Rising antibiotic resistance is a global threat that is projected to cause more deaths than all cancers combined by 2050. In this review, we set to summarize the current state of antibiotic resistance, and to give an overview of the emerging technologies aimed to escape the pre-antibiotic era recurrence. We conducted a comprehensive literature survey of >150 original research and review articles indexed in the Web of Science using “antimicrobial resistance,” “diagnostics,” “therapeutics,” “disinfection,” “nosocomial infections,” “ESKAPE pathogens” as key words. We discuss the impact of nosocomial infections on the spread of multi-drug resistant bacteria, give an overview over existing and developing strategies for faster diagnostics of infectious diseases, review current and novel approaches in therapy of infectious diseases, and finally discuss strategies for hospital disinfection to prevent MDR bacteria spread.

Background Klebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage. Methods We computationally analyzed a large collection of K. pneumoniae ST395 genomes (n = 297) both sequenced in this study and reported previously. By applying multiple bioinformatics tools, we investigated the core-genome phylogeny and evolution of ST395 as well as distribution of accessory genome elements associated with antibiotic resistance and virulence features. Results Clustering of the core-SNP alignment revealed four major clades with eight smaller subclades. The subclades likely evolved through large chromosomal recombination, which involved different K. pneumoniae donors and affected, inter alia, capsule and lipopolysaccharide antigen biosynthesis regions. Most genomes contained acquired resistance genes to extended-spectrum cephalosporins, carbapenems, and other antibiotic classes carried by multiple plasmid types, and many were positive for hypervirulence markers, including the siderophore aerobactin. The detection of “hybrid” resistance and virulence plasmids suggests the occurrence of the convergent ST395 pathotype. Conclusions To the best of our knowledge, this is the first study that investigated a large international collection of K. pneumoniae ST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage.

Background: The dissemination of mobile colistin resistance (mcr) genes is a serious healthcare threat because polymyxins represent “last-line” therapeutics for multi-drug-resistant Gram-negative pathogens. This study aimed to assess the prevalence of colistin resistance and mcr genes and characteristics of clinical Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) isolates and plasmids carrying these genes in Russia. Methods: A total of 4324 Eco and 4530 Kpn collected in the frame of sentinel surveillance in 2013–2018 were tested for susceptibility to colistin and other antibiotics using the broth microdilution method. mcr genes were screened by real-time PCR. Phylogeny, genomic features and plasmids of mcr-positive isolates were assessed using whole-genome sequencing and subsequent bioinformatic analysis. Results: Colistin resistance was detected in 2.24% Eco and 9.3% Kpn. Twenty-two (0.51%) Eco and two (0.04%) Kpn from distant sites carried mcr-1.1. Most mcr-positive isolates co-harbored ESBLs and other resistance determinants to various antibiotic classes. The mcr-positive Eco belonged to 16 MLST types, with ST359 being most common; Kpn belonged to ST307 and ST23. mcr-1.1 was carried mainly in IncI2 (n = 18) and IncX4 (n = 5) plasmids highly similar to those identified previously in human, animal and environmental isolates. Conclusion: This study demonstrated a dissemination of “typical” mcr-bearing plasmids among diverse Eco and Kpn genotypes and across a wide geographic area in Russia. Given the frequent association of mcr with other resistance determinants and potential clinical impact, the continual surveillance of this threat is warranted.