Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Routine Use of Biomarkers to Rationalize Antibiotic Use During Febrile Episodes in Pediatric Bone Marrow Transplantation Units.

BACKGROUND: Children frequently develop fever after hematopoietic stem cell transplant (HSCT). Although the etiology of many febrile episodes (FEs) is not an infection, patients often receive broad-spectrum antibiotics in response. METHODS: To improve the judicious use of antibiotics in pediatric HSCT patients, we performed a prospective cohort study of children receiving an HSCT in Clínica Imbanaco (Cali, Colombia) between September 2016 and December 2019. We assessed all FEs occurring during 3 periods (infusion, neutropenic and engraftment). We measured procalcitonin and C-reactive protein (CRP) sequentially during each FE and compared levels among patients with fever due to significant infection (FSI) versus fever not attributable to infection (FNI) in each transplant period. RESULTS: There were 166 FEs in 95 patients. FSI accounted for 12%, 42% and 42% of FE during infusion, neutropenic and engraftment periods, respectively. CRP had better discriminatory capacity for FSI versus FNI in the infusion period [area under the curve (AUC) 0.80 (95% confidence interval [CI], 0.62-0.96) for a CRP level of 50 mg/L]. Neither biomarker performed well in the neutropenic period. During the engraftment period, a CRP of 65 mg/L had an AUC of 0.81 (95% CI, 0.65-0.96), while a procalcitonin level of 0.25 ng/mL had an AUC of 0.83 (95% CI, 0.63-1.0). In contrast to procalcitonin, the CRP's pattern of change throughout the first 3 days of fever in each transplant period was different in FSI compared with FNI. CONCLUSION: Sequential measurement of biomarkers, especially CRP, may allow clinicians to more appropriately manage antibiotic use in pediatric HSCT units.

The combined expression patterns of Ikaros isoforms characterize different hematological tumor subtypes.

A variety of genetic alterations are considered hallmarks of cancer development and progression. The Ikaros gene family, encoding for key transcription factors in hematopoietic development, provides several examples as genetic defects in these genes are associated with the development of different types of leukemia. However, the complex patterns of expression of isoforms in Ikaros family genes has prevented their use as clinical markers. In this study, we propose the use of the expression profiles of the Ikaros isoforms to classify various hematological tumor diseases. We have standardized a quantitative PCR protocol to estimate the expression levels of the Ikaros gene exons. Our analysis reveals that these levels are associated with specific types of leukemia and we have found differences in the levels of expression relative to five interexonic Ikaros regions for all diseases studied. In conclusion, our method has allowed us to precisely discriminate between B-ALL, CLL and MM cases. Differences between the groups of lymphoid and myeloid pathologies were also identified in the same way.