05/02/2023 | Press release | Distributed by Public on 05/02/2023 00:28
Early diagnosis of bacterial infections in critically ill patients is challenging, as the clinical manifestation is non-specific. Furthermore, the results from microbial cultures may be delayed, resulting in delayed antibiotic treatment, which is associated with increased mortality. Neutrophil activation is an early and major response to bacterial infections. Calprotectin constitutes 40-60% of cytosolic protein content in neutrophils and is an early marker for neutrophil activation.
Several studies have shown rapid release of calprotectin upon stimulation with endotoxin and/or E.Coli 1,2 and the ability of calprotectin to predict bacterial infections before onset of clinical symptoms3. With early diagnosis of bacterial infections delayed treatment will be avoided as well as deterioration due to severe infection/sepsis4.
A health economic model is employed to estimate the cost-effectiveness of analysis of calprotectin for early detection of bacterial infection and thus, the earlier start of antibiotic treatment compared to other diagnostic biomarkers. The model has been developed, based on the results from a previous study showing ability of calprotectin to detect bacterial infections before onset of clinical symptoms and antibiotic prescription3.
Figure 1. Decision-tree structurewith a predictive test
The analysis is based on patients admitted to an intensive care unit (ICU) in Sweden, with inclusion and exclusion criteria from literature applied. The model allows for different diagnostic outcomes based on correctly and incorrectly diagnosis of bacterial infection and timing of antibiotic treatment:
The comparators included in the analysis are:
In the base-case scenario, analysis of calprotectin is employed predictively, differently to the comparators that are employed diagnostically. This means that the proportion of calprotectin tests taken predictively is 100%, while the comparators are set to 0%.
The base-case results show that predictively measuring of calprotectin in an ICU setting, using the GCAL® calprotectin assay reduces total costs by approximately 13 000 - 18 000 EUR per patient, overall mortality rate by 0.11, and mean length of stay in an ICU and general ward by 1.3 - 2 days and 6.9 - 8 days, respectively.
Δ Total cost (EUR) |
Δ Deaths |
Δ Mean days ICU |
Δ Mean days ward |
|
Calprotectin |
Reference |
Reference |
Reference |
Reference |
White blood cell count |
+12 683 |
+0.11 |
+1.27 |
+7.12 |
Procalcitonin |
+13 756 |
+0.11 |
+1.42 |
+7.27 |
C-reactive protein |
+13 700 |
+0.11 |
+1.46 |
+6.88 |
No test |
+17 522 |
+0.11 |
+1.97 |
+7.82 |
Table 1. Base-case outcomes (difference compared to calprotectin) per comparator/per patient
Sensitivity analysis was applied to various uncertain parameters in the model. These parameters included:
In all sensitivity analyses, calprotectin remains the dominant option when key model inputs are varied.
The base-case scenario in the presented model identified calprotectin as cost-effective biomarker for a patient cohort presented in a Swedish ICU. Compared to the comparators, PCT, CRP and WBCs calprotectin, analysed by the GCAL® Calprotectin Immunoassay was shown to save total costs, reduce the mean duration of in-patient care, and reduce in-hospital mortality in those patients. Although this study focuses on a health economic perspective, the main rationale of analysis of calprotectin is from a clinical perspective, since early diagnosis of severe infections and sepsis reduces both delays in treatment and mortality. From this aspect, data from the health economic model support previous studies, where early detection of severe infections and sepsis has both cost-saving and life-saving impact in the ICU setting.
*have been presented at the International Symposium on Intensive Care and Emergency Medicine (ISICEM) meeting in Brussels.
Authors: A Havelka1 M Lipcsey2 M Hultström2 A Larsson3
1)Gentian Diagnostics, Stockholm, Sweden, 2)Uppsala University, Department of Surgical Sciences, Anesthesiology, Uppsala, Sweden, 3)Akademiska University Hospital, Department of Medical Sciences, Clinical Chemistry, Uppsala, Sweden