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.

antibiotic dosage antibiotics continuous veno-venous hemofiltration high volume hemofiltration pharmacodynamics pharmacokinetics septic shock

Journal

Journal of translational internal medicine
ISSN: 2450-131X
Titre abrégé: J Transl Int Med
Pays: Poland
ID NLM: 101673826

Informations de publication

Date de publication:
Dec 2019
Historique:
entrez: 4 2 2020
pubmed: 6 2 2020
medline: 6 2 2020
Statut: epublish

Résumé

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. 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. 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: 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.

Sections du résumé

BACKGROUND 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 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 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:
CONCLUSIONS 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.

Identifiants

pubmed: 32010602
doi: 10.2478/jtim-2019-0031
pii: jtim-2019-0031
pmc: PMC6985915
doi:

Types de publication

Journal Article

Langues

eng

Pagination

155-169

Informations de copyright

© 2019 Dominique Breilh et al., published by Sciendo.

Déclaration de conflit d'intérêts

Conflict of Interest The authors declare to have no competing interests.

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Auteurs

Dominique Breilh (D)

Laboratory of Clinical Pharmacokinetics and Clinical Pharmacy, INSERM U1034, Haut-Lévêque Hospital, CHU Bordeaux, University of Bordeaux, Segalen, Pessac, France.

Patrick M Honore (PM)

Intensive Care Department, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, Brussels, Belgium.

David De Bels (D)

Intensive Care Department, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, Brussels, Belgium.

Jason A Roberts (JA)

University of Queensland Centre for Clinical Research, Faculty of Medicine & Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia.

Jean Baptiste Gordien (JB)

Laboratory of Clinical Pharmacokinetics and Clinical Pharmacy, INSERM U1034, Haut-Lévêque Hospital, CHU Bordeaux, University of Bordeaux, Segalen, Pessac, France.

Catherine Fleureau (C)

CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, F-33000 Bordeaux, France.

Antoine Dewitte (A)

CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, F-33000 Bordeaux, France.

Julien Coquin (J)

CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, F-33000 Bordeaux, France.

Hadrien Rozé (H)

CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, F-33000 Bordeaux, France.

Paul Perez (P)

Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Unité de Soutien Méthodologique à la Recherche Clinique et Épidémiologique, France.

Rachid Attou (R)

Intensive Care Department, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, Brussels, Belgium.

Sebastien Redant (S)

Intensive Care Department, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, Brussels, Belgium.

Luc Kugener (L)

Intensive Care Department, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, Brussels, Belgium.

Marie-Claude Saux (MC)

Laboratory of Clinical Pharmacokinetics and Clinical Pharmacy, INSERM U1034, Haut-Lévêque Hospital, CHU Bordeaux, University of Bordeaux, Segalen, Pessac, France.

Herbert D Spapen (HD)

Ageing & Pathology Research Group, Vrije Universiteit Brussel, Brussels, Belgium.

Alexandre Ouattara (A)

CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, F-33000 Bordeaux, France.
Biology of Cardiovascular Diseases, INSERM, UMR 1034, University of Bordeaux, F-33600 Pessac, France.

Olivier Joannes-Boyau (O)

CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, F-33000 Bordeaux, France.

Classifications MeSH