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Fluoroquinolones and macrolides may, due to a potential drug‐drug interaction, increase the concentration of any concomitantly administered direct oral anticoagulant (DOAC) and thereby increase the risk of severe bleeding. However, clinical evidence for such an effect is scarce. The present study aimed to evaluate the association between the use of fluoroquinolones or macrolides and bleeding events in patients with concomitant DOAC use. This was a nationwide cohort study including 19 288 users of DOACs in 2008‐2018 using information from Swedish national health registers. We compared the incidence of bleeding events associated with use of fluoroquinolones or macrolides using doxycycline as a negative control. Cox regression was used to calculate crude and adjusted hazard ratios (aHRs) in time windows of various length of follow‐up after the start of antibiotic use. The incidence rates for fluoroquinolones and macrolides ranged from 12 to 24 and from 12 to 53 bleeding events per 100 000 patients in the investigated time windows. The aHRs (95% confidence interval) for use of fluoroquinolones and macrolides were 1.29 (0.69‐2.44) and 2.60 (0.74‐9.08) at the concomitant window, 1.31 (0.84‐2.03) and 1.79 (0.75‐4.29) at 30 days, and 1.34 (0.99‐1.82) and 1.28 (0.62‐2.65) at 150 days, respectively. With regard to fluoroquinolones, the present study suggests that the risk of bleeding when combined with DOACs, if any, is small. Codispensation of macrolides in patients on DOACs was not associated with an increased risk of bleeding. However, due to the small number of macrolide users, the results must be interpreted with caution. [ABSTRACT FROM AUTHOR]

ABSTRACT Daptomycin, a lipopeptide antibiotic with excellent activity against Gram-positive bacteria, is excreted primarily by the kidneys. Development of effective chromatographic methodologies for the determination of daptomycin in human specimens is necessary for clinical use. This study developed a simple and validated ultra-high-performance liquid chromatography method coupled to ultraviolet detection for determination of daptomycin in human plasma and urine. After the pretreatments involving protein precipitation, the supernatants were separated using a 2.3 µm particle size octadecylsilyl column, and the run time was 1 min. The calibration curves were linear over the concentration ranges of 2-200 mg/L for plasma and 25-300 mg/L for urine. Intra- and inter-assay precision and accuracy values of plasma were within 13.5 and 92-100% and within 10.7 and 100-107%, respectively. Those of urine were within 5.0 and 101-104% and within 3.7 and 100-101%, respectively. The validated method was applied to the determination of plasma and urine samples in patients receiving 4-6 mg/kg of intravenous daptomycin, resulting in sufficient sensitivity for evaluating the plasma exposure and urinary excretion. In conclusion, the present method with acceptable analytical performance can be helpful for evaluating the pharmacokinetic disposition of daptomycin in clinical settings. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]