Limitations:
We acknowledge several limitations in our study. Administrative data sources may contain miscoded or inaccurate information. For example, the use of ICD-9 code to study CDAD may potentially misclassify CDAD if physicians or hospital coders did not code for this diagnosis or if test results were not back at the time of hospital discharge. However, the ICD-9 code (ICD-9-CM 008.45) for C. difficile has been described and validated previously with 78% sensitivity and 99.7% specificity for correctly identifying and classifying admissions.
An administrative definition of C. difficile may also include some patients who had colonization rather than true disease; however, patients in our study were ill enough to require hospitalization, and so this proportion may likely be smaller. In addition, it is a well-established fact that CF patients have high rates of colonization, and therefore testing may be limited to cases where there is only a high index of suspicion. On the other hand, given CDI’s atypical presentation in CF with lack of diarrhea, there are chances that this diagnosis may either have been overlooked, or a formed stool sample may have been rejected by the lab, causing an underestimate of the disease burden.
Administrative databases also offer limited ability to adjust for the severity of underlying CF disease or use of concomitant medications (immunosuppressive drugs, antibiotics, CFTR modulators, mucolytics). We recognize the possibility of detection bias, with patients with more severe disease being more likely to be tested for C. difficile . The possibility of this bias (i.e., more frequent testing for C. difficile among those hospitalized patients with more severe disease) playing a role in our results cannot be completely ruled out as an explanation for the increasing disparity in outcomes of hospitalized CF patients with and without C. difficile infection. We are also not able to determine time of onset of C. difficile infection relative to the hospitalization.