Overcoming Antibiotic Resistance with Novel Paradigms of Antibiotic Selection

Abstract

Conventional antimicrobial susceptibility tests, including phenotypic and genotypic methods, are insufficiently accurate and frequently fail to identify effective antibiotics. These methods predominantly select therapies based on the antibiotic response of only the lead bacterial pathogen within pure bacterial culture. However, this neglects the fact that, in the majority of human infections, the lead bacterial pathogens are present as a part of multispecies communities that modulate the response of these lead pathogens to antibiotics and that multiple pathogens can contribute to the infection simultaneously. This discrepancy is a major cause of the failure of antimicrobial susceptibility tests to detect antibiotics that are effective in vivo. This review article provides a comprehensive overview of the factors that are missed by conventional antimicrobial susceptibility tests and it explains how accounting for these methods can aid the development of novel diagnostic approaches.

Genotypic resistance determined by whole genome sequencing versus phenotypic resistance in 234 Escherichia coli isolates

“…It is important to take into account that this study only focuses on unimicrobial bacterial cultures of E. coli as the lead bacterial pathogen in the frame of multimicrobial infections leading to E. coli bacteremia. These multispecies communities might critically influence the antibiotic resistance gene expression of the lead pathogen, often resulting in a lack of accuracy of antimicrobial susceptibility testing of one micro-organism to predict the in vivo success or failure of antibiotic therapy 17 .…”

Reduced Antibiotic Resistance in the Rhizosphere of Lupinus albus in Mercury-Contaminated Soil Mediated by the Addition of PGPB

“…We therefore consider the convenience of verifying the profile of antibiotic resistance of a PGPB prior to considering its use in environmental recovery processes or agricultural or forestry exploitation. The use of a cenoantibiogram can contribute to a better understanding of the behavior of soil, whose phenotype can be the result of different causal factors: Heterogeneous composition in terms of species and strains of the community in a phenomenon of cooperative inactivation [ 82 , 83 , 84 ]. Variability in the numerical quotas of each of the populations that make up the community [ 85 , 86 , 87 ].…”

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

“…Relapses in infection can often be attributed to flawed antimicrobial susceptibility testing (27)(28)(29)(30). Conventional antimicrobial susceptibility testing methods cannot always predict the efficacy of antibiotic treatment in vivo (27), and do not factor in biofilm or polymicrobial communities (28,30). To bridge this disconnect between conventional antimicrobial susceptibility testing and the in vivo environment, researchers have developed biofilm models that attempt to capture the infection environment and increase diagnostic accuracy.…”

“…Relapses in infection can often be attributed to flawed antimicrobial susceptibility testing (27)(28)(29)(30). Conventional antimicrobial susceptibility testing methods cannot always predict the efficacy of antibiotic treatment in vivo (27), and do not factor in biofilm or polymicrobial communities (28,30).…”