Is the subcutaneous route an alternative for administering ertapenem to older patients? PHACINERTA study.


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
01 12 2019
Historique:
received: 06 02 2019
revised: 02 08 2019
accepted: 06 08 2019
entrez: 16 11 2019
pubmed: 16 11 2019
medline: 26 9 2020
Statut: ppublish

Résumé

Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria. To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons. Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0-24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386. Ten (mean ± SD age=87±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184±90 versus 51±66 mg/L, P=0.001). The mean individual AUCs (1126.92±334.99 mg·h/L for IV versus 1005.3±266.0 mg·h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted. SC administration of ertapenem is an alternative to IV administration in older patients.

Sections du résumé

BACKGROUND
Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria.
OBJECTIVES
To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons.
METHODS
Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0-24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386.
RESULTS
Ten (mean ± SD age=87±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184±90 versus 51±66 mg/L, P=0.001). The mean individual AUCs (1126.92±334.99 mg·h/L for IV versus 1005.3±266.0 mg·h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted.
CONCLUSIONS
SC administration of ertapenem is an alternative to IV administration in older patients.

Identifiants

pubmed: 31730164
pii: 5571139
doi: 10.1093/jac/dkz385
doi:

Substances chimiques

Anti-Bacterial Agents 0
Ertapenem G32F6EID2H

Banques de données

ClinicalTrials.gov
['NCT02505386']

Types de publication

Clinical Trial Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3546-3554

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Claire Roubaud Baudron (C)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.
Univ. Bordeaux, INSERM UMR 1053, BaRITOn, F-33000 Bordeaux, France.

Rachel Legeron (R)

CHU Bordeaux, Service Pharmacie à Usage Intérieur, département de Pharmacie Clinique, F-33000 Bordeaux, France.

Julien Ollivier (J)

CHU Bordeaux, Service Pharmacie à Usage Intérieur, département de Pharmacie Clinique, F-33000 Bordeaux, France.

Fabrice Bonnet (F)

CHU Bordeaux, Service de Médecine Interne et Maladies Infectieuses, Hôpital Sain-André, F-33000 Bordeaux, France.

Carine Greib (C)

CHU Bordeaux, Service de Médecine Interne et Maladies Infectieuses, Hôpital Haut Lévêque, F-33000 Bordeaux, France.

Florent Guerville (F)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Charles Cazanave (C)

CHU Bordeaux, Service des Maladies Infectieuses et Tropicales, Hôpital Pellegrin, F-33000 Bordeaux, France.
Univ. Bordeaux, INRA, USC EA 3671, Infections humaines à mycoplasmes et à chlamydiae, F-33000 Bordeaux, France.

David Kobeh (D)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Véronique Cressot (V)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Nicolas Moneger (N)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Marie-Neige Videau (MN)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Elise Thiel (E)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Carine Foucaud (C)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Aurélie Lafargue (A)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Albane de Thezy (A)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Jessica Durrieu (J)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Isabelle Bourdel Marchasson (I)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.
Univ. Bordeaux, CNRS UMR 5536 RMSB, F-33000 Bordeaux, France.

Geneviève Pinganaud (G)

CHU Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France.

Dominique Breilh (D)

CHU Bordeaux, Service Pharmacie à Usage Intérieur, département de Pharmacie Clinique, F-33000 Bordeaux, France.
Univ. Bordeaux, INSERM UMR 1034, Pharmacokinetics and Pharmacodynamics (PK/PD) Group, F-33000 Bordeaux, France.

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