A New Pharmacokinetic-Pharmacodynamic Model To Characterize the Inoculum Effect of Acinetobacter baumannii on Polymyxin B In Vitro-Reference-Cited by-同舟云学术

A New Pharmacokinetic-Pharmacodynamic Model To Characterize the Inoculum Effect of Acinetobacter baumannii on Polymyxin B In Vitro

Published:2022-01-18 Issue:1 Volume:66 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Akrong Grace¹²,Chauzy Alexia¹²,Aranzana-Climent Vincent¹²³,Lacroix Mathilde¹²⁴,Deroche Luc¹²,Prouvensier Laure¹⁵,Buyck Julien M.¹²^ORCID,Couet William¹²⁵^ORCID,Marchand Sandrine¹²⁵^ORCID

Affiliation:

1. INSERM U1070, Poitiers, France

2. Université de Poitiers, Poitiers, France

3. Pharmacometrics, Department of Pharmacy, Uppsala University, Uppsala, Sweden

4. Institut ROCHE, Boulogne-Billancourt, France

5. Département de Toxicologie et de Pharmacocinétique, CHU de Poitiers, Poitiers, France

Abstract

The inoculum effect (i.e., reduction in antimicrobial activity at large starting inoculum) is a phenomenon described for various pathogens. Given that limited data exist regarding inoculum effect of Acinetobacter baumannii , we evaluated killing of A. baumannii by polymyxin B, a last-resort antibiotic, at several starting inocula and developed a PKPD model to capture this phenomenon. In vitro static time-kill experiments were performed using polymyxin B at concentrations ranging from 0.125 to 128 mg/L against a clinical A. baumannii isolate at four starting inocula from 10 5 to 10 8 CFU/mL.

Funder

Conseil Régional Aquitaine

Institut National de la Santé et de la Recherche Médicale

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01789-21

Reference42 articles.

1. Inoculum effect of β-lactam antibiotics

2. Inoculum Effect