risk factors for death in pediatric cdi 1187
associated with the presence of certain underlying comorbid- ities is consistent with previous published studies that were conducted primarily among adults.12–14 Several studies have shown that children with malignancy had an increased inci- dence of CDI and worse outcomes.15,16 Even after controlling for patient characteristics and additional clinical factors such as severity of illness, children with malignancies, hematologic or immunologic conditions and cardiovascular disease were still identified to be at an increased risk of mortality. To our knowledge, this is a novel finding, and suggests the need for additional studies to better understand this association and highlights the need for targeted prevention or treatment practices in subpopulations of children. Inconsistent findings have been reported regarding the role
of gastric acid suppression and the development of CDI; however, available data regarding the role of gastric acid sup- pression and CDI-related outcomes, especially in pediatrics, are limited.17–22 A recent population-based study of patients diagnosed with CDI between 1991 and 2005 evaluated the association between gastric acid suppression and outcomes related to CDI. In this study, no association between gastric acid suppression and severe complicated CDI including death was identified.17 In contrast to those results, our study found a statistically significant association between gastric acid suppression and death. These discordant findings are not surprising given that the majority of the CDI cases in the previous study were diagnosed prior to the changing epide- miology of CDI, the study was limited by a small sample size, and the outcome was a composite endpoint. It is important to note that gastric acid suppression could be an indicator for severity of illness that may not have been adequately captured in our model. Nonetheless, this significant association was identified after multivariable modeling. In addition, we found that underlying severity of illness was an independent risk factor for mortality by creating a composite severity of illness variable. While this is not a validated measure, our finding that mortality increased with an increasing severity of illness score suggests that this measure captured variability in the under- lying degree of illness. Antimicrobial use has been studied extensively with regard
to development of CDI; however, few studies have assessed the role of antimicrobial use on outcomes associated with CDI.23–28 In our study, we found no association between in-hospital mortality and antimicrobial use, total number of antimicrobial drug classes used, and timing of antimicrobial exposure. While antimicrobial exposure may have played a significant role in the development of CDI, according to our study findings, antimicrobial exposure was not a risk factor for in-hospital mortality in patients with CDI. Recent studies conducted among adults with CDI suggests
that metronidazole therapy may be associated with increased rates of treatment failure compared with oral vancomycin and that oral vancomycin is superior to metronidazole for treating adult patients with severe CDI.29–35 However, available data on the comparative effectiveness of C. difficile treatments among
pediatric patients are limited. Our study did not identify an association between CDI treatment and mortality. To our knowledge, this is the first pediatric study to assess whether treatment was independently associated with mortality. However, these results should be interpreted with caution due to the small proportion of children who received oral vancomycin during our study period and the likelihood that oral vancomycin is given to sicker patients. Additional studies are urgently needed to answer this important question in pediatric patients. Our study found that having ≥1 of the aforementioned independent risk factors increased the probability of death from 0% up to 35% depending on the combination of factors. Overall, the probability of death was the highest (~35%) among children ≥13 years of age, who received gastric acid suppression, had all 3 of the severity of illness markers, and had a malignancy. We also evaluated potential risk factors for CDI-related readmission within 8 weeks of an initial CDI test. Given the limitations of the dataset, we were unable to assess recurrent CDI as defined by current clinical practice guidelines.1 To capture patients that were readmitted to the hospital due to their CDI, we defined a CDI-related readmission as a repeat test for C. difficile and treatment within 48 hours of the readmission. We found there to be a statistically significant association between patients readmitted and the presence of any comorbidities, malignancy, and metabolic disease. In addition, patients with a CDI-related readmission were sig- nificantly less likely to have cardiovascular disease and hospital-onset CDI. This could be due to the fact that patients with cardiovascular disease and hospital-onset CDI were more likely to have prolonged length of stays, decreasing the like- lihood of recurrence of CDI following discharge. Many studies have evaluated risk factors for recurrent CDI in adults; however, limited data are available regarding risk factors for CDI-related readmissions in children.12,36–38 Our study has several limitations. PHIS datasets do not
potential misclassification, we used a previously validated case- finding tool with 79.82% sensitivity, 99.93% specificity, a positive predictive value of 81.31%, and a negative predictive value of 99.92%. These findings indicate that this method of identifying pediatric patients with CDI in administrative data is reliable and accurate.10 In addition, although we limited our analysis to the first admission for which a patient had a CDI diagnosis, it is possible that we could have included patients that
include autopsy results or death certificates; therefore, we were unable to assess mortality attributable to CDI. All of the hospitals that contribute data to the PHIS dataset are free- standing children’s hospitals, and these results might not be generalizable to all institutions. However, PHIS hospitals represent a wide variety of geographic and metropolitan areas. PHIS datasets also do not include laboratory data. Therefore, we were unable to evaluate whether potential laboratory para- meters or specific strains of CDI are associated with increased risk formortality. In addition, due to the lack of laboratory data, we were unable to confirm a CDI diagnosis. However, to avoid
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