記述言語：英語   出版者・発行元：(一社)日本薬物動態学会  

ダプトマイシンが投与された成人患者47名に由来する110個の血漿中濃度データを用いて母集団薬物動態(PK)モデルを構築した。目標とする血漿中濃度時間曲線下面積(AUC)/最小発育阻止濃度(MIC)比、ピーク濃度/MIC比および安全性を考慮したトラフ濃度の閾値をそれぞれ>600、>60および24.3mg/Lとした。腎機能をクリアランスの有意な共変量とした。全患者に標準用量(6mg/kg)のダプトマイシンが投与されMIC値が0.25および0.5mg/Lの場合のシミュレーションによる有効域達成の確率は、90%以上であった。種々の用量でPKシミュレーションを行った結果、MIC値が1mg/Lでクレアチニンクリアランス>60mL/minの場合、時間ごとに10mg/kgの投与が最適であった。

記述言語：英語   出版者・発行元：Drug Metabolism and Pharmacokinetics  

Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8–10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach. A total of 110 plasma concentrations from 47 adult patients who received daptomycin in general wards were enrolled for population PK modeling. The target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio, target peak/MIC ratio, and threshold of the trough concentration for safety were set to >666, >60, and 24.3 mg/L, respectively. Renal function was indicated as a significant covariate for daptomycin clearance. The simulated probability of target attainment was more than 90% at MIC values of 0.25 and 0.5 mg/L in all patients at the standard dose (6 mg/kg). In contrast, comprehensive simulation assessments recommended 10 mg/kg every 24 h in patients with creatinine clearance >60 mL/min for MIC values of 1.0 mg/L. We propose a new simplified daptomycin dosing regimen stratified by renal function and MIC values based on PK model-based simulation analyses. The proposed regimen is expected to maximize clinical efficacy and minimize adverse events.

DOI： 10.1016/j.dmpk.2022.100444

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Microbial Genomics  

Helicobacter cinaedi is an enterohepatic Helicobacter that causes bacteremia and other diseases in humans. While H. cinaedi-like strains are isolated from animals, including dog isolates belonging to a recently proposed H. canicola, little is known about the genetic differences between H. cinaedi and these animal isolates. Here, we sequenced 43 H. cinaedi-or H. canicola-like strains isolated from humans, hamsters, rats and dogs and collected 81 genome sequences of H. cinaedi, H. canicola and other enterohepatic Helicobacter strains from public databases. Genomic comparison of these strains identified four distinct clades (clades I–IV) in H. cinaedi/canicola/‘magderbugensis’ (HCCM) complex. Among these, clade I corresponds to H. cinaedi sensu stricto and represents a human-adapted lineage in the complex. We identified several genomic features unique to clade I. They include the accumulation of antimicrobial resistance-related mutations that reflects the human association of clade I and the larger genome size and the presence of a CRISPR-Cas system and multiple toxin-antitoxin and restriction-modification systems, both of which indicate the contribution of horizontal gene transfer to the evolution of clade I. In addition, nearly all clade I strains but only a few strains belonging to one minor clade contained a highly variable genomic region encoding a type VI secretion system (T6SS), which could play important roles in gut colonization by killing competitors or inhibiting their growth. We also developed a method to systematically search for H. cinaedi sequences in large metagenome data sets based on the results of genome comparison. Using this method, we successfully identified multiple HCCM complex-containing human faecal metagenome samples and obtained the sequence information covering almost the entire genome of each strain. Importantly, all were clade I strains, supporting our conclusion that H. cinaedi sensu stricto is a human-adapted lineage in the HCCM complex.

DOI： 10.1099/mgen.0.000830

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Microbial Genomics  

Serratia marcescens is an important nosocomial pathogen causing various opportunistic infections, such as urinary tract infec-tions, bacteremia and sometimes even hospital outbreaks. The recent emergence and spread of multidrug-resistant (MDR) strains further pose serious threats to global public health. This bacterium is also ubiquitously found in natural environments, but the genomic differences between clinical and environmental isolates are not clear, including those between S. marcescens and its close relatives. In this study, we performed a large-scale genome analysis of S. marcescens and closely related species (referred to as the ‘S. marcescens complex’), including more than 200 clinical and environmental strains newly sequenced here. Our analysis revealed their phylogenetic relationships and complex global population structure, comprising 14 clades, which were defined based on whole-genome average nucleotide identity. Clades 10, 11, 12 and 13 corresponded to S. nematodiphila, S. marcescens sensu stricto, S. ureilytica and S. surfactantfaciens, respectively. Several clades exhibited distinct genome sizes and GC contents and a negative correlation of these genomic parameters was observed in each clade, which was associated with the acquisition of mobile genetic elements (MGEs), but different types of MGEs, plasmids or prophages (and other inte-grative elements), were found to contribute to the generation of these genomic variations. Importantly, clades 1 and 2 mostly comprised clinical or hospital environment isolates and accumulated a wide range of antimicrobial resistance genes, including various extended-spectrum β-lactamase and carbapenemase genes, and fluoroquinolone target site mutations, leading to a high proportion of MDR strains. This finding suggests that clades 1 and 2 represent hospital-adapted lineages in the S. marc-escens complex although their potential virulence is currently unknown. These data provide an important genomic basis for reconsidering the classification of this group of bacteria and reveal novel insights into their evolution, biology and differential importance in clinical settings.

DOI： 10.1099/mgen.0.000793

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景】膵移植後の真菌感染症は臓器生着率、患者死亡率に相関するとされる一方で、抗真菌剤の予防投与を支持するエビデンスは限られており、全例予防投与を行うことに対してのコンセンサスは得られていない。</p><p>【方法】当科ではこれまで膵移植患者に対する抗真菌薬予防投与を行っておらず、移植後の真菌症発症率を検討した。対象は2015年から2022年4月までに当科で行った膵移植患者47例とし、真菌症の定義は術後半年以内に「β-D-グルカン陽性」または「培養で真菌陽性」で、かつ臨床症状があり真菌症として加療したものとした。</p><p>【結果】47例中10例（20％）が真菌症と診断された。移植後から発症まで期間は中央値13日（4-113日）であった。真菌症の発症と術後半年以内の移植膵機能廃絶とは有意に相関していた（P<.001）。臓器保存液の培養では31例中1例（2％）が、ドナー十二指腸液培養では17例中12例（71％）がカンジダ陽性であった。いずれかがカンジダ陽性であった13例中4例（31％）が、術後真菌症をきたしたのに対して、どちらも培養陰性であった5例は真菌症を認めなかった（P=.082）。</p><p>【結語】膵移植後真菌症は術後早期に発症し、その後の移植膵機能廃絶と有意に相関していた。また真菌症発症のリスク評価に臓器保存液と十二指腸液培養が有用である可能性が示唆された。</p>

DOI： 10.11386/jst.57.supplement_s298_1

CiNii Research

記述言語：日本語  

記述言語：日本語  

記述言語：日本語