[Pathogenetic conditions of treatment of infections caused by antibiotic-resistant strains Klebsiella pneumoniae]

Abstract

Klebsiella pneumoniae belongs to the Enterobacteriaceae family and is responsible for 70% of human infections. From 20 to 80% strains of Klebsiella pneumoniae reveal resistance to first line antibiotics, including cephalosporins, fluoroquinolones and aminoglycosides, as well as carbapenems. Due to the resistance found in MDR (multidrug resistant) Klebsiella pneumoniae is classified according to the sequence types (ST), which are defined on the basis of the nucleotide sequence in the 7 loci (mdh, infB, tonB, gapA, phoE, pgi, and rpoB). Klebsiella pneumoniae uses several methods to protect against the effects of the human immune system. It affects receptors that recognize patterns expressed on epithelial cells and the immune system that are responsible for initiating signal cascades and phagocytic influences, including Toll-like receptors (TLRs) 2 and 4. Activates interleukins (IL) 12 (IL-12) and IL-23p40 by natural stimulation and leads to a decrease in the level of activation of interferon gamma (IFN-γ), IL-17, tumor necrosis factor (TNF-α) and IL-1β, resulting in neutrophil and macrophage inflow and induction of humoral and cellular responses. Capsular polysaccharides and other components of the bacterial cell membrane protect it from the natural mechanisms of resistance, making it resistant to beta-defensins against bacteria. Increased virulence of Klebsiella pneumoniae is related to the protein structure associated with the capsule, especially in strains with increased virulence (HV - hypervirulent), lipopolysaccharides (LPS), siderophores and cilia (fimbriae). Today, two main types of Klebsiella pneumoniae strains are distinguished depending on the mechanism of resistance to antibiotics: strains that express beta-lactamases with extended spectrum (ESBL - extended spectrum beta-lactamases) that are resistant to cephalosporins and monobactams and strains that reveal the expression of carbapenemases, which they show resistance to available beta-lactams, including carbapenes. Polymyxins are useful in the treatment of patients infected with Klebsiella pneumoniae NDM (New Delhi metallo-beta-lactamase), where the effectiveness of therapy is greater when colistin is used together with carbapenem or rifampicin or tigecycline. The introduced abivactam in combination with ceftazidime is a promising therapeutic combination in severe infections. Similar clinical assessments were obtained with sulbactam, especially in combination with meropenem and colistin.

Keywords: Klebsiella pneumoniae; pathomechanism; resistance; treatment.