Addressing Antibiotic Failure—Beyond Genetically Encoded Antimicrobial Resistance

Abstract

Antibiotic failure can be defined as any clinical situation where treatment with antibiotics fails to cure the patient and remove the infection. Genetically-determined antibiotic resistance certainly contributes to antibiotic failure in the clinic, but this is not the only reason why antibiotics fail and it is likely not the most common cause of antibiotic failure. In this perspective article, we outline several widespread examples of situations where antibiotic treatment fails, even in the absence of formal resistance, including biofilm associated-infections (65% of all infections) as well as infections in sepsis (19.7% of all deaths) and immune compromised individuals. We then discuss various strategies that are being employed to address the issue of antibiotic failure and emphasize that antibiotic failure should be given increased awareness and resources to address this underappreciated but critical issue.

Molecular Characterization of Escherichia coli Causing Urinary Tract Infections Through Next-Generation Sequencing: A Comprehensive Analysis of Serotypes, Sequence Types, and Antimicrobial and Virulence Genes

“…There is an increased probability of the spread of such bacterial species from one person to another in the community, from patient to patient, and from healthcare workers (HCWs) to patients in hospital settings. Infections with drug-resistant bacteria result in treatment failures [ 1 ].…”

Metabolic specialization drives reduced pathogenicity inPseudomonas aeruginosaCF clinical isolates

“…In persistent infections, genetic variants with high antibiotic resistance, tolerance to other stresses, host and immune evasion capabilities or low virulence are specifically selected for since they provide higher within-host fitness [16][17][18] . However, it is still unclear if and how metabolic specialization directly contribute(s) to persistence 12,21 .…”

“…While antibiotic resistance is a major cause of treatment failure, other less characterized mechanisms rooted in the complexity of the host-pathogen interactions are also substantial contributors to persistence 2 . Genetic variants with high tolerance to stresses, host and immune evasion capabilities and low virulence are often specifically selected for in persistent infections since they provide higher within-host fitness 3,4 . In people with cystic fibrosis (pwCF), for example, opportunistic pathogens such as Pseudomonas aeruginosa colonize the airways and establish persistent infections lasting for more than 30 years.…”

Biotransformation-coupled mutasynthesis for the generation of novel pristinamycin derivatives by engineering the phenylglycine residue

“…Antibiotics are undoubtedly the most important and impactful medical advancement of all time and a cornerstone of modern medicine. 1,2 However, the rapid emergence of (multi)drugresistant pathogens endangers their efficacy and poses a serious threat to global human health. 3 According to a recent estimate, more than 1.2 million people died worldwide in 2019 due to drug-resistant bacterial infections.…”