Objective. To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Materials and Methods. The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics. Results. Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%). Conclusions. The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.

Objective. To assess the possibility of standard disk application as an antibiotic source for determination of the minimal inhibitory concentrations (MICs) by serial microdilution method. Materials and Methods. A simple method of working solutions preparation using standard paper discs as an antibiotics source available in most microbiological laboratories is proposed. A multiple determination of antibiotic MICs for E. coli ATCC 25922 and P. aeruginosa ATCC 27853 strains was conducted. Results. Of the 576 MIC values determined by the modified method, 78.5% of the results corresponded to the control strains reference values, and 20.8% of the results were categorized as acceptable values. Conclusions. Use of standard disks as an antibiotics source for the working solutions preparation greatly simplifies a testing by serial microdilution method and makes it available to most microbiological laboratories.

Objective. To assess a susceptibility to antibiotic combinations in nosocomial carbapenemase-producing Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolates using a modified method of multiple combination bactericidal testing (MCBT). Materials and Methods. A total of 178 isolates (63 K. pneumoniae isolates, 31 P. aeruginosa isolates, 84 A. baumannii isolates) obtained in the 2013-2017 from hospitalized patients in 28 public health organizations in 4 Belarus regions were included in the study. All isolates were producers of the different carbapenemases (OXA-48, KPC, NDM, VIM, OXA-23, and OXA-40). The susceptibility to antimicrobial agents was determined by an automated method and a broth microdilution method. A modified MCBT method was used for determination of susceptibility to antibiotic combinations. Antibiotic concentrations corresponding to the threshold pharmacokinetic/pharmacodynamics (PK/PD) concentrations for standard doses of antimicrobial agents were used for testing antibiotic combinations. A total of 11 primary and 11 additional antibiotic combinations were tested. Results. The meropenem MIC values were 4 or more times higher than the threshold PK/PD concentrations for most isolates studied. A total of 42.9% of K. pneumoniae strains, 51.6% of P. aeruginosa strains and 2.4% of A. baumannii strains were non-susceptible to colistin. Using the modified MCBT method, antibiotic combinations with bactericidal activity were detected for 177 (99.4%) isolates; 3 or more antibiotic combinations were bactericidal for 155 isolates (87.1%). The colistin-containing combinations were the most active, including against isolates with colistin MIC values above the threshold PK/PD concentration. The bactericidal activity of meropenem + amikacin and amikacin + levofloxacin combinations against 51.9% of K. pneumoniae colistin-resistant isolates was determined. The meropenem + colistin (85.7%) and imipenem + colistin (84.1%) combinations were the most active against P. aeruginosa. All the colistincontaining combinations were bactericidal against nearly 100% of A. baumannii isolates. Conclusions. Species-level and strain-level specificity of bactericidal activity for the different antibiotic combinations was found.

Aim of research. To study resistance levels to different antibiotics of pyelonephritis etiologic agents, revealing of extended-spectrum beta-lactamases producers among agents and development of an algorithm of microbiological diagnostics and rational antibacterial therapy of pyelonephritis. Materials and methods. A total of 115 clinical strains of enterobacteria (70 - Escherichia coli , 35 - Proteus spp. , 10 - Klebsiella pneumoniae ) isolated from urine of patients with acute and chronic pyelonephritis were included in the research. The sensitivity of microorganisms to antibacterial agents was determined by disc diffusion method. The extended-spectrum beta-lactamases (ESBL) production was carried out by using the double disk diffusion method. The genodetection of ESBL of various groups in etiologic agents of pyelonephritises was determined by means of polymerase chain reaction (PCR). Results. The resistance of microorganisms, etiologic agents of pyelonephritises to antibiotics of various groups was evaluated. The study revealed high prevalence of extended-spectrum β-lactamases producers concerning to CTX-M group. Conclusion. The data obtained during the study about levels and resistance mechanisms of enterobacteria to antibacterial agents of different groups were the base for development of the algorithm of microbiological diagnostics and rational antibacterial therapy of pyelonephritis.

Objective : to estimate the resistance prevalence of P. aeruginosa to antipseudomonal antibiotics and reveal metallo-beta-lactamases producers among carbapenem resistant clinical isolates. Materials and methods. The subject of the study is clinical isolates of P. aeruginosa resistant to antibacterial drugs. The resistance of P. aeruginosa clinical isolates to antipseudomonal antibiotics was estimated, antimicrobial resistance phenotypes and associated resistance variants were analyzed, and production of metallo-beta-lactamases was detected using phenotypical screening method. Results. High levels of P. aeruginosa resistance to the most of antibacterial drugs, except carbapenems, were revealed. The local features of antimicrobial resistance in different hospitals were established. A total of 19 metallo-beta-lactamase producers were isolated in 6 hospitals of three republican regions. All metallo-beta-lactamase producers have the same phenotype, indicating of clonal prevalence. No carbapenem resistant isolates was resistant to colistin. Conclusion. It is necessary to carry out multi-facet research aimed at the detection of carbapenem resistance mechanisms and epidemiological marking of resistant isolates in order to reveal epidemically significant P.aeruginosa metallo-beta-lactamase producing clones in time and to develop the infection control measures to restrain its circulation.