Abstract

BackgroundVancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.Materials and methodsThe ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated.ResultsPharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P<0.01). The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate.ConclusionOur ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections.

Despite RBC contamination of APs below commonly accepted thresholds for Rh immunogenicity, AP transfusion can provoke non-D Rh antibody formation. RBC-derived microparticles, smaller but more numerous than RBCs, are volumetrically comparable and may be a hitherto underappreciated antibody stimulus. Further microparticle research will guide considerations of extended phenotypic matching of platelet components.

Hemophilia B is an X-linked recessive bleeding disorder caused by abnormalities of the coagulation factor IX gene (F9). Insertion mutations in F9 ranging from a few to more than 100 base pairs account for only a few percent of all hemophilia B cases. We investigated F9 to elucidate genetic abnormalities causing severe hemophilia B in a Japanese subject. We performed PCR-mediated analysis of F9 and identified a large insertion in exon 6. Next, we carried out direct sequencing of a PCR clone of the whole insert using nested deletion by exonuclease III and S1 nuclease. We identified an approximately 2.5-kb SINE-VNTR-Alu (SVA)-F element flanked by 15-bp duplications in the antisense orientation in exon 6. Additionally, we carried out exontrap analysis to assess the effect of this retrotransposition on mRNA splicing. We observed that regular splicing at exons 5 and 6 of F9 was disturbed by the SVA retrotransposition, suggesting that abnormal FIX mRNA may be reduced by nonsense-mediated mRNA decay. In conclusion, this is the first report of SVA retrotransposition causing severe hemophilia B; only five cases of LINE-1 or Alu retrotranspositions in F9 have been reported previously.

BackgroundCandidemia is associated with high mortality, and its prognostic factors need to be examined in more detail in order to improve its management. A case of breakthrough (BT) candidemia is defined as the development of candidemia during antifungal therapy. The microbiological characteristics of and appropriate clinical practices for BT candidemia remain unclear.ObjectivesThe primary objective of the present study was to identify the prognostic factors of candidemia, while the secondary objective was to elucidate the microbiological characteristics of patients with BT candidemia.Materials and methodsA total of 121 patients diagnosed with candidemia between January 2007 and December 2016 were enrolled in this study. The primary outcome was the 30-day mortality rate.ResultsThe overall incidence of candidemia was 0.056 cases/1000 inpatients. Among the 126 Candida isolated, C. albicans accounted for 36%, C. parapsilosis 26%, C. glabrata 12%, C. guilliermondii 14%, C. tropicalis 3%, C. pelliculos 1%, and other unidentifiable Candida species 8%. The 30-day mortality rate was 33%. In a multivariate Cox hazard analysis, C. albicans, the absence of antifungal therapy, age, lung disease, and mechanical ventilation were associated with a high mortality rate, whereas C. parapsilosis, the removal of a central venous catheter, and surgical wards were associated with a lower mortality rate. Fourteen patients had BT candidemia. A significant difference was observed in the proportion of C. guilliermondii and other Candida species exhibiting resistance to fluconazole and voriconazole, between patients with and without BT candidemia. Resistance to fluconazole was prominent in patients that developed candidemia with a history of azole antifungal agents.ConclusionThe prompt initiation of antifungal therapy and removal of central venous catheter were essential for better outcomes. A class switch to other antifungal agents needs to be considered in empirical antifungal therapy for BT candidemia with a history of exposure to azole antifungal agents.