Addition of teicoplanin or vancomycin for the treatment of documented bacteremia due to gram-positive cocci in neutropenic patients with hematological malignancies: microbiological, clinical and economic evaluation.

A prospective, randomized, double-blind trial was conducted on 124 febrile patients with hematological malignancies to compare teicoplanin with vancomycin as an addition to the initial empiric amikacin-ceftazidime regimen after documented bacteremia due to gram-positive cocci. At enrollment, patients in both groups were comparable with respect to age, sex, underlying hematologic disorders and duration of neutropenia. Rates of therapeutic success were 55/63 (87.3%) in the teicoplanin group and 56/61 (91.8%) in the vancomycin group (p = 0.560). The mean duration of treatment was similar, being 12.2 and 11.4 days, respectively (p = 0.216). Patients treated with teicoplanin remained febrile for slightly longer than those treated with vancomycin (4.9 vs. 4.0 days) (p = 0.013). Thirteen patients experienced an adverse drug reaction, but without any significant difference in the two arms. Isolated staphylococci showed a progressive and significant decrease in susceptibility to both glycopeptides during the 8 study years. The economic analysis performed showed that the addition of vancomycin is cost-saving.

Growth, spread, and extracellular localization of herpes simplex virus 1 in Vero cells in the presence of an anti-gD plaque inhibiting monoclonal antibody.

Evidence for a direct cell-to-cell virus transfer could be provided by an agent that inhibits plaque formation without interfering with the processes that determine plaque growth in the exit and reinfection pathway of virus transfer. We studied the process of Vero cell infection by herpes simplex virus type 1 laboratory strain F [HSV-1 (F)] in the presence of monoclonal antibody (mAb) F10, an anti gD mAb that inhibits plaque development but does not neutralize virus infectivity in the absence of complement. In virus growth curves, cell associated virus was inhibited at low (0.01) but not at high (10) MOI when all cells are simultaneously infected, showing that the target of the mAb is the process of progressive cells recruitment and not the rate of virus replication. The mAb slightly inhibited virus exit and delayed virus entry. However these two additional inhibitory activities were not responsible for inhibition of virus spread, at least at early time of infection. In fact inhibition of virus spread, as measured by reduction of infectious centers (IC) from infected monolayers, could be appreciated before the appearance of extracellular virus in control cultures. We obtained electron microscope evidence that, both in the absence and in the presence of mAb, extracellular virus was initially concentrated at the interspaces between adjacent cell membranes, with little or no virus present at free cell surfaces. At more advanced stages of infection, only virus at free cell surfaces was found. The results of the study of virus replication in the presence of the mAb confirmed the hypothesis of the existence of a pathway of virus transfer between adjacent cells independent from extracellular virus. However, no electron microscope evidence for a direct cell-to-cell virus passage or for a modification of virus transfer brought about by the plaque inhibiting mAb was obtained. Interestingly, electron microscope studies suggested a targeting of the virions to different extracellular spaces, intercellular spaces and free cell surfaces, in intact and damaged cells respectively.

Identification of an 85 kDa phosphoprotein as an immunodominant protein specific for human herpesvirus 7-infected cells.

The reactivity of human cord blood sera was directed most frequently in Western blot assays to a protein with an apparent molecular mass of 85 kDa that belongs to the p85 complex, a family of antigenically related proteins identified previously in our laboratory with the aid of two MAbs. We show that the 85 kDa protein is phosphorylated. As antibodies present in the human sera were directed in part to proteins carrying cross-reactive epitopes between human herpesvirus 6 (HHV-6) and 7 (HHV-7), it is remarkable that reactivity to the 85 kDa phosphoprotein was maintained after preabsorption of the sera with HHV-6 antigen, but abolished after preabsorption with HHV-7 antigen. Therefore, the 85 kDa phosphoprotein may be considered a major determinant of the human immune response to HHV-7, discriminating HHV-6 from HHV-7 infection.