Analysis to determine cost-effectiveness of procalcitonin-guided antibiotic use in adult patients with suspected bacterial infection and sepsis.

PURPOSE: Results of a study incorporating real-world results into a predictive model to assess the cost-effectiveness of procalcitonin (PCT)-guided antibiotic use in intensive care unit patients with sepsis are reported. METHODS: A single-center, retrospective cross-sectional study was conducted to determine whether reductions in antibiotic therapy duration and other care improvements resulting from PCT testing and use of an associated treatment pathway offset the costs of PCT testing. Selected base-case cost outcomes in adults with sepsis admitted to a medical intensive care unit (MICU) were assessed in preintervention and postintervention cohorts using a decision analytic model. Cost-minimization and cost-utility analyses were performed from the hospital perspective with a 1-year time horizon. Secondary and univariate sensitivity analyses tested a variety of clinically relevant scenarios and the robustness of the model. RESULTS: Base-case modeling predicted that use of a PCT-guided treatment algorithm would results in hospital cost savings of $45 per patient and result in a gain of 0.0001 quality-adjusted life-year. After exclusion of patients in the postintervention cohort for PCT test ordering outside of institutional guidelines, the mean inpatient antibiotic therapy duration was significantly reduced in the postintervention group relative to the preintervention group (6.2 days versus 4.9 days, p = 0.04) after adjustment for patient sex and age, Charlson Comorbidity Index score, study period, vasopressor use, and ventilator use. Total annual hospital cost savings of $4,840 were predicted. CONCLUSION: Real-world implementation of PCT-guided antibiotic use may have improved patients' quality of life while decreasing hospital costs in MICU patients with undifferentiated sepsis.

Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients.

Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta mRNAs, and TNF-induced nuclear factor of kappaB-DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-alpha and IL-1beta mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.

Toxic effect of zinc on NF-kappaB, IL-2, IL-2 receptor alpha, and TNF-alpha in HUT-78 (Th(0)) cells.

Zinc deficiency decreased cellular immune response. Zinc supplementation reverses this response. High concentration of zinc intake is reported to alter immune response. We hypothesize that higher concentration of zinc adversely affects T-cell immune response. In this study, we examined whether higher concentration of zinc affects expression of IL-2, IL-2Ralpha, and TNF-alpha, and NF-kappaB activation in HUT-78 (Th(0)) cells. The results show that HUT-78 cells incubated in 15, 50, and 100 microM zinc medium had significantly higher intracellular zinc contents and faster growth after 4 days of incubation, compared to the cells incubated in 1 microM zinc medium. After PMA/PHA stimulation, 1 microM zinc showed significant decreases in NF-kappaB activation, and in the levels of IL-2, IL-2Ralpha, and TNF-alpha production and mRNAs compared to 15 microM zinc. The cells incubated in higher concentrations of zinc (50 and 100 microM zinc) showed mild to moderate decreases in the levels of IL-2, IL-2Ralpha, and TNF-alpha production and mRNAs, and in NF-kappaB activation compared to those incubated in 15 microM zinc medium. These data indicate that not only low level of zinc, but also high levels of zinc decrease Th1 function.