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Table of contents




                 PART I        GENERAL INTRODUCTION                                     11

                CHAPTER 1      Introduction  to  antibiotic  pharmacokinetic  considerations  in
                               critically ill patients and outline of this thesis       13

                CHAPTER 2      A narrative review of predictors for beta-lactam antibiotic exposure
                               during empirical treatment in critically ill patients    29

                 PART II       ANALYTIC METHODS AND POPULATION PHARMACOKINETIC
                               MODELING                                                 49

                CHAPTER 3      Simultaneous  determination  of  nine  beta-lactam  antibiotics
                               in  human  plasma  by  an  ultrafast  hydrophilic-interaction
                               chromatography-tandem mass spectrometry                  51

                CHAPTER 4      High-throughput  analysis  for  the  simultaneous  quantification  of
                               nine  beta-lactam  antibiotics  in  human  plasma  by  UPC2-MS/MS:
                               method development, validation, and clinical application   65

                CHAPTER 5      Dose  optimization  of  cefotaxime  as  pre-emptive  treatment  in
                               critically ill adult patients: a population pharmacokinetic study   85

                CHAPTER 6      Population pharmacokinetics and target attainment of ciprofloxacin
                               in critically ill patients                              101

                CHAPTER 7      Pooled  population  pharmacokinetic  analysis  for  exploring
                               ciprofloxacin pharmacokinetic variability in intensive care patients   121

                 PART III      TARGET ATTAINMENT AND THERAPEUTIC DRUG MONITORING
                               IN CLINICAL PRACTICE                                    139

                CHAPTER 8      Failure of target attainment of beta-lactam antibiotics in critically ill
                               patients and associated risk factors: a two-center prospective study
                               (EXPAT)                                                 141

                CHAPTER 9      Health care costs of target attainment of beta-lactam antibiotics in
                               critically ill patients: a retrospective analysis of the EXPAT study   163

                CHAPTER 10     Barriers  and  facilitators  in  the  clinical  implementation  of  beta-
                               lactam therapeutic drug monitoring in critically ill patients: a critical
                               review                                                  179
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