In vivo adaptive antimicrobial resistance in Klebsiella pneumoniae during antibiotic therapy

Abstract

Klebsiella pneumoniae is one of the leading pathogens contributing to antimicrobial resistance. The emergence of carbapenem-resistant K. pneumoniae (CRKP) has put the use of clinical antimicrobial agents in a dilemma. In particular, CRKP exhibiting resistance to ceftazidime/avibactam, tigecycline and colistin have raised great clinical concern, as these are the last-resort antibiotics for the treatment of CRKP infections. Within-host evolution is a survival strategy closely related to the emergence of antimicrobial resistance, while little attention has been paid to the in vivo genetic process of conversion from antibiotic-susceptible to resistant K. pneumoniae. Here we have a literature review regarding the in vivo evolution of resistance to carbapenems, ceftazidime/avibactam, tigecycline, and colistin in K. pneumoniae during antibacterial therapy, and summarized the detailed resistance mechanisms. In general, acquiring blaKPC and blaNDM harboring-plasmid, specific mutations in blaKPC, and porin genes, such as ompK35 and ompK36, upregulation of blaKPC, contribute to the development of carbapenem and ceftazidime/avibactam resistance in vivo. Overexpression of efflux pumps, acquiring plasmid-carrying tet (A) variants, and ribosomal protein change can lead to the adaptive evolution of tigecycline resistance. Specific mutations in chromosomes result in the cationic substitution of the phosphate groups of lipid A, thus contributing to colistin resistance. The resistant plasmid might be acquired from the co-infecting or co-colonizing strains, and the internal environment and antibiotic selection pressure contribute to the emergence of resistant mutants. The internal environment within the human host could serve as an important source of resistant K. pneumoniae strains.

Molecular evaluation of aminoglycosides resistance and biofilm formation in Klebsiella pneumoniae clinical isolates: A cross‐sectional study

“…Clonal complex 258 (CC258) is one of the CRKP clones disseminating all over the world 6 . In particular, CRKP exhibiting resistance to colistin and tigecycline have raised important clinical concern, as these are the last‐line drugs for the treatment of these isolates 7 . The worldwide prevalence of colistin‐resistant K. pneumoniae simplified by chromosomal and plasmid‐mediated LPS changes have steadily increased with increased colistin usage for treating CRKP isolates 8 .…”

“…6 In particular, CRKP exhibiting resistance to colistin and tigecycline have raised important clinical concern, as these are the last-line drugs for the treatment of these isolates. 7 The worldwide prevalence of colistin-resistant K. pneumoniae simplified by chromosomal and plasmid-mediated LPS changes have steadily increased with increased colistin usage for treating CRKP isolates. 8 Colistin-resistant K. pneumoniae infections are increasing in intensive care units, particularly in patients who ultimately depend on vascular catheters for long-term or shortterm use.…”

Comparison of bloodstream and non-bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae in the intensive care unit: a 9-year respective study

“…In our study, we have identified the prior use of carbapenems within 90 days as an independent risk factor for CRKP BSIs. It is possible that the production of carbapenemase and porin deficiency contribute to carbapenem resistance in K. pneumoniae during carbapenem therapy ( 30 ). And clinical retrospective analysis has revealed that previous exposure to carbapenems has been proven to have a significant correlation with the acquisition of CRKP compared to CSKP ( 17 ).…”

Interactions and Implications of Klebsiella pneumoniae with Human Immune Responses and Metabolic Pathways: A Comprehensive Review

“…Research has also unveiled the emergence of ceftazidime/avibactam resistance in clinical strains during antimicrobial treatment, attributed to specific mutations in the bla_KPC gene. 45 …”