving sepsis plus three defined risk factors (PPV > 70%) in a patient with length of ICU stay >20 days; lack of clinical improvement with combined antibiotic treatment against established bacterial strains; evidence of sepsis accompanied with multifocal Candida colonization of sterile body spaces. Candida colonization without risk factors requires continuous monitoring. The most important presumption to accept the preemptive strategy for a certain patient is to have a serious clinical conviction that there is an invasive fungal infection but it is still pending to be proved.