RESUMEN
The ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to protect and potentiate the activity of antifungal agents against a lethal Trichosporon beigelii infection in myelosuppressed mice was evaluated in this study. Mice were rendered neutropenic by 2 consecutive-day intraperitoneal injections of cyclophosphamide (200mg/kg). Recombinant hG-CSF, given subcutaneously at daily doses of 15, 60, and 120µg/kg for 6 days, shortened the period of neutropenia and increased the number of circulating neutrophils in a dose-dependent manner. When rhG-CSF was administered to neutropenic mice before challenge with T. beigelii (5×106 CFU), it protected against the lethal infection, resulting in improved survival and decreased numbers of fungal cells in the lung, liver, spleen and kidney. However, when the inoculum size increased to 7×106 CFU, a poorer result was obtained using a dose of 60µg/kg of rhG-CSF, suggesting that the activity of rhG-CSF is dependent on the severity of the T. beigelii infection. Combined with fluconazole (10 mg/kg) or amphotericin B (1mg/kg), rhG-CSF improved the median survival time from 16 days with fluconazole (59%) and 12 days with amphotericin B (41%) alone to 20 days (93%) and 16 days (55%) in neutropenic mice treated with rhG-CSF plus fluconazole or amphotericin B, respectively. However, the combination of rhG-CSF and itraconazole did not produce significant improvement in survival or clearance of fungal cells from the organs of neutropenic mice. These findings show that rhG-CSF may be a useful immunomodulator against Trichosporon infections in neutropenic mice and the therapeutic outcome improves when used in combination with fluconazole or amphotericin B.
RESUMEN
Infection is a major complication associated with increased morbidity and mortality in patients on hemodialysis. We analyzed the incidence and type of infection occurring in 4841 patients on hemodialysis between 1986 and 1993 in our hospital and 11 other hemodialysis centers. Infection was noted in 193 patients (4.98 infections/1000 patients/year). Pneumonia (n=71) and bacteremia (n=24) were the 2 most common infections, followed by tuberculosis (n=14), herpes zoster infections (n=12) and infections at the vascular access site (n=12). The most commonly isolated organism in pneumonia, bacteremia and vascular access site infections wasStaphylococcus aureus. Analysis of the prognosis of patients with pneumonia showed a mortality rate of 50% in patients greater than 60 years old, which was significantly higher than that of younger patients (6.7%,P<0.01), whereas the mortality rate in patients with bacteremia was not different between the 2 age groups (60.0% vs. 57.9%, respectively). We also analyzed changes in immunological function and nutritional status in 16 patients on hemodialysis and 21 healthy control subjects. Although the phagocytic and bactericidal activities of neutrophils and monocytes were not different between the groups, superoxide production, the percentage of natural killer cells and the degree of blastoid transformation with phytohemagglutinin stimulation were significantly lower in hemodialysis patients. Low levels of Niderman's index and serum albumin and transferrin indicated poor nutritional status in these patients. Furthermore, the degree of Niderman's index and serum albumin significantly correlated with impairment of immunological function, such as reduced blastoid transformation and the number of lymphocytes. Our results suggest that analysis of the patterns of infection in patients on hemodialysis should provide better management and that improvement of malnutrition may ameliorate impaired immunity in hemodialysis patients.
