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Low-passage isolates of Borrelia burgdorferi induced arthritis when injected into the hind paws of irradiated hamsters, while high-passage isolates did not. To examine a possible mechanism for induction of arthritis, peritoneal exudate cells were coincubated with high- and low-passage isolates of B. burgdorferi, and the resultant conditioned medium was assayed for interleukin-1 (IL-1) activity. Comparable amounts of IL-1 activity were detected in culture supernatants generated by high- and low-passage spirochetes and were dependent on the number of spirochetes added. Live B. burgdorferi stimulated greater release ofIL-1 activity than did heat-killed organisms. No evidence ofrelease of IL-1 due to shedding of soluble components from spirochetes was obtained. A recombinant human IL-1 receptor antagonist blocked the proliferative activity of conditioned medium in a murine thymocyte assay for IL-1 activity. The greater ability of lowpassage spirochetes to survive in vivo may be more important than the ability to induce IL-1 production in the pathogenesis of Lyme arthritis. [ABSTRACT FROM PUBLISHER]

The role of the macrophage in destruction of virulent treponemes is disputed. A major obstacle has been the inability to demonstrate quantitative phagocytosis of treponemes by macrophages. Treponema pallidum pertenue was attached to polycarbonate filters for assessment of treponemal phagocytosis by macrophages. The disappearance of treponemes due to phagocytosis was measured by enumeration with immunofluorescence. Resident and lipopolysaccharide-activated macrophages were found to phagocytize treponemes equally well. The phagocytosis of killed treponemes by macrophages was enhanced by opsonization with immune serum. Macrophages successfully phagocytized Staphylococcus aureus organisms when they were incubated on filters under identical conditions. Treatment of macrophages with cytochalasin B, a known inhibitor of phagocytosis, prevented the disappearance of treponemes and phagocytosis of S. aureus. In addition, fluorescent treponemal debris was observed only inside macrophages cultured with treponemes. These results demonstrate that macrophages can phagocytize pathogenic treponemes on polycarbonate filters. [ABSTRACT FROM PUBLISHER]

ABT-719 is a 2-pyridone antimicrobial which inhibits DNA gyrase activity. It has considerable subcutaneous (sc) and oral efficacy in the treatment of experimental pyelonephritis induced in carrageenan-treated mice by clinical isolates of Enterococcus faecalis, Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa. Therapeutic ED50s, defined here as producing a 2 log10 reduction in kidney bacterial burden, provide a reliable end point for comparison of drug efficacy in this experimental infection. Therapeutic ED50s for ABT-719 against these infections were equal to or up to ten-fold lower than those for ciprofloxacin, used as a reference because of similarity in mode of action. Against E. faecalis, the therapeutic ED50s for ABT-719 were 4.5–13.6 mg/kg.day for sc administration and 6.8–8.9 mg/kg.day for oral administration. ABT-719 was more potent than ciprofloxacin and vancomycin against the E. faecalis strains, which showed ciprofloxacin and vancomycin resistance covering a range of MICs. Against E. faecium, the therapeutic ED50s for ABT-719 were 8.8 mg/kg.day (sc) and 9.4 mg/kg.day (oral). Against an isolate of E. faecium showing ciprofloxacin and vancomycin resistance the ED50 for ABT-719 to achieve a 1 log10 reduction in kidney bacterial burden was 17.9 mg/kg.day by sc administration. While ABT-719 had lower efficacy against this isolate than against others, ciprofloxacin and vancomycin failed to show efficacy. Against E. coli, the therapeutic ED50, for ABT-719 was 1.1 mg/kg.day (oral), and against P. aeruginosa, this value was 2.7 mg/kg.day (oral) with values against both of these pathogens similar to those for ciprofloxacin. ABT-719, which represents the new 2-pyridone compound class, has promise for the treatment of urinary tract infections, as suggested by the significant efficacy seen against experimental pyelonephritis caused by E. coli, P. aeruginosa and susceptible and resistant enterococci. [ABSTRACT FROM PUBLISHER]