Therapeutic effect of antibiotics in the compromised host : an experimental study

The present study was performed in a model of Klebsiella pneumoniae pneumonia and septicemia in rats. This experimental model was used because in leukopenic patients septicemia is a real threat, and K.pneumoniae is one of the pathogens that may be recovered [68, 74, 99, 116, 122, 124]. The experimental design including the infectious disease model is described in chapter 2. The role of the antibiotic dosage schedule as a determinant of therapeutic activity was investigated in relation to various factors such as the severity of infection (chapter 3) , the presence of host defense factors (chapter 4), and the kinetics of antibacterial activity in vitro and in vivo for different classes of antibiotics (chapter 5) . From the three classes of antibiotics, the 8-lactams, the aminoglycosides and the quinolones, ceftazidime, gentamicin and ciprofloxacin were selected as investigational drug, respectively, because of their antibacterial activity against clinically important pathogens and their broad antibacterial spectrum. In addition, the in vitro susceptibility in terms of MBC values of the K.pneumoniae strain used was similar for the three drugs tested, which facilitated a good evaluation of their therapeutic efficacy. The therapeutic effect of ceftazidime, gentamicin and ciprofloxacin in relation to the duration of infection and the bacterial growth rate is described in chapter 6. Finally in chapter 7 the experimental results obtained are discussed with reference to the observations of other investigators. The chapters 3 through 6 represent the appendix papers.