Platelets: versatile effector cells in pneumonia and sepsis

The role of platelets in infection and immunity is an exciting new theme, which is rapidly evolving. In this thesis we studied the involvement of platelets in the host response to pneumonia and sepsis. We made use of well established mouse models in which mice were infected with a bacterial inoculum via the airways, where after either clinical symptoms and mortality were scored, or experiments were terminated at predefined time points in order to obtain insight in bacterial growth, dissemination and in host responses. Platelets were investigated in this setting by (dose dependently) depleting the cell type or genetically altering diverse platelet signaling pathways or responses. We also aimed to better understand the role of platelet activation in a clinical setting and investigated the influence of pre-existing antiplatelet therapy on disease outcome in a prospectively followed sepsis cohort. Our main results were that low platelet counts render animals more susceptible to uncontrolled growth and dissemination of bacteria, resulting in enhanced mortality. On the other hand, platelets can contribute to organ damage caused by severe infection, exemplifying the double-edged-sword character of the action of these cells. Platelet-expressed P-selectin and Protease activated receptor 4 seemed indispensable for adequate host response, while platelet Toll-like receptor signaling was found to be of insignificant importance during severe infection. The time that platelets were merely viewed upon as cells important for primary hemostasis is way beyond us. In this thesis we make a strong argument that platelets play a multifaceted role in infection

[Carbapenems: take it when needed but leave it if you can]

Surveillance data and literature have shown a worldwide increase in infections with resistant bacteria, which has led to increased prescriptions of carbapenems, which in turn has led to increased carbapenem resistance. There is also an increasing use of carbapenems in the Netherlands, a county usually very conservative in antibiotic use. Carbapenem sparing strategies are essential in an attempt to prevent further rise of infections caused by carbapenem resistant bacteria. This article discusses carbapenem sparing strategies with old forgotten antibiotics and novel antibiotics from a Dutch perspective