Carbapenem-resistant Klebsiella pneumoniae in the Balkans: Clonal distribution and associated resistance determinants.

Carbapenems are considered to be among the last line antibiotics against extended-spectrum ß-lactamase producing Enterobacterales. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been frequently reported and its spread in Europe is indisputable and poses an enormous threat to hospitalized patients which is of growing concern. This review aims to record prevalence of CRKP in the Balkan region and to review the current knowledge about this life-threatening pathogen. In this review, we summarize data about clinical isolates of carbapenem-resistant K. pneumoniae from Greece, Croatia, Romania, Bulgaria, Serbia, Slovenia, Montenegro, Bosnia-Herzegovina and Albania from published reports between 2000 and 2023. Among Balkan countries, Greece and Romania are the ones with the most reports about CRKP. Since 2007, KPCs are the dominant carbapenemases in both countries. KPC-2 and NDM-1-producing K. pneumoniae strains have been identified as the most frequent CRKP in Croatia, Bulgaria, Serbia, and Slovenia. OXA-48 enzyme has been identified in most Balkan countries. In addition, since 2018, CRKP sequence type 11 (ST11) seems to have replaced ST258 in Balkan Peninsula, while ST15 continues to thrive throughout the years. Not only efficacy of colistin against CRKP has decreased dramatically during the last ten years but colistin resistance mechanism is based on alterations of chromosomal mgrB gene, rather than the already known mcr genes.Moreover, ceftazidime-avibactam-resistant CRKP were detected mostly in Greece. Emergence of CRKP poses a severe threat to the Balkan countries. Due to the narrow therapeutic window, it is essential to prevent the spread of multiresistant K. pneumoniae strains.

mcr Genes Conferring Colistin Resistance in Enterobacterales; a Five Year Overview.

The present review aims to study and detect the global emergence of mcr genes in E. coli, K. pneumoniae and Salmonella spp., isolates from human specimens over the last six years. Nowadays the rise of multidrug-resistant superbugs has made essential the return of drugs that were previously abandoned. A clear example is colistin, which acts against multidrug - resistant gram - negative pathogens, including Enterobacterales. Colistin resistance is an unfortunate fact, with the emergence of mcr genes conferring resistance to colistin in Enterobacterales posing the most recent threat. Literature about mcr genes and their spread in E. coli, K. pneumoniae and Salmonella spp. is cited, focusing on the emergence of mcr genes in human specimens since 2015. The data were taken from the PubMed and Scopus databases. It seems that the mcr-1 gene continues to be the protagonist among the three species. E. coli is the dominant species harbouring mcr genes. Moreover, plasmid - mediated colistin resistance is also conferred upon other species that carry different genes resistant to antibiotics. There are only scarse reports on human Salmonella spp isolates harbouring mcr genes. Finally, the emergence of the mcr-9 gene in all of them is quite remarkable. CONCLUSION: Plasmid - mediated colistin resistance in Enterobacterales is a global issue and has been worsening over the years. The continuous mutations of mcr gene subtypes underline the need for better surveillance, constant investigation and wise use of colistin, especially in countries with high levels of antibiotic resistance.