In vitro synergistic activity of fosfomycin in combination with other antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae isolated from patients in a hospital in Thailand

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes high morbidity and mortality worldwide. The purpose of the study was to assess the synergistic activity of fosfomycin in combination with other antimicrobial agents against CRKP isolated from patients in Songklanagarind Hospital, Thailand. Methods: A total of 35 K. pneumoniae isolates were obtained from patients in Songklanagarind Hospital. The MICs of imipenem and meropenem were determined in all isolates by broth microdilution. In all CRKP isolates, the presence of carbapenemase and extended-spectrum beta-lactamase (ESBL) genes was investigated by PCR, while the production of these enzymes was determined by combined disk test. In the carbapenemase-genes-negative CRKP isolates, the porin loss and efflux pump were characterized by SDS-PAGE and broth microdilution, respectively. Finally, the synergistic effects of fosfomycin and other antimicrobial agents were evaluated by checkerboard analysis. Results: Twenty-one of 35 K. pneumoniae isolates were classified as CRKP. Most of CRKP isolates carried bla(NDM-1) (n = 18), bla(SHV) (n = 21), bla(CTX-M) (n = 21), and bla(TEM) (n = 16). In fosfomycin-based combination, the result showed that the highest synergistic activity in this study was observed in the combination of fosfomycin and gentamicin (61.9%). Conclusion: These findings suggested that the fosfomycin and gentamicin combination might be useful as a possible treatment option for CRKP infection. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study assessed the synergistic activity of fosfomycin in combination with other antimicrobial agents against CRKP, with promising results for the combination of fosfomycin and gentamicin. These findings suggest that this combination could be a useful treatment option for CRKP infection.