Abstract
This thesis discusses two colonizing bacteria which both have the capability to be an innocent bystander as well as an opportunistic pathogen, which are Staphylococcus aureus and Pseudomonas aeruginosa. They can, among other things, cause pneumonia or surgical site infections (the latter mainly being S. aureus related). It is not
... read more
always clear which bacterium will cause problematic infections, nor in which patient this will happen. However, we would need to know this if we want to give the patients at risk medication that can prevent it from happening.
In chapter 2 we analyzed previously collected data from two studies on intensive care unit (ICU) patients, for the occurrence of ICU acquired pneumonia caused by S. aureus. S. aureus ICU pneumonia occurred in 1.1-1.3% of the patients, with S. aureus colonization at ICU admission being the most important risk factor for its development. Performing a Fine and Gray competing risks analysis we found a subdistribution hazard ratio (SHR) of 9.6-14.5 for colonized vs. non-colonized patientsThe most important other risk factor that was found was MV at ICU admission, with a SHR of 3.7-7. Chapter 3 describes the development of a risk prediction model for prediction of S. aureus surgical site infection (SSI) within the first 90 days after undergoing cardiothoracic surgery. We found that prior S. aureus colonization was the main independent risk factor for the development of S. aureus SSI after surgery, with an odds ratio of 3.1. Other independent risk factors were BMI, diabetes mellitus and type of procedure (undergoing coronary artery bypass grafting being associated with a higher risk compared to other procedures). The research results presented in chapter 4 address the occurrence of P. aeruginosa ICU pneumonia. In the analysis we found that, similar as for S. aureus, the occurrence of P. aeruginosa ICU pneumonia was rather low, being 1.3% throughout ICU stay. P. aeruginosa colonization at ICU admission, present in 9.2% of those tested, was associated with a SHR of 8.8 compared to non-colonized patients, after accounting for competing events. Again, MV at ICU admission was also associated with a higher occurrence (SHR was 5.3). In chapter 5 the study protocol of ASPIRE-ICU is summarized. This international prospective study was designed to create an optimal assessment of the population at risk of ICU pneumonia caused by S. aureus or P. aeruginosa, including extensive in-depth analyses into pathogen and host biomarkers. We aimed to enroll 2,000 patients on mechanical ventilation at ICU admission or (expected to be) shortly thereafter, of which 50% SA colonized and 50% non-colonized, which were followed for occurens of SA and PA ICU pneumonia. Chapter 6 discusses the analysis regarding the primary objective of ASPIRE-ICU, which is to assess the occurrence of S. aureus ICU pneumonia and to relate it to the risk factors that were collected. We found a weighted occurrence of 4.9 events of S. aureus ICU pneumonia per 1,000 ICU days. We saw that S. aureus ICU pneumonia occurred approximately 3.6 times more frequently in S. aureus colonized patients than in non-colonized. Apart from this we found that the occurrence was varying between European regions, as was the risk for the colonized patients.
In chapter 7 we use data from ASPIRE-ICU to create a risk prediction model for S. aureus ICU pneumonia, using information available at ICU admission. In this analysis, a model with SA colonization status, neurotrauma, and prior antibiotic use was best at identifying patients at highest risk for SAIP. This chapter finishes off with insights in possible trial efficiency strategies for S. aureus ICU pneumonia, demonstrating that the most efficient enrollment criterion remains SA colonization status
show less
