Vancomycin pharmacokinetics and pharmacodynamics

OBJECTIVES: The trough concentration of vancomycin and the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus . However, the use of similar pharmacokinetic principles in determining antibiotic efficacy against other gram-positive cocci is lacking. We performed a pharmacokinetic/pharmacodynamic analysis (association of target trough concentration values and AUC/MIC with therapeutic outcome) of vancomycin in patients with Enterococcus faecium bacteraemia...

INTRODUCTION: LYSC98 is a novel vancomycin derivative used for gram-positive bacterial infections. Here we compared the antibacterial activity of LYSC98 with vancomycin and linezolid in vitro and in vivo. Besides, we also reported the pharmacokinetic/pharmacodynamic (PK/PD) index and efficacy-target values of LYSC98. METHODS: The MIC values of LYSC98 were identified through broth microdilution method. A mice sepsis model was established to investigate the protective effect of LYSC98 in vivo...

Vancomycin is used for the treatment of bone and joint infections (BJI), but scarce information is available about its pharmacokinetic/pharmacodynamic (PK/PD) characteristics. We aimed to identify the risk factors associated with the non-achievement of an optimal PK/PD target in the first therapeutic drug monitoring (TDM). Methods: A retrospective study was conducted in a tertiary hospital from January 2020 to January 2022. Patients with BJI and TDM of vancomycin on day 2 of treatment were included. Initial vancomycin fixed doses (1 g every 8 h or 12 h) was decided by the responsible doctors...

Dalbavancin is a novel long-acting semi-synthetic lipoglycopeptide. It is licensed for acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Many studies on dalbavancin alternative use in clinical practice have been published recently, including osteomyelitis, prosthetic joint infections (PJIs), and infective endocarditis (IE). Thus, we conducted a narrative review on dalbavancin efficacy in difficult-to-treat infections, such as osteomyelitis, PJIs, and IE...

Vancomycin is a glycopeptide antibiotic used for prophylaxis and treatment of infections caused by methicillin-resistant Staphylococcus aureus. Although major organ sizes and functions mature during infancy, pharmacokinetic studies, especially those focused on infants, are limited. Changes in extracorporeal membrane oxygenation-related drug disposition largely contribute to changes in pharmacokinetics. Here, pharmacokinetic profiles of vancomycin in an infant receiving extracorporeal membrane oxygenation therapy are presented...

PURPOSE: Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics-pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection...

BACKGROUND: Vancomycin is commonly used to treat methicillin-resistant staphylococcal infections in neonates. Consensus on its ideal dosing in neonates has not been achieved. Model-based dosing recently has evolved as an important tool to optimize vancomycin initial dosing. The aim of this is to evaluate a population pharmacokinetic model-based approach in achieving the vancomycin therapeutic target of an AUC0-24 400 as recommended by the recent IDSA treatment guidelines. This model was implemented as a simple Excel calculator to individualize and optimize vancomycin initial dosing in neonates...

OBJECTIVES: The pharmacokinetics/pharmacodynamics (PK/PD) characteristics of fidaxomicin (FDX) and vancomycin (VCM) against Clostridioides difficile infection (CDI) are yet to be elucidated because of the lack of an established PK/PD analysis method for intestinal infections and unabsorbed oral drugs. Here, we developed a feces-based PK/PD analysis method and determined the fecal PK/PD index with target values for FDX and VCM against CDI. METHODS: Antimicrobial susceptibility, time-kill curves, and post-antibiotic effects (PAEs) of FDX and VCM against C...

BACKGROUND: Vancomycin guidelines by the Infectious Diseases Society of America and American Society of Health-System Pharmacists endorse Bayesian-software-assisted area under the curve (AUC24h ) in their 2020 update. At this time, there are limited clinical data that support its use. OBJECTIVES: The purpose of this study is to evaluate the safety benefits and efficacy outcomes of using Bayesian-assisted AUC24h dosing compared to trough dosing. METHODS: Hospitalized patients from before February 1, 2020, (preimplementation of AUC24h dosing) and after August 1, 2020, (postimplementation) were reviewed...

BACKGROUND: Vancomycin area-under-the-curve (AUC) monitoring is associated with reduced nephrotoxicity but may increase cost and workload for personnel compared to trough monitoring. OBJECTIVE: The purpose of this study was to compare the accuracy of vancomycin AUC calculated by open-access, online, trough-only calculators to AUCs calculated by the trapezoidal method (TM) using peak and trough concentrations. METHODS: This retrospective, multi-center study included adults ≥18 years old with stable renal function who received vancomycin with steady-state peak and trough concentrations...

Antimicrobial resistance (AMR) is a major threat to global health due to the wide use of antibacterial drugs. Multiple studies show that the pharmacokinetic/pharmacodynamic (PK/PD) studies of antibiotics are an approach to prevent/delay AMR. The pharmacokinetic parameters of antibiotics are the basis of PK/PD studies, and therapeutic drug monitoring (TDM) is the key method to obtain pharmacokinetic information. We developed an ultra-performance liquid chromatography-tandem mass spectrometry to determine 18 antibacterial drugs (piperacillin, cefazolin, cefuroxime, cefoperazone, ceftriaxone, cefepime, aztreonam, meropenem, imipenem, levofloxacin, moxifloxacin, azithromycin, clindamycin, tigecycline, linezolid, vancomycin, voriconazole and caspofungin) in human plasma for practical clinical usage...

OBJECTIVES: Sitafloxacin is one of the newer generation fluoroquinolones with highly active against multidrug-resistant (MDR) bacteria. Our objectives were to identify the sitafloxacin pharmacokinetic/pharmacodynamic (PK/PD) index and breakpoints against MDR isolate in the urinary tract infection model. METHODS: Forty-eight MDR isolates underwent sitafloxacin and levofloxacin microdilution susceptibility testing. A 24 h in vitro model was established that simulated the healthy subjects urodynamics of sitafloxacin fumarate injection...

PURPOSE: Vancomycin-resistant enterococci (VRE) have recently become a major cause of nosocomial infections and a global public health concern. Tedizolid exhibits powerful antibacterial activity against VRE in vitro, but its pharmacokinetic/pharmacodynamic (PK/PD) parameters remain unclear. Therefore, we aimed to determine the PK/PD indices of tedizolid action on VRE and the mechanisms underlying the PK/PD indices differences of tedizolid against VRE and methicillin-resistant Staphylococcus aureus (MRSA)...

Background: Dosing strategies of β-lactams and vancomycin should be optimized according to pharmacokinetic/pharmacodynamic principles. However, there is no available data indicating the implementation of extended infusion (EI) or continuous infusion (CI) administration in the management of neonatal sepsis. Methods: A nationwide cross-sectional survey was conducted and the pediatricians from 31 provinces in China were enrolled. A multidisciplinary team created the questionnaire, which had three sections and a total of 21 questions with open- and closed-ended responses...

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) utilization is increasing on a global scale, and despite technological advances, minimal standardized approaches to pharmacotherapeutic management exist. This objective was to create a comprehensive review for medication dosing in ECMO based on the most current evidence. DATA SOURCES: A literature search of PubMed was performed for all pertinent articles prior to 2022. The following search terms were utilized: ECMO, pharmacokinetics, pharmacodynamics, sedation, analgesia, antiepileptic, anticoagulation, antimicrobial, antifungal, nutrition...

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Vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets have not been validated in the neonatal population as no specifically designed studies are available. The main goal of this study was to analyze the therapeutic vancomycin regimen, the 24-h area under the curve (AUC24 ), and the trough plasma concentration ( Ct ) obtained that achieved clinical and microbiological effectiveness in a cohort of neonates. This was an observational, prospective, single-center study covering a period of 2 years. Eligible patients were neonates and young infants who were undergoing treatment with intravenous vancomycin for ≥72 h with ≥1 Ct available...

A high daptomycin dose has been suggested for treating vancomycin-resistant Enterococcus faecium (VREf) infections. However, even a 12 mg/kg daptomycin dose might be insufficient for treating VREf with high daptomycin minimum inhibitory concentrations (MICs). Additionally, animal pharmacodynamic and infection models to confirm the efficacy of 12 mg/kg daptomycin are lacking. Male Wistar rats were used for pharmacokinetic profiling and for the development of an infective endocarditis (IE) model. Daptomycin-susceptible dose-dependent VREf (DSE) (MIC of 0...

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24 ) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S...

Linezolid, vancomycin, teicoplanin, tigecycline, imipenem, meropenem, voriconazole, and micafungin are eight special-grade antimicrobials commonly used for patients with severe infections. Changes in the pharmacodynamics and pharmacokinetics of critically ill patients severely affect the efficacy of antimicrobial drugs. Therefore, conventional or standard dosing regimens do not achieve satisfactory anti-infective effects. In the current study a simple and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously determining the concentrations of the above-mentioned eight antimicrobials in human plasma only 3 min after one-step magnetic solid phase extraction pre-treatment...