Addressing the antimicrobial resistance crisis

Over the past decade, Klebsiella pneumoniae has emerged as a major clinical and public health threat. In this Review, Wyres, Lam and Holt discuss how genomics approaches have advanced our understanding of K. pneumoniae taxonomy, ecology and evolution as well as the diversity and distribution of clinically relevant determinants of pathogenicity and antimicrobial resistance.

In this Review, Berman and Krysan define and distinguish resistance and tolerance, and discuss the current understanding of the molecular, genetic and physiological mechanisms that contribute to those phenomena. Distinguishing tolerance from resistance might provide important insights into the reasons for treatment failure in some settings.

In this Review, van Belkum and colleagues discuss routinely used antimicrobial susceptibility testing (AST) methods, explore current efforts to improve phenotypic AST systems — including new emerging technologies as well as genomic and gene-based antimicrobial resistance detection methods — and highlight the challenges and opportunities for new rapid AST systems.

With rising rates of antibiotic resistance, it is essential that new antibiotics are developed. In this Review, Theuretzbacher et al. take stock of the preclinical antibiotic pipeline and discuss challenges and opportunities for the discovery and development of novel antibacterial therapies.

New antibacterial agents are urgently needed to address the global increase in resistance. In this Review, Theuretzbacher and colleagues critically review the current published literature and publicly available information on antibacterial agents in all phases of clinical development.

In this Viewpoint article, seven experts discuss the challenges that are contributing to the decline in antibiotic drug discovery and development, and the international and national initiatives aimed at incentivizing research and the development of new antibiotics to improve the economic feasibility of antibiotic development.

The continued rise in antimicrobial resistance shows that the current efforts to combat the crisis are not enough. More global leadership from policymakers and the industry is needed.

To control antimicrobial resistance (AMR) will require approaches to develop, share and preserve antibiotics that are scaled to the scientific, economic and ethical dimensions of the crisis. The three cooperative, interdisciplinary, international councils proposed in this Comment by Carl Nathan exemplify what this will require.

Resistance to the current first-line antimalarials threatens the control of malaria caused by Plasmodium falciparum and underscores the urgent need for new drugs with novel modes of action. Small-Saunders, Hagenah and Fidock present the argument that the parasite’s chloroquine resistance transporter (PfCRT) constitutes a promising target to combat multidrug-resistant malaria.

This month’s Genome Watch examines how novel machine learning-enabled molecular diagnostic approaches can predict antibiotic resistance when ge-netic variation falls short.

This study finds that phages produced by Pseudomonas aeruginosa form a shield around the bacteria and protect them from antibiotics.

This study developed an assay to screen for drugs that inhibit transfer of antimicrobial resistance plasmids between bacteria.

This study used deep sequencing to identify a super-spreading event of Mycobacterium tuberculosis.

A large screen for antimalarial drugs identified protease inhibitors that target three stages of the malaria parasite.

This study found that pathogen transmission from vaccinated hosts to contact individuals can cause a reduction in virulence.