piperacillin--tazobactam-drug-combination and Kidney-Failure--Chronic

We analysed the pharmacokinetics of meropenem and piperacillin-tazobactam in patients undergoing a standardised session of sustained low efficiency haemodiafiltration (SLED-HDF) to inform the dosing of these drugs in an acute setting.. Six stable patients with end-stage kidney disease.. An open-label pilot pharmacokinetic study of meropenem and piperacillin-tazobactam. SLED-HDF was undertaken for 4 h. Plasma drug concentrations were measured pre- and post-filter and in the effluent at multiple time points. The pharmacokinetic data was analysed using non-compartmental methods. The fraction of time that individual plasma concentration profiles were predicted to remain above the MIC break-points for commonly isolated gram-negative pathogens during a prolonged SLED-HDF session was assessed using two targets; fT > MIC (fraction of time above the MIC) and the more aggressive fT > 4 × MIC (fraction of time above 4 × MIC).. Meropenem total and SLED-HDF clearance ranged from 141 to 180 mL/min and 126-205 mL/min, respectively. Piperacillin total and SLED-HDF clearance values ranged from 131 to 252 mL/min and 135-162 mL/min, respectively. Our results suggest that prolonged SLED-HDF (12 h) will only maintain a sufficient meropenem and piperacillin-tazobactam plasma concentration to achieve a target of fT > MIC for gram-negative pathogens (MIC 2 mg/L-meropenem, 8 mg/L-piperacillin-tazobactam) for less than 40% of the time. Plasma concentrations would be inadequate to achieve the more aggressive target of 100 % fT > 4xMIC target recommended for critically unwell patients.. The pharmacokinetic data obtained from this pilot study demonstrate significant quantities of meropenem and piperacillin are removed during a SLED-HDF session. This may lead to subtherapeutic concentrations of piperacillin and meropenem over the duration of HDF session.. Australasian Clinical Trials Registry Network (ACTRN12616000078459).

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Hemodiafiltration; Humans; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Pilot Projects; Piperacillin, Tazobactam Drug Combination

Topics: Adenocarcinoma; Aged; Cefazolin; Cefepime; Diabetes Mellitus, Type 2; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Kidney Failure, Chronic; Male; Pancreatic Neoplasms; Pancreatitis; Peritoneal Dialysis; Piperacillin, Tazobactam Drug Combination; Sleep Apnea Syndromes

Topics: Administration, Intravenous; Aged; Bacteremia; beta-Lactamase Inhibitors; Chryseobacterium; Diagnosis, Differential; Humans; Kidney Failure, Chronic; Male; Piperacillin, Tazobactam Drug Combination; Polymerase Chain Reaction; Renal Dialysis; Treatment Outcome

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; beta-Lactamases; Clostridioides difficile; Enterobacter cloacae; Female; Humans; Imipenem; Kidney Failure, Chronic; Kidney Transplantation; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Respiratory Insufficiency; Vancomycin

Topics: Anti-Bacterial Agents; Humans; Kidney Failure, Chronic; Legionnaires' Disease; Male; Middle Aged; Myoclonus; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions.. A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters.. Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h(-1), intraquartile range=0.052 h(-1)) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered.. There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.

Topics: Academic Medical Centers; Acute Kidney Injury; Adult; Aged; Alabama; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Drug Monitoring; Female; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Multivariate Analysis; Ohio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Renal Dialysis