Technologies to address antimicrobial resistance

Abstract

Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.

Keywords: AMR; antibiotics; bacterial infections; vaccines.

Fig. 1.

Percentage of Enterobacteriaceae strains from a US surveillance study that show increasing resistance to 10 antibiotics over a 10-year period. Data from Rhomberg and Jones (2).

Fig. 2.

Increase in predicted efficacious dose of GSK1322322 from 726 mg BID (1.45 g⋅d⁻¹) at candidate selection to 1,500 mg BID (3 g⋅d⁻¹) by phase 2.

Fig. 3.

Total upper daily dose of common antibiotics compared to drugs approved in 2013 from other therapy areas. Body weight of 70 kg was used for doses given as milligrams per kilogram of body weight (10, 11). CNS, central nervous system; CV, cardiovascular; Metab Dis, metabolic disease.

Fig. 4.

Evolution of vaccine technologies and platforms. CMV, cytomegalovirus; GAS, group A Streptococcus; GBS, group B Streptococcus; HBV, hepatitis B virus; HCV, hepatitis C virus; HEV, hepatitis E virus; Hib, type B Haemophilus influenzae; HIV, human immunodeficiency virus; HPV, human papillomavirus; MenA, meningococcus A; MenACWY, meningococcus ACWY; MenB, meningococcus B; MenC, meningococcus C; Pneumo, pneumococcus; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; VLP, virus-like particles.