Simple determination of urine cefazolin concentration in pediatric patients with urinary tract infections using high-performance liquid chromatography.

Recently, global health concerns regarding increasing multidrug resistance have arisen. This study aimed to develop a simple, inexpensive and rapid high-performance liquid chromatography-ultraviolet (HPLC-UV) method for determining urinary concentrations of a first-generation cephem antibiotic in pediatric patients with urinary tract infections (UTIs). HPLC-UV was used to analyze urinary cefazolin concentrations at a detection wavelength of 254 nm. The assay used contained 10-fold diluted urine with an internal standard (cephapirin). The standard calibration curve for cefazolin was linear in the concentration range of 31.25-500 µg/ml (r2  > 0.999). The retention times of cefazolin and the internal standard were 4.2 and 4.9 min, respectively. The within- and between-day coefficients of variation were in the concentration ranges 1.2-15.2 and 5.5-19.2%, respectively. The urinary cefazolin concentration of a pediatric patient with a UTI was 1,476.6 µg/ml, which was over 700-fold higher than the minimum inhibitory concentration of cefazolin (≤2 µg/ml). The developed method is applicable to the confirmation of appropriate use for UTI treatment as therapeutic drug monitoring of cefazolin. Therefore, the findings of this study may contribute to the appropriate use of antibiotics to prevent antimicrobial resistance in pediatric patients with UTIs.

Negative effects of rivaroxaban observed in a patient with multiple common risks triggered by a bicycle accident.

The negative effects of anticoagulants are well-known in patients with renal impairment, drug-drug interaction, lower physical conditions, and multiple comorbidities. We highlight that even in patients with controllable multiple risks for rivaroxaban use, add-on inevitable risks will lead to negative effects greater than those expected.

Midazolam Intoxication in a Premature Neonate.

PURPOSE: We report the case of a male neonate with a respiratory disorder who developed adverse cardiorespiratory symptoms after the continuous infusion of midazolam. METHODS: To clarify the cause of cardiogenic shock, we performed whole exome sequencing and screened relative single-nucleotide variants of 2 cytochrome P450 (CYP) isoforms, CYP3A4 and CYP3A5, which play a dominant role in the metabolic elimination of midazolam. We measured endogenous cortisol 6ß-hydroxylation clearance to phenotypically assess CYP3A activity. FINDINGS: The CYP3A activity level in the patient was significantly lower than the mean CYP3A activity level in healthy adults. Three intronic mutations in the CYP3A4 and CYP3A5 isoforms were detected in the patient. IMPLICATIONS: Our findings suggest that the midazolam concentration in plasma was achieved at above the steady-state concentration during continuous infusion used to sedate neonates receiving mechanical ventilatory support. Evaluation of the drug-metabolizing ability based on CYP3A might be useful if adverse electrophysiologic variables or the induction of tachycardia occur because of delayed elimination.