Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study

Abstract

Background

Augmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).

Methods

In this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before ( Control period) and after ( Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.

Results

During the study period, 177 patients were included ( control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.

Conclusions

Higher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.

Contributors

Cédric Carrié: [e-mail]

Grégoire Chadefaux: [e-mail]

Noémie Sauvage: [e-mail]

Hugues de Courson: [e-mail]

Laurent Petit: [e-mail]

Karine Nouette-Gaulain: [e-mail]

Bruno Pereira: [e-mail]

Matthieu Biais: [e-mail]

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 27 November 2019

Publication date PMC-release: 27 November 2019

Publication date Collection: 2019

Volume: 23

Affiliations

[1 ]GRID grid.414263.6, Anesthesiology and Critical Care Department, , Hôpital Pellegrin, CHU Bordeaux, ; 33000 Bordeaux, France

[2 ]ISNI 0000 0001 2106 639X, GRID grid.412041.2, University Bordeaux Segalen, ; 33000 Bordeaux, France

[3 ]ISNI 0000 0004 0639 4151, GRID grid.411163.0, Biostatistics Unit, Délégation Recherche Clinique & Innovation, , CHU de Clermont-Ferrand, ; Clermont-Ferrand, France

Article

Publisher ID: 2621

DOI: 10.1186/s13054-019-2621-4

PMC ID: 6881978

PubMed ID: 31775840

Copyright statement: © The Author(s). 2019

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Categories

Subject: Research

Custom metadata

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