Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients

ABSTRACT The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m2 polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 ± 13.0 years [standard deviation]; mean weight, 96.7 ± 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CLS) and elimination half-life (t 1/2) of cefepime were 35.9 ± 6.0 ml/min and 12.9 ± 2.6 h during CVVH versus 46.8 ± 12.4 ml/min and 8.6 ± 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CLS, respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CLSof cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC ≤ 8 μg/ml) during CVVH or CVVHDF.

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Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.6.2421-2428.2005 ◽

2005 ◽

Vol 49 (6) ◽

pp. 2421-2428 ◽

Cited By ~ 46

Author(s):

Douglas N. Fish ◽

Isaac Teitelbaum ◽

Edward Abraham

Keyword(s):

High Performance ◽

Continuous Venovenous Hemofiltration ◽

Systemic Clearance ◽

Pharmacokinetics And Pharmacodynamics ◽

Drug Infusion ◽

Dosing Interval ◽

Adult Intensive Care Unit ◽

Drug Concentrations ◽

Elimination Half ◽

Higher Doses

ABSTRACT The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n = 6 patients) or hemodiafiltration (CVVHDF; n = 6 patients). Patients (mean ± standard deviation age, 50.9 ± 15.9 years; weight, 98.5 ± 15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL S ) and elimination half-life (t 1/2) of imipenem were 145 ± 18 ml/min and 2.7 ± 1.3 h during CVVH versus 178 ± 18 ml/min and 2.6 ± 1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL S , respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 μg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC = 4 to 8 μg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.

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Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2016-0022 ◽

2016 ◽

Vol 27 (6) ◽

Cited By ~ 1

Author(s):

Koji Goto ◽

Yuhki Sato ◽

Norihisa Yasuda ◽

Seigo Hidaka ◽

Yosuke Suzuki ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

High Performance ◽

Total Body Clearance ◽

Dose Interval ◽

Serum Levels ◽

Filtration Fraction ◽

Total Body ◽

Body Clearance

AbstractBackground:The duration of time for which the serum levels exceed the minimum inhibitory concentration (MIC) is an important pharmacokinetics (PK)/pharmacodynamics (PD) parameter correlating with efficacy for the antibiotic, ceftriaxone (CTRX). However, no reports exist regarding the PK or PD in patients undergoing continuous renal replacement therapy (CRRT). The purpose of this study was to examine the PK and safety of CTRX in patients undergoing CRRT in order to establish safer and more effective regimens.Methods:CTRX (1 g once a day) was intravenously administered four or more times to nine patients undergoing CRRT. Blood was collected after administration to measure CTRX concentrations in serum and the filtration fraction of CRRT by high-performance liquid chromatography. In addition to calculating PK parameters from serum CTRX, we (a) estimated by simulation CTRX concentrations when the dose interval was extended to once every 2 or 3 days, (b) calculated CTRX clearance via CRRT from CTRX concentrations in the filtration fraction, and (c) assessed the safety of CTRX use.Results:Total body clearance and the half-life of CTRX were 7.46 mL/min (mean) and 26.5 h, respectively, in patients undergoing CRRT. CTRX was found in the filtration fraction, and the estimated clearance by CRRT was about 70% of total body clearance. Simulations revealed that even when the dose interval is increased to 2 or 3 days, CTRX would retain its efficacy.Conclusions:Our findings suggest that, depending on the condition of patients undergoing CRRT, CTRX could be used safely against pathogens with a CTRX MIC ≤2 µg/mL, even when extending the dose interval.

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Pharmacokinetics of Levofloxacin and Ciprofloxacin during Continuous Renal Replacement Therapy in Critically Ill Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.10.2949-2954.2001 ◽

2001 ◽

Vol 45 (10) ◽

pp. 2949-2954 ◽

Cited By ~ 57

Author(s):

Rebecca S. Malone ◽

Douglas N. Fish ◽

Edward Abraham ◽

Isaac Teitelbaum

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Effective Drug ◽

Continuous Venovenous Hemofiltration ◽

Drug Concentrations

ABSTRACT The pharmacokinetics of intravenously administered levofloxacin and ciprofloxacin were studied in intensive care unit patients during continuous venovenous hemofiltration (CVVH; four patients received levofloxacin, and five received ciprofloxacin) or hemodiafiltration (CVVHDF; six patients received levofloxacin, and five received ciprofloxacin). Levofloxacin clearance was substantially increased during both CVVH and CVVHDF, while ciprofloxacin clearance was affected less. The results of this study suggest that doses of levofloxacin of 250 mg/day and ciprofloxacin of 400 mg/day are sufficient to maintain effective drug concentrations in the plasma of patients undergoing CVVH or CVVHDF.

