Antibiotic Rotation in the Intensive Care Unit

Antibiotic resistance poses a substantial and escalating global problem, hindering effective infection treatment and contributing to increased disease burden and healthcare costs (Chapter 2). Interventions to prevent resistance or infections by antibiotic-resistant bacteria include antibiotic stewardship, aiming to optimize antibiotic use by considering both immediate patient benefits and long-term community effects. Exploring various bacteria types, resistance manifestations, and treatment strategies (Chapter 3), efforts often focus on reducing antibiotic use. However, this is not always feasible due to the positive effects of antibiotics in treating infections. This thesis examines antibiotic interventions, particularly antibiotic rotation, which involves systematically varying the type of antibiotic administered. The hypothesis is that such variation makes it more challenging for resistant bacteria to establish and spread within a hospital setting. While extensively studied in hospitals, especially for severe Gram-negative infections, this thesis investigates how antibiotic rotation might help reduce resistant bacteria in critically ill patients in the Intensive Care Unit. The goal is not to use more or less antibiotics but to apply the same antibiotics differently, presenting a novel approach. Scientific research on such interventions is limited, and studying them poses methodological and statistical challenges. Chapter 4 proposes a method to quantify the effects of two commonly used antibiotic rotation interventions: antibiotic cycling and mixing. Antibiotic cycling involves using a different drug for all patients every six weeks, while antibiotic mixing involves using a different drug for each patient. These interventions represent extremes in varying antibiotic use. Chapter 5 describes the study execution, concluding no observed differences in effectiveness between the two interventions and no variations over time in various Intensive Care units. Observations are based on monthly point-prevalence measurements in European Intensive Care units, utilizing an ecological analysis on a group level rather than individual patients. Chapter 6 conducts a similar group analysis to investigate the individual likelihood of acquiring an antibiotic-resistant bacterium, finding no differences. Conducting a statistical analysis from both ecological and individual perspectives is essential due to potential differences in who benefits from the intervention: group interests and individual interests. These may or may not align and can introduce biases leading to incorrect interpretations of outcomes. Chapter 4 introduces various methodological and statistical precautions to mitigate biases. However, numerous factors challenging to measure require additional research to provide specific recommendations for antibiotic rotation. Chapter 7 proposes avenues for further research. Ultimately, the goal is to choose antibiotics at both the departmental and patient levels to achieve the best possible balance between prevention and treatment, enhancing patient care at both levels. The study's findings contribute to the understanding of antibiotic rotation's efficacy and underscore the need for continued research in this critical area of antibiotic resistance management.