Effect of combinations of antibiotics, phages, and depolymerase on biofilms of the drug-resistant Klebsiella pneumoniae strain

Introduction . Klebsiella pneumoniae poses a serious threat to global healthcare due to the high proportion of multidrug-resistant isolates. Moreover, the formation of biofilms by bacteria significantly complicates the treatment of infections. Objective . To evaluate the effectiveness of the individual and combined action of antibiotics and bacteriophages or polysaccharide depolymerase on biofilms of a clinically significant strain K. pneumoniae . Materials and methods . The work used the K. pneumoniae strain with multidrug resistance (9faiz), 4 antibiotics of various classes (gentamicin, levofloxacin, meropenem and chloramphenicol), 3 bacteriophages of various genera (Dlv622, Seu621 and FRZ284), and 1 polysaccharide depolymerase (Dep622). Experiments were carried out on the formed biofilms by treating 24-hour K. pneumoniae films with antimicrobial agents individually or in combinations. The ability of the strain to form biofilms was evaluated by staining with crystalline violet. The comparison between the average optical density values was carried out using a t-test and was considered significant at p ≤ 0.05. Results . The individual use of antibiotics peak concentrations (C max ) or depolymerase concentration of 100 MED (minimum effective dose — MED) did not lead to a significant decrease in biofilm biomass, whereas bacteriophages in a titer of 5×10 9 PFU/mL (plaque-forming unit per mL) statistically significantly reduced its biomass by 27–31% (p < 0.05) Most combinations of phages and antibiotics did not lead to a significant increase in the efficiency of biofilm destruction. Only the combination of phage FRZ284 with gentamicin statistically significantly showed an additional decrease in biofilm biomass by 27% (p < 0.05). Conclusions . The results show the need for individual selection of antimicrobial combinations to combat K. pneumoniae biofilms due to the possible effect of synergy and antagonism effects on the outcome of therapy.