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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: The clinical implications of free linezolid monitoring have not been fully clarified in critically ill patients. The aim of this study was to evaluate the variability in pharmacokinetics of free linezolid and its relationship with susceptibility to meticillin-resistant Staphylococcus aureus (MRSA) in critically ill patients. Twenty critically ill MRSA-infected patients receiving intravenous linezolid were enrolled. Blood specimens were collected by 12-h sampling after dosing at Day 7. The medians (interquartile range) of the minimum free concentration, area under the concentration–time curve of total and free linezolid from 0 to 24h (AUC0–24 and fAUC0–24, respectively) and percentage bound were 9.9μg/mL (5.2–15μg/mL), 495μgh/mL (291–695μgh/mL), 385μgh/mL (242–528μgh/mL) and 23% (15–28%), respectively. The medians of the AUC0–24 and fAUC0–24 to minimum inhibitory concentration ratios (AUC/MIC and fAUC/MIC) were 248 (144–347) and 192 (109–264), respectively. Two patients failed to achieve adequate levels of AUC/MIC and fAUC/MIC for linezolid. The percentage bound of linezolid in hypoalbuminaemic patients was significantly lower than in non-hypoalbuminaemic patients. A significant correlation was observed between fAUC0–24 and creatinine clearance. In addition, the fAUC0–24 was correlated with the minimum free concentration. In conclusion, the plasma level of free linezolid was variable in critically ill patients with renal dysfunction and hypoalbuminaemia. This finding suggests that the monitoring of free linezolid is necessary in critically ill patients. [Copyright &y& Elsevier]

Polarization switching processes in ferroelectric capacitors with epitaxial Pb(Zr,Ti)O 3 (PZT) thin films grown on SrRuO 3 /SrTiO 3 (100) were investigated using piezoresponse imaging technique with and on the top electrodes using atomic force microscopy. PZT thin films had only 180° domains because of a tetragonal structure and completely (001)-orientations. Piezoresponse measurements revealed that the polarization switching process changed as the switching pulse voltage increased. At lower switching pulse voltage regions (∼1.4 V c ), the polarization switching occurred from only the latent nuclei. On the other hand, at higher switching pulse voltage (>2 V c ), the new nucleations during switching period were observed. Activation field can be also estimated 310-370 kV/cm. [ABSTRACT FROM AUTHOR]

Combination therapy with vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) increases the risk of acute kidney injury (AKI). Teicoplanin (TEIC) has a lower risk of AKI than VCM. Currently, the difference in AKI risk after TEIC–PIPC/TAZ combination therapy and VCM–PIPC/TAZ combination therapy is controversial. This study aimed to compare AKI incidence after treatment with these two drug combinations using propensity score matching analysis. This single-center cohort study used data extracted from patients' medical records. We included patients who received TEIC–PIPC/TAZ therapy (TEIC group) or VCM–PIPC/TAZ therapy (VCM group). After propensity score matching, AKI incidence, AKI stage, 30-day mortality, and time to AKI incidence were compared between the groups. After propensity score matching, 94 patients were matched in each group. AKI incidence was significantly lower in the TEIC group than in the VCM group (10.6% vs. 23.4%, odds ratio [95% confidence interval]: 0.39 [0.17–0.88], p = 0.03). AKI stage, 30-day mortality, and time to AKI incidence were not significantly different between the groups. This study suggested that AKI incidence may be lower in patients undergoing combination therapy with TEIC–PIPC/TAZ than in those receiving therapy with VCM–PIPC/TAZ. To prevent the occurrence of AKI, clinicians may need to choose TEIC instead of VCM for patients receiving PIPC/TAZ. [ABSTRACT FROM AUTHOR]

Plasma daptomycin has not been fully characterized in diabetic and obese patients. This study aimed to evaluate the associations of plasma daptomycin with glycation of serum albumin and obesity. Infectious patients (n = 70) receiving intravenous daptomycin were enrolled. The plasma concentration of total and free daptomycin were determined using liquid chromatograph-tandem mass spectrometer. The associations of the plasma concentrations of daptomycin with clinical factors including serum albumin fractionations and physical status (obese including overweight, body mass index ≥ 25.0) were investigated. Daptomycin doses were adjusted using total body-weight. The serum albumin level was positively and negatively correlated with the plasma concentration of total daptomycin and its free fraction proportion, respectively. The serum non-glycated albumin was negatively correlated with the free fraction proportion. The dose-normalized plasma concentration of total daptomycin was higher in the obese patients than in non-obese patients when the body-weight was corrected with total and adjusted values. For the dose adjustment with lean body-weight, no difference was observed in the dose-normalized plasma concentration of total daptomycin between the physical statuses. For each body-weight correction method, physical status did not affect the dose-normalized plasma concentration of free daptomycin. The glycation of serum albumin and obesity did not associate with dose-normalized plasma free daptomycin. In obese patients, daptomycin dosage adjustment with total body-weight and adjusted body-weight may lead to an apparent excessive exposure resulting in overdosage compared to lean body-weight. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study was to develop a simultaneous determination method for voriconazole (VRCZ) and its N-oxide (VNO) in human plasma and to apply it to clinical samples. Design and methods: Plasma specimens were deproteinized with acetonitrile and then injected into an HPLC-UV system. VRCZ and VNO were separated on an ODS column filled with 2.3-μm particles using an isocratic mixture of acetonitrile/methanol/phosphate buffer 25/10/65 (v/v/v). Plasma concentrations of VRCZ and VNO in 25 patients were determined. Results: Both VRCZ and VNO were linear (r >0.999) over the concentration ranges of 0.1–8.0mg/L. The run time for quantification of the analytes was 4min. Interindividual variation in the plasma concentration of VRCZ that ranged from less than 0.1 to 6.96mg/L was observed. VNO concentrations weakly depended on VRCZ dosage. Conclusions: The present method can contribute to the optimization of antifungal therapy using VRCZ. [Copyright &y& Elsevier]

A cell culture of Cupressus lusitanica was used to investigate the reaction of a plant to certain airborne chemicals. Compared with laboratory and field methods using intact plants or tissues, a cell culture is advantageous because it is not affected by environmental factors, and the experiments are easier to reproduce. When exposed to an elicitor, our cell line produces 10 monoterpenes and β-thujaplicin, which is a strong phytoalexin. These monoterpenes are emitted into the vapor phase and are expected to play a role in airborne signaling. In the present study, the cells were exposed to monoterpene vapors, and the volatiles present in the culture flasks were monitored. When the culture cells were exposed to low doses of sabinene, we detected γ-terpinene and p-cymene. After exposure to γ-terpinene, we found p-cymene and terpinolene, whereas p-cymene exposure resulted in terpinolene emission. By contrast, the other seven monoterpenes we investigated did not induce any emissions of other monoterpenes. These results strongly suggest that in C. lusitanica a signaling cascade exists that starts with the emission of sabinene and moves to γ-terpinene, p-cymene, and finally to terpinolene, which accelerates the production of the phytoalexin β-thujaplicin. [ABSTRACT FROM AUTHOR]

The article describes a case of a bilateral developmental glaucoma suspected from megalophthalmos revealed during obstetric ultrasonography. The patient, a male neonate delivered normally in the 38th week of gestation, underwent trabeculotomy on his 17th day of life and the intraocular pressure (IOP) was well controlled. He was referred to an ophthalmologist for megalophthalmos and elevated IOP on the 10th day after birth. Details of the findings of his ophthalmic examination are provided.

Abstract: Background: The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole (ITZ), is not fully known. Methods: Oral solution of ITZ was administered in 46 immunocompromised patients as a single 200mg dose for at least 12days. The plasma concentrations of ITZ, active OH-ITZ, and keto-itraconazole (keto-ITZ), an inactive metabolite, 12h after administration were determined by LC–UV or LC–MS/MS. Results: The mean±SD of plasma concentrations of ITZ, OH-ITZ, and keto-ITZ were 833±468, 798±454, and 3.94±2.68μg/l, respectively. A greater correlation coefficient was observed between plasma concentrations of ITZ and OH-ITZ (r =0.90, P <0.01) than between OH-ITZ and keto-ITZ (r =0.44, P <0.01). Plasma concentration of OH-ITZ was inversely correlated with concentration ratio of keto-ITZ to OH-ITZ (r =−0.52, P <0.01). Plasma concentrations of ITZ and OH-ITZ were correlated with serum concentration of albumin (r =0.36, P =0.01 and r =0.37, P =0.01) and estimated glomerular filtration rate (r =−0.27, P =0.08 and r =−0.35, P =0.02). Conclusions: The pharmacokinetic variability of OH-ITZ was associated with saturated metabolism to keto-ITZ, serum concentration of albumin, and renal function in immunocompromised patients. The plasma concentration of OH-ITZ was strongly correlated with that of ITZ. Prevention of fungal infections can be improved by determining the plasma concentration of ITZ or OH-ITZ. [Copyright &y& Elsevier]

We report a patient with frosted branch-like appearance retinal vasculitis associated with peripheral capillary nonperfusion and full-field electroretinographic changes. A 62-year-old man presented with sudden bilateral decreased vision accompanied by headaches. His best-corrected visual acuity was 0.01 in both eyes. Fundus examination and fluorescein angiography showed bilateral frosted branch-like appearance retinal vasculitis, and spectral-domain optical coherence tomography showed severe macular edema in both eyes. The cerebrospinal fluid analyses showed an increased lymphocyte count and protein levels. He was treated with systemic corticosteroid therapy, and his best-corrected visual acuity improved to 0.8 OD and 1.0 OS at 6 months after onset. However, fluorescein angiography showed a lack of capillary perfusion in the periphery, and the oscillatory potentials on full-field electroretinography were severely reduced in both eyes. These findings indicated extensive retinal ischemia and inner retinal dysfunction, and that fluorescein angiography and full-field electroretinograms can be useful during follow-up of eyes with frosted branch-like appearance retinal vasculitis. [ABSTRACT FROM AUTHOR]