In vitro Investigation of Antibiotic Combinations against Multi- and Extensively Drug-Resistant Klebsiella pneumoniae

Abstract

Objectives: Community and hospital acquired K. pneumoniae infections have become a ubiquitous medical issue due to the limited treatment options and high mortality rate therefore the aims of this study are in vitro investigation of double antimicrobial combinations against multidrug resistant (MDR) and extensively drug resistant (XDR) isolates. Materials and Methods: Antimicrobial susceptibility of twelve isolates from eight Bulgarian hospitals was determined to study the interaction effect of selected double combinations in accordance to fractional inhibitory concentration (FIC) method. Furthermore, the isolates were subjected to genotyping by Multilocus sequence typing (MLST) and detection of carbapenemase genes by multiplex PCR. The results were assessed by groups of strains with either NDM or KPC carbapenemase. Results: Nine antimicrobial combinations: meropenem-colistin, meropenem-fosfomycin, meropenem-gentamicin, meropenem-rifampicin, meropenem-tigecycline, colistin-fosfomycin, colistin-gentamicin, colistin-rifampicin and colistin-tigecycline were tested for synergism on twelve K. pneumoniae, producing either KPC-2 (KPC-KP, 41.7%, 5/12) or NDM-1 (NDM-KP, 58.3%, 7/12). The isolates were distributed in three sequence types: ST11 (58.3%, 7/12), ST15 (25%, 3/12) and ST258 (16.7%, 2/12). All KPC-KP (ST258 and ST15) originated from three hospitals. The rest were NDM-1 carriers isolated from six hospitals and belonged to ST11. The highest synergistic effect was determined for MER-GEN (83.3%, 10/12) and COL-RIF (83.3%, 10/12). The MER-FOS combination was most efficient against NDM-KP, opposite to the KPC strains. Antagonism was not observed for any combinations. Conclusions: The evaluated joint synergistic effect of the MER-GEN and COL-RIF may facilitate the treatment options for patients infected with NDM- and KPC-KP, whereas MER-FOS is highly synergetic against NDM-KP.