Using Imipenem and Cilastatin During Continuous Renal Replacement Therapy

Cotton, Alison; Franklin, Bryony Dean; Brett, Stephen; Holmes, Amie L.

doi:10.1007/s11096-005-1636-x

Cited by 10 publications

(7 citation statements)

References 13 publications

(33 reference statements)

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“…This increase is in part due to the utilization of larger-surface-area hemofilters and higher ultrafiltration rates. The CVVHDF clearance of imipenem has generally been greater than that observed with CVVH; values have ranged from 18.7 to 57 ml/min, with higher values being observed in patients who had greater Q UFD rates (9,10,21).…”

Section: Discussionmentioning

confidence: 91%

“…The influences of CRRT on the removal of drugs have also been noted to be markedly variable, although there is a clear trend in the last 10 to 15 years toward higher clearances with all agents that have been evaluated throughout this time period (3,9,12,21). The clearances of imipenem by CVVH ranged from 6.5 to 13.3 ml/min in the 1990s and have increased to 22.9 to 36.0 ml/min during the last decade (9,10,21).…”

Section: Discussionmentioning

confidence: 99%

“…The clearances of imipenem by CVVH ranged from 6.5 to 13.3 ml/min in the 1990s and have increased to 22.9 to 36.0 ml/min during the last decade (9,10,21). This increase is in part due to the utilization of larger-surface-area hemofilters and higher ultrafiltration rates.…”

Section: Discussionmentioning

confidence: 99%

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Influence of Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodiafiltration on the Disposition of Doripenem

Cirillo

Vaccaro

Balis

et al. 2011

Antimicrob Agents Chemother

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‫؍‬ 5). Healthy volunteers were also assessed (n ‫؍‬ 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysisdependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3-and 5-fold greater, respectively, than those in healthy subjects: for doripenem, 98 g ⅐ h/ml for CVVH and 77 g ⅐ h/ml for CVVHDF versus 32 g ⅐ h/ml for healthy subjects, and for doripenem-M-1, 24 g ⅐ h/ml for CVVH and 22 g ⅐ h/ml for CVVHDF versus 4.7 g ⅐ h/ml for healthy subjects. The mean sieving coefficients and saturation coefficients were >0.67 for both doripenem and doripenem-M-1. During CVVH and CVVHDF, respectively, the percentages of administered doripenem dose removed were 38% and 29%, and clearances of doripenem were 22 and 25 ml/min. Both CVVH and CVVHDF efficiently removed doripenem and doripenem-M-1. Despite significant removal of drug by CVVH and CVVHDF, a single 1-hour, 500-mg doripenem infusion produced significantly higher plasma concentrations of doripenem, higher systemic exposure (area under the plasma concentration-time curve from time zero to 12 h after the start of infusion [AUC 0-12 ]), and longer half-life (t 1/2 ) in subjects receiving CVVH or CVVHDF than in healthy volunteers. The recovery of drug in ultrafiltrate and ultrafiltrate/dialysate and the enhanced rate of reduction of plasma concentrations indicate that CVVH and CVVHDF significantly augmented residual total body clearance of doripenem in subjects receiving CRRT. Doripenem dosage regimens for patients receiving CRRT thus need to be adjusted.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodiafiltration on the Disposition of Doripenem

Cirillo

Vaccaro

Balis

et al. 2011

Antimicrob Agents Chemother

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“…This means that insufficient information is obtained to permit extrapolation to another group of patients with other systems or haemodiafiltration dosage. This is particularly relevant for β-lactam antibiotics or azoles 16 17. This high variability of concentrations is largely due to changes in the patient with renal failure (including weight, plasma proteins and non-renal clearance of drugs)18 19 and the equipment used (haemofiltration system, flow or membrane used by the system) 5 20 21…”

Section: Discussionmentioning

confidence: 99%

Individualised antimicrobial dosing in critically ill patients undergoing continuous renal replacement therapy: focus on total drug clearance

et al. 2017

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BackgroundContinuous renal replacement therapy (CRRT) is common practice in critical care patients with acute renal failure.ObjectivesTo evaluate the adequacy of antimicrobial doses calculated based on the total drug clearance and dose recommended by different guides in critically ill patients undergoing CRRT.MethodsRetrospective observational study. Patients admitted to a critical care unit during May 2014 to May 2016 and subjected to CRRT were included. The recommended dose was established as the product of the usual dose of the drug by total drug clearance.Results177 antimicrobial agents, used in 64 patients were analysed; 45 (25.4%) antimicrobials were given in an insufficient dose (<20%) according to the theoretical calculation. Following the recommendations in the revised guidelines, between 10% and 20% of antimicrobials were given in insufficient doses. A higher success rate of treatment in those patients not receiving a low drug dosage was seen (35.2% vs 24.0%).ConclusionsThere is a great disparity between the antimicrobial dose prescribed, recommended and calculated based on drug clearance in critically ill patients undergoing CRRT.

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“…Total clearances were higher than previously published (158.82 to 506.83 mL/ min) with membrane clearance ranging from 9% to 18%. [31] Ertapenem and doripenem The newer carbapenems ertapenem and doripenem are more stable after reconstitution and have a longer t1/2. Mistry et al showed that hemodialysis cleared approximately 30% of the ertapenem dose.…”

Section: Imipenemmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

Breilh

Honoré

Bels

et al. 2019

Journal of Translational Internal Medicine

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Background: Hemofiltration rate, changes in blood and ultrafiltration flow, and discrepancies between the prescribed and administered doses strongly influence pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents during continuous veno-venous hemofiltration (CVVH) in critically ill patients. Methods: Ancillary data were from the prospective multicenter IVOIRE (hIgh VOlume in Intensive caRE) study. High volume (HV, 70 mL/kg/h) was at random compared with standard volume (SV, 35 mL/kg/h) CVVH in septic shock patients with acute kidney injury (AKI). PK/PD parameters for all antimicrobial agents used in each patient were studied during five days. Results: Antimicrobial treatment met efficacy targets for both percentage of time above the minimal inhibitory concentration and inhibitory quotient. A significant correlation was observed between the ultrafiltration flow and total systemic clearance (Spearman test: P < 0.005) and between CVVH clearance and drug elimination half-life (Spearman test: P < 0.005). All agents were easily filtered. Mean sieving coefficient ranged from 38.7% to 96.7%. Mean elimination half-life of all agents was significantly shorter during HV-CVVH (from 1.29 to 28.54 h) than during SV-CVVH (from 1.51 to 33.85 h) (P < 0.05). Conclusions:This study confirms that CVVH influences the PK/PD behavior of most antimicrobial agents. Antimicrobial elimination was directly correlated with convection rate. Current antimicrobial dose recommendations will expose patients to underdosing and increase the risk for treatment failure and development of resistance. Dose recommendations are proposed for some major antibiotic and antifungal treatments in patients receiving at least 25 mL/kg/h CVVH.

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Using Imipenem and Cilastatin During Continuous Renal Replacement Therapy

Abstract: The heterogeneity of the studies identified prevents them being analysed as a single group. For meaningful dosage recommendations to be made, further studies are required using larger populations and with more detail regarding liver dysfunction and duration of renal failure.

Cited by 10 publications

References 13 publications

Influence of Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodiafiltration on the Disposition of Doripenem

Influence of Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodiafiltration on the Disposition of Doripenem

Individualised antimicrobial dosing in critically ill patients undergoing continuous renal replacement therapy: focus on total drug clearance

Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

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