ABSTRACT
Pathophysiological changes involved in drug disposition in critically ill patients should be considered in order to optimize the dosing of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Plasma vancomycin concentrations from 54 critically ill patients were analyzed simultaneously by a population pharmacokinetic approach. A nomogram for dosing recommendations was developed and was internally evaluated through stochastic simulations. The plasma vancomycin concentration-versus-time data were best described by a one-compartment open model with exponential interindividual variability associated with vancomycin clearance and the volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and the volume of distribution, respectively. Characterization based on the presence of mechanical ventilation demonstrated a 20% decrease in vancomycin clearance. External validation (n = 18) was performed to evaluate the predictive ability of the model; median bias and precision values were 0.7 mg/liter (95% confidence interval [CI], -0.4, 1.7) and 5.9 mg/liter (95% CI, 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion to critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications for targeting dosing rates to reach the therapeutic range (20 to 30 mg/liter).
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Creatinine/metabolism , Critical Illness/therapy , Respiration, Artificial , Vancomycin , Aged , Drug Monitoring , Female , Humans , Infusions, Intravenous , Intensive Care Units , Male , Nomograms , Vancomycin/blood , Vancomycin/pharmacokinetics , Vancomycin/therapeutic useSubject(s)
Anaphylaxis/diagnosis , Angina, Unstable/diagnosis , Insect Bites and Stings/diagnosis , Kounis Syndrome/diagnosis , Allergens/immunology , Anaphylaxis/prevention & control , Angina, Unstable/therapy , Animals , Emergency Medical Services , Humans , Hydrocortisone/therapeutic use , Hymenoptera/immunology , Insect Bites and Stings/therapy , Kounis Syndrome/therapy , Male , Middle Aged , Nitroglycerin/therapeutic use , Spasm , Venoms/immunologyABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Tachycardia, Ventricular/diagnosis , Electrocardiography, Ambulatory , Acute Coronary Syndrome/complications , Diagnostic Errors , Emergency Medical Services/methods , Emergency Treatment/methods , Unnecessary ProceduresSubject(s)
Humans , Female , Middle Aged , Aortic Valve Insufficiency/etiology , Endocarditis, Bacterial/complications , Erysipelothrix Infections/complications , Aortic Valve Insufficiency/diagnosis , Endocarditis, Bacterial/diagnosis , Erysipelothrix/pathogenicity , Erysipelothrix Infections/diagnosisSubject(s)
Pulmonary Alveolar Proteinosis , Aged , Humans , Male , Pulmonary Alveolar Proteinosis/diagnosisSubject(s)
Anesthesia, Spinal , Meningitis, Pneumococcal/etiology , Postoperative Complications/etiology , Punctures/adverse effects , Wound Infection/etiology , Adult , Bacteremia/etiology , Bacteremia/microbiology , Ceftriaxone/therapeutic use , Cerebrospinal Fluid/microbiology , Consciousness Disorders/etiology , Dexamethasone/therapeutic use , Equipment Contamination , Foot , Humans , Male , Meningitis, Pneumococcal/blood , Meningitis, Pneumococcal/cerebrospinal fluid , Meningitis, Pneumococcal/drug therapy , Needles , Neuroma/surgery , Penicillin Resistance , Peripheral Nervous System Neoplasms/surgery , Postoperative Complications/blood , Postoperative Complications/cerebrospinal fluid , Postoperative Complications/drug therapy , Postoperative Complications/microbiology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purification , Vancomycin/therapeutic use , Wound Infection/microbiologyABSTRACT
No disponible
Subject(s)
Male , Adult , Humans , Anesthesia, Epidural , Meningitis, Pneumococcal/drug therapy , Meningitis, Pneumococcal/etiology , Postoperative Complications/etiology , Postoperative Complications/microbiology , Punctures/adverse effects , Wound Infection/etiology , Bacteremia/etiology , Bacteremia/microbiology , Ceftriaxone/therapeutic use , Cerebrospinal Fluid/microbiology , Consciousness Disorders/etiology , Dexamethasone/therapeutic use , Equipment Contamination , Meningitis, Pneumococcal/blood , Meningitis, Pneumococcal/cerebrospinal fluid , Needles , Penicillin Resistance , Postoperative Complications/blood , Postoperative Complications/cerebrospinal fluid , Postoperative Complications/drug therapy , Peripheral Nervous System Neoplasms/surgeryABSTRACT
No disponible
