Prediction of treatment success in patients with Enterococcus faecium bacteremia using vancomycin AUC/MIC ratio: A multicenter retrospective study.

Background: Although vancomycin is commonly used to treat Enterococcus faecium infections, there are no clear guidelines for the optimal 24-h area under the concentration time curve to minimum inhibitory concentration (AUC/MIC) ratio. This study aimed to determine the target AUC/MIC ratio associated with vancomycin-treated E. faecium infection outcomes.

Risk stratification of AUC upward deviation in patients with low serum creatinine levels treated with vancomycin: a multicenter retrospective study.

Introduction: In patients with diminished muscle mass, serum creatinine (SCr) levels may be misleadingly low, potentially leading to overestimations of kidney function and unexpectedly high blood levels of vancomycin. This study aimed to identify factors contributing to this discrepancy and develop a flowchart for stratifying the risk of excessive vancomycin exposure, measured as an upward deviation in the area under the concentration-time curve (AUC) in patients with low SCr levels.

Methods: We analyzed data from patients who received vancomycin and had an SCr value <0.

CKD-Induced Oxidative Twitch Muscle Atrophy is Mediated by Transforming Growth Factor-β.

Background: Understanding the vicious cycle driving renal impairment progression and skeletal muscle atrophy in chronic kidney disease (CKD) is crucial. Therefore, this study aimed to examine the role of transforming growth factor-beta (TGF-β) in promoting skeletal muscle atrophy in CKD.

Methods: A combined model of 2/3 nephrectomy and unilateral ureteral ligation, as we previously reported, was used for CKD mice.

Establishment and validation of downsized hollow-fibre infection model and pharmacokinetics/pharmacodynamics analysis of VAN on Enterococcus faecium.

Objectives: This study clarified the target values of VAN against Enterococcus faecium using pharmacokinetics/pharmacodynamics (PK/PD) analysis and compared a downsized hollow fibre infection model (HFIM) with a conventional HFIM.

Methods: VAN was administered subcutaneously and blood concentrations were measured to calculate the PK parameters. PD studies were performed in an infected mouse model by administering VAN at doses ranging from 25 to 400 mg/kg based on PK parameters.

Shortening the interval between the first and the second dose of vancomycin facilitates rapid achievement of the target AUC without increasing the risk of acute kidney injury, provided the AUC on the second day is appropriately controlled: a multicenter retrospective study.

Background: The impact of shortening or extending a vancomycin dosing interval on early attainment of target blood levels and acute kidney injury (AKI) remains unclear. We investigated the relationship between the interval of the first and second doses of vancomycin and early area under the concentration-time curve (AUC) and AKI.

Methods: Patients (≥ 18 years) who started vancomycin and had trough/peak blood samples were included.

External validation of a flowchart related to achieving the target area under the concentration-time curve for vancomycin: A retrospective multicenter study.

During therapeutic drug monitoring (TDM) for vancomycin (VCM), the area under the concentration-time curve (AUC) is important for balancing efficacy versus toxicity. In a previous study, we developed a decision tree (DT) model to achieve the target AUC during TDM over the follow-up period (AUC). This study aimed to validate the DT model for achieving the target AUC.

Influence factors of metronidazole-related CNS disorders: an analysis of the Japan adverse drug event report and FDA adverse event reporting system.

Background: Metronidazole (MNZ) can be administered for various infections. The impact of comorbidities/concomitant drugs on MNZ-induced central nervous system (CNS) disorders remains unclear.

Research Design And Methods: We assessed the risk of metronidazole-related CNS disorders using the Japan Adverse Drug Event Report (JADER, May 2023) and the US Food and Drug Administration Adverse Event Reporting System (FAERS, Q1 2023), excluding comorbidities/concomitant drugs.

Development and validation of a population pharmacokinetic model of vancomycin for patients of advanced age.

Background: Population pharmacokinetic (PPK) models of vancomycin (VCM) commonly use creatinine clearance (CLcr) as a covariate for clearance (CL). However, relying on CLcr in patients of advanced age may lead to inaccuracies in estimating VCM clearance. Therefore, this study aimed to develop and validate a new PPK model specifically for patients aged 75 years and older.

Combined dual β-lactams and diazabicyclooctane β-lactamase inhibitor is highly effective against Mycobacterium abscessus species in vitro.

Objective: Mycobacterium abscessus pulmonary disease is a refractory infectious disease. Developing an effective treatment is urgent as the number of patients infected with M. abscessus species (MABS) is increasing worldwide.

Carbon monoxide alleviates endotoxin-induced acute lung injury via NADPH oxidase inhibition in macrophages and neutrophils.

Sepsis is a life-threatening condition caused by severe infection and often complicates acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) due to the collapse of the oxidative and inflammatory balance induced by microbial pathogens, including lipopolysaccharides (LPS). In sepsis-related ARDS/ALI, NADPH oxidase (NOX) and toll-like receptors (TLR) in neutrophils and macrophages are key players in initiating oxidative and inflammatory imbalances. Although NOX and TLR activation has been linked to carbon monoxide (CO), the mechanism by which CO affects sepsis-related ARDS/ALI through NOX and TLR remains unknown.

Treatment success prediction in patients with methicillin-resistant coagulase-negative staphylococci infections, using vancomycin AUC24/MIC ratio: a multicentre retrospective cohort study.

Background: Although vancomycin is commonly used to treat methicillin-resistant coagulase-negative staphylococci (MRCoNS) infections, there are no clear guidelines for the optimal 24 h AUC24/MIC ratio. This study aimed to determine the target AUC24/MIC ratio associated with vancomycin-treated MRCoNS infection outcomes.

Methods: This multicentre retrospective cohort study included adult patients who received vancomycin for ≥5 days for bloodstream infections caused by MRCoNS between January 2018 and December 2023.

Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis.

Background: Nacubactam (NAC), a new diazabicyclooctane β-lactamase inhibitor, is being developed for use together with aztreonam (AZT) and cefepime (CFPM). However, the effective clinical dosages of AZT/NAC and CFPM/NAC have not yet been established. We have previously shown that free time above instantaneous MIC (fT > MICi) is a valuable pharmacokinetic (PK)/pharmacodynamic parameter for β-lactam (BL)/NAC in a mouse thigh infection model.

Development of a pharmacokinetic/pharmacodynamic evaluation model for osteomyelitis and usefulness of tedizolid as an alternative to vancomycin against MRSA osteomyelitis.

Objectives: This study aimed to develop a suitable osteomyelitis model for pharmacokinetic/pharmacodynamic (PK/PD) evaluation and to investigate the target PK/PD values of vancomycin and tedizolid against methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.

Methods: An osteomyelitis model was established by implanting an MRSA-exposed sterilized suture in the tibia of normal mice and mice with cyclophosphamide-induced neutropenia. The suitability of the osteomyelitis mouse model for PK/PD evaluation was assessed using vancomycin as an indicator.

Investigating the hypothermic effects of fluoroquinolone antimicrobials on non-bacterial fever model mice.

Background: Fluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever.

Methods: CPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast.

Identification of Patients Who Require Two-Point Blood Sampling for the Peak and Trough Values Rather Than One-Point Blood Sampling for the Trough Value for the Evaluation of AUC of Vancomycin Using Bayesian Estimation.

Objectives: It is recommended to adjust the dose of vancomycin (VCM) with a target area under the concentration-time curve (AUC) of 400-600 μg·h/mL. Factors that affect the deviation between AUCs are estimated from the trough value alone and the trough and peak values using practical AUC-guided therapeutic drug monitoring (PAT) for vancomycin. In this study, factors that affect AUC were evaluated.

Hydrosulphide-methaemoglobin-albumin cluster: a hydrogen sulphide donor.

Methaemoglobin (metHb) possesses inherent characteristics that facilitate reversible binding to hydrogen sulphide. Exogenous hydrogen sulphide supplementation imparts beneficial bioactive effects, including antioxidant and anti-inflammatory; hence, we hypothesized that the metHb-hydrogen sulphide complex could act as a hydrogen sulphide donor for medication. In this study, we prepared a hydrosulphide-metHb-albumin (HS-metHb-albumin) cluster and examined its applicability as a hydrogen sulphide donor in the mice model of hepatic ischemia-reperfusion injury.

T-cell immunosuppression in sepsis is augmented by sciatic denervation-induced skeletal muscle atrophy.

Skeletal muscle atrophy is a known risk factor for immunosuppressive conditions and for a poor prognosis in sepsis. However, its immunopathology has not been experimentally elucidated. This study investigated the effects of skeletal muscle atrophy on the immunopathology of sepsis.

SARS-CoV-2 mRNA vaccine-related myocarditis and pericarditis: An analysis of the Japanese Adverse Drug Event Report database.

Background: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines and myocarditis/pericarditis in the Japanese population has not been systematically investigated. This study was aimed at clarifying the association between SARS-CoV-2 mRNA vaccines (BNT162b2 and mRNA-1273) and myocarditis/pericarditis as well as influencing factors by using the Japanese Adverse Drug Event Report database.

Methods: Reporting odds ratios (RORs) and 95 % confidence intervals (95 % CIs) for the association between the vaccines and myocarditis/pericarditis were calculated using data from the database (April 2004-December 2023).

Predictive Value of Vancomycin AUC/MIC Ratio for 30-day Mortality in Patients with Severe or Complicated Methicillin-Resistant Staphylococcus aureus Infections: A Multicenter Retrospective Study.

Background: Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC/MIC ratio associated with treatment outcomes of infections treated with vancomycin.

Methods: This retrospective multicenter cohort study included adult patients receiving ≥ 5 days of vancomycin for severe/complicated MRSA infections (e.

Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy.

A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin.

Analysis of Risk Factors for Developing Tuberculosis in Patients Who Received Prophylactic Latent Tuberculosis Infection Treatment with Experience of Biologic Medications.

Biologic medications have dramatically improved the treatment outcomes of immunological inflammatory diseases, but their immunosuppressive effects put patients at risk for tuberculosis (TB). We investigated the risk factors for developing TB in patients treated for latent tuberculosis infection (LTBI) who also had experience of using biologic medications. At Keio University Hospital, we retrospectively investigated patients treated with anti-mycobacterial drugs before or concurrently with biologic medications from January 2012 to August 2020.

Elucidating the binding properties of methemoglobin in red blood cell to cyanide, hydrosulfide, and azide ions using artificial red blood cell.

Methemoglobin (metHb), the oxidized form of hemoglobin, lacks the ability of reversible oxygen binding; however, it has a high binding affinity to toxic substances such as cyanide, hydrosulfide, and azide. This innate property of metHb offers the clinical option to treat patients poisoned with these toxins, by oxidizing the endogenous hemoglobin in the red blood cells (RBCs). The binding properties of naked metHb (isolated from RBC) with these toxins has been studied; however, the binding behaviors of metHb under the intracellular conditions of RBC are unclear because of the difficulty in detecting metHb status changes in RBC.