Infection
Attributable costs of patients with candidemia and potential implications of polymerase chain reaction–based pathogen detection on antifungal therapy in patients with sepsis,☆☆

https://doi.org/10.1016/j.jcrc.2012.07.011Get rights and content

Abstract

Purpose

The purposes of this study were to calculate attributable costs of candidemia in patients with severe sepsis and to obtain preliminary data regarding the potential effects of polymerase chain reaction–based pathogen detection on antifungal therapy for these patients.

Methods

Patients treated between 2004 and 2010 because of severe sepsis were included into this retrospective analysis. The hospital management provided annual fixed costs per patient-day; data for variable intensive care unit costs were taken from the literature. Multiplex polymerase chain reaction (PCR) was used (VYOO®, SIRS-Lab, Jena, Germany) for pathogen detection in the blood.

Results

Thirty-two patients with candidemia were identified. Of 874 patients with sepsis, propensity score matching found 32 corresponding patients with sepsis but without candida infection but similar risk factors for developing candidemia. Attributable costs of candidemia were 7713.79 Euro (cost increase, 19.4%). Initiation of antifungal therapy was reduced from 67.5 (52.4, 90) hours in the group, where candida infection was determined by blood culture, to 31.0 (28.0, 37.5; P < .01) hours after detection by multiplex PCR.

Conclusions

Candidemia increases costs of care in patients with septic shock. Polymerase chain reaction–based pathogen detection significantly reduces the time to initiation of antifungal therapy. This might impact on the clinical course of the disease but need to be confirmed in further trials.

Introduction

Invasive candida infections are a significant burden for the health care system. The incidence of invasive candidosis was described with 19 to 29 infections per 100 000 inhabitants in a large US study between 1996 and 2003 [1]. On the intensive care unit (ICU), infection rates were reported to be 15.8 per 10 000 patient-days or 6.7 per 1000 admissions [2], [3]. Invasive candida infection is associated with an increased ICU length of stay; crude mortality for invasive candidosis was estimated to be 61.8% [2].

Diagnosis of invasive candida infections is difficult. Microbiological cultures in upper airway secretions often reveal Candida spp, but these findings are rarely associated with invasive fungal infection [4]. Invasive fungal infection is commonly accompanied by candidemia [5]. Thus, a positive blood culture result or a positive culture result from a normally sterile body fluid should usually be required to initiate the administration of systemic antimycotics [6]. However, positive blood culture results for Candida species are a rare event and occur with an incidence of 1.42 per 1000 ICU-days [7]. This is in contrast to the frequent isolation of Candida spp from other sources in patients with sepsis [8], [9].

Time to initiation of antifungal therapy is an important factor to avoid an unfavorable outcome [10], [11], [12]. The dilemma between the diagnostic uncertainty and the need for fast initiation of therapy remains an unresolved issue in the daily care of ICU patients. A preemptive antifungal treatment [13], [14], [15] in the presence of risk factors has been addressed as measures against the consequences of the diagnostic gap. However, the implementation is still a matter of debate.

Polymerase chain reaction (PCR)–based pathogen detection may offer a solution for this problem because PCR results are available within 1 working day and deliver more positive results compared with blood cultures in patients with presumed sepsis [16]. A recent meta-analysis concluded that PCR had a sensitivity of 0.95 and a specificity of 0.92 to diagnose candidemia [17]. Indeed, PCR-based detection of fungi has proven to be effective in the guidance of patients after stem cell transplantation [18]. Because the PCR is currently not able to replace culture methods, the application of PCR in clinical practice would significantly add to the costs of patient care. However, availability of data to assess cost-effectiveness is limited. Olaechea et al [19] estimated the additional costs for candida infections to 16 000 Euro in medical ICU patients. In the United States, costs of care associated with the therapy of candidemia were between $34 123 and $44 536, depending on the insurance status [20]. However, attributable costs of invasive candida infections in surgical ICU patients are not available.

The goal of this analysis was to estimate the attributable costs for candidemia in patients with severe sepsis. A second goal was to obtain preliminary results regarding the potential effects of PCR-based pathogen detection on the initiation of antifungal therapy for these patients.

Section snippets

Patients

This study was a retrospective propensity score–matched analysis comparing the costs of ICU therapy in patients with candidemia and those in patients with sepsis but without evidence of fungal infection. Patients eligible for inclusion into interventional and observational studies for severe sepsis and septic shock between 2004 and 2010 were identified from the study screening logs. All patients with at least 1 blood culture positive for Candida spp were considered having an invasive candida

Results

Between January 2004 and April 2010, 1032 patients with sepsis were available in the sepsis database. One hundred fifty-eight patients were excluded because of antifungal therapy for any reason other than candidemia, resulting in 874 patients eligible for propensity score matching; 32 patients with positive blood culture for Candida spp were included into the candida group.

Discussion

The main finding of this study is that attributable costs of candidemia in patients with severe sepsis were 7713.79 Euro, representing an increase in costs by 19.4% in comparison with septic patients without candidemia. Median total costs of the ICU stay were extremely high in the candida group and non–candida group. Moerer et al [22] had calculated the median total costs of about €20 000 for surgical ICU patients with sepsis by using the same algorithm as in this study. This difference is

Acknowledgments

This study was supported by a grant from Pfizer Pharma GmbH. VYOO® kits and technical processing have been provided by SIRS-Lab GmbH. Annual fixed costs were calculated by Thomas Kräplin, Department of Billing and Controlling, Jena University Hospital.

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    Institution in which work was done: Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.

    ☆☆

    Conflicts of interest: K.R. and E.S. are shareholders of SIRS-Lab GmbH. E.S. and S.S. are inventors of a technique related to VYOO®.

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