Urine Reagent Strip (Blood-Urobilinogen-Glucose-Protein-pH)

Resistant pathogens have become a major healthcare problem in children with cancer, causing different kinds of infections such as the bloodstream ones, most common, and most frequently described and the urinary tract ones, of which less data are available. We analyzed and compared the proportions, and the trends of resistance in pathogens isolated from blood and urines in children with cancer followed in IRCCS Istituto Giannina Gaslini, Genova, Italy, from January 2007 to December 2018. Overall, 345 strains detected in urines and 282 in bloodstream infections were analyzed. Enterobacteriales were the most frequently isolated pathogens. During the study period in urines, there was a significant increase of resistance to ceftazidime, ciprofloxacin, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole, but pathogens from blood were significantly more frequently resistant to amikacin, piperacillin/tazobactam, and combination therapy piperacillin/tazobactam+amikacin, even if with a decreasing trend during the study period. These data confirm the importance of surveillance of isolated microorganism and antibiotic resistance in cancer children.

Rationale Nintedanib, an oral, triple angiokinase inhibitor, is used alongside docetaxel in the management of locally recurrent non-small-cell lung cancer and idiopathic pulmonary fibrosis. The present study deals with the identification and characterization ofin vitroandin vivostable and reactive (if any) metabolites of nintedanib and sheds light on some novel metabolites of the drug which have not been reported previously. Methods The study involved an oral administration of the drug to male Wistar rats, followed by collection of the biological matrices (urine, plasma and feces) at specific intervals for determination ofin vivometabolites. In addition,in vitrostudies were performed on human and rat liver microsomes in the presence of appropriate co-factors. The samples were subjected to protein precipitation and nitrogen evaporation prior to ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry analysis. The toxicities of all the metabolites were assessedin silico, employing ADMET Predictor (TM). Results A total of 18 metabolites of nintedanib were identified in all the matrices, of which nine were found to be novel and unreported previously. The unreported metabolites were elucidated as oxidative, demethylated and glucuronide conjugates of nintedanib. Interestingly, acetonitrile adducts of a few metabolites (low concentration) were also observed. No reactive metabolites were observed in this study. Conclusions Characterization of hitherto unknownin vitroandin vivometabolites of nintedanib adds to the existing knowledge on the metabolism of the drug. Identification on the basis of the solvated adducts can be a useful approach for characterization of minor metabolites, which remain undetected owing to sensitivity issues.