Sulfamethoxazole [BSA]

Purpose Serum markers of renal function have not been characterized in patients treated with itraconazole (ITZ). This study aimed to evaluate the associations between plasma ITZ and its hydroxylated metabolite (OH-ITZ) concentrations and serum markers of renal function in patients with hematopoietic or immune-related disorder. Methods This study enrolled 40 patients with hematopoietic or immune-related disorder who are receiving oral ITZ solution. Plasma concentrations of ITZ and OH-ITZ at 12 h after dosing were determined at steady state. Their relationships with serum levels of creatinine and cystatin C and their estimated glomerular filtration rate (eGFR) were evaluated. Results The free plasma concentration of ITZ had no correlation with serum creatinine and serum creatinine-based estimated glomerular filtration rate (eGFR-cre). The free plasma concentration of OH-ITZ was positively and negatively correlated with serum creatinine and eGFR-cre, respectively. The free plasma concentrations of ITZ and OH-ITZ had no association with serum cystatin C and serum cystatin C-based eGFR. Serum creatinine was higher by 16% after than before starting ITZ treatment, while eGFR-cre was lower by 9.3%. The serum creatinine ratio after/before ITZ treatment was positively correlated with the free plasma concentration of OH-ITZ. The patients co-treated with trimethoprim-sulfamethoxazole had higher serum creatinine. Concomitant glucocorticoid administration did not significantly alter serum cystatin C. Conclusions Patients with hematopoietic or immune-related disorder treated with oral ITZ had a higher level of serum creatinine. Although serum creatinine potentially increases in conjunction with the free plasma concentration of OH-ITZ, concomitant ITZ administration has a slight impact on the eGFR-cre level in clinical settings.

We used graphical user interface-based automated analytical tools from Next Gen Diagnostics (Mountain View, CA) and 1928 Diagnostics (Gothenburg, Sweden) to analyze whole genome sequence (WGS) data from 102 unique blood culture isolates of Staphylococcus aureus to predict antimicrobial susceptibly, with results compared to those of phenotypic susceptibility testing. Of 916 isolate/antibiotic combinations analyzed using the Next Gen Diagnostics tool, there were 9 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 8 for clindamycin and 1 for minocycline. Of 612 isolate/antibiotic combinations analyzed using the 1928 Diagnostics tool, there were 13 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 9 for clindamycin, 3 for trimethoprim-sulfamethoxazole. and 1 for rifampin. Trimethoprim-sulfamethoxazole was not assessed by Next Gen Diagnostics, and minocydine was not assessed by 1928 Diagnostics. There was complete concordance between phenotypic susceptibility/resistance and genotypic prediction of susceptibility/resistance using both analytical platforms for oxacillin, vancomycin, and mupirocin, as well as by the Next Gen Diagnostics analytical tool for levofloxacin (the 1928 Diagnostics tool did not assess levofloxacin). These results suggest that, from a performance standpoint, with some caveats, automatic bioinformatics tools may be acceptable to predict susceptibility and resistance to a panel of antibiotics for S. aureus. (C) 2020 Elsevier Inc. All rights reserved.