Die Wirkung von menschlichem Granulozytenkolonien stimulierendem Faktor auf neutropenische, C. albicans-infizierte Mäuse: Beschleunigte Normalisierung der Granulozytenzahl und Verstärkung der Resistenz gegenüber C. albicans

The treatment of systemic candidal infection in neutropenic patients continues to be a major problem, and only 20% of patients survive despite treatment with amphotericin B (Amph B). Granulocyte colony-stimulating factor (G-CSF) is a haemopoietic glycoprotein that appears to control the survival, cycle, activation, proliferation and maturation of neutrophil granulocytes and promote recovery from neutropenia. Confirming previous results, we observed that subcutaneous (s.c.) injection of recombinant human (rh) G-CSF in mice (30 μg kg-1 daily) increased the circulating leucocyte count (fourfold) on day 5 of treatment, and led to an expansion of the bone marrow myeloid compartment. The in vivo effect of rhG-CSF on murine resistance to systemic Candida albicans infection was also studied in neutropenic mice. Neutropenia was induced by intraperitoneal injection of a single dose of cyclophosphamide (CPA, 200 mg kg-1) 4 days before C. albicans infection and 2 days before rhG-CSF treatment. rhG-CSF administration showed a protective role on mice infected intravenously (i.v.) with one million C. albicans spores; all the untreated control mice died within 8 days after infection, whereas about 40% of mice treated with rhG-CSF remained alive for the same period. Furthermore, the survival rate was greater in host animals treated with combined Amph B and rhG-CSF than in those treated with Amph B alone. The number of C. albicans colony-forming units (CFU-C. albicans) in the kidney of infected mice was lower in the rhG-CSF-treated group than in the non-treated control mice. This suggests that the severity of infection is decreased in rhG-CSF-treated host animals.SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Efficacy of a short-term amphotericin B + flucytosine combination therapy followed by itraconazole monotherapy in acute and chronic AIDS-associated cryptococcosis

The authors report the clinical and microbiological findings of a 6-month follow-up of nine AIDS patients affected with cryptococcosis. Among these, seven patients suffered from meningoencephalitis and two from disseminated infection. The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg-1 day-1 i.v. plus flucytosine at doses of 100 mg kg-1 day-1 i.v. during the first 15 days followed by itraconazole at doses of 400 mg day-1 p.o. in the following 15 days. The maintenance treatment included itraconazole at doses of 200 mg day-1 p.o. indefinitely. During the 6-month follow-up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia. In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid. In three patients with meningoencephalitis the three-drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6-month follow-up. The two patients with haematogenous cryptococcosis did not relapse after the 6-month follow-up