Mechanisms regulating fetal transfer of olmesartan, an angiotensin-II receptor type 1 antagonist, are important as potential determinants of life-threatening adverse fetal effects. The purpose of this study was to examine the olmesartan transport mechanism through the basal plasma membrane (BM) of human syncytiotrophoblasts forming the placental barrier. Uptake of olmesartan by human placental BM vesicles was potently inhibited by dehydroepiandrosterone sulfate (DHEAS), estrone 3-sulfate, and bromosulfophthalein, which are all typical substrates of organic anion transporter (OAT) 4 localized at the BM of syncytiotrophoblasts, and was increased in the absence of chloride. In tetracycline-inducible OAT4-expressing cells, [(3) H]olmesartan uptake was increased by tetracycline treatment. Olmesartan uptake via OAT4 was concentration dependent with a Km of 20 μM, and was increased in the absence of chloride. [(3) H]Olmesartan efflux via OAT4 was also observed and was trans-stimulated by extracellular chloride and DHEAS. Thus, OAT4 mediates bidirectional transport of olmesartan and appears to regulate fetal transfer of olmesartan at the BM of syncytiotrophoblasts. Efflux transport of olmesartan via OAT4 from syncytiotrophoblasts to the fetal circulation might be facilitated in the presence of an inwardly directed physiological chloride gradient and extracellular DHEAS.

What is known and objective Implementation of an antifungal stewardship programme is a recognized need. However, there is insufficient information to confirm the impact of antifungal stewardship interventions. Further, few studies have evaluated the clinical effects of an antifungal stewardship intervention using 1‐3, β‐D‐glucan (βDG) testing. The aim of the present study was to evaluate the impact of implementing an antifungal stewardship with monitoring of βDG values on antifungal use and clinical outcomes. Methods A single institutional prospective cohort study was conducted to evaluate the impact of implementing daily reviews of antifungal agents and monitoring patients who measured βDG values since August 2013. Antifungal consumption and clinical outcomes in patients with Candida bloodstream infection were compared before and after the intervention. Results After implementation of the programme, parental antifungal use was significantly reduced compared to that before intervention (P = 0.006). In the after‐intervention group, the rate of 60‐day clinical failure in patients with Candida bloodstream infection was significantly reduced, from 80.0% (28/35) to 36.4% (8/22) (P < 0.001), and the rate of 60‐day mortality associated with Candida bloodstream infection tended to be reduced, from 42.9% (15/35) to 18.2% (4/22) (P = 0.081) compared to the before‐intervention group. The incidence of adverse events associated with antifungal agents was significantly lower in the after‐intervention group than in the before‐intervention group (51.4% [18/35] vs 13.6% [3/22], P = 0.004). What is new and conclusion Our findings suggest that daily review of the use of antifungal agents and monitoring of measured βDG values was highly effective in reducing antifungal consumption and improving the clinical outcomes of patients with Candida bloodstream infection.

Summary Background Matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF MS) has the potential to permit early organism identification and optimization of antibiotic therapy. However, MALDI‐TOF MS combined with antimicrobial stewardship is available at only a limited number of institutions. Here, we evaluated the clinical impact of implementing MALDI‐TOF MS combined with antimicrobial stewardship intervention in patients with bloodstream infections. Methods We conducted a single‐centre, prospective cohort study to evaluate the clinical impact of implementing MALDI‐TOF MS combined with antimicrobial stewardship intervention in patients with bloodstream infections. Processes and clinical outcomes in patients with bloodstream infections were compared before and after implementation of MALDI‐TOF MS. Results Compared with the conventional identification method, MALDI‐TOF MS combined with antimicrobial stewardship intervention significantly decreased the time to organism identification (48.6 ± 46.0 hours vs 78.1 ± 38.9 hours, P < 0.001), effective antimicrobial therapy (12.9 ± 19.0 hours vs 26.2 ± 44.8 hours, P < 0.001) and optimal antimicrobial therapy (53.3 ± 55.0 hours vs 91.7 ± 88.7 hours, P < 0.001. Moreover, the rate of clinical failure (14.0% vs 33.3%, P < 0.001) and incidence of adverse events (7.5% vs 23.9%, P < 0.001) was lower in the MALDI‐TOF MS group than in the conventional identification group. A multivariate Cox proportional hazard analysis indicated that implementation of MALDI‐TOF MS was a protective factor against clinical failure in patients with bloodstream infections (hazard ratio, 0.61; 95% confidence interval, 0.38‐0.99; P = 0.047). Conclusions Implementation of the MALDI‐TOF MS combined with antimicrobial stewardship intervention facilitated early optimization of antimicrobial therapy with a remarkable concomitant reduction in clinical failure and adverse events in patients with bloodstream infections.

Background Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, few reports have shown the impact of antimicrobial stewardship on clinical outcomes. Methods To evaluate the clinical outcomes of implementing a prospective audit with intervention and feedback without carbapenem pre‐authorisation, we conducted a single‐centre, prospective cohort study in patients who received carbapenem injection. Subjects were allocated to groups receiving antimicrobial agents before (non‐intervention group) or after (intervention group) the implementation of an antimicrobial stewardship programme in the clinical setting. Results The intervention facilitated the rate of choice of effective antimicrobials on day 2 from the onset of infection (from 63.2% to 90.2%; P < 0.001). Moreover, the rates of clinical failure‐free survival (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47‐0.89; P = 0.008) and re‐infection‐free survival (HR, 0.35; 95% CI, 0.18‐0.68; P = 0.002) were significantly higher in the intervention group than in the non‐intervention group. A multivariate Cox proportional hazard analysis indicated that non‐implementation of antimicrobial stewardship was a significant risk factor for clinical failure in patients receiving carbapenem injection (HR, 1.56; 95% CI, 1.11‐2.19; P = 0.010). Conclusions Our prospective audit with intervention and feedback strategy without carbapenem restriction facilitated the choice of optimal antimicrobials at an early stage of infection and improved clinical outcomes in patients who received carbapenem.

Voriconazole is a broad-spectrum triazole antifungal agent with potent activity against a range of medically important fungal pathogens. 1,2 Voriconazole is often recommended as the primary treatment for acute invasive aspergillosis and as salvage therapy for serious fungal infections caused by rare moulds such as those of the Scedosporium and Fusarium species in adults, and for the treatment of Candida infections in nonneutropenic adults. 3,4 Voriconazole can be used to prevent invasive fungal infections in immunocompromised patients. 5,6 In several cases with Aspergillus infections, long-term, even lifelong antifungal therapy may be required to control the disease. 3,4 Voriconazole is available in both intravenous and oral forms. Thus, switching from intravenous to oral medication among patients whose clinical condition allows for intake of oral