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Comparison of adsorption of selected antibiotics on the filters in continuous renal replacement therapy circuits: in vitro studies

Journal of Artificial Organs ◽

10.1007/s10047-019-01139-x ◽

2019 ◽

Vol 23 (2) ◽

pp. 163-170 ◽

Cited By ~ 2

Author(s):

Dariusz Onichimowski ◽

Hubert Ziółkowski ◽

Krzysztof Nosek ◽

Jerzy Jaroszewski ◽

Elżbieta Rypulak ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Drug Concentration ◽

Initial Level ◽

Clinical Importance ◽

Study Drug ◽

Crystalloid Fluid ◽

Drug Concentrations

Abstract The aim of this study was to assess the adsorption of selected antibiotics: vancomycin, gentamicin, ciprofloxacine and tigecycline in an experimental continuous veno-venous hemofiltration circuit with the use of both polyethyleneimine-treated polyacrylonitrile (PAN) and the polysulfone (PS) filter membranes. The crystalloid fluid dosed with one of antibiotic was pumped from a reservoir through a hemofiltration circuit (with PAN or PS membrane) and back to reservoir. All ultrafiltrate was also returned to the reservoir. During the procedures samples were collected from the post-hemofilter port at 5, 15, 30, 45, 60, 90, and 120 min. To determine spontaneous degradation of the antimicrobials, an additional bag with each study drug was prepared, which was not attached to the hemofiltration circuit. The samples from these bags were used as controls. In the case of vancomycin, gentamycin and tigecycline there was a statistically significant decrease in the drug concentration in the hemofiltration circuit in comparison to the control for PAN membrane (P < 0.05, P < 0.001, P < 0.001, respectively). In the case of ciprofloxacine adsorption was reversible and the drug concentrations increase to achieve the initial level for both membranes. Our studies indicated that a large portion of the administered dose of antibiotics may be adsorbed on a PAN membrane. In the case of gentamicin and tigecycline this amount is sufficiently big (over 90% of the administered dose) to be of clinical importance. In turn, adsorption on PS membranes is clearly lower (up to 10%) and may be clinically unimportant.

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Pharmacological Principles of Antibiotic Prescription in the Critically Ill

Anaesthesia and Intensive Care ◽

10.1177/0310057x0203000203 ◽

2002 ◽

Vol 30 (2) ◽

pp. 134-144 ◽

Cited By ~ 81

Author(s):

M. Pinder ◽

R. Bellomo ◽

J. Lipman

Keyword(s):

Renal Replacement Therapy ◽

Inflammatory Response ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Drug Prescription ◽

Relevant Literature ◽

Third Space ◽

Drug Concentrations ◽

Dosing Regimens

The goal of antimicrobial prescription is to achieve effective drug concentrations. Standard antimicrobial dosing regimens are based on research performed often decades ago and for the most part with patients who were not critically ill. More recent insights into antibiotic activity (e.g. the importance of high peak/MIC ratios for aminoglycosides and time above MIC for β-lactam antibiotics), drug pharmacokinetics (e.g. increased volume of distribution and altered clearances) and the pathogenesis of sepsis (e.g. third space losses and altered creatinine clearances) have made re-evaluation of dosing regimens necessary for the critically ill. The inflammatory response associated with sepsis results in a rapid decrease in serum albumin levels, large fluid shifts and third space losses, initially with a high cardiac output. In turn these changes result in increased creatinine clearance and increased renal drug clearance. Unless these effects are offset by ensuing renal and/or hepatic impairment, with subsequent drug accumulation, antibiotic levels may be too low for optimal efficacy. The institution of continuous renal replacement therapy separately affects antibiotic clearances, and therefore dosing, even further. This article reviews relevant literature and offers principles for more effective and appropriate antibiotic dosing in the critically ill, based on the pharmacokinetic and pharmacodynamic principles of the main antibiotic groups (aminoglyosides, glycopeptides, β-lactams, carbapenems and quinolones) and knowledge of the pathophysiology of the inflammatory response syndrome. Finally it also provides some guidance on the basic principles of drug prescription for patients receiving continuous renal replacement therapy.

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