The dynamic interaction between host and pathogens after trauma

Abstract

The neutrophil is the first line of defense against invading bacteria. Neutrophils are recognized by its granules and characteristic nuclear segmentation. Neutrophils’ main functions are to phagocytize and, after fusion of the phagolysosome, subsequently degrade the bacteria. After severe trauma, neutrophil dysfunction can occur. A possible consequence is an increased susceptibility to bacterial infections. Part 1 describes heterogeneity within the neutrophil pool in both health and disease. The heterogeneity can be based on receptor expression, cell density, nuclear segmentation, age or their influence on other cells(e.g. T- or cancer cells) (Chapter 2). The term ‘subset’ refers to neutrophils with similar physical characteristics and can mostly be found in inflammatory conditions. In homeostasis ‘subsets’ are much less clear. We found that there is indeed heterogeneity between circulating neutrophils, be it in a more gradual form. A process that was named competitive phagocytosis showed that within the circulating neutrophil pool of healthy adults some neutrophils are more able to phagocytize bacteria compared to others in a non-random way (Chapter 3). Another much studied neutrophil ‘subset’ in disease is the low-density neutrophil, that segregates in the mononuclear layer during density centrifugation. We confirmed the hypothesis that there is a spectrum in neutrophil density in homeostasis which can be related to neutrophil function (bacterial containment, T-cell suppression)(Chapter 4). In Chapter 5 we investigated the accuracy of an automated hematology analyzer in the detection of banded neutrophils after trauma. The automated analyzer was unable to detect banded neutrophils after trauma, were it did accurately detect banded in infection. Suggesting a structural difference between the cells under different conditions. The underlying mechanisms or purpose of this heterogeneity is still not fully understood. In Part 2 the focus is shifted towards infectious complications after trauma, with a special emphasis on fracture-related infections (FRI). Staphylococcus aureus is one of the most important causative pathogens in FRI and is also known for causing metastatic infections. It is hypothesized that this is due to intracellular survival of the bacterium. Chapter 6 reviews the cellular penetration and efficacy against intracellular S. aureus of the most relevant antibiotics. Bacterial identification in FRI is of paramount importance for choosing effective (antibacterial) treatment. In our hospital a standardized tissue sampling protocol for bacterial identification in FRI was introduced. The protocol consisted of obtaining five or more separate, intra-operative deep tissue samples, avoidance of cross-contamination, and a specific culture protocol. Evaluation of the protocol showed increased awareness of the problem at hand in both surgeons and microbiologists, and increased certainty on causative micro-organisms (Chapter 7). In Chapter 8 & 9 the effect of two different protocols for the treatment of FRI were evaluated. The use of early broad-spectrum antibiotics was safe in terms of emergence of antibiotic resistance. Based on our findings, we recommend starting empiric broad-spectrum antibiotic therapy directly after tissue sampling and surgical debridement. Antibiotic therapy should at least cover infections with the most important causative pathogen (S. aureus) and the presence of a potential biofilm should be considered