TY - JOUR

T1 - The importance of understanding the infectious microenvironment

AU - Bjarnsholt, Thomas

AU - Whiteley, Marvin

AU - Rumbaugh, Kendra P.

AU - Stewart, Philip S.

AU - Jensen, Peter

AU - Frimodt-Møller, Niels

N1 - Funding Information: We would like to acknowledge Jill Story for preparing the figure. KPR received grants supporting the basis of this work from the US National Institutes of Health (NIH; R21 AI137462-01A1) and the Ted Nash Long Life Foundation; PSS received grants from NIH (1R01NR16986) and the Lundbeck Foundation; MW received grants from NIH (1R01GM116547, R01DE023193, 5R01DE020100); and TB received grants from the Lundbeck Foundation. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022

Y1 - 2022

N2 - Standard doses of antibiotics do not efficiently treat chronic infections of the soft tissue and bone. In this Personal View, we advocate for improving treatment of these infections by taking the infectious microenvironment into account. The infectious microenvironment can cause sensitive bacteria to lose their susceptibility to antibiotics that are effective in standard laboratory susceptibility testing. We propose that bacteria behave substantially different in standard laboratory conditions than they do in actual infections. The infectious microenvironment could impose changes in growth and metabolic activity that result in increased protection against antibiotics. Therefore, we advocate that improved antibiotic treatment of chronic infection is achievable when antibiotics are recommended on the basis of susceptibility testing in relevant in vitro conditions that resemble actual infectious microenvironments. We recommend establishing knowledge of the relevant conditions of the chemical and physical composition of the infectious microenvironment. Recent advances in RNA sequencing, metabolomics, and microscopy have made it possible for the characterisation of the microenvironment of infections and to validate the clinical relevance of in vitro conditions to actual infections.

AB - Standard doses of antibiotics do not efficiently treat chronic infections of the soft tissue and bone. In this Personal View, we advocate for improving treatment of these infections by taking the infectious microenvironment into account. The infectious microenvironment can cause sensitive bacteria to lose their susceptibility to antibiotics that are effective in standard laboratory susceptibility testing. We propose that bacteria behave substantially different in standard laboratory conditions than they do in actual infections. The infectious microenvironment could impose changes in growth and metabolic activity that result in increased protection against antibiotics. Therefore, we advocate that improved antibiotic treatment of chronic infection is achievable when antibiotics are recommended on the basis of susceptibility testing in relevant in vitro conditions that resemble actual infectious microenvironments. We recommend establishing knowledge of the relevant conditions of the chemical and physical composition of the infectious microenvironment. Recent advances in RNA sequencing, metabolomics, and microscopy have made it possible for the characterisation of the microenvironment of infections and to validate the clinical relevance of in vitro conditions to actual infections.

U2 - 10.1016/S1473-3099(21)00122-5

DO - 10.1016/S1473-3099(21)00122-5

M3 - Review

C2 - 34506737

AN - SCOPUS:85125551096

VL - 22

SP - e88-e92

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

SN - 1473-3099

IS - 3

ER -