In vitro immunologic and virologic effects of interleukin 15 on peripheral blood mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients.

Interleukin 15 (IL-15) is a cytokine that shares receptor subunits and functional activity, such as T-cell and B-cell stimulation, with IL-2. The effect of IL-2 on immune function and human immunodeficiency virus (HIV) viral load in HIV-infected patients is being actively studied. Thus, we examined how IL-15 compares with IL-2 in several in vitro immunologic and virologic assays in order to explore whether a rationale exists for pursuing initial clinical therapeutic trials with IL-15. The effects of IL-15 on induction of lymphokine-activated killer (LAK) cells, gamma interferon (IFN-gamma) production from HIV-positive peripheral blood mononuclear cells (PBMCs), and HIV production from PBMCs were studied. Induction of LAK cells by IL-15 was found in eight of eight HIV-positive donors. Incubation of PBMCs from some donors with IL-15 (1, 10, 50, and 100 ng/ml) induced production of IFN-gamma. The effect of IL-15 was compared with that of IL-2 on HIV replication in PBMCs from five HIV-positive patients and four HIV-negative donors whose PBMCs were infected in vitro with HIV. Levels of HIV p24 antigen were moderately lower in the presence of 10 ng of IL-15 per ml than with 10 ng of IL-2 per ml, but they were similar for 100 and 500 ng of each cytokine per ml. In summary, IL-15 can induce LAK cell activity in HIV-seropositive patients and can stimulate IFN-gamma production from PBMCs of some donors. IL-15 stimulates levels of HIV production from PBMCs which are similar to or moderately lower than those obtained with IL-2, depending on cytokine concentration.

Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation.

In a molecular, microbiologic, and case-control study to describe the epidemiology of ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection, 32 unique isolates were recovered over 31 months from the blood of patients hospitalized in a 900-bed hospital in Chicago. Multivariate analysis revealed cases occurred more frequently in debilitated nursing home patients with central venous catheters than in younger, healthier patients. Mortality rates were similar for cases and controls. Case-patients were less likely to die if they received appropriate antibiotic treatment within 3 days of bacteremia onset (P = .02). Pulsed-field gel electrophoresis analysis indicated a polyclonal outbreak, with strain-specific temporal and geographic clustering. Isoelectric focusing results suggested that a predominant enzyme, TEM-10, was responsible for the ceftazidime resistance. The resistance gene was usually carried on a large conjugative plasmid. The polyclonality of the resistant strains suggests that ceftazidime resistance due to TEM-10 is now endemic in Chicago.