Vancomycin pharmacokinetics and pharmacodynamics

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...

INTRODUCTION: Currently, antibiotic treatment is often a standard dosing regimen in bone and joint infections (BJI). However, it remains unknown if exposure at the target-site is adequate. The aim of this review is to gain more insight in the relationship between the target site concentration of antibiotic and the minimal inhibitory concentration to target the bacteria in bone and joint infections (BJI). AREAS COVERED: A literature search was performed by Erasmus MC Medical library...

BACKGROUND: The anti-biofilm efficacy of dalbavancin (DAL) has been evaluated in static models. The comparative activity of DAL alone and with rifampicin (RIF) against biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) was evaluated using an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model. METHODS: Two MRSA strains (HUB-4, HUB-5) were evaluated with the Calgary Device System and the dynamic CDC-Biofilm Reactor over 144 h. Dosage regimens simulated the human PK of DAL (1500 mg, single dose), vancomycin (VAN) (1000 mg/12 h) and linezolid (LZD) (600 mg/12 h), alone and with RIF (600 mg/24 h)...

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PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24 /MIC) and trough concentration (Ctrough ) during the initial 72 h of treatment...

BACKGROUND: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices...

This study aimed to examine the risk factors of augmented renal clearance (ARC) and the association between ARC and vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices in Chinese adult patients. A prospective, observational, multicenter study was conducted, and 414 adult patients undergoing vancomycin therapeutic drug monitoring (TDM) were enrolled. Clinical and PK/PD data were compared between ARC and non-ARC groups. Independent risk factors were examined using a multivariate logistic regression analysis...

Objective: The study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients. Methods: With PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated...

OBJECTIVE: Although vancomycin dosage recommendations in the pediatric setting for methicillin-resistant Staphylococcus aureus (MRSA) infection indicate that ≥60 mg/kg/day is correlated to a desired area under the vancomycin concentration time curve from 0 to 24 hours to minimum inhibitory concentration ratio (AUC0-24 hr /MIC) ≥400, for some patients this dosage is inadequate or relates to toxicity. This study purposed to explore vancomycin dosing for pediatrics with various degrees of renal function...

Objective: To explore the efficacy and safety of vancomycin as measured by pharmacokinetic/pharmacodynamic parameters in children with severe infection in the Pediatric Intensive Care Unit (PICU) and to determine the appropriate threshold for avoiding nephrotoxicity. Methods: The medical records of hospitalized children with severe infection treated with vancomycin in the PICU of a tertiary pediatric hospital from September 2018 to January 2021 were retrospectively collected...

This study aimed to investigate the effect of a structural pharmacokinetic (PK) model with fewer compartments developed following sparse sampling on the PK parameter estimation and the probability of target attainment (PTA) prediction of vancomycin. Two- and three-compartment PK models of vancomycin were used for the virtual concentration-time profile simulation. Datasets with reduced blood sampling times were generated to support a model with a lesser number of compartments. Monte Carlo simulation was conducted to evaluate the PTA...

PURPOSE: Several studies have shown that polypharmacy is the main cause of drug interactions, and the prevalence and the level of the severity varied with the duration of stay in the hospital, sex and race of the patients. The aims of this investigation were to identify the drug-drug interactions in hospitalized pediatric patients associated with polypharmacy, and to categorize the drug interactions in pharmacokinetic or pharmacodynamic interactions according to their level of severity...

Purpose: The purpose of this study was 1) to predict the requisite vancomycin daily dose ( D van ) used in the target patients suffering from both bacterial infection and hematological malignancies and 2) to construct a vancomycin-dose-graphical tool to assist clinicians to develop vancomycin dosing regimens and further 3) to establish a programming process for vancomycin dynamic dosage adjustment to help clinicians to adjust vancomycin dosing regimens according to physiological and pathogenic factors of the target patients...

The revised consensus guidelines for optimizing vancomycin doses suggest that maintaining the area under the concentration-time curve to minimal inhibitory concentration ratio (AUC/MIC) of 400-600 mg·h/L is the target pharmacokinetic/pharmacodynamic (PK/PD) index for efficacy. AUC-guided dosing approach uses a first-order pharmacokinetics (PK) equation to estimate AUC using two samples obtained at steady state and one-compartment model, which can cause inaccurate AUC estimation and fail to achieve the effective PK/PD target early in therapy (days 1 and 2)...

The human microbiome project has revolutionized our understanding of the interaction between commensal microbes and human health. By far, the biggest perturbation of the microbiome involves use of broad-spectrum antibiotics excreted in the gut. Thus, pharmacodynamics of microbiome changes in relation to drug exposure pharmacokinetics is an emerging field. However, reproducibility studies are necessary to develop the field. A simple and fast high-performance liquid chromatography-photodiode array detector (HPLC) method was validated for quantitative fecal vancomycin analysis...

INTRODUCTION: The Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) is a hemoperfusion device that can remove pathogens from central circulation. However, the effect of Seraph 100 on achieving pharmacodynamic (PD) targets is not well described. We sought to determine the impact of Seraph 100 on ability to achieve PD targets for commonly used antibiotics. METHODS: Estimates of Seraph 100 antibiotic clearance were obtained via literature. For vancomycin and gentamicin, published pharmacokinetic models were used to explore the effect of Seraph 100 on ability to achieve probability of target attainment (PTA)...

The dosage regimen of vancomycin, teicoplanin and daptomycin remains controversial for critically ill patients undergoing continuous renal replacement therapy (CRRT). Monte Carlo simulation was applied to identify the optimal regimens of antimicrobial agents in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections based on the mechanisms of different CRRT modalities on drug clearance. The optimal vancomycin dosage for patients received a CRRT doses ≤ 30 mL/kg/h was 20 mg/kg loading dose followed by 500 mg every 8 h, while 1 g every 12 h was appropriate when 35 mL/kg/h was prescribed...

BACKGROUND: The most recent vancomycin monitoring guideline recommends targeting a value for area under the curve (AUC) of 400 to 600 mg*h/L, with an assumed minimum inhibitory concentration (MIC) of 1 mg/L. Few studies have investigated the effect of this method on vancomycin dosing regimens, relative to a target trough concentration of 15 to 20 mg/L. OBJECTIVE: To compare vancomycin dosing regimens generated with the 2 monitoring methods. METHODS: This retrospective chart review included hospitalized patients who received vancomycin between May 2019 and April 2020...

Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors...

INTRODUCTION: Antibiotics are commonly prescribed in critical care, and given the large variability of pharmacokinetic (PK) parameters in these patients, drug PK frequently varies during therapy with the risk of either treatment failure or toxicity. Therefore, adequate antibiotic dosing in critically ill patients is very important. AREAS COVERED: This review provides an overview of the basic principles of PK and pharmacodynamics of antibiotics and the main patient and pathogen characteristics that may affect the dosage of antibiotics and different approaches to adjust doses...