Susceptibility to antibiotic combinations among nosocomial carbapenemase-producing Gram-negative bacteria isolated in Belarus

Abstract

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